ANION SENSING IN POLAR MEDIA BY FLUORECENT SMALL 
MOLECULE RECEPTORS VIA HALOGEN BONDING 
by 
HANNAH JOSEPHINE BATES 
A DISSERTATION 
Presented to the Department of Chemistry and Biochemistry 
and the Division of Graduate Studies of the University of Oregon 
in partial fulfillment of the requirements 
for the degree of 
Doctor of Philosophy 
September 2022 
DISSERTATION APPROVAL PAGE 
Student: Hannah Josephine Bates 
Title: Anion Sensing in Polar Media by Fluorescent Small Molecule Receptors via 
Halogen Bonding 
This dissertation has been accepted and approved in partial fulfillment of the 
requirements for the Doctor of Philosophy degree in the Department of Chemistry and 
Biochemistry by: 
Dr. Ramesh Jasti Chairperson 
Dr. Darren Johnson Co-Advisor 
Dr. Michael Haley Co-Advisor 
Dr. Amanda Cook Core Member 
Dr. Keat Ghee Ong Institutional Representative 
and 
Krista Chronister Vice Provost for Graduate Studies 
Original approval signatures are on file with the University of Oregon Division of Graduate 
Studies. 
Degree awarded September 2022.  
ii 
© 2022 Hannah Josephine Bates 
iii 
DISSERTATION ABSTRACT 
Hannah Josephine Bates 
Doctor of Philosophy 
Department of Chemistry and Biochemistry 
September 2022 
Title: Anion Sensing in Polar Media by Fluorescent Small Molecule Receptors via 
Halogen Bonding 
Anions are a ubiquitous class of molecule which play critical roles in 
many of the environments with which humans concern themselves. From our physiology 
to nuclear waste to our water supply, anions have been the focus of much of the host-
guest chemistry to have emerged within the last five decades. Host-guest chemists have 
used supramolecular tools, including halogen and hydrogen bonding, along with many 
others, to reversibly binding these and many other analytes. The purposes of binding are 
as wide ranging as real-time molecular recognition, catalysis, mechanically interlocked 
molecules, purification, and many others. Due to the many factors that can contribute to 
the efficacy of host-guest systems, including solvent effects, pocket size, molecular 
geometry, pH and others, most systems must be fined tuned for their particular 
application. One frequently encountered challenge is the competitive nature of any polar 
solvents, especially water, in solution state binding. Halogen bonding has recently come 
onto the scene as a potential answer to this problem, often demonstrating higher binding 
affinities than comparable hydrogen bonding molecules in polar environments. Despite 
its promise, much remains to be learned about how to best deploy halogen bonding 
motifs. 
iv 
This lacuna motivates the work covered in this thesis, which explores the design 
principles behind incorporating halogen bond donors effectively in a variety of 
arylethynyl; systems which were inspired by similar hydrogen bonding scaffolds 
published by the Johnson and Haley groups. After examining the successes and pitfalls of 
these halogen bond receptors in Chapter 3, Chapters 4 and 5 go on to report on the use of 
halogen bond and hydrogen bond systems in tandem, which are shown to bind the 
chloride anion notably well in appreciably polar organic solvents. These studies, suggest 
that the accepted definition of a halogen bond, as presented by IUPAC and discussed in 
Chapter 1, biases chemists to place undue importance on ensuring that the location of a 
polarizing group is as close as possible to the halogen-bond donor. Finally, future studies 
that can help flush out the ideas established in this thesis are reviewed in Chapter 6.  
This dissertation includes published and unpublished co-authored material. 
v 
CURRICULUM VITAE 
NAME OF AUTHOR: Hannah Josephine Bates 
GRADUATE AND UNDERGRADUATE SCHOOLS ATTENDED: 
University of Oregon, Eugene 
Sarah Lawrence College, Bronxville 
DEGREES AWARDED: 
Doctor of Philosophy, Chemistry, 2022, University of Oregon 
Master of Science, Chemistry, 2022, University of Oregon 
Bachelor of Art, Chemistry, 2018, Sarah Lawrence College 
AREAS OF SPECIAL INTEREST: 
Physical Organic Chemistry 
Supramolecular Chemistry  
Anion Recognition  
Halogen Bonding  
PROFESSIONAL EXPERIENCE: 
Associate Scientist, Thermo Fisher Scientific, May – December 2021 
Graduate Research Fellow, University of Oregon, 2019 – 2022  
Graduate Teaching Fellow, University of Oregon, 2018 – 2019 
GRANTS, AWARDS, AND HONORS: 
ARCS Scholar Award, ARCS Foundation Oregon, 2018-2021 
PUBLICATIONS: 
H. J. Bates, T. P. de Faria, A. S. Trom, F. I. D. Longnight, M. P. Miller, L. N. Zakharov, 
M. M. Haley & D. W. Johnson, manuscript in prep.
T. P. de Faria, H. J. Bates, A. S. Trom, F. I. D. Longnight, M. P. Miller, L. N. Zakharov, 
M. M. Haley & D. W. Johnson, manuscript in prep.
vi 
  
J. P. Bard, H. J. Bates, C.-L. Deng, L. N. Zakharov, M. M. Haley, J. Org. Chem. 2019, 
acs.joc.9b02132. 
 
 
  
 
 
vii 
  
ACKNOWLEDGMENTS 
 
I would like to take this space to thank the countless people who offered me 
support through my time in grad school as well as before it. Let me begin by thanking my 
parents, who kept a home secure enough that my curiosity could grow uninhibited and 
were always a source of unconditional love. I also am so grateful to my younger siblings, 
Mason, Austin and Riley who, despite their youth, never fail to inspire me with their 
amazing strengths. Another thank you is deserved by the many STEM students at Sarah 
Lawrence College including: Brooke, Isabella, Ellie, Ella, Sarah, and so many others; 
there was such a beautiful and tight-knit, field-spanning scientific community at SLC and 
it wouldn’t have existed without you guys. Another shout out to Emma, Ollie, and Jules 
for being friends I could talk to when I needed a break from science. Finally, a thank you 
to my many amazing professors from SLC, who taught me so much; Prof. Mike Siff and 
Prof. Colin Abernethy deserve a special shout out. As an advisor, Mike ensured that all of 
his mentees knew exactly how seriously we should take college (reminding all of us that 
school was not “real life”, no matter how important it felt) and helping me keep a cool 
head until the calmer winds prevailed once again. As a lecturer, Colin transferred his 
enthusiasm for the field of chemistry to every student who walked through his doors; 
beyond being just engaging though, Colin was a safe harbor for any question, chemistry 
related or not, he was already ready to lend a hand or an ear as the situation required. 
Without the support of all of the aforementioned people I would have never made it all 
the way to grad school.  
 This brings me to the myriad of amazing people that I have met in grad school. 
First, let me thank my advisors, Professors Darren Johnson and Mike Haley who have 
viii 
done an admirable job wrangling much of my chaotic energy into a productive four-year 
stint here at UO. Thanks to my other committee members, Ramesh Jasti, Amanda Cook 
and Keat Ghee Ong, who all gave me both the opportunity to graduate and some amazing 
advice my 3rd year that I still think about frequently. Another thank you to my advisors 
from Thermo Fisher, Adam York, Dan Cash and Eric Welch who made sure that my 6 
months there were filled with lots of learning and laughs alike. Also, a huge shout out to 
the front office staff at UO, Janet, Christi, Kathy, Jim and Rob who keep this program 
running and the people in it as happy as possible.  
Next let me give a hearty thank all of my labmates, past and present, in the DWJ, 
Haley labs and beyond – Jess, Sean, Merideth, Jordan, Hazel, Josh, Jeremy, Chun-lin, 
Trevor, Ngoc-Minh, Jacob, Henry, Thaís, Scout, Faith, Luca, Willow, Alex, Grace, Ben, 
Jack, Kiana, Efrain, Nolan, Gabby, Bella, Allison, Nick, Olivia, Mark, Russell and Haley 
– the amazing people that I met in grad school were easily my favorite part of the
experience. Jeremy, Chun-lin, Jess, Hazel, and Thaís you guys have taught me so much 
and never fail to pick up the phone when I need advice or to bounce ideas off of 
someone. Jordan, you made every new member to the lab (myself included) feel so 
welcome when they joined and were always the first to person make the fun-loving and 
balanced culture of our lab a talked-about priority. Sean, you introduced me to 
motorcycles and consequently ensured every day to and from work was something to 
smile about. Thaís, Scout and Faith whether board games or titrations you guys saturated 
every moment with fun, love and support and I am unspeakably grateful for our palio-
ship. Willow, Luca and Alex I am so happy my time here has overlapped with your own 
and that I can leave knowing that the lab is in good hands that will continue to guide it 
ix 
  
steadily. Ben, you have been such an amazing friend, housemate and confidant for the 
past four years and know that Massachusetts is a great spot to consider for your post grad 
school aspirations.  
Finally thank you to my fiancé, David. The past seven years have been filled with 
things that I never could have expected but together we handled them with so much more 
grace than I ever could have alone, and I am so grateful for the support, sage advice, good 
food and comfort that you never seem to run out of. No matter what the lab held for me I 
always look forward to coming home to you and Ezra and Kali (our two desperately 
snuggly kittens that never fail to put a smile on my face).  
 
x 
To David and Thaís – 
The past several years have often been trying, but that hardship was always salved by your 
generous love and friendship. Both of you, in your own inimitable ways, have  
shown me new and beautiful meanings to the word “partner”  
and I could not be more grateful to have you in my life. 
xi 
TABLE OF CONTENTS 
Chapter Page 
I. INTRODUCTION  ................................................................................................... 1 
II. AMPLIFICATION OF THE QUANTUM YIELDS OF 2‐λ5‐PHOSPHA- 
QUINOLIN-2-ONES THROUGH PHOSPHORUS CENTER MODIFICATION .... 11 
2.1 Introduction ...................................................................................................... 11 
2.2 Results and Discussion .................................................................................... 13 
2.3 Conclusion ....................................................................................................... 19 
2.4 Experimental Section ....................................................................................... 20 
III. TOWARDS THE MOLECULAR RECOGNITION OF THE HYDROSULFIDE
AND CHLROIDE ANIONS WITH AN ARYL ETHYNYL RECEPTOR ................ 25 
3.1 Introduction to DWJ-Haley Lab Receptors and Halogen Binding .................. 25 
3.2 Methods............................................................................................................ 28 
3.3 Results and Discussion .................................................................................... 30 
3.4 Conclusion ....................................................................................................... 36 
IV. SUBSTITUENT EFFECTS IN A SERIES OF COMPACT ARYLETHNYL
“MONODENTATE” HALOGEN BONDING HOSTS FOR ANION ....................... 38 
4.1 Introduction ...................................................................................................... 38 
4.2 Results and Discussion .................................................................................... 40 
4.3 Conclusion ....................................................................................................... 48 
V. FUTURE RECEPTORS AND FUTURE DIRECTIONS: AN UPDATE ON
CURRENT WORK AND WHERE IT IS GOING...................................................... 49 
5.1 Introduction ...................................................................................................... 49 
xii 
Chapter Page 
5.2 Synthesis of Tridentate Hybrid Receptor 1 ...................................................... 50 
5.3 Results and Discussion of Tridentate Hybrid Receptor 1 ................................ 51 
5.4 Synthesis of Quinoline-Based Receptor 2 ....................................................... 53 
5.5 Computation Work with Library of Receptors ................................................ 55 
5.5 Conclusion ....................................................................................................... 57 
VI. CONCLUSION...................................................................................................... 58
APPENDICES ............................................................................................................. 61 
A. Supplementary Information For Chapter 2 ....................................................... 61 
B. Supplementary Information For Chapter 3 ....................................................... 113 
C. Supplementary Information For Chapter 4 ....................................................... 122 
D. Supplementary Information For Chapter 4 ....................................................... 181 
REFERENCES CITED ................................................................................................ 203 
xiii 
  
LIST OF FIGURES 
 
Figure Page 
 
 
1. Figure 1.1 – Examples from the literature of phosphate receptors  
 containing a) bis-urea motifs, b) hydrogen-bond donors and ferrocene  
 motifs, and c) indoles. ............................................................................................ 03 
2. Figure 1.2 – Receptor scaffolds for a) Gen 1, hydrogen-bonding where X=N,  
 N+–R, CH; R= H, Me, F, OMe; R'= H, tBu, CF3, SO2Me, SO2CF3 ; R''= H,  
 NO2, CF3, OMe and b) Gen 2, halogen bonding where X=N, CH; R= H, Me,  
 R'= H, tBu, CF3, SO2Me, SO2CF3; Z= H, I, Br. The central aromatic ring  
 containing X is referred to as the core of the receptor, and the ligands attached  
 to the core referred to as arm(s). ............................................................................ 05 
 
3. Figure 1.3 – A pictogram that represents halogen bonding where blue is 
  associated with low electron density and red is associated with  
 high electron density. ............................................................................................. 06 
4. Figure 1.4 –The first XB receptor (a) informing modifications for a hydrosulfide 
receptor (b). ............................................................................................................ 07 
5. Figure 1.5 – Family of One-Armed Receptors studied in Chapter Four............... 08 
6. Figure 2.1 – Well-studied coumarin and carbostyril scaffolds (top) compared to 
phosphaquinolinone analogues (bottom). .............................................................. 12 
7. Figure 2.2 – Absorption (solid lines) and fluorescence (dotted lines) spectra of 2 in 
CHCl3 at 298 K. ..................................................................................................... 15 
8. Figure 2.3 – Selected bond length and dihedral angle in the optimized S0 and S1 
structures of 2f calculated by DFT and TD-DFT methods at the PCM(CHCl3)-
PBE0/TZVP level of theory, respectively. ............................................................ 17 
9. Figure 2.4 – a) Characteristic PN-heterocycle dimer for 2f with the O···N  
 distance (Å) shown as well as b) bond angles and c) torsional angles formed  
 within monomers upon dimerization. Ellipsoids drawn at 30% probability. ........ 19 
10. Figure 3.1 – Original DWJ-Haley pyridinium halogen bonding receptor and the 
second iteration derived from it, designed to sense hydrosulfide anions .............. 26 
11. Figure 3.2 – Crystallographic data of receptor 1 binding DCM ........................... 31 
12. Figure 3.3 – Absorbance data and binding isotherm for receptor 1 with TBACl in 
CHCl3 ..................................................................................................................... 33 
xiv 
13. Figure 4.1 – Previously studied bis-arylethynyl XB receptor, a. Novel “one-armed”
neutral, b, and charged, c, arylethynyl receptors. .................................................. 40 
14. Figure 4.2 – ESP maps of the entire family of receptors with the σ-hole values
underneath each structure. Neutral structures are depicted on the left and
methylated structures on the right. ......................................................................... 41 
15. Figure 4.3 – Hammett plot between 5a-d and I–. The slope of the line indicated
that substituents in this receptor has little role in affecting the sensitivity of the
halogen-bond donor. .............................................................................................. 45 
16. Figure 4.4 – Crystals structures of: a, 5a binding to chloride; b, 5a binding to iodide;
c, 5b binding to iodide; and d, 5d binding to iodide. ............................................. 46 
17. Figure 5.1 – The two receptors that will be the focus of this chapter. .................. 49 
18. Figure 5.2 – (a) Representative 1H NMR titrations of the tridentate receptor 1
with TBACl,  and (b) the binding isotherm associated with that titration ............. 52 
19. Figure 5.3 – Family of one arm receptors discussed in chapter 4 and
Table 5.3 ................................................................................................................ 56 
xv 
LIST OF TABLES 
Table Page 
1. Table 2.1 – Photophysical Properties and HOMO–LUMO Energy Gaps of
Heterocycles 2a ...................................................................................................... 15 
2. Table 2.2 – Dimerization Constants and Energies for 2 ....................................... 18 
3. Table 4.1 – Binding constants, in M–1, of charged receptors 5a-d with guest
chloride and their calculated sigma-hole values in kJ/mol. ................................... 44 
4. Table 4.2 – XB or HB distances, in Å, of receptors 5a, 5b, and 5d binding to
chloride or iodide as calculated from their crystal structures in Figure 4. ............. 46 
5. Table 5.1 – Titrations done with receptor 1 & the halides at r.t. in ACN 10%
DMSO via 1H NMR .............................................................................................. 53 
6. Table 5.2 – Summarized the calculated energy value of sigma holes for XB
donors in all of the receptors discussed in Chapters 4 and 5 (first eight entries
refer to the one arm family..................................................................................... 56 
xvi 
  
LIST OF SCHEMES 
 
Scheme Page 
 
 
1. Scheme 2.1 – Synthesis of Phosphaquinolinones 2............................................... 14 
2. Scheme 3.1 – Synthetic route to access second generation DWJ-Haley XB anion 
receptor .................................................................................................................. 29 
 
3. Scheme 4.1 – Synthetic pathway and yields for the formation of the neutral, 4a-d,  
 and charged, 5a-d, receptors. ................................................................................. 42 
4. Scheme 5.1 – The synthetic route to host receptor 1. ............................................ 51 
5. Scheme 5.2 – Synthetic scheme for the R = Bn of the derivatives of  
 receptor 2 ............................................................................................................... 55 
 
 
xvii 
CHAPTER ONE 
INTRODUCTION 
This chapter contains work in the process of being published and was written by Thaís P. 
de Faria and Hannah Bates, with editorial assistance from Douglas H. Banning, Dr. 
Trevor A. Shear, and Professors Michael M. Haley and Darren W. Johnson. This review 
article accounts the science and history behind anion binding, host-guest chemistry, some 
of the first papers on the project and foreshadows future work. However, it is by no 
means a comprehensive review of the field, rather a few pertinent examples have been 
selected for discussion to give a general sketch of the state of the field.  
Anions are prevalent in the human body and vital to life. They play a variety of 
different roles from producing electrical signals to maintaining cell volume.1 While there 
are many anions present in living systems, chloride (Cl–) and the protic forms of 
phosphate (i.e. HPO42-, H2PO4–) play a critical role in maintaining basic metabolic 
pathways within the human body.  
Two types of phosphorous species (organic and inorganic) are prevalent in our 
body's biological processes. An example of organic phosphates are the nucleotide 
phosphates found in adenosine monophosphate, diphosphate, and triphosphate (AMP, 
ADP, and ATP, respectively), molecules known for supplying energy for most biological 
reactions, participating in metabolism, and transferring genetic information.2 Inorganic 
phosphates, on the other hand, play a part in bone formation and help maintain bone 
density.3 They are normally seen in adult human serum at concentration levels of 0.8-1.45 
1 
mM;4 however, when present in excess, inorganic phosphates can ultimately lead to 
cardiovascular disease due to vascular calcification and renal failure.5 Deficient 
concentration of inorganic phosphate can lead to negative physical effects, like 
osteomalacia, central nervous system dysfunction, and muscle weakness, amongst many 
other disorders.6 
Chloride anions are found within human cells in concentration levels between 5 
and 15 mM1 and are vital to cellular processes, including balancing the charges of 
transfer proteins and building membrane potential. The natural role and regulation of Cl– 
is so critical that there are even chloride transport channels in intracellular organelles and 
the plasma membrane.7,8 Mutations of these channels lead to disruption of chloride 
movement in and out of the cell and have been linked to many genetic diseases, such as 
cystic fibrosis and the degeneration of muscles.9 
Because these anions play such important roles within the human body, there is 
significant interest for their detection and monitoring in physiologically-relevant media. 
Previous approaches to quantify the concentration of these anions has largely involved 
dialysis and sample dilution,10,11 microelectrodes (for measurement within individual 
cells),12,13 and imaging using yellow fluorescent proteins.14,15 These detection methods all 
have major drawbacks, including difficulty in performing the measurements, pH 
sensitivity, and low selectivity. Because of these challenges, the use of supramolecular 
chemistry in this area of research has been of growing interest, as supramolecular host-
guest chemistry is well studied and often allows for the ability to fine-tune the electronic 
and steric properties of the hosts used.16–19 Recently, attention has shifted to the use of 
2 
these small molecule sensors that can reversibly bind and display either a colorimetric or 
fluorescent response upon anion binding and, finally, can be performed in vivo.2,20–25 
Many research groups have been attempting to conquer the feat of designing and  
developing a small molecule receptor that displays a selective preference for reversibly 
binding one targeted anion over others, that is sensitive enough to detect minute 
concentrations, and that exhibits some form of optoelectronic response to binding.19,26,27 
One example of a small molecule receptor that has shown reversible binding to 
dihydrogenphosphate (H2PO4–) in dimethyl sulfoxide (DMSO) involves a scaffold with a 
hydrogen-bond donating (bis)thiourea motif (Figure 1.1a); however, the receptor has a 
modest limit of detection, requiring at least ~1 mM concentration of analyte for 
detection.28 Another example of promising binding to H2PO4– in acetonitrile includes a 
redox-based sensor that contains a ferrocene unit in addition to hydrogen-bond (HB) 
donors (Figure 1.1b).29 The HB units provide initial binding, but after oxidation of 
ferrocene, the host-guest interactions get further stabilized with the electrostatic 
interactions of the ferrocenium moieties.30 In addition to binding strongly with the 
phosphate anion, it also binds well with fluoride, and, therefore, lacks selectivity. A more 
recent example of phosphate anion detection comes from Sessler et al., who synthesized 
a. b. O c. NO2
O ONH
O
S NH HN S N NNH HN O
NH HN
HN
Fe N N
H H
Figure 1.1. Examples from the literature of phosphate receptors containing a) bis-
urea motifs, b) hydrogen-bond donors and ferrocene motifs, and c) indoles. 
3 
an indole-based receptor that showed promising colorimetric response upon binding 
(Figure 1.1c); however, this receptor lacks water solubility.31 
Some examples of successful receptors and sensors that are able to detect chloride 
through non-covalent interactions include: 1) nucleic acid-based hosts that can detect 
anions over a wide pH range, but they either lack anion specificity because of their ion-
pairing recognition mechanism or lack functionality for targeting some cellular 
compartments;32–35 2) chloride-templated rotaxanes that use redox-active interlocked 
systems to act as electrochemical sensors for anions, although binding only occurred in 
minimally polar solvents and did not show fully reversible oxidation;36 3) foldamers that 
have the ability to selectively coil around chloride and bind it tightly (albeit, the energy of 
organization of the helix was only optimal in certain solvents);37–42 and numerous 
others.43–46  
The original, or Gen 1, host-guest receptors to emerge from the Johnson and 
Haley labs have shown to bind a range of anions through non-covalent, reversible 
interactions.47–52 The tunable scaffold includes urea (HB) motifs (Figure 1.2a) as well as 
three functional groups (R, R', and R'') that can be synthetically modified to optimize the 
optoelectronics, selectivity, and binding properties of the receptors. In addition, the 
conjugated backbone of the arylethynyl scaffold has allowed for some receptors to show 
a fluorometric response upon binding.47–49 Finally, all but one of the recent 
Johnson/Haley receptors have only demonstrated anion binding in organic media or wet 
organic solvents, which does not necessarily reflect a physiologically-relevant 
environment. 
4 
Figure 1.2. Receptor scaffolds for a) Gen 1, hydrogen-bonding where X=N, N+–R, 
CH; R= H, Me, F, OMe; R'= H, tBu, CF3, SO2Me, SO2CF3 ; R''= H, NO2, CF3, OMe 
and b) Gen 2, halogen bonding where X=N, CH; R= H, Me, R'= H, tBu, CF3, 
SO2Me, SO2CF3; Z= H, I, Br. The central aromatic ring containing X is referred to as 
the core of the receptor, and the ligands attached to the core referred to as arm(s).  
The most promising arylethynyl bis-urea scaffold to show chloride binding in 
water was synthesized and studied by Michelle Watt et al. in 2015.21 The way that 
solubility was achieved in this case was by protonating the core pyridine nitrogen using 
1% TFA in water. The most notable result in this paper was that a “turn-on” fluorescence 
was reported in water/DMSO mixtures and increased with a higher percentage of water 
added, peaking at about 80% water.21 The observed fluorescence was attributed to a 
mechanism called “aggregation-induced emission” (AIE), that occurs through J-
aggregation and is widely used in fluorophores to sense analytes.53 Although titration  
studies demonstrated a strong selectivity for chloride, the receptor exhibited weak 
binding (Ka ≤ 100 M–1) in DMSO/H2O mixtures and the fluorescence was not strong 
enough for in vivo cell studies. Alas, the search for a water-soluble arylethynyl  receptor 
that can selectivly bind to chloride in aqueous media and displays strong fluorescent 
properties has continued in the Johnson and Haley laboratories. 
Firstly, to accomplish the goal of using our supramolecular receptors in 
physiological environments, we have to optimize the reversible interactions in polar, 
5 
protic solvents, like water. Sensing anions in water is a difficult mission for chemists due 
to the inherently low charge density which is a consequence of the large anion size. This 
makes the non-covalent electrostatic interactions between anions and receptors less 
efficient. In addition to this, anions have high free energies of solvation in water;54 
consequently, the receptors must energetically compete with the medium.55 According to 
Hunter et al., a promising strategy to achieve aqueous anion detection employs halogen 
bonding (XB) interactions, which exhibit stronger anion binding in polar, protic solvents 
than their HB analogs.56 
Halogen bonding is a type of reversible non-covalent binding interaction that has 
been gaining interest in the scientific community since it was first reported.57 The nature 
of this interaction was defined by IUPAC in 201358 as: R—X···Y, where X is a 
polarizable halogen covalently bound to an R group and Y is an electronically-dense 
halogen bond acceptor (Figure 1.3). This attractive interaction is facilitated by the 
δ–
X = I, Br
X δ+
Figure 1.3. A pictogram that represents halogen bonding where 
blue is associated with low electron density and red is 
associated with high electron density.  
halogen atom's ability to shift electron density with the help of the covalently bonded R 
group and, thus, reveal an area of positive electrostatic potential, named the σ-hole for its 
electron deficiency, directly opposite to the R–X σ-bond.59 Since the σ-hole is located on 
the opposite side of halogen, X, to the R—X bond, the covalently attached “R” 
substituent influences the size of the partially positive hole with its electron-withdrawing 
 6 
character. Conventinal wisdom holds that more withdrawing the substituent, R, the larger 
the σ-hole and, therefore, the stronger the binding to the XB acceptor. Surrounding the σ-
hole is an area of high electronegativity and this feature gives the σ-hole its strong 
directionality, demonstrating a strong preference for non-covalent bonding at a 180˚ angle 
from the XB acceptor.60,61  
New anion receptors, or Gen 2 receptors (Figure 1.2b), were developed in the 
Johnson/Haley lab to utilize halogen bonding. In place of the bis-urea hydrogen binding 
motif found in Gen 1 receptors, iodine was installed as a halogen bond donor in the 
binding pocket. To enhance the XB interactions, strong electron-withdrawing functional 
groups at the R’ positions can be used to increase the polarization of XB donors, and 
consequently, the strength of binding.  
Dr. Jessica Lohrman synthesized and characterized the first XB Johnson and 
Haley receptor (Figure 1.4a).62 It was shown to bind to the halide anion family, as well as 
produce a “turn-on” fluorescence response; however, the receptor was not sufficiently 
soluble in water for biological studies. Since the desired applications of this receptor 
Figure 1.4. a) The first XB receptor informing modifications for b) a hydrosulfide 
receptor.  
require water solubility, modifications to achieve solvation in aqueous media must be 
made. This receptor inspired another XB receptor, Figure 1.4b, for use with the 
hydrochacogenide guests, mainly hydrosulfide, HS-, which will be discussed in more 
detail in Chapter 3. 
7 
We then set out to explore what is herein described as Gen 3 receptors (Figure 
1.5). These receptors were highly influenced by the results of Dr. Lohrman’s XB 
receptor.62 With the target analyte, chloride, proving to be too small for the binding 
pocket available in the “two-arm” receptor, more simplified “one-armed” analogues were 
designed with: the purpose of simplifying/creating a smaller pocket for the receptors, 
converting their preference of binding chloride over iodide and studying their geometry 
of binding. 
Figure 1.5. Family of One-Armed Receptors studied in Chapter Four 
 We investigated the meta isomer of the mono-dentate receptor and discovered 
that, in addition to halogen bonding, this receptor also utilizes hydrogen-bonding to non-
covalently bind to anionic guests. The small hybrid–part XB, part HB–pocket was able to 
reverse the preference of binding seen in Gen. 2 receptors, now binding the smaller 
halides better than the larger (i.e. the target analyte, chloride, exhibited strongest 
binding). This study also revealed that the strongest contributor to the XB donor’s σ-hole 
is the methyl pyridinium ion located on the core aryl ring and that the tunable functional 
groups on the XB donor’s aryl ring play little part in increasing strength of binding 
through thorough theoretical, solution- and solid-state experimental structure/property 
relationship studies.  
8 
Finally, in Chapter Five, the fourth generation of Johnson and Haley receptors 
will be discussed. This chapter features two hybrid receptors (which use both HB and XB 
to bind anions). One receptor contains a quinoline backbone that enables the molecule to 
preorganize into what we anticipate being its preferred binding geometry. Its binding 
pocket consists of a triazole-polarized XB donor as well as multiple HB donors. We 
anticipate this hybrid receptor to demonstrate an optospectroscopic shift upon binding, 
allowing anion affinity to be measured by UV-Vis as well as 1H NMR. Notably, 
depending upon the identity of the HB donors, this molecule could have a preoganized 
state in either its cationic or neutral form. This allows for the molecule to reduce the 
entropic energy penalty associated with maintaining a single rigid conformation, like the 
one associated with binding. The second receptor is a larger version of the one-arm 
receptors discussed in Chapter Four, bearing a urea HB donor and pyridnium polarized 
XB donor. This receptor was designed to have a smaller pocket that seen in the 
bisarylethynyl receptors discussed in Chapter Three, with the aim of flipping the 
prefernce of the host receptor so that it demonstrates higher bind affinities for the smaller 
halides over the larger ones.  
Finally, yet to be mentioned is the contents of Chapter Two, which features work 
done on P, N containing heterocyclic fluorophores. This relatively new class of molecule 
is actually a spin off project, derived from the unexpected product produced when a 
previous graduate student used a phosphorous containing catalyst on a precursor to one of 
the DWJ/Haley lab HB receptors. The synthesis as well as the photophysical properties of 
this molecule are discussed and analyzed in detail in this chapter.  
9 
Considering the significance of anions and the important roles they play in 
biological and environmental systems, the need for monitoring their concentrations in 
aqueous media cannot be understated. Hydrogen bonding has long been used by nature 
and synthetic chemists alike for this purpose. And, while halogen bonding had been used 
in solid state crystallographic engineering for some time, it is only within the last two 
decades that solution-state XB has come onto the scene as an alternative molecular 
recognition strategy with particular promise in more competitive, polar solvents 
compared to that of their HB counterparts. In this short time, the field of halogen bonding 
has already demonstrated successful applications not just in molecular recognition but 
also in transmembrane transport, catalysis, template-directed synthesis, molecular 
motion, and many others niches as well. Despite this rapid expansion of research into 
halogen bonding, the number of reported receptors is still dwarfed by that of their 
hydrogen bonding analogues and much research remains to be done. This research is sure 
to be concomitant to further investigation of other sigma-hole driven interactions, like 
those seen in chalcogen and pnictogen bonding. There also is much to be learned about 
how to best use these complementary tools in tandem for even greater selectivity and 
strength of binding. With so much promise and still much nuance left to elucidate it is 
certain that the use of halogen bonding for anion binding, as well as a myriad of other 
applications, will continue to garner increasing attention for years to come.     
10 
CHAPTER TWO 
AMPLIFICATION OF THE QUANTUM YIELDS OF 
2‐λ5‐PHOSPHAQUINOLIN-2-ONES THROUGH  
PHOSPHORUS CENTER MODIFICATION 
This chapter includes previously published and co-authored material from Bard, J.P., 
Bates, H.J., Deng, C.-L., Zakharov, L.N., Johnson, D.W., Haley, M.M. “Amplification of 
the Quantum Yields of 2-λ5-Phosphaquinolin-2-ones Through Phosphorus Center 
Modification.” J. Org. Chem. 2020, 85, 85–91. This work highlights our work on 
understanding the effects of placing a phenyl group in place of the traditional phenoxy 
group on the P center of the phosphaquinolinone scaffold. It draws structure-property 
relationships with both the sumpramolecular and photophysical properties.  
2.1 Introduction. 
Small molecule fluorophores are used ubiquitously throughout many different 
fields, including chemical biology, molecular probe development, and materials for 
industrial and environmental sensing.1–4 In many of these applications, a fluorophore 
must exhibit a few characteristics to be considered optimal: large Stokes shift, high 
brightness, and red-shifted emission. One such example of a molecule that meets these 
specifications is coumarin (Figure 2.1).5–14 An impressive number of coumarin-
containing compounds have been reported throughout the literature that are collected 
either from in-lab syntheses or by isolation from natural sources.15,16 This scaffold has 
11 
been the subject of a variety of synthetic modifications, diversification by adding groups 
onto the backbone, or incorporation of the coumarin system into larger ring networks.17–19 
Through these modifications, a tremendous breadth of understanding upon the structure–
activity relations has been developed20–24 that have guided the design of many useful 
derivatives, which have emerged for applications in chemosensing and many other 
areas.25–31  
Figure 2.1 Well-studied coumarin and carbostyril scaffolds (top) compared to 
phosphaquinolinone analogues (bottom).  
Alongside the many derivatives of the parent coumarin scaffold, there is the 
nitrogen-containing structural analogue known as carbostyril (Figure 2.1).32–37 Though 
not as widely utilized as coumarin, carbostyril is the subject of many structure–property 
relationship studies, and it shows promise for use in both pharmaceutical discovery and 
fluorescence imaging applications.38,39 These carbostyril analogues expand on the 
applications of the coumarin family through modifying the lactone core to a lactam. With 
further alteration of this core, new applications, functionality, and fluorescent properties 
are expected from this widely used fluorophore.  
Recently, we reported a series of phosphorus- and nitrogen-containing (PN) 
phosphaquinolinone 1 derivatives (Figure 2.1).40,41 This scaffold, which is one of only a 
handful of similar heterocycles,42–52 is also an isostere to carbostyril and coumarin, with 
12 
the only difference being the replacement of the lactam carbonyl with an isolobal, chiral 
phosphorus center. We have performed a variety of structure–property studies that looked 
at the effects of both acene core modification and substitution at various points on the 
scaffold.40,41,53–56 In these studies, it was found that the emission wavelength can be 
moderately red-shifted through careful substitution of various groups on the backbone, 
affording significant Stokes shifts and modest quantum yields. On the basis of these 
design principles, this moiety has recently been implemented in a fluorescent receptor for 
HSO – 4 in acidic media, showing promise for future applications of this scaffold that take 
advantage of both its exceptional hydrogen bonding capabilities and its inherent 
fluorescence.54 As clearly shown for the coumarin and carbostyril motifs, systematic 
modification of various structural aspects can lead to very useful derivatives. In our 
continuing efforts to study the 2-λ5-phosphaquinolin-2-one skeleton, the next facet that 
we wanted to explore was the variation of the group attached to the phosphorus center. 
Disclosed herein is the substitution of a phenyl ring in place of the standard phenoxy 
upon the phosphorus center, generating a racemic mixture of heterocycle 2 (Figure 2.1). 
We also hypothesize that this would increase the quantum yield through rigidifying the 
scaffold. With these modifications, the reported compounds could have greater potential 
for applications in phosphorus-containing chemosensors and fluorophores, expanding on 
this pre-existing group of molecules.57–65 
2.2 Results and Discussion. 
The synthesis of 2 starts from key arylethynylaniline intermediate 3, prepared 
following previously reported methods.40 Aniline 3 is then reacted with diphenyl 
13 
phenylphosphonite (PhP(OPh)2) in pyridine at 100 °C. Subsequent hydrolysis in THF at 
60 °C furnishes phenyl-appended heterocycles 2 in modest to good yields (Scheme 2.1). 
Scheme 2.1 Synthesis of Phosphaquinolinones 2. 
The photophysical properties of 2a–2f in CHCl3 are shown in Figure 2.2 and are 
compiled in Table 2.1. All derivatives share a common λmax at ca. 300 nm, and the lowest 
energy absorption peaks range from 343 to 381 nm. The absorption coefficients for this 
scaffold stay within the range of 1.5 × 104 (for 2a) to 2.2 × 104 M–1 cm–1 (for 2e and 2f). 
The λem values range from 447 (for 2a) to 515 nm (for 2f) with Stokes shifts on the order 
of 6350–7000 cm–1. Interestingly, the emission spectra of 2 show a ca. 20 nm 
bathochromic shift from those of the analogous congeners of 1,40 and the quantum yields 
of this scaffold show a dramatic improvement, on the order of a 4–5-fold increase in most 
cases. Brightness values range from 6.84 × 103 (for 2b) to 1.14 × 104 M–1 cm–1 (for 2a), 
which are now on par with several optimized coumarin derivatives.66  
Fluorescence lifetime measurements were also performed (Figure C.6), and the 
radiative (kr) and nonradiative (knr) decay rate constants were determined. The kr values 
range from 0.06 to 0.19 ns–1, and the knr values vary from 0.06 to 0.18 ns–1, showing 
either equal rates or a slightly larger knr in most cases.  
14 
Figure 2.2 Absorption (solid lines) and fluorescne (dotted lines) specta 2 in CHCl3 at 298 K.  
Table 2.1 Photophysical properties and HOMO-LUMO Energy Gaps of Heterocycles 2a 
These values elucidate a potential explanation for the increased quantum yields 
when compared to similar values of phosphaquinolinones 1.40 For 1, the kr values range 
from 0.10 to 0.30 ns–1, which show similar values, whereas the knr values vary from 0.30 
to 3.0 ns–1, which are substantially faster in most cases. The diminished ratio of knr to kr
seen for 2 may suggest that the reduced degrees of freedom may indeed be the cause of 
the increased quantum yields.  
15 
To gain further understanding of these experimental results, the frontier orbitals 
for heterocycles 2 were calculated (Tables 4.1 and C.1–C.7). The narrowest HOMO–
LUMO gap is seen for 2f (3.90 eV), and the largest is for 2a (4.40 eV). This trend arises 
because of a higher magnitude of HOMO destabilization than that of the stabilization of 
the LUMO with more donating substituents (Table C.1). These values also follow a 
similar trend to the optical gaps (Tables 4.1 or C.1). TD-DFT was then used to examine 
the S0 to S1 transition. It was found that the S0 to S1 transition is dominated by the 
HOMO–LUMO transition (Table C.1). Additionally, the distributions of the HOMOs and 
LUMOs show a slightly more pronounced separation due to a larger HOMO localization 
at the phosphorus center (Figure C.4). These observations suggest that π to π* transitions 
are dominant, but there may be some intramolecular charge transfer (ICT) occurring in 
the excited state. The emission of 2 was then examined in solvents of varying polarities 
(Figures C.7–C.13 and Tables C.11–C.16). In these studies, bathochromatic shifting is 
observed in every case with more polar solvents. Compound 2f showed the greatest 
shifting, ranging from emission wavelengths of 504 to 531 nm and Stokes shifts of 6070 
and 7070 cm–1 in cyclohexane and acetonitrile, respectively.  
The TD–DFT optimized S1 state near the Franck–Condon geometry of 2f shows 
that the dihedral angle between the parent core and appended 4-cyanophenyl substituent 
becomes smaller compared to the ground state (Figure 4.3). Additionally, the C–C bond 
connecting them is shortened by ca. 0.035 Å. The considerable geometric changes lead to 
a more conjugated system at the S1 state, in which the HOMO–LUMO energy gap 
decreases by 0.9 eV (Figure C.5); thus, the computed emission wavelength of 541 nm is 
16 
within the observed emission maxima (Table 4.1). These computational results could 
further explain the large Stokes shift for this type of PN-heterocycle.  
Figure 2.3 Selected bond length and dihedral angle in the optimized S0 and S1 structures of 2f 
calculated by DFT and TD-DFT methods at the PCM(CHCl3)-PBE0/TZVP level of theory, 
respectively.  
In addition to improved fluorescence properties, we were curious to see how 
phenyl substitution would affect the strength of hydrogen bond dimerization we typically 
observe for phosphaquinolinones. Variable concentration (VC) NMR experiments were 
performed in water-saturated CDCl3 to assess the strength of dimerization (Tables 2.2 and 
C.17–C.21, Figures C.14–C.23w). Heterocycles 2 exhibit dimerization strengths of 22
(for 2e and 2f) to 82 M–1 (for 2b). While these values are roughly 70–80% smaller than 
those measured for the analogous congeners of 1, the strengths of dimerization for 2 
again exceed those of many typical head-to-tail hydrogen bonded dimers.67 This result 
suggests that this new entry into the phosphaquinolinone family can still be implemented 
in supramolecular systems, as found in 1.54  
17 
Table 2.2 Dimerization Constants and Energies for 2 
Single crystals suitable for X-ray diffraction were grown by slowly diffusing pentane into 
a CHCl3 solution of 2f, and the resultant data are shown in Figures 4.4 and C.1–C.3. The 
structure of 2f still features the typical meso-dimer between racemates (Figure 2.4a); 
however, the N···O distance in the dimer of 2f (2.874 Å) is longer than those of 
heterocycles 1 (2.768–2.821 Å),40 which supports the observation that the molecule 
should form a weaker dimer in the solution-state as well. This weakened hydrogen 
bonding interaction can potentially be explained by examining the pseudo six-membered 
ring formed between the monomers. The N···O–P (115.53°), O–P–N (116.66°), and P–
N···O (104.57°) angles formed between the participating atoms in the dimer formation 
show significant deviation from the ideal 120° orientation (Figure 4.4b), likely caused by 
the large O–P–N–H torsional angle of 55.35° (Figure 2.4c). With an angle so much larger 
than the analogous angle found in the crystal structures of several derivatives of 1 (ca. 
30– 40°),40 there is a less ideal orientation for the two monomers to associate, slightly 
weakening the interaction overall. By comparing optimized geometries of the meso-dimer 
of 2f and its −OPh analogue, there are some additional steric clashes in 2f among the C–
18 
H atoms in the phenyl ring and N–H moieties, according to the noncovalent interactions 
(NCI) plot (Figure C.24). Moreover, the natural bond orbital (NBO) analyses predict a 
total contribution of the nO → σNH* interactions of 23.1 kcal mol–1 for 2f and 25.0 kcal 
mol–1 for the respective −OPh analogue (Figure C.25). Therefore, the strength of 
dimerization may decrease to some degree due to the weaker primary hydrogen bonding 
and extra steric hindrance, in agreement with the observed diminished Kdim for 2.  
Figure 2.4 a) Characterization PN-heterocycle dimer for 2f with the O···N distance (Å) shown as 
well as b) bond angles and c) torsional angles formed within monomers upon dimerization. 
Ellipsoids drawn at 30% probability.  
2.3. Conclusion.  
In summary, we have shown the effects of the attachment of a phenyl group on the 
phosphorus center of the phosphaquinolinone scaffold. This new class of PN-
heterocycles not only has large Stokes shift values (up to 7000 cm–1) but also shows a 
marked 4–5-fold increase in the quantum yield when compared to previously reported 
phenoxy-substituted compounds. Additionally, this modification retains the strong 
dimerization strengths of the scaffold in both the solid and solution states. This new 
19 
modification deepens the fundamental understanding of the phosphaquinolinone scaffold 
and allows for further possibilities in the applications of this scaffold as a biologically or 
industrially relevant fluorophore, like the coumarin and carbostyril scaffolds. 
2.4. Experimental Section 
General  
All air- or water-free reactions were performed under a N2 atmosphere using 
Schlenk techniques. Column chromatography was performed using silica gel (240–300 
mesh), with solvent systems being referenced to the most abundant solvent. NMR spectra 
were acquired at room temperature on a Varian Inova 500 instrument (1H: 500 MHz, 13C: 
126 MHz, 19F: 471 MHz, 31P: 202 MHz) or a Bruker Avance III HD 500 apparatus 
equipped with a Prodigy multinuclear cryoprobe (1H: 500 MHz, 13C: 126 MHz). 1H and 
13C chemical shifts (δ) are expressed in parts per million (ppm) relative to residual CHCl3 
shifts (1H: 7.26 ppm, 13C: 77.16 ppm) or residual DMSO shifts (1H: 2.50 ppm, 13C: 39.52 
ppm). 31P and 19F NMR spectra are referenced to 85% H3PO4 (δ 0 ppm) and to CFCl3 (δ 0 
ppm), respectively, as the external standards. UV–vis spectra were recorded using an 
Agilent Technologies Cary 60 UV–vis spectrophotometer in HPLC-grade CHCl3. 
Fluorescence emission spectra were recorded using a Horiba Jobin Yvon FluoroMax-4 
fluorimeter exciting at 365 nm. Quantum yields (φ) were determined through a 
comparison of the emission and absorption intensities of the analyte to that of a 0.1 M 
H2SO4/quinine sulfate solution.68 Fluorescence lifetime measurements were recorded 
using a Horiba FluoroHub Single Photon Counting Controller with a TemPro 
Fluorescence Lifetime System attachment. High-resolution mass spectra (HRMS) were 
 20 
recorded on a Waters XEVO G2-XS mass spectrometer. 2-Ethynylanilines 3a–3f40 and 
phenyl diphenylphosphonite (PhP(OPh)2)69 were prepared as previously described.  
General Synthetic Procedure for Phosphaquinolinone 2 
2-Ethynylaniline3 (1.0 equiv.) and PhP(OPh)2 (2.0 equiv.) were dissolved in pyridine (ca. 
0.35 M). The vessel was sealed and heated to 100 °C for 24 h in an oil bath. The mixture 
was then diluted with toluene, and the solvent was removed in vacuo. This was repeated 
three times to remove all residual pyridine. The crude material was dissolved in THF, and 
ca. five drops of water were added. The solution was stirred at 60 °C for 1 h before being 
dried (Na2SO4), filtered, and concentrated in vacuo. The crude mixture was then purified 
by column chromatography on silica gel. Reported yields are given for >95% pure 
material (by 1H NMR spectroscopy), though subsequent recrystallization from hexanes 
and CH2Cl2 was used to achieve analytically pure material. 
Phosphaquinolinone 2a 
Compound 2a was synthesized from 3a (462 mg, 1.9 mmol, 1 equiv.) and PhP(OPh)2 
(1.11 g, 3.8 mmol, 2 equiv.). Column chromatography (1:1 EtOAc:CH2Cl2, Rf = 0.20) 
gave 2a (149 mg, 21%) as a pale brown solid: mp > 250 °C; 1H NMR (500 MHz, 
DMSO-d6) δ 10.28 (d, J = 3.8 Hz, 1H), 8.14 (d, J = 2.0 Hz, 1H), 8.05 (d, J = 30.1 Hz, 
1H), 7.82 (ABm, J = 8.4 Hz, 4H), 7.81–7.77 (m, 1H), 7.69–7.64 (m, 2H), 7.58–7.51 (m, 
1H), 7.49–7.43 (m, 2H), 7.21 (d, J = 8.5 Hz, 1H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 
143.1 (d, J = 3.8 Hz), 140.9 (d, J = 11.7 Hz), 139.3, 135.8, 133.8, 132.6, 132.5 (d, J = 2.7 
Hz), 132.4 (d, J = 137.0 Hz), 132.2 (d, J = 10.8 Hz), 128.6 (d, J = 13.2 Hz), 128.1 (d, J = 
6.1 Hz), 126.9 (d, J = 115.9 Hz), 119.2, 119.0 (d, J = 9.9 Hz), 118.5, 117.7 (d, J = 8.1 
 21 
Hz), 110.6, 102.1; 31P{1H} NMR (202 MHz, DMSO-d6) δ 7.77; HRMS (ASAP) [M + 
H]+ calcd for C22H15N3OP 368.0953, found 368.0977. 
Phosphaquinolinone 2b  
Compound 2b was synthesized from 3b (700 mg, 2.4 mmol, 1 equiv.) and PhP(OPh)2 
(1.40 g, 4.8 mmol, 2 equiv.). Recrystallization from CH2Cl2 and hexanes gave 2b (580 
mg, 58%) as a yellow solid: mp > 250 °C; 1H NMR (500 MHz, DMSO-d6) δ 10.14 (d, J 
= 4.1 Hz, 1H), 8.16 (d, J = 30.1 Hz, 1H), 8.06 (d, J = 2.2 Hz, 1H), 7.85 (d, J = 8.3 Hz, 
2H), 7.80 (d, J = 8.4 Hz, 2H), 7.73–7.63 (m, 3H), 7.53 (td, J = 7.4, 1.5 Hz, 1H), 7.49–
7.43 (m, 2H), 7.25 (d, J = 8.5 Hz, 1H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 142.5 (d, 
J = 3.7 Hz), 141.1 (d, J = 12.0 Hz), 139.9, 132.7 (d, J = 136.9 Hz), 132.6, 132.4 (d, J = 
2.7 Hz), 132.2 (d, J = 10.7 Hz), 130.5, 128.5 (d, J = 13.2 Hz), 128.1 (d, J = 6.1 Hz), 
127.4 (d, J = 3.7 Hz), 126.5 (d, J = 116.3 Hz), 124.5 (q, J = 271.2 Hz), 120.6 (q, J = 32.3 
Hz), 118.6 (d, J = 13.0 Hz), 118.5, 117.4 (d, J = 7.9 Hz), 110.5; 31P{1H} NMR (202 
MHz, DMSO-d6) δ 7.86; 19F NMR (471 MHz, DMSO-d6) δ −59.92; HRMS (ASAP) [M 
+ H]+ calcd for C22H15N2OF3P 411.0874, found 411.0909.
Phosphaquinolinone 2c 
Compound 2c was synthesized from 3c (645 mg, 2.6 mmol, 1 equiv.) and PhP(OPh)2 (1.5 
g, 5.1 mmol, 2 equiv.). Column chromatography (1:1:1 hexanes:EtOAc:CH2Cl2, Rf = 
0.10) followed by two rounds of recrystallization from CH2Cl2 and hexanes gave 2c (300 
mg, 31%) as a yellow solid: mp > 250 °C; 1H NMR (500 MHz, DMSO-d6) δ 9.80 (d, J = 
4.2 Hz, 1H), 7.99 (d, J = 29.8 Hz, 1H), 7.83 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.5 Hz, 2H), 
7.73 (d, J = 2.5 Hz, 1H), 7.69–7.57 (m, 2H), 7.56–7.49 (m, 1H), 7.48–7.38 (m, 3H), 7.11 
22 
(d, J = 8.7 Hz, 1H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 141.3 (d, J = 12.0 Hz), 
139.4, 138.3 (d, J = 3.7 Hz), 132.8 (d, J = 136.6 Hz), 132.5, 132.3, 132.2, 130.7, 129.9, 
128.5 (d, J = 13.1 Hz), 128.1 (d, J = 6.2 Hz), 126.5 (d, J = 116.8 Hz), 123.6, 120.2 (d, J = 
12.6 Hz), 118.6, 118.4 (d, J = 8.1 Hz), 110.3; 31P{1H} NMR (202 MHz, DMSO-d6) δ 
7.69; HRMS (ASAP) [M + H]+ calcd for C21H15N2OPCl 377.0611, found 377.0641.  
Phosphaquinolinone 2d 
Compound 2d was synthesized from 3d (151 mg, 0.69 mmol, 1 equiv.) and PhP(OPh)2 
(463 mg, 1.4 mmol, 2 equiv.). Column chromatography (1:1:1 hexanes:EtOAc:CH2Cl2, 
Rf = 0.20) gave 2d (144 mg 61%) as a yellow solid: mp > 250 °C; 1H NMR (500 MHz, 
CDCl3) δ 7.73 (d, J = 8.1 Hz, 2H), 7.66 (d, J = 30.4 Hz, 1H), 7.71–7.66 (m, 2H), 7.54 (d, 
J = 8.2 Hz, 2H), 7.47–7.42 (m, 2H), 7.38–7.32 (m, 3H), 7.06 (t, J = 7.5 Hz, 1H), 6.97 (d, 
J = 8.0 Hz, 1H), 6.83 (br s, 1H); 13C{1H} NMR (126 MHz, CDCl3) δ 141.5 (d, J = 11.8 
Hz), 141.0 (d, J = 3.0 Hz), 138.8 (d, J = 4.3 Hz), 132.7 (d, J = 10.8 Hz), 132.6 (d, J = 2.8 
Hz), 132.5, 132.2 (d, J = 139.3 Hz), 131.5, 131.2, 128.6 (d, J = 13.8 Hz), 128.4 (d, J = 
6.2 Hz), 126.0 (d, J = 119.5 Hz), 121.4, 119.4 (d, J = 12.1 Hz), 118.8, 117.3 (d, J = 7.7 
Hz), 111.6; 31P{1H} NMR (202 MHz, CDCl3) δ 10.52; HRMS (ASAP) [M + H]+ calcd 
for C21H16N2OP 343.1000, found 343.1030.  
Phosphaquinolinone 2e 
Compound 2e was synthesized from 3e (549 mg, 2.0 mmol, 1 equiv.) and PhP(OPh)2 (1.3 
g, 4.0 mmol, 2 equiv.). Column chromatography (1:1:1 EtOAc:CH2Cl2, Rf = 0.25) gave 
2e (520 mg, 65%) as a yellow solid: mp > 250 °C; 1H NMR (500 MHz, CDCl3) δ 7.73 (d, 
J = 8.0 Hz, 2H), 7.72–7.67 (m, 2H), 7.68 (d, J = 30.3 Hz, 1H), 7.53 (d, J = 8.1 Hz, 2H), 
 23 
7.48– 7.39 (m, 3H), 7.37–7.32 (m, 2H), 6.90 (d, J = 8.4 Hz, 1H), 6.48 (br s, 1H), 1.35 (s, 
9H); 13C{1H} NMR (126 MHz, CDCl3) δ 144.4, 141.7 (d, J = 12.1 Hz), 141.5, 136.4, 
132.7 (d, J = 10.8 Hz), 132.5, 132.5, 132.4 (d, J = 139.2 Hz), 129.1, 128.5 (d, J = 13.6 
Hz), 128.4 (d, J = 6.4 Hz), 127.6, 125.8 (d, J = 119.9 Hz), 119.0, 118.9 (d, J = 8.4 Hz), 
116.9 (d, J = 7.3 Hz), 111.4, 34.4, 31.5; 31P{1H} NMR (202 MHz, CDCl3) δ 10.44; 
HRMS (ASAP) [M + H]+ calcd for C25H24N2OP 399.1628, found 399.1629. 
Phosphaquinolinone 2f 
Compound 2f was synthesized from 3f (430 mg, 1.7 mmol, 1 equiv.) and PhP(OPh)2 (969 
g, 3.3 mmol, 2 equiv.). Column chromatography (1:1:1 hexanes:EtOAc:CH2Cl2, Rf = 
0.25) gave 2f (200 mg, 31%) as a pale yellow solid: mp > 250 °C; 1H NMR (500 MHz, 
CDCl3) δ 7.73–7.65 (m, 2H), 7.71 (d, J = 8.6 Hz, 2H), 7.59 (d, J = 30.4 Hz, 1H), 7.53 (d, 
J = 8.2 Hz, 2H), 7.47–7.42 (m, 1H), 7.37–7.31 (m, 2H), 6.98–6.93 (m, 2H), 6.88 (d, J = 
8.5 Hz, 1H), 6.60 (br s, 1H), 4.04 (q, J = 7.0 Hz, 2H), 1.43 (t, J = 7.0 Hz, 3H); 13C{1H} 
NMR (126 MHz, CDCl3) δ 153.5, 141.6 (d, J = 12.0 Hz), 140.7, 132.8 (d, J = 10.7 Hz), 
132.7, 132.6 (d, J = 3.0 Hz), 132.5, 132.1 (d, J = 140.4 Hz), 128.5 (d, J = 13.8 Hz), 128.4 
(d, J = 6.4 Hz), 126.7 (d, J = 119.9 Hz), 119.9, 119.8 (d, J = 11.8 Hz), 118.8, 118.2 (d, J 
= 7.7 Hz), 114.8, 111.5, 64.3, 15.0; 31P{1H} NMR (202 MHz, CDCl3) δ 10.51; HRMS 
(ASAP) [M + H]+ calcd for C23H20N2O2P 387.1261, found 387.1283.  
 24 
CHAPTER THREE 
TOWARDS THE MOLECULAR RECOGNITION OF THE 
HYDROSULFIDE AND CHLROIDE ANIONS 
WITH AN ARYL ETHYNYL RECEPTOR 
3.1. Introduction to DWJ-Haley Lab Receptors and Halogen Binding. 
Research groups at the University of Oregon have been collaborating to 
synthesize supramolecular receptors for ion recognition for over a decade now.1–7 Like 
many in the supramolecular field of host guest chemistry much of our efforts have been 
focused on anions, which are conventionally thought of as more difficult to bind that their 
cationic counterparts, due to their relatively high pH sensitivity, powerful solvation 
energies and lower charge density.8–10 Most of the receptors out of the DWJ and Haley 
laboratories were rigid and highly conjugated diethynyl system that not only can bind 
anions but also have an inherent fluorescence that allows for spectroscopic recognition 
upon binding. Originally the receptors featured HB donors, with amine and urea 
functional groups, and were used to bind the halide anions: chloride, bromide and iodide. 
Eventually, through careful design and several structure-property relationship studies, the 
binding capabilities of these hosts were expanded to include oxoanions -  nitrate, 
phosphate and perchlorate - as well as hydrochalcogenides - hydrosulfide and 
hydroselenide.2,4,11  
While these guests were bound by HB donors with appreciable affinities, 
competition from similar guest molecules became apparent when attempting to bind them 
in highly competitive polar solvents like DMSO and water.6,11,12 As stated earlier in this 
dissertation (see Chapter I), XB donors have typically demonstrated stronger binding in 
25 
more competitive environments 
when compared to analogous HB 
donors.13 With this in mind, Dr. 
Jess Lohrman synthesized and 
characterized a XB receptor from 
the traditional arylethynyl core 
seen in DWJ-Haley lab receptors 
(see structure 0 in Figure 3.1).3 
This scaffold maintained the 
highly extended conjugation that 
gave previous hydrogen bonding 
analogues of these scaffolds their 
inherent fluorescence but, in place 
of the traditional HB donors, two 
Figure 3.1 – Comparison between (top) the previously 
published “first generation” DWJ-Haley XB receptor 0 & iodine atoms were installed to act 
(bottom) the current generation XB receptor 1 that is the 
focus of this chapter  as the XB donors. These XB 
donors were polarized by sulfonyl functional groups, bridging acetylene units and a 
methylated pyridinium core to yield a sigma hole. When titrated with the halides in 
DMSO, the receptor 0 demonstrated Kas ranging from 690 to 3600 M-1 with the strongest 
binding affinity being demonstrated for the largest halide, iodide.  
Having proven the utility of anion binding with this class of XB receptors, the 
next step was to investigate whether XB interactions would also be an effective strategy 
for binding the hydrochalcogenides, initially hydrosulfide (HS-), in highly polar media, 
26 
like those encounters in cells. With this purpose in mind, XB receptor 1 was designed, 
building upon the design principles mentioned above. The new structure maintained the 
highly conjugated arylethynyl scaffold, enabling spectroscopic measurement of binding 
interactions by UV-Vis. Additionally, the central pyridine ring was inverted, giving a 
1,2,6- orientation between the two ethynyl arms and the central pyridine nitrogen, as 
opposed to the original 1,3,5 geometry. This orients the pyridine’s lone pair towards the 
intended internal binding pocket of 1. Previous work with similar urea-based systems has 
shown that an internally-directed pyridine core has weakened overall binding to Cl- and 
HS- while concomitantly demonstrating a higher selectivity for HS- over Cl-, compared to 
its benzene ring analog.2 This is possibly explained as a destabilizing electron-electron 
repulsion between the pyridine’s lone pair and the anionic guest, Cl-. However, if the 
guest anion has a polarized hydrogen atom, then this internal lone pair could also serve as 
a HB acceptor to the anion’s HB donor.14 In a system like the one seen in receptor 1 it is 
postulated that, with a protic guest, the host could coordinate the guest with bidentate 
halogen bond donation and a single point of hydrogen bond acceptance at the pyridine 
core. However, further studies will have to be done to confirm this as the rigid 180 ° 
directionality of XB donors might hold the guest molecule too far away to experience 
either attractive or repulsive forces from the lone pair of the pyridine core.  
To mitigate this electron repulsion between the pyridine lone pair and to add a 
hydrogen bond donation site, a charged pyridinium core created by either protonation or 
methylation (1+H and 1+Me in Figure 3.1) would serve as a very strong receptor for the 
halides. Additionally, the charge of the pyridinium moiety would both serve to further 
polarize the XB donating iodine atoms through induction, thus creating stronger XB 
27 
donors, as well as add a site of HB donor to the central pocket! It should be noted, 
however, that this would not be an effective strategy for making an HS- host, as that 
hydrochalcogenide is a particularly nucleophilic guest. A previous group member, Dr. 
Hazel Fargher, had documented similar problems with a neutral HB host and 
hydroselenide (HSe-) in which the nucleophile attacked one of the acetylene carbons, 
causing decomposition to begin within minutes of guest addition.12 The assumption while 
designing the next generation of XB receptors was that any positively charged host (like 
1+H or 1+Me) would open itself up to decomposition by the reactive 
hydrochalcogenides, which would likely result in breaking the aromaticity of the 
molecule in order to accommodate the addition of HS-. This vulnerability drove many of 
the changes seen between receptor 0 and the iterations of receptor 1.  The methane 
sulfonyl group was exchanged for a trifluoro methyl group, which is less challenging 
synthetically and won’t promote inviting unwanted reactions with the guest (but is 
otherwise a relatively similar EWG, having a p of 0.54, compared to the 0.72 of SO2Me 
– although the lion’s share of the polarization in receptor 0 came from the methylate
pyridinium).15 The pyridine ring was inverted, as discussed above, and the protonated or 
methylated pyridinium functionalities (1+H and 1+Me) were set to be exclusively used 
with the less reactive halide guests.   
3.2 Methods. 
The modular nature of the synthesis of receptor 1 makes it easily tunable and 
synthetically accessible. In the initial attempt to synthesize receptor 1 (Appendix A for 
Chapter 3 – Scheme A.2), a triazene functional group was incorporated on the  
28 
trifluoromethyl sidearms via a Sandmeyer reaction;16 however, an alternative synthetic 
path was required because the triazene moiety produced an impurity which made 
isolation of the final product impractical. To avoid this impurity, Scheme 3.1 was 
developed, wherein the aniline side arms were left unprotected, completely side stepping 
the reaction required to append the triazene species, and still furnishing the final product. 
To start, 4-trifluormethylaniline is iodinated under acidic conditions to create 2-iodo-1-
methyl-4-(trifluoromethyl) benzene, 2, in very good yield. Afterwards, a Sonogashira 
cross-coupling with trimethylsilyl acetylene (TMSA) provides the trimethylsilyl-
protected ethynyl aniline 3.3,17,18 This was subsequently deprotected with a basic workup 
to afford the respective terminal acetylene that is immediately subjected to a second 
Sonogashira cross coupling with 2, 6-dibromopyridine, at a 2.5:1 molar ratio, to obtain 
the dianiline 4.19 After being purified via silica gel flash column chromatography 
followed by recrystallization, the final step is a variant on the Sandmeyer reaction which  
KI, KIO TMSA, NHNH2 3 NH
2
HCl, MeOH 2 Pd(PPh3)2Cl2, CuI
F C H2O F C I THF, DIPA
F3C
3 3 TMS
80% 39%
2 3
1. K2CO3 THF, MeOH
2. 2,6 Dibromopyridine N NaNO2
Pd(PPh3)4, CuI F3C CF3 HI, KI NF3C CF3
50 °C -10 °C 
THF, DIPA NH2 H2N ACN
21% I 30% I
4 1
Scheme 3.1 – Synthetic route to access second generation DWJ-Haley XB anion receptor 1 
cleaves the amine and installs two iodines inside the binding pocket. The final receptor is 
purified through recrystallizations and a series of plugs to give 1 in 30% yields.3 This 
reaction pathway not only avoids the aforementioned impurities, but it also removes the 
low-yielding protection step altogether.  
29 
3.3 Results and Discussion. 
To corroborate the identity of the scaffold and give valuable information about 
solid-state host-guest interactions, crystals of 1 suitable for x-ray crystallography were 
obtained via slow evaporation of a concentrated solution of 1 and TBACl in 
dichloromethane (DCM) (Figure 3.2). The C(I) bond lengths fell around a normal range 
of 2.100 or 2.0092 Å and all aryl protons demonstrated a C(H) bond length ranging from 
0.949 to 0.951 Å. The receptor can be seen in its W-conformation, with the XB donors 
directed outside of the intended binding pocket. Interestingly, in place of the desired Cl- 
guest, a molecule of DCM was bound in a 2:1 host:DCM ratio. The W-conformation 
adopted by the host is likely due to the size of the DCM molecule. This geometry allows 
for C-H groups meta to the XB donor to coordinate with the Cl atoms of the DCM (at 
C(H)-Cl distances of 3.779 Å and 3.769 Å). Notably, one of the C-H groups of the DCM 
can be seen interacting with the internal pyridine nitrogen (C(H) ··· N distance = 3.248 
Å) of the host molecule, perhaps supporting some of the earlier speculation on the 
benefits of having a lone pair in the pocket of the host. Finally, a third C-H HB, from a 
second host receptor, also coordinates to one of the guest’s Cls (C(H)-Cl = 3.678 Å) to 
complete multidentate binding of DCM in a 2:1 host-guest complex.  Contrary to what 
30 
was expected or intended, the 
coordination of the guest with 1 occurs via 
HBing rather than XBing.  This result 
served to emphasize the challenge of 
predicting binding geometry and although 
it is hard to say for certain whether a 
smaller guest, capable of more 
energetically favorable interactions, 
would persuade the receptor to adopt the 
intended U-shaped conformation, it is 
Figure 3.2: Crystallographic data of receptor 1 
binding DCM abundantly clear that the DCM molecule 
is too large for such a geometry. 
To build upon the initial host-guest interactions seen with receptor 1 in the solid-
state as well as previous success demonstrated by previous DWJ-Haley HB receptors, 
initial investigations into the binding nature of this host in solution were undertaken. Cl- 
was chosen as the first guest to be tested because these anions are relatively similar in 
size (Cl- having an ionic radius of 1.81 Å relatively the 1.84 Å of S-2) but Cl- is far less 
volatile, dangerous, and difficult to work with than HS-. These were carried out with 
tetrabutylammonium chloride (TBACl) as a Cl- source in chloroform, a non-competitive 
solvent (λ cutoff < 245 nm). CHCl3 has a relatively low dielectric constant, ε =4.8, in 
comparison to water, where ε = 80.4, which solvates charges, but not large organic host 
receptors, especially well.20 As mentioned before, this is one of the greatest challenges 
associated with anion binding in aqueous environments. Consequently, the non-
31 
competitive nature of CHCl3 mitigated the likelihood that weak binding interactions will 
be out competed by solvent interactions and therefore can be observed. There are a 
number of ways in which binding data can be obtained so that binding strength can be 
calculated; these include isothermal titration calorimetry (ITC), UV-Vis, Fluorescence, 
potentiometric or NMR spectroscopy titration data. 1H, and 19F NMR titrations were 
tested as possible routes for determining the association constant of this receptor (1); 
however, none of these NMR active atoms played a direct enough role in coordination of 
the guest during the solution state binding event to track anion binding. As a result, 
titrations were performed using UV-Vis spectroscopy instead (Figure 3.3a). These 
allowed for the generation of an isotherm which plots the relative absorbance units at the 
λ max (275 nm & 325 nm)of the host as a function of the concentration of guest relative 
to the concentration of host (Figure 3.3b).21 With nonlinear regression analysis, utilizing 
a 1:1 host-guest complexation fitting model, titration isotherms can be used to quantify 
the binding affinity of the H-G system. Here, BindFit is used to process the raw UV-Vis 
data collected.22 In a typical isotherm, the absorbance of the host is expected to increase 
for a period before binding saturation is seen, indicating saturation of the host receptor. In 
the isotherm of receptor 1, no leveling off is seen, indicating weak to negligible binding. 
This was supported by a highly variable association constant measuring anywhere in the 
range of 0.3 - 6.7  103 M-1. 
32 
A 0.35 0.33 B
0.3
0.25 0.28 325 nm
0.2 0.23 274 nm
0.15
0.1 0.18
0.05
0 0.13
250 300 350 0 100 200 300
Wavelength  (nm) [G]/[H]
Figure 3.3 – (a) Absorbance data & (b) binding isotherm for host 1 with TBACl in 
CHCl3. 
From both the work of Dr. Jess Lohrman with receptor 0 and similar receptors 
from Dr. Orion Berryman, it has been demonstrated that the bisarylethynyl receptor’s 
pocket size is preferential to the iodide anion due to its larger size, which is likely a 
contributing factor to the limited interaction between chloride and the neutral host, and 
might explain the weak binding discussed above.3,23 Restrictive 180° XB angles do not 
allow binding in the internal pocket close. For chloride to be coordinated to both XB 
donors, it would have to fit further inside the pocket which would pull it off course of the 
sigma hole and hit the electron belt instead. Another possible explanation for the apparent 
weak binding of receptor 1 is the neutral charge of the molecule. The neutral analog of 
receptor 1 was a relatively ineffective host compared to that of the hypothetical cationic 
versions of the receptor, 1+H and 1+Me.3 A final consideration for this point is the 
internal facing pyridine core – which, when neutral, selects for HS- over Cl-, but has been 
shown to decrease binding strength for both.2  
When designing the receptor at the center of this chapter, 1, the main guest of 
interest was HS-. But the other guest of interest hadn’t been forgotten; it was  
hypothesized that the pyridinium core (seen in 1+H and 1+Me) would enhance Cl- 
33 
Absorbance Units (AU) 
Absorbance Units (AU)
binding. The cationic core holds much promise in the form of an additional HB donor as 
well as in the generation of a charged species, with attractive electrostatics for the anionic 
guests. To this end, several protonation experiments were carried out in DCM. Initial 
protonation attempts were carried out by introducing the host to a variety of acids. It 
wasn’t until using triflic acid (CF3SO3H) that precipitate of the supposed pyridinium was 
able to be collected. Many of the initial acids likely failed because they are less effective 
in organic solvents, having higher pKas than those reported in water because of their 
relatively unstable conjugate bases. Triflic acid, having a sufficiently charge disperse 
conjugate base, was finally able to protonate the core pyridine (that might look 
misleadingly basic in organic conditions, considering it also has a decent ability to 
delocalize charge). When an 1H NMR spectrum was taken of the protonated compound in 
acetone-d6 it did demonstrate an expected shift in all of the resonance environments. 
However, it was notable that there was not an easily identifiable peak associated with the 
proton assumed to be on the pyridine. This is likely due to exchange with the solvent 
under the highly acidic conditions in which the NMR spectrum was taken. This could 
potentially be resolved by taking the NMR spectrum in another solvent, at a lower 
temperature, in an acidic solvent system (like 1% TFA acetone-d6 or similar) or with a 
shorter time delay between collection. But regardless of how we choose to trouble shoot 
characterizing that receptor, it quickly became clear that the protonated 1+H was too 
labile to be applied in practical settings for anion recognition (1+Me presents a more 
promising target, with regards to stability of the host as it would not be directly 
influenced as easily by changing pH).  
34 
Due to its high acidity, the receptor 1+H proved unstable in water, deprotonating 
upon any aqueous treatment. This means that, while this receptor would likely show 
stronger binding when protonated, the pyridinium is too acidic to be used successfully in 
the more competitive polar environments it was designed to compete in. Though it should 
be noted that despite its water instability, it is still likely possible to do titrations with the 
protonated receptor in organic solvents. Thus, knowing that this wouldn’t be a newly 
developed small molecule fluorescent probe able to compete with water for anions, as we 
had wanted, we decided to forgo further characterization (like fluorescent studies) and 
instead move on to a new hybrid host design.  
If the next generation of receptors are to be successful in the aim of getting into 
water and cells, then they should abide (as closely as possible) to Lipinski’s rule of five, 
which is a set of parameters intended to assess how likely a small molecule is to be cell 
permeable.24  These parameters include having a molecular mass of less than 500 amu, as 
well as limiting the amount of HB donors and acceptors to less than 5 and 10, 
respectively. Future chapters in this thesis feature receptors which do a much better job 
following these general rules of thumb, with the hope of find more success not only in 
aqueous environment, but in vivo applications specifically. This was accomplished by 
abandoning the two-arm structure for a more compact, lighter “one arm” motif and 
leverage the best parts of both HB and XB systems by using both in tandem! While initial 
experiments with receptors 1 and 1+H seemed less successful than we might have hoped 
there is still much promise to be found in the 1+Me scaffold. The methylated pyridinium 
could serve to further polarize the XB donors, add an electrostatic attraction to all anion 
guests, as well as append 3 additional C-H HB donors to the inside of the pocket. This 
35 
final change might also serve to shrink the effective size of pocket, potentially switching 
the preference for larger halides seen in receptor 0.   
3.4. Conclusion. 
In conclusion, a new fluorescent aryl ethynyl receptor with XB capabilities was 
synthesized and characterized. Characterizations were carried out via 1H NMR, 19F NMR, 
UV-vis spectroscopy, and X-Ray crystallography. Preliminary data suggests that the 
neutral host does not strongly bind chloride, even in a non-competitive solvent, which 
bodes ill for its ability to bind the more reactive HS- guest. This supports data previously 
seen by XB hosts out of the DWJ and Haley lab, which showed a preference for larger 
halides.3 While there have been many efficient and clever Cl- receptors published since 
Park and Simmons’ first host in 1968, few of them are both fluorescent and sufficiently 
strong enough to bind chloride in water.19,25 Continued efforts shall be made in 
optimizing this receptor to close the gap between anion and cation binding in aqueous 
media. This remains incredibly important for applications in vivo, where the high 
solvation energy of anions make them significantly more difficult to track and quantify 
than their positively charged counterparts.   
Bridge to Chapter IV. 
The next generation of XB receptors, alluded to in the above paragraphs, are the 
focus of the next two Chapters, IV and V, which explore a derivatized family of one-
armed arylethynyl hybrid, or XB and HB, receptors and then another new tridentate 
hybrid receptor, respectively. The family of one-armed receptors were intended to 
36 
elucidate some of the more fundamental preferences for mixed HB and XB systems with 
a simpler host and, hopefully, so more promise for in vivo studies. This is in part 
motivated by the difficulty our colleague Dr. Jess Lohrman experienced trying to 
solubilize the receptor into polar environments, making it nonviable for work in cells, as 
well as the weak bind that the large flexible bis-arylethynyl XB host scaffold, 0,  
displayed towards Cl-, given its huge pocket.3 Additionally, in her receptor, chloride was 
bound out of pocket, something thought to be due to the scaffold’s large pocket size. 
Thus, new receptors (in Chapters 4 and 5) were tailor-made with smaller pockets, to 
increase the receptors’ affinity towards Cl- anion recognition.  
37 
CHAPTER FOUR 
SUBSTITUENT EFFECTS IN A  
SERIES OF COMPACT ARYLETHNYL  
“MONODENTATE” HALOGEN BONDING HOSTS FOR ANION 
This chapter includes previously published and co-authored material from T. P. de Faria, 
H. J. Bates, A. S. Trom, F. I. D. Longnight, M. P. Miller, L. N. Zakharov, M. M. Haley & 
D. W. Johnson, manuscript in prep. This work investigates the structural changes, made
by modification of tunable groups with various EWGs and EDGs, to assess the influence 
of substituent effects in neutral versus charged receptors in this series. The results of the 
comparison of experimental binding trends and theoretical calculations will heavily 
influence future designs of small-molecule, halogen-bonding receptors from this scaffold 
family to bind to smaller anions more successfully and selectively in polar solvents.  
4.1. Introduction. 
 Anions are ubiquitous in nature—they play especially critical roles within our 
cells as well as in our external environment. Some of the most fundamental anions, the 
halides (I—, Br—, Cl—, F—), are crucial to human health and well-being. Examples include 
the misregulation of chloride in cells associated with disease states like cystic fibrosis1 
and iodine deficiency causing thyroid disease and goiter formation.2 Despite their 
significance, non-covalent binding of these anions still proves to be difficult for several 
reasons, but most notably because the entire halide family shares the same spherical 
shape, similar basicities for the three heaviest halides, and only slightly increasing sizes, 
leaving little margin for error when designing a suitable selective binding pocket. 
38 
Additionally, anions are well-solvated, particularly by the polar, protic media that make 
up many of the more interesting applications of these systems, in vivo sensing, for 
example.3-5 In fact, the Hofmeister series illustrates how, especially as halides get 
smaller, the energy required to free a halide anion from water becomes increasingly 
costly in energetic terms.6,7 In spite of these challenges, there have been many 
supramolecular systems that successfully bind anions, like chloride, in competitive polar 
protic solvents.8-12 Many of these hydrogen bonding hosts feature multi-dentate 
coordination that seems necessary for these hosts to compete in aqueous media. Further 
preorganization through macrocyclization often further enhances binding, although can 
be synthetically challenging and may make cellular uptake and compatibility less likely, 
per Lipinski’s Rules, for in vivo cell studies.13,14  
Recent work in the field of host-guest chemistry has expanded the supramolecular 
toolset beyond that of traditional hydrogen-bonding (HB) to now also include sigma-hole 
interactions, like those seen in halogen-15, chalcogen-16 and pnictogen-17 bonding.18 
Previous studies by other groups have shown that halogen-bonding (XB), while often 
comparable in strength to hydrogen-bonding, tends to be favored in polar protic 
solvents.9,19,20 For this reason, our group, among many others, has recently begun 
investigating halogen bonding as a tool for binding halides and other anions.21–24 The 
work we present here was largely influenced by our previously studied bis-aryl-ethynyl 
or “two-armed” receptors (Figure 4.1a), whose pocket size seemed to be too large to 
accommodate our target anion, chloride.22 
A crystallographic study showed the “two-arm” receptor changing configurations 
and binding chloride out of the intended pocket, unlike larger anions like iodide which fit 
39 
well. The new studies reported herein focus in on a compact “one-armed” structure 
(Figure 4.1b and 4.1c) that (1) eliminates the pre-determined pocket in hopes to shift 
binding preference to chloride over iodide and (2) enables the study of small, discreet 
changes on binding geometry.25,26  
This paper will also describe the modification of the R substituents and how 
various electron-withdrawing and -donating groups affect the binding affinity in neutral 
vs charged receptors in this family. These results will allow for a number of observations 
to be made about the fundamental nature of the halogen bond—something often 
Figure 4.1. Previously studied bis-arylethynyl XB receptor, a. Novel “one-armed” neutral, b, 
and charged, c, arylethynyl receptors. 
reductively characterized as an attractive R–X -- :A interaction (where R is a sufficiently 
electron withdrawing atom, X is a halide and A is an anion or other Lewis base)— 
through a structure-property relationship study.27
4.2. Results and Discussion. 
Electrostatic potential surface (ESP) maps were generated for all potential neutral, 
4a-d, and charged, 5a-d, host receptors (Figure 4.2) to see which synthetic alteration 
would have the greatest effect on the XB donor’s ability to noncovalently bind guests: the 
40 
positively charged N-methylpyridinium core, or the tunable R groups attached to the 
“arm” of the receptors. The results of the maps corroborate trends our group has seen in 
previous computational studies.22 When looking at the area of partial positivity—
quantified and described as Vs,max—created from the σ-hole of the XB donor, it shows a 
Figure 4.2. ESP maps of the entire family of receptors with the σ-hole values underneath each 
structure. Neutral structures are in panel a, and methylated structures in panel b. This figure clearly 
illustrates the outsized effect the methylated pyridinium unit plays in polarizing our halogen bond 
donor (compared to the changing ID of the FG para to it).  
decrease in magnitude of about 11 kcal/mol as the R-groups para to the iodo XB 
donor become more electron-donating in the neutral pyridyl receptors 4a-d. In the 
pyridine-N-Me cationic receptors 5a-d, the change is similar with a 9 kcal/mol 
decrease across the series of electron withdrawing/donating R-groups. However, 
when comparing the neutral receptors with similar σp values as their charged 
41 
analogues, the Vs,max values significantly increase with a ~54-58 kcal/mol 
difference providing evidence that what contributes more in the XB σ-hole 
enhancement of these arylethynyl scaffolds is the presence of the cationic N-
methylpyridinium core, despite its distance from the XB donor. 
To further verify this theoretical trend, all the scaffolds were synthesized for later 
solution-state binding studies, according to the modular synthetic path shown in 
Scheme 4.1. The starting aniline with the desired R-group was iodinated using KI 
Scheme 4.1. Synthetic pathway and yields for the formation of the neutral, 4a-d, and charged, 
5a-d, receptors. 
and KIO3 to furnish 1a-d. Diazotization of the aniline group followed by trapping 
with Et2NH afforded triazenes 2a-d. Next, Sonogashira cross-coupling with 3-
ethynylpyridine gave compounds 3a-d. The triazene group was then transformed 
42 
into an iodine, the XB donor chosen for each of our scaffolds, by heating with HI/I2 
to produce neutral hosts 4a-d. The neutral receptors were transformed into the 
charged receptors through alkylation using MeI with I– as the counter ion, 5a-d • I–. 
To enhance the apparent association constants for these charged receptors, the iodide 
counterion was then exchanged for the less competitive PF –6  (5a-d • PF6–). 
The solution-state binding trend seen between our group’s previously studied two-arm 
analogue and the series of halides showed that the preferred binding pocket fit best with 
the largest anion, iodide;22 bromide demonstrated the second-strongest affinity and 
chloride last. To test the hypothesis that the two-arm pocket was too large to 
preferentially bind chloride over larger anions, 1H NMR titrations were performed with 1 
mM solutions of single arm host receptor, 5a • PF6–, and 20-30 mM guest solutions of the 
tetrabutylammonium salts of chloride, bromide, and iodide in CD3CN. Association 
constants (Ka) were determined by tracking proton peaks and fitting the change in 
chemical shift to a 1:1 binding model using the Bindfit software.28,29 Receptor 5a • PF6– 
bound to Cl–, Br–, and I– with Ka values of 137, 104, and 103 M–1, respectively, 
demonstrating a modest yet inverse trend seen from our previous two-arm host analogue. 
This provides evidence that by changing the size of the pocket and reducing the entropic 
penalty associated with the previous host’s pre-organization, it is possible to shift the 
preference of anionic guest to slightly favor chloride despite the fact that iodide typically 
features stronger halogen bonding interactions in polar solvents, presumably due to lower 
solvation energies.30 The proton peaks that exhibited the largest change in chemical 
environment helped to elucidate the solution-state binding geometry of the receptors, 
which matched that of the calculated lowest energy state of the charged receptor (Figure 
43 
4.2) with the iodine XB donor facing the methylated pyridinium core. In all cases, the 
two hydrogens active in binding the halide guests are the pyridyl C–H in between the 
alkyne and the N atom, and one of the C–Hs of the pyridinium methyl group (Figure 
C1). A similar geometry was observed in the solid-state crystal data of our analogous 
bidentate XB host receptor that showed binding with the XB donor twisted out of the too-
large pocket and HB participation by the polarized C–Hs on the core and the methyl of 
the pyridinium. Neutral receptors 4a-d did not show measurable binding to chloride in 
acetonitrile, demonstrating that XB donors with σ-holes with Vs,max of ~17-29 kcal/mol 
may not be significantly electron-withdrawn to participate in halogen binding. Charged 
receptors 5a-d•PF6–  , and most notably those with lower σp values, were still able to bind 
to chloride in a trend that follows well with their calculated Vs,max values (Table 4.1). 
Table 4.1. Binding constants, in M–1, of charged receptors 5a-d with guest chloride and their 
calculated sigma-hole values in kJ/mol. 
5a • PF – 5b  6 • PF –6  5c • PF –6  5d • PF –6  
Ka with Cl– (M–1) 137 ± 5 120 ± 6 98 ± 4 85 ± 2 
Vs,max (kJ/mol) 82.8 80.0 77.2 73.8 
With the binding constants determined, we sought out to better comprehend the 
receptors’ binding sensitivity to chloride through the use of the Hammett 
relationship (log(K R Ha /Ka ) vs σp) by fitting the Kas to eq 1. 
R
log 𝐾aH =  𝜌σp +  ε (1)𝐾a
Plotting these values against the σp of the R substituents revealed that there is a 
weak linear response between the Ka and the electron-donating/-withdrawing nature of 
the substituent (Figure 4.3). The equation inset in Figure 4.3 describes the parameters of 
44 
Figure 4.3. Hammett plot between 5a-d and I–. The slope of the line indicated that substituents 
in this receptor has little role in affecting the sensitivity of the halogen-bond donor. The dotted 
lines represent the 95% confidence interval. 
the linear fit, resolved through linear regression. The slope of the line’s positive 
magnitude tells us that chloride binding is favored with more electron-withdrawing para 
R substituents. The value of ρ, 0.173, reveals that the halogen bond in this system is less 
sensitive to substituent effects compared to the standard, benzoic acid; therefore, the σp of 
the tunable R group is a statistically insignificant predictor of binding sensitivity in the 
one-armed arylethynyl receptor, further corroborating the hypothesis that the 
methylpyridinium dominates this family of receptors’ binding affinity compared to the 
para R–X’s σp values. This result is contrary to what we found for CH H-bond donors in 
related neutral bis-arylethynyl urea scaffolds. The CH hydrogen-bonding motifs in those 
systems were more susceptible to para substituent effects than that of our novel XB 
receptor with a ρ value of 0.71.31 It remains to be determined if substituent effects in 
charged CH receptors would be mitigated by the overall charge of the host, a topic we 
will address in the future.  
After getting a handle on the one-armed XB receptors’ binding geometries 
and properties in solution-state, we set out to study solid-state binding geometries. 
Crystals suitable for x-ray diffraction were grown of 5a,d • – I  (Figures 4.4b and 4.4d) 
45 
from a 2:1 mixture of CH2Cl2:acetone via slow evaporation. These structures revealed 
that the solid-state geometry of binding is similar to what we see in solution-state. 
Atomic distances calculated in the crystal structures were less than the sum of the 
van der Waals radii of the guest and the iodine XB donor, the aryl H, and the 
methyl H. These results indicate supramolecular binding occurs with not only our 
intentional XB donor, but also with the polarized CHs as H-bond donors.  
Table 4.2. XB or HB distances, in Å, of receptors 5a, 5b, and 5d binding to chloride or iodide as 
calculated from their crystal structures in Figure 4.4. 
5a • Cl– 5a • I– 5b • I– 5d • I– 
C–H – aryl -- X distance (Å) 2.904 3.173 2.928 3.187 
C–Hme -- X– distance (Å) 2.833 3.522 3.626 3.558 
C–I -- X– distance (Å) 3.403 3.705 N/A 3.824 
When comparing the binding distances in 5a and 5d, both binding I–, in the 
solid-state (Table 4.2), there is little difference in either of the C–H--I– distances of 
the HB donors – about 0.01-0.03 Å. The distance between the XB donor and 
a c
b d
Figure 4.4. Crystals structures of: a, 5a binding to chloride; b, 5a binding to iodide; c, 5b 
binding to iodide; and d, 5d binding to iodide. 
46 
iodide, C–I--X–, however, shows an order of magnitude greater difference with 
0.12 Å. Receptor 5a, with the most electron-withdrawing substituent, showed a 
closer distance of guest to XB donor than 5d, the receptor with the most electron-
donating substituent, suggesting that even in solid-state binding, there is a slight 
preference for substituents with electron-withdrawing characteristics. 
Crystals of 5a • Cl– were grown from a 1:2 acetone:CH3CN mixture via 
evaporation. When comparing the SO2CF3 receptor, 5a, binding to the largest guest, 
I–, and smallest guest, Cl–, an even larger shift is observed. The aryl C–H--I– distance 
changes by 0.27 Å, the methyl C–H--I– by 0.69 Å, and the C–H--X– by 0.30 Å with 
the guest halide becoming more tightly bound to the receptor with decreasing size 
of the anion. This trend is also shown subtly in the solution-state binding studies 
with a stronger Ka observed for chloride over iodide by 27 M–1. 
Finally, crystals of 5b – • I  (Figure 4.4c) were grown from a mixture of 1:1:1 
CH2Cl2:acetone:CH3CN. The crystals in this sample showed solid state binding of 
iodide with only the HB donors, C–H(aryl and methyl)--I–, which appeared to hold 
no trend with the previous bonding distances. The aryl C–H to iodide distance is 
2.93 Å, the second shortest aryl C–H to iodide distance of the four crystal structures; 
however, the methyl C–H to iodide distance is 3.63 Å, the largest methyl C–H to iodide 
distance. Notably, this structure is showing a binding geometry with the XB donor facing 
away from the iodide guest and not participating in binding at all. This result begs further 
investigation to help understand the significance of solvent effects in supramolecular 
binding through crystal packing of host-guest molecules.  
47 
Conclusion 
In conclusion, the data reported for this compact series of receptors suggest that 
when designing XB receptors with an arylethynyl foundation, a charged pyridinium core 
will provide a greater enhancement to the size and strength of the σ-hole than any 
adjacent functional groups. This knowledge allows for the purpose of the R group to shift 
away from that of only a XB enhancer to, instead, a number of other purposes including 
being a modular handle for other desired applications, such as polymerization, increased 
water-solubility, various cell compartment targeting functional groups, fluorophores, etc. 
without disrupting the most important portion of the anion recognition (the charge-
polarized XB donor). Additionally, recognizing that the R-group does not contribute 
significantly to the polarization of the XB donor in these charged hosts allows for future 
host-guest chemists to dodge the synthetic pitfalls that come with appending extremely 
electron withdrawing functional groups, like SO2CF3. These design principles, in addition 
to the binding demonstrated by the halogen/hydrogen bonding receptor in a polar solvent, 
will inform future host receptors for the halide anions.  
48 
CHAPTER FIVE 
FUTURE RECEPTORS AND FUTURE DIRECTIONS: AN UPDATE 
ON CURRENT WORK AND WHERE IT IS GOING 
5.1. Introduction. 
Throughout the previous chapters of this thesis, several host receptors were 
discussed in detail. Their strengths and weaknesses have been scrutinized to further the 
understanding of effective host-guest design principles, motivated by the prospect of 
more selective future hosts. In this chapter, two final hybrid XB-HB scaffolds will be 
explored for their potential as hosts for the halide anions (Figure 5.1). Specifically, both 
hybrid receptors were designed to have a smaller binding pocket than the receptors 
discussed in Chapter 3, and thus should show a 
preference for the smaller Cl– anion. The 
deliberate use of XB and HB donors in tandem is 
also expected to show some of the HB enhanced XB 
that Berryman and coworkers have discussed in past 
publications (see red dashed line in Figure 5.1).1 
These interactions have been shown to both further 
strengthen and stabilize the XB donor as well as 
preorganize the binding pocket into the geometry 
hypothesized to be best for binding.  These hosts (1 and 2) 
Figure 5.1. The two also feature functional moieties and strategies developed 
receptors that will be the 
focus of this chapter. in previous studies: this includes i) reliable anion 
49 
recognition motifs used in the early generation of XB and HB hosts developed in the 
DWJ/Haley laboratories; ii) urea (or related guanidine) HB donors, iii) acetylene bridging 
units, and iv) XB polarization via a pyridinium group (discussed in Chapters 3 and 4) or 
the well-known iodotriazoles popularized by Beer et al..2–11 In addition to these motifs, 
there are design strategies derived from the success of the family of one arm receptors, 
discussed in Chapter 4. Both receptors 1 and 2 feature XB and HB donors working in 
tandem to bind anion guests, which produced appreciable affinity for the halide anions in 
the more polar organic solvent, ACN. Additionally, much like the family of one-armed 
receptors, the size of the binding pocket of receptors 1 and 2 is smaller compared to the 
large cavity seen in the earliest generations of the DWJ-Haley XB receptors (reviewed in 
Chapter 3).  Our hypothesis is that the smaller binding pocket of 1 and 2 will invert the 
preference of the host to preferentially bind Cl– over the iodine anion, I–.6  
The beginning of this chapter will focus on the synthesis and results from receptor 
1. The latter half will focus on the synthesis of receptor 2, further design principles that 
inspired the scaffold, and some computational work which compares 2 to the receptors 
discussed in Chapter 4.  
 
5.2. Synthesis of Tridentate Hybrid Receptor 1. 
 Tridentate hybrid receptor 1 was synthesized in seven steps (Scheme 5.1). The 
first five synthetic steps were performed by Thaís de Faria.  First, benzocaine is iodinated 
under acidic conditions to yield intermediate 1.1. A TMS protected alkyne is then 
deprotected and installed through Sonogashira cross-coupling of 1.1 with the acetylene. 
The ethynylaniline precursor 1.2 is then subjected to a second Sonogashira cross-
 50 
I
Br
N
NH2 KI, KIO NH2 1. TMSA, K2CO3 THF, MeOH NH3 2
HCl, MeOH 2. 1.1, Pd(PPh3)2Cl2, CuI Pd(PPh3)4, CuIO O O
H2O, 50 °C I N2, THF, TEA N2, 50 °C
O O O TMS THF, TEA
1.1 1.2
H
N
10 mol% CF3
NH2 NH NH2
O Br OCN5 mol% CuI, NaI O I
O Dioxane, 110 °C O toluene, 55 °C
N overnight N overnight
1.3 1.4
CF3 CF3 CF3
O NH MeI O NH AgPF O NH6
NH NH
110 °C Acetone, Water
NH
O I O I O I PF6
70% 95%
O O I O
N N N
1.5 1.6 1
Scheme 5.1. The synthetic route to host receptor 1. 
coupling reaction with 4-bromo-3-iodopyridine to yield 1.3. The bromine on the pyridine 
moiety is exchanged for iodine because iodine is known to be a stronger XB donor.12 
Next, a urea HB donor is installed via addition of trifluoromethylphenyl isocyanate to the 
aniline moiety on 1.4.  Neutral receptor 1.5 was refluxed with MeI to yield a pyridinium 
moiety, which was expected to polarize the XB donor. Finally, 1.6 undergoes a counter 
ion exchange with AgPF6, to give the final host receptor in good yield (95%).  
5.3. Results and Discussion of Tridentate Hybrid Receptor 1. 
 To test the anion binding ability of 1, titrations with the halides Cl–, Br–, and I– 
were performed in 10% DMSO in ACN. Unlike previous generations of XB hosts (like 
those discussed in Chapter 3) the incorporation of HB donors enabled the binding 
constant to be measured by 1H NMR spectroscopy, which concomitantly gives  
51 
information about binding geometry and stoichiometry (example shown in Figure 5.1a). 
The downfield chemical shift of the urea protons (starred in Figure 5.2) indicates their 
participation in binding and can be plotted against the concentration of guest (16-42 mM) 
present, relative to that of host (0.73-1.90 mM), and fitted to 1:1 binding isotherms 
through non-linear regression to give the association constants reported in Table 5.1.13,14  
2.5
2 Predicted N(H) 1Predicted N(H) 2
Predicted C(H)
1.5 Experimental N(H)1
Experimental N(H)2
Experimental C(H)
1
0.5
0
0 10 [G]/[H] 20 30
A B 
Figure 5.2.  (a) Representative 1H NMR spectroscopy titrations of the tridentate receptor 
1 with TBACl, where the urea protons are starred and CH HB donor is marked with a 
triangle, and (b) the binding isotherm associated with that titration. 
Interestingly a third peak can also be seen shifting over the course of the titration 
(marked with a triangle in Figure 5.2) this is suspected to correspond to the hydrogen in 
the meta position, relative to our XB donor, acting as a C(H) HB donor. This suggests  
that, with the smaller anions, the iodine XB donor flips out of pocket and the anionic 
guest experiences tridentate coordination from exclusively HB donors, rather than the 
intended hybrid binding.  
These binding affinities indicates that the new receptor design successfully 
inverted the preference of the XB hosts to the smaller halide, Cl– (the reverse trend 
demonstrated by the first DWJ-Haley XB receptor reviewed in Chapter 3) as Cl– shows 
the strongest affinity for the receptor 1. This is an important finding because it highlights 
52 
𝜹 - 𝜹 0
that it is possible to tailor binding pocket size in future generations of these hosts to 
improve guest selectivity. Interestingly, Receptor 1 shows a stronger affinity for Cl– than 
for Br–, indicating that the size of the binding pocket is an important factor in anion 
binding and this small pocket favored smaller anions.  
If the size trend was to continue, it would be expected that then the affinity for I– 
would be even weaker. Instead, I– binding demonstrated a complexity not seen in the 
titrations with either Cl– or Br–. This is likely due to I– binding with this host differently 
from the other two halides, as indicated by the appearance of new peaks which growing 
in up field of the original receptor, suggesting a second species forming in solution. 
Additionally, when titrated with TBAI, the host peaks shifting only weakly downfield 
and decreasing in the intensity of the host peaks as more guest is added. Further 
experiments will be done to discern whether this is due to slow exchange, aggregation, 
some other complex binding pattern, or decomposition. These include performing 
diffusion-ordered spectroscopy (DOSY) NMR experiments (to assess whether 
aggregation is occurring), increasing the delay between scans (to better resolve any slow 
exchange), and performing VT NMR if both methods fail to elucidate clearer results. 
Additionally, post titration samples could be condensed and analyzed to verify whether 
decomposition has occurred. Solid state data from x-ray quality crystals could also help 
elucidate whether the larger anion is potentially binding out of pocket and/or interacting 
with more than one host molecule at a time. Finally, it should be noted that this titration 
of receptor 1 is conducted a fairly polar solvent system, which is relatively competitive, 
and demonstrates a marked improvement in anion recognition over that observed from 
data obtained in CHCl3, in the titrations discussed in Chapter 3. 
53 
Table 5.1. Titrations done with receptor 1 & the halides at r.t. in ACN 10% DMSO via 1H NMR - 
*the titration sets obtained for the I– anion cannot be fitted to a 1:1 binding model with 1 (consistent 
with the other anions) because there is a complex binding event occurring (See appendix D for 
more details) it is possible that slow exchange or higher order aggregation is occurring with the I– 
anion that was not seen with the  Cl– and Br– anions. 
Halide Anion Guest Ka (M-1) Ionic Radii (pm)15 
Cl– 440 181 
Br– 90 196 
I– * 220 
 
Synthesis of Quinoline-Based Receptor 2.  
The quinoline-based receptor 2 highlights all the design features discussed over 
the course of this thesis. Its extended π system gives the host (and many of its 
intermediates) an inherent bright fluorescence opening the door to equal parts beautiful 
and useful applications, like bio-imaging.16–18 It is also likely that the binding of this 
receptor could be tracked by 1H NMR, fluorimetry or UV-Vis spectroscopy. A new motif 
is seen in the triazole ring, bearing the pendant XB donor. Triazoles are seen throughout 
host-guest chemistry literature as an effective means of polarizing XB donors while 
maintaining a charge neutral molecule.10,19–21 Finally, the nitrogen atom in the quinoline 
backbone enables the preorganization of the molecule into a hydrogen bonded 6-
membered ring (shown in blue in Figure 5.1) with the guanidino HB donor group, which 
would reduce the entropic penalty associated with maintaining the conformation 
predicted to be most favorable for binding.22  
The synthesis for receptor 2 (Scheme 5.2) began with the protection of the amine 
functional group on the 2-aminoquinoline by acetyl chloride under basic conditions to 
afford 2.1. After this, the lone pair on the nitrogen atom in the amino group coordinated 
n-BuLi for a regioselective iodination in the 3-position of the quinoline intermediate,23 
before then undergoing deprotection by refluxing in acid overnight. 2-Amino 3-
 54 
iodoquinoline (intermediate 2.3) then is subjected to a Sonogashira cross coupling with 
the selectively deprotected 1,4-bis(trimethylsilyl)butadiyne (2.3a). The outermost diyne 
relative to the quinoline is then iodinated with n-iodosuccinimide, which undergoes a 
click reaction with benzyl azide to furnish the XB triazole ring in 2.6. Finally, the HB 
donor is added via either a cyanamide or isocyanate addition. Precursors 2.1-2.4 were 
synthesized and characterized completely and, while the latter intermediates and receptor 
2.5-2 were synthesized, they were not fully isolated and characterized due to time 
constraints. Synthesis of 2 was confirmed by high resolution MS; more details on all of 
these molecules’ properties can be found in Appendix D. 
O
Cl
1. nBuLi
TEA O 2. I I HCl I2 O
N NH2 DCM
.t. N N
1. Et2O, N2 Dioxane
0 °C to r -70 °C to 0 °C N N r.t. then reflux N NH2
H 2. -70 °C to -50 °C H
98% 2.1 73% 2.2 96% 2.3
TMS 1. MeLi•LiBr H2. NH4Cl
TMS  Et2O, RT TMS 2.3a
Quant.
TMS I
I 1. AgFaq, 20 minPd(PPh3)4, CuI 2. NIS, 1h
N NH2  THF, TEA N NH H2O, ACN, r.t. N NH
89% 2 31% 2
2.3 2.4 2.5
I N N N
N
4 mol% Lutidine, CuI(PPh3)3, N N10 mol % Sc(OTf)
N 33Bn H2NCN
I I
DMF H2O, 100° C
N NH N NH2 66% N NH2 H
N NH2
2.5 2.6 2
Scheme 5. 2 Synthetic scheme for derivatives of receptor 2 (R = benzyl).  
5 .5. Computation Work with Library of Receptors.  
Although empirical tests were not performed with receptor 2, computational work by 
Michael Miller was used to determine the energy levels Figure 5.3 Family of one 
arm receptors discussed in 
associated with σ-hole formation in nearly all the receptors chapter 4 and Table 5.3 
55 
discussed in this thesis for direct comparisons between the systems. All calculations are 
done with Gaussian 09, using B97D3 as the level of theory 
and def2tzvp as the basis set.  
These are listed in Table 5.3 and a variety of 
observations can be made from them. First, as established in 
Chapter 4, it is clear the primary driver behind XB donor polarization in the family of 
one-armed receptors (easily referenced in Figure 5.3) is the methylation of the pyridine 
moiety; the cationic hosts are always more than 50 kcal/mol stronger than their neutral 
analogs. This is particularly notable because it suggests that the IUPAC definition of the 
XB interaction (discussed in detail in Chapter 1) might be biasing host guest chemists to 
ascribe an undue significance to place EWG groups as near as possible to the XB donor. 
In the family of one arm hosts the nearest EWG (the pendant R-groups listed in Table 
5.3) are much less effective at forming the σ-hole needed for XB donation when 
compared to the methylation of the nitrogen atom on the other side of the molecule.  
The complexity of effectively polarizing the XB donors is further emphasized by 
the results of the calculations done on receptor 1, in which after methylation of the much 
closer nitrogen atom, the σ-hole value actually decreases by 4 kcal/mol. This result is 
surprising to us given the previously noted influence of the positive charge on the σ-hole. 
To verify and study this result, we would perform 1H NMR spectroscopy titrations to be 
done with the neutral version of receptor 1 (labelled 1.5 in Scheme 5.1) to determine 
binding constants and compare with the methylated receptor. Finally, the calculated σ-
hole value for the quinoline receptor shows that the triazole moiety will elicit similar 
energy levels comparable to an aryl ring with an appended EWG. Although further 
 56 
empirical and computation data must be collected to reinforce this idea, the suggestion 
that electron-deficient aryl rings can be used as comparable drivers of XB donors, relative 
to the much more regularly used triazole units, could open the door to novel XB host 
designs in future receptors.  
Table 5.3. Summary of the calculated energy value of sigma holes for XB donors in all of the 
receptors discussed in Chapters 4 and 5 (first 8 entries refer to the one arm family in Chapter 4) 
Chapter Number Receptor Name Sigma Hole Energy (kcal/mol) 
4 4a Neutral SO2CF3 28.5 
4 4b Neutral CF3 24.3 
4 4c Neutral H 19.0 
4 4d Neutral t-Bu 17.5 
4 5a Methylated SO2CF3 82.8 
4 5b Methylated CF3 80.0 
4 5c Methylated H 77.2 
4 5d Methylated t-Bu 73.8 
5 2 Quinoline Receptor 26.8 
5 1 Neutral 11.8 
5 1.5 Methylated 7.1 
5.6. Conclusion. 
 The receptors presented in this chapter highlight the complexity of designing an 
effective XB donor. Despite the nuance involved with XB host design, the latest 
generation of DWJ-Haley XB-HB hybrid receptors, like 1 (and those discussed in  
Chapter 4), have demonstrated a noteworthy ability to bind Cl– in polar solvents. These 
will undoubtedly pave the way towards future DWJ-Haley receptors and their use in 
aqueous media, fulfilling a long sought-after goal of binding these important anion 
species in critical environments, such as in vivo and in aqueous ecological environments.  
 57 
CHAPTER SIX 
CONCLUSIONS AND OUTLOOKS 
The research in this thesis discussed many of the most recent XB and HB 
receptors to come out of the DWJ and Haley laboratories for anion recognition. Chapter 
Two begins by exploring modifications made to improve the quantum yield, and other 
photophysical properties of a relatively newly discovered P-N containing heterocyclic 
fluorophore. This family of molecules beautifully highlights the nuanced understanding 
that can be derived from thorough structure-property relationships. It also sets the 
groundwork for thinking about many of the other fluorescent molecules discussed 
throughout this thesis.  
In Chapter Three the second XB receptor to come out of the DWJ and Haley 
group is discussed. This receptor was designed with two goals in mind: first, binding the 
hydrochacogenide, HS- and second, competing in a significant way with polar media. 
While falling short of these goals the failed hypothesis did reinforce fundamental design 
principles suggested by the first DWJ and Haley XB receptor (also discussed in Chapter 
Three). These design principles were then used to conceptualize and synthesize the much 
more successful receptors that are the subject of Chapters Four and Five.  
In Chapter Four a family of one-armed receptors capable of binding the halide 
anions in the polar solvent acetonitrile are discussed. In this family the size of the pocket 
is sufficiently shrunk to flip the preference of the XB guest to bind the smaller halide (Cl-
) over that of the larger halides (Br- or I-). This family demonstrated some HB 
58 
coordination of these anions, making it the first hybrid receptor to be published by the 
DWJ and Haley labs.  
Finally, In Chapter Five, two more hybrid receptors are explored. The first is a 
slightly larger one-arm receptor that demonstrate a similar preference for the smaller 
halide (Cl-) with an even larger association constant in more competitive solvent 
conditions (10% DMSO in ACN). It also was the subject of relatively surprising 
computation work, which suggested that methylating the pyridine ring (on which the XB 
donor is appended) had a minimal effect on the size of the σ-hole, bucking the outsized 
effect that methylation had with the earlier XB receptors. This result begs much further 
investigation. The small pocket of this receptor could also be an interesting case study in 
the effect of changing the identity of the XB donor (namely, from I to Br) and how that 
effects the halide guest preference, given a slightly less crowded pocket. Also mentioned 
in Chapter Five is the synthesis of a quinoline based scaffold that combines many of the 
design principles explored through the rest of the thesis. It has fluorescent properties, can 
preorganize into the state hypothesized to be best for binding and could be synthesized in 
either a neutral or cationic motif, depending upon the pH the receptor is intended to be 
utilized at. Further synthesis and characterization remain to be done with the quinoline 
receptor and should be finished shortly.   
The receptors discussed in Chapters Four and Five, in particular, present a library 
of receptors which seem to buck the IUPAC definition of a halogen bond as a simple 
interaction between R—X···Y, where X is a polarizable halogen covalently bound to an 
R group and Y is an electronically-dense halogen bond acceptor. This definition biases 
supramolecular chemists to give undue important to the electron withdrawing nature of 
59 
groups closest to the XB donor. In Chapter 4 it is shown that the much closer functional 
groups (which ranged from highly electron withdrawing to slightly electron donating) 
had a meager effect on XB polarization, relative to the methylation of the pyridine ring 
on the otherside of the molecule. But, as evidence by the receptors explored in Chapter 5, 
the answer is not as simple as adding a cation charge anywhere on the XB donor 
molecule. On the contrary, despite its signifigantly closer position to the XB donor in this 
receptor the methylation of the pyridine ring served to only marginally increase the size 
of the σ-hole.  
In conclusion, anions are an incredibly important class of molecule that are 
ubiquitious in human physiology and ecological niches around the world. Unfortunately, 
given their signifigance, the environments in which they are most pertinent (polar, 
aqueous ones) are also the mediums in which anions are the hardest to pin down. Their 
low charge density, high solvation energy and pH sensitivy makes them more difficult to 
bind than their cationic counterparts in water. Water’s ability to act as both an HB donor 
and acceptor makes it a highly competitive solvent for any synthetic host looking to bind 
anions. This makes XB an incredibly attractive tool, as study after study has shown that 
these σ-hole interactions outcompete the HB counterparts in competitive polar media in 
otherwise analogous host receptors. Despite this promise, and the growing interest of the 
past two decades, much still remains to be discovered about the best way to polarize and 
utilize XB donors for anion coordination. This, along with puzzling out how to best use 
this tool in tandem with other recognition techniques, including the other σ-hole 
interactions (chalcogen and pnictogen bonding) or anion···π interactions, is sure to drive 
research interests for decades to come.  
 60 
APPENDIX A 
SUPPLEMENTARY CONTENT FOR CHAPTER TWO 
Experimental Details 
1. Crystallographic Data for 2f
General. Diffraction intensities for 2f were collected at 173 K on a Bruker Apex2 
CCD diffractometer using CuK radiation, = 1.54178 Å. Space group was determined 
based on systematic absences. Absorption correction was applied by SADABS.1 Structure 
was solved by direct methods and Fourier techniques and refined on F2 using full matrix 
least-squares procedures. All non-H atoms were refined with anisotropic thermal 
parameters. H atoms were refined in calculated positions in a rigid group model except the 
H atom at the N atom involved in H-bond which was found on the residual density map 
and refined with isotropic thermal parameter. In the crystal structure the main molecules 
form a dimer unit via N-H•••O H-bonds which are packed in columns. Solvent molecules 
CHCl3 fill out empty space between such the columns and are highly disordered. These 
disordered solvent molecules were treated by SQUEEZE.2 The corrections of the X-ray 
data by SQUEEZE are 220 electron/cell; the required values are 232 electron/cell for four 
CHCl3 molecules in the full unit cell. All calculations were performed by the Bruker 
SHELXL-2014 package.3 
Crystallographic Data for 2f: C24H20Cl3O2P, M = 505.74, 0.15 x 0.08 x 0.06 mm, T 
= 173(2) K, Monoclinic, space group P21/c, a = 17.7865(8) Å, b = 8.1543(4) Å, c = 
18.4012(8) Å,  = 117.199(3), V = 2373.7(2) Å3, Z = 4, Dc = 1.415 Mg/m3, μ(Cu) = 4.335 
mm–1, F(000) = 1040, 2θmax = 133.15°, 13893 reflections, 4116 independent reflections 
[Rint = 0.0465], R1 = 0.0570, wR2 = 0.1562 and GOF = 1.021 for 4116 reflections (257 
parameters) with I>2(I), R1 = 0.0699, wR2 = 0.1630 and GOF = 1.021 for all reflections, 
max/min residual electron density +0.588/–0.275 eÅ–3. CCDC 1944053. 
61 
Figure A.1. ORTEP drawing of 2f with selected bond lengths listed; thermal ellipsoids 
drawn at 30% probability. Crystals grown with slow diffusion of pentane into a solution of 
2 in CHCl3. 
Figure A.2. ORTEP drawing of the racemic dimer of 2f; thermal ellipsoids drawn at 30% 
probability. 
62 
Figure A.3. ORTEP drawing of the crystal packing of 2f looking down the b-axis. 
63 
2. Frontier Orbital Values and TD-DFT Excitations 
Ground state calculations 
 
Table A.1. Calculated Frontier Orbitals and First Excitation Values for 2a 
S0 → S1 
cmpd EHOMO ELUMO EDFT computed (nm), 
osc. Strength 
2a –6.800 –2.405 4.395 341, 0.505 
2b –6.750 –2.319 4.431 337, 0.535 
2c –6.531 –2.296 4.235 354, 0.392 
2d –6.510 –2.294 4.303 348, 0.486 
2e –6.481 –2.178 4.207 358, 0.361 
2f –6.353 –2.146 3.896 389, 0.195 
a
 Calculated at the PBE0/TZVP level of theory; values reported in eV. 
 
 
Figure A.4. Frontier orbital shapes (isovalue = 0.3) of heterocycles 2; calculated at the 
PBE0/TZVP level of theory. 
 
Excited state calculations 
These initial structures were optimized using the functional PBE04,5 (25% full-range HF 
exchange) and TZVP basis set6 as implemented in Gaussian 09.7 In addition, all the 
optimized structures were confirmed by frequency analysis and the number of imaginary 
frequencies was zero. TD-DFT vertical excitation calculations and geometry optimization 
of the first excited state (S1) were performed at the same level of theory. The PCM solvation 
model8,9 was used to account for the solvent effects of the chloroform. 
 
64 
 
 
Figure A.5. HOMO-LUMO pictorial representations (isovalue = 0.3), energies and their 
differences (ΔE) in the optimized S0 and S1 structures of 2f calculated by the DFT and 
TD-DFT methods at the PCM(CHCl3)-PBE0/TZVP level of theory, respectively. 
 
  
65 
 
3. Geometry Optimizations and Coordinates 
Ground state geometries 
Table A.2. Cartesian coordinates of the optimized geometry of 2a determined at the 
PBE0/TZVP level of theory 
Atom        x           y                z 
C         -4.85224       -0.99453        0.24314 
C         -5.06467        0.36876       -0.01362 
C         -3.99796        1.19772       -0.26557 
C         -2.68944        0.69768       -0.26948 
C         -2.46321       -0.67090       -0.00881 
C         -3.55816       -1.49676        0.24538 
N         -1.62915        1.54068       -0.48129 
P         -0.05268        1.09981       -0.96544 
C          0.01373       -0.57214       -0.28708 
C         -1.13106       -1.21587        0.02816 
C          1.32888       -1.22391       -0.17733 
C          2.32937       -1.00360       -1.13093 
C          3.55719       -1.62907       -1.02594 
C          3.81064       -2.48996        0.04330 
C          2.82419       -2.71342        1.00652 
C          1.60209       -2.08011        0.89538 
O          0.24116        1.20873       -2.43673 
H         -6.07224        0.76605       -0.01630 
H         -4.16680        2.24964       -0.46799 
H         -3.38832       -2.54835        0.44662 
H         -1.86453        2.51486       -0.62006 
H         -1.06114       -2.25919        0.32868 
H          2.13135       -0.35505       -1.97675 
H          4.32091       -1.45850       -1.77493 
H          3.02505       -3.37115        1.84342 
H          0.85418       -2.23445        1.66438 
C          5.07615       -3.13557        0.15614 
N          6.10029       -3.65817        0.24771 
C          1.00594        2.19506        0.01314 
C          1.97814        2.94304       -0.64517 
66 
 
C          0.86604        2.29013        1.39720 
C          2.80595        3.78889        0.08033 
H          2.07444        2.85806       -1.72158 
C          1.69724        3.13388        2.11728 
H          0.10786        1.70840        1.91080 
C          2.66562        3.88319        1.45833 
H          3.56138        4.37440       -0.43113 
H          1.59006        3.20904        3.19339 
H          3.31411        4.54305        2.02388 
C         -5.95519       -1.85468        0.50419 
N         -6.85123       -2.54976        0.71725 
Zero-point correction = 0.306046 (Hartree/Particle); Thermal correction to energy = 
0.328311; Thermal correction to enthalpy = 0.329256; Thermal correction to Gibbs free 
energy = 0.252414; Sum of electronic and zero-point energies = -1426.281789; Sum of 
electronic and thermal energies = -1426.259523; Sum of electronic and thermal enthalpies 
= -1426.258579; Sum of electronic and thermal free energies = -1426.335421. 
 
 
Table A.3. Cartesian coordinates of the optimized geometry of 2b determined at the 
PBE0/TZVP level of theory 
Atom        x           y                z 
C          4.33256        0.25239        0.07266 
C          4.36740       -1.12574       -0.14433 
C          3.19680       -1.82533       -0.36097 
C          1.96424       -1.16425       -0.36534 
C          1.91814        0.22872       -0.13593 
C          3.11747        0.91433        0.07864 
N          0.79435       -1.87023       -0.54497 
P         -0.71412       -1.24659       -1.00223 
C         -0.55995        0.42532       -0.35685 
C          0.66485        0.93655       -0.08900 
C         -1.78476        1.23382       -0.22255 
C         -2.83620        1.11740       -1.14210 
C         -3.97972        1.88534       -1.01112 
C         -4.09599        2.78768        0.05013 
67 
 
C         -3.05815        2.90828        0.97984 
C         -1.92102        2.13323        0.84339 
O         -1.06879       -1.33987       -2.44972 
H          5.31560       -1.64935       -0.14765 
H          3.22816       -2.89645       -0.53066 
H          3.08031        1.98498        0.25349 
H          0.90195       -2.87056       -0.65853 
H          0.72898        1.98857        0.18318 
H         -2.74143        0.43697       -1.98120 
H         -4.78302        1.79523       -1.73288 
H         -3.15443        3.59763        1.81044 
H         -1.13530        2.20738        1.58703 
C         -5.27351        3.57973        0.18954 
N         -6.22685        4.22181        0.30316 
C         -1.87332       -2.16682        0.02964 
C         -2.99233       -2.74612       -0.56830 
C         -1.67521       -2.28375        1.40740 
C         -3.90785       -3.44425        0.21021 
H         -3.13095       -2.64787       -1.63956 
C         -2.59376       -2.97976        2.18044 
H         -0.80363       -1.83295        1.87151 
C         -3.70888       -3.55955        1.58133 
H         -4.77702       -3.89756       -0.25393 
H         -2.44117       -3.07162        3.25034 
H         -4.42561       -4.10321        2.18781 
C          5.58540        1.02927        0.31687 
F          5.71872        2.05264       -0.54614 
F          6.68573        0.27257        0.20460 
F          5.60776        1.57440        1.54852 
Zero-point correction = 0.312616 (Hartree/Particle); Thermal correction to energy = 
0.335712; Thermal correction to enthalpy = 0.336656; Thermal correction to Gibbs free 
energy = 0.257793; Sum of electronic and zero-point energies = -1670.857410; Sum of 
electronic and thermal energies = -1670.834315; Sum of electronic and thermal enthalpies 
= -1670.833370; Sum of electronic and thermal free energies = -1670.912234. 
 
68 
 
Table A.4. Cartesian coordinates of the optimized geometry of 2c determined at the 
PBE0/TZVP level of theory 
Atom        x           y                z 
C          4.76530       -0.84753       -0.21352 
C          4.95235        0.51406        0.01777 
C          3.85707        1.32309        0.25213 
C          2.56393        0.79136        0.25768 
C          2.37737       -0.58478        0.01677 
C          3.49994       -1.39313       -0.21621 
N          1.46788        1.61180        0.44837 
P         -0.06873        1.13040        0.96633 
C         -0.10263       -0.53610        0.28870 
C          1.05876       -1.16265       -0.01869 
C         -1.40505       -1.21599        0.17783 
C         -2.41834       -1.00066        1.12223 
C         -3.63596       -1.64912        1.01591 
C         -3.86748       -2.52873       -0.04558 
C         -2.86886       -2.74659       -1.00019 
C         -1.65681       -2.09032       -0.88811 
O         -0.35888        1.22487        2.42868 
H          5.95108        0.93373        0.01736 
H          4.00140        2.38257        0.43708 
H          3.36185       -2.45261       -0.39989 
H          1.67299        2.59782        0.54848 
H          1.01106       -2.21043       -0.31023 
H         -2.23659       -0.33867        1.96189 
H         -4.40883       -1.48285        1.75717 
H         -3.05318       -3.41765       -1.83095 
H         -0.90062       -2.23953       -1.65088 
C         -5.12144       -3.19771       -0.15958 
N         -6.13694       -3.74019       -0.25236 
C         -1.17198        2.18283        0.00032 
C         -2.19830        2.86079        0.65770 
C         -1.02047        2.31216       -1.38225 
C         -3.06654        3.67011       -0.06545 
H         -2.30167        2.75103        1.73180 
69 
 
C         -1.89224        3.11874       -2.10022 
H         -0.22075        1.78506       -1.89284 
C         -2.91380        3.79763       -1.44141 
H         -3.86269        4.20063        0.44554 
H         -1.77547        3.22002       -3.17380 
H         -3.59348        4.42828       -2.00484 
Cl         6.14889       -1.86580       -0.50514 
Zero-point correction = 0.298482 (Hartree/Particle); Thermal correction to energy = 
0.320018; Thermal correction to enthalpy = 0.320963; Thermal correction to Gibbs free 
energy = 0.245463; Sum of electronic and zero-point energies = -1793.507492; Sum of 
electronic and thermal energies = -1793.485956; Sum of electronic and thermal enthalpies 
= -1793.485012; Sum of electronic and thermal free energies = -1793.560511. 
 
 
Table A.5. Cartesian coordinates of the optimized geometry of 2d determined at the 
PBE0/TZVP level of theory 
Atom        x           y                z 
C          4.87957       -2.33820       -0.55510 
C          5.40340       -1.07460       -0.27234 
C          4.56839       -0.01982        0.04974 
C          3.18339       -0.20570        0.09586 
C          2.63866       -1.47362       -0.19415 
C          3.51235       -2.52485       -0.51570 
N          2.34180        0.85710        0.37539 
P          0.75066        0.75975        0.93800 
C          0.26395       -0.80418        0.19669 
C          1.21640       -1.68909       -0.18898 
C         -1.17160       -1.12470        0.11863 
C         -2.06875       -0.69107        1.10523 
C         -3.41442       -1.00319        1.02777 
C         -3.89511       -1.75842       -0.04594 
C         -3.01376       -2.19077       -1.04236 
C         -1.67175       -1.86848       -0.95930 
O          0.53974        0.85819        2.41437 
H          6.47569       -0.91258       -0.30076 
H          4.98133        0.95935        0.27178 
70 
 
H          3.08676       -3.49915       -0.73586 
H          2.80016        1.74837        0.51685 
H          0.89018       -2.67426       -0.51917 
H         -1.69940       -0.12656        1.95449 
H         -4.09666       -0.67053        1.80128 
H         -3.38796       -2.76407       -1.88250 
H         -1.00217       -2.17782       -1.75409 
C         -5.28099       -2.08196       -0.12992 
N         -6.40367       -2.34505       -0.19896 
C         -0.07738        2.10620        0.06374 
C         -0.88916        2.97892        0.78798 
C          0.06664        2.26802       -1.31618 
C         -1.55170        4.01136        0.13447 
H         -0.98883        2.84211        1.85939 
C         -0.59871        3.29914       -1.96466 
H          0.70009        1.58949       -1.87873 
C         -1.40739        4.16985       -1.23917 
H         -2.18113        4.69171        0.69792 
H         -0.48711        3.42552       -3.03617 
H         -1.92673        4.97494       -1.74843 
H          5.53887       -3.16167       -0.80375 
Zero-point correction = 0.308146 (Hartree/Particle); Thermal correction to energy = 
0.328403; Thermal correction to enthalpy = 0.329347; Thermal correction to Gibbs free 
energy = 0.257198; Sum of electronic and zero-point energies = -1334.037270; Sum of 
electronic and thermal energies = -1334.017013; Sum of electronic and thermal enthalpies 
= -1334.016068; Sum of electronic and thermal free energies = -1334.088218. 
 
 
Table A.6. Cartesian coordinates of the optimized geometry of 2e determined at the 
PBE0/TZVP level of theory 
Atom        x           y                z 
C          4.35248        0.21049        0.07235 
C          4.33995       -1.17064       -0.16139 
C          3.16166       -1.86961       -0.36931 
C          1.93366       -1.21055       -0.35366 
C          1.90847        0.17770       -0.11411 
71 
 
C          3.12016        0.85067        0.09372 
N          0.74735       -1.90753       -0.51892 
P         -0.74060       -1.26142       -0.99010 
C         -0.56897        0.40515       -0.33619 
C          0.66375        0.89745       -0.06005 
C         -1.78056        1.23340       -0.20894 
C         -2.83472        1.12515       -1.12718 
C         -3.96518        1.91354       -1.00623 
C         -4.06710        2.83118        0.04353 
C         -3.02744        2.94420        0.97248 
C         -1.90413        2.14776        0.84649 
O         -1.09672       -1.34365       -2.43972 
H          5.27024       -1.72536       -0.18728 
H          3.19132       -2.94032       -0.54750 
H          3.06805        1.91990        0.27852 
H          0.84423       -2.90826       -0.63491 
H          0.73924        1.94775        0.21772 
H         -2.75058        0.43374       -1.95842 
H         -4.76930        1.82839       -1.72779 
H         -3.11227        3.64495        1.79488 
H         -1.11817        2.21716        1.59035 
C         -5.22999        3.64586        0.17141 
N         -6.17152        4.30702        0.27540 
C         -1.92693       -2.16603        0.02901 
C         -3.05613       -2.71550       -0.57772 
C         -1.73891       -2.29931        1.40660 
C         -3.99141       -3.39891        0.19059 
H         -3.18671       -2.60599       -1.64895 
C         -2.67669       -2.98045        2.17009 
H         -0.85902       -1.87219        1.87731 
C         -3.80214       -3.52974        1.56168 
H         -4.86839       -3.82863       -0.28143 
H         -2.53109       -3.08441        3.23994 
H         -4.53410       -4.06162        2.16049 
C          5.63766        1.00664        0.30357 
C          5.74841        2.11833       -0.75049 
H          5.77949        1.69730       -1.75979 
72 
 
H          4.90443        2.81180       -0.70109 
H          6.66472        2.69643       -0.59303 
C          6.88485        0.12698        0.20409 
H          6.88632       -0.66501        0.95924 
H          6.97790       -0.33603       -0.78307 
H          7.77572        0.74011        0.36767 
C          5.60079        1.63565        1.70446 
H          5.53400        0.86334        2.47670 
H          6.51095        2.21793        1.88161 
H          4.74564        2.30666        1.82388 
Zero-point correction = 0.420029 (Hartree/Particle); Thermal correction to energy = 
0.445957; Thermal correction to enthalpy = 0.446901; Thermal correction to Gibbs free 
energy = 0.362564; Sum of electronic and zero-point energies = -1491.024374; Sum of 
electronic and thermal energies = -1490.998446; Sum of electronic and thermal enthalpies 
= -1490.997502; Sum of electronic and thermal free energies = -1491.081839. 
 
 
Table A.7. Cartesian coordinates of the optimized geometry of 2f determined at the 
PBE0/TZVP level of theory 
Atom        x           y                z 
C          4.47588       -0.49543       -0.11516 
C          4.55087        0.88383        0.10641 
C          3.39489        1.62204        0.31345 
C          2.14145        1.01628        0.30167 
C          2.05466       -0.37183        0.06988 
C          3.22937       -1.10406       -0.13277 
N          0.98169        1.76709        0.45969 
P         -0.51584        1.18392        0.96994 
C         -0.42817       -0.48686        0.30598 
C          0.77737       -1.03553        0.01956 
C         -1.67841       -1.25610        0.18321 
C         -2.71804       -1.10476        1.11169 
C         -3.88606       -1.83701        0.99485 
C         -4.04100       -2.73965       -0.06140 
C         -3.01604       -2.89482       -1.00048 
C         -1.85444       -2.15464       -0.87810 
73 
 
O         -0.83990        1.26621        2.42738 
H          5.50541        1.39434        0.12376 
H          3.46976        2.69084        0.48664 
H          3.17401       -2.17336       -0.30815 
H          1.11904        2.76509        0.55595 
H          0.80395       -2.08652       -0.26323 
H         -2.59360       -0.42479        1.94740 
H         -4.67904       -1.71914        1.72410 
H         -3.14145       -3.58368       -1.82771 
H         -1.07896       -2.25603       -1.62926 
C         -5.24310       -3.49585       -0.18623 
N         -6.21661       -4.10928       -0.28810 
C         -1.68565        2.14206       -0.01896 
C         -2.78685        2.71979        0.61264 
C         -1.51424        2.28933       -1.39736 
C         -3.71017        3.44529       -0.13109 
H         -2.90542        2.59902        1.68402 
C         -2.44008        3.01266       -2.13633 
H         -0.65624        1.84030       -1.88745 
C         -3.53719        3.59020       -1.50293 
H         -4.56501        3.89692        0.36070 
H         -2.30706        3.12759       -3.20671 
H         -4.25970        4.15509       -2.08268 
O          5.54569       -1.30193       -0.32098 
C          6.84268       -0.72057       -0.29182 
C          7.84268       -1.82535       -0.52364 
H          7.01082       -0.23888        0.68006 
H          6.92205        0.04825       -1.07137 
H          8.85712       -1.41944       -0.50995 
H          7.76385       -2.58608        0.25638 
H          7.67376       -2.30144       -1.49231 
Zero-point correction = 0.368617 (Hartree/Particle); Thermal correction to energy = 
0.393025; Thermal correction to enthalpy = 0.393970; Thermal correction to Gibbs free 
energy = 0.312175; Sum of electronic and zero-point energies = -1487.682390; Sum of 
electronic and thermal energies = -1487.657981; Sum of electronic and thermal enthalpies 
= -1487.657037; Sum of electronic and thermal free energies = -1487.738831. 
Representative excited state geometry 
74 
 
 
Table A.8. Cartesian coordinates for compound 2f (S1) 
Atom        x           y                z 
C          4.19754        0.83011        0.04258 
C          4.43859       -0.30536       -0.75296 
C          3.34960       -0.99099       -1.24675 
C          2.02893       -0.57501       -0.98158 
C          1.76910        0.59205       -0.18219 
C          2.87518        1.25433        0.31293 
N          0.98402       -1.27177       -1.48236 
P         -0.70551       -1.07234       -1.17069 
C         -0.75456        0.54008       -0.40889 
C          0.43970        1.06313        0.08325 
C         -2.03546        1.16742       -0.22284 
C         -3.26152        0.49519       -0.47023 
C         -4.47749        1.09997       -0.26071 
C         -4.54758        2.42475        0.21555 
C         -3.34562        3.11750        0.45118 
C         -2.13156        2.50968        0.23727 
O         -1.47016       -1.33310       -2.42262 
H          5.44102       -0.64467       -0.97311 
H          3.50091       -1.87627       -1.85654 
H          2.75354        2.14216        0.92323 
H          1.20261       -2.08660       -2.04452 
H          0.38969        1.94048        0.71954 
H         -3.25594       -0.52378       -0.83955 
H         -5.39269        0.55342       -0.45885 
H         -3.38120        4.14509        0.79654 
H         -1.23161        3.09014        0.40068 
C         -5.79638        3.04886        0.44241 
N         -6.82004        3.56105        0.62818 
C         -1.02320       -2.31567        0.10097 
C         -1.88954       -3.36767       -0.20702 
C         -0.43713       -2.24196        1.36922 
C         -2.16463       -4.33891        0.74848 
H         -2.34218       -3.41212       -1.19192 
75 
 
C         -0.71523       -3.21626        2.31544 
H          0.22229       -1.41627        1.61968 
C         -1.57745       -4.26674        2.00635 
H         -2.84004       -5.15319        0.50835 
H         -0.26328       -3.15571        3.29972 
H         -1.79397       -5.02592        2.75041 
O          5.14428        1.57982        0.58991 
C          6.52855        1.25640        0.38195 
C          7.34720        2.28195        1.12018 
H          6.73510        1.27453       -0.69282 
H          6.71378        0.24638        0.76081 
H          8.40933        2.06646        0.98366 
H          7.14692        3.28556        0.73949 
H          7.12518        2.25966        2.18909 
 
Geometries of 2 meso-dimer and analogous 1 meso-dimer  
Table A.9. Cartesian coordinates for compound 2f·2f (meso-dimer) 
Atom        x           y                z 
P         -1.95724        0.60235       -0.15810 
O         -1.13426        0.91794        1.07453 
O         -4.86819       -5.45211       -0.32378 
N         -1.72792       -0.90711       -0.85743 
N         -6.92721        6.54145        1.19270 
C         -3.73766        0.57706        0.11224 
C         -4.39950       -0.59867        0.11116 
H         -5.45545       -0.58653        0.37173 
C         -3.84837       -1.89655       -0.20763 
C         -2.54204       -2.01925       -0.69556 
C         -2.07237       -3.28570       -1.07125 
H         -1.07359       -3.37896       -1.48229 
C         -2.86947       -4.39809       -0.93597 
H         -2.50799       -5.37646       -1.22553 
76 
 
C         -4.17029       -4.28817       -0.42388 
C         -4.65455       -3.04354       -0.07520 
H         -5.65812       -2.91755        0.30781 
C         -4.41821        1.86371        0.36187 
C         -5.70140        2.08442       -0.14977 
H         -6.17936        1.31735       -0.74569 
C         -6.35626        3.28249        0.06722 
H         -7.34684        3.44695       -0.33573 
C         -5.72281        4.29106        0.79408 
C         -4.43772        4.09287        1.29858 
H         -3.95194        4.87940        1.86064 
C         -3.79259        2.88822        1.08154 
H         -2.80197        2.72981        1.49055 
C         -6.39194        5.54025        1.01540 
C         -1.60300        1.78258       -1.48582 
C         -0.61820        2.74784       -1.31084 
H         -0.06610        2.78759       -0.38140 
C         -0.34559        3.65095       -2.33102 
H          0.42602        4.39841       -2.19596 
C         -1.06490        3.59304       -3.51740 
H         -0.85633        4.29959       -4.31093 
C         -2.05424        2.62939       -3.69172 
H         -2.61274        2.58634       -4.61790 
C         -2.32146        1.72118       -2.67885 
H         -3.08473        0.96234       -2.81326 
C         -6.18694       -5.38880        0.20600 
H         -6.80431       -4.74129       -0.42516 
H         -6.15489       -4.95833        1.21243 
77 
 
C         -6.73651       -6.79556        0.23574 
H         -7.74918       -6.78877        0.63901 
H         -6.76584       -7.21498       -0.76966 
H         -6.11603       -7.43412        0.86410 
H         -0.75384       -1.07946       -1.13391 
P          1.95156       -0.64866        0.19274 
O          1.08688       -0.96110       -1.01172 
O          4.69506        5.48289        0.53051 
N          1.68726        0.83535        0.93440 
N          7.06869       -6.35013       -1.57736 
C          3.71838       -0.55160       -0.13926 
C          4.34473        0.64290       -0.10761 
H          5.39135        0.67402       -0.40224 
C          3.76786        1.90828        0.28504 
C          2.47046        1.97330        0.80554 
C          1.97625        3.20980        1.24574 
H          0.98434        3.25755        1.68084 
C          2.74001        4.34850        1.13996 
H          2.35923        5.30349        1.47902 
C          4.03159        4.29657        0.59628 
C          4.54060        3.08158        0.18481 
H          5.53862        2.99783       -0.22352 
C          4.43069       -1.80350       -0.46702 
C          5.73087       -2.00838        0.00685 
H          6.19822       -1.25657        0.63004 
C          6.41634       -3.17373       -0.28147 
H          7.41988       -3.32672        0.09277 
C          5.79805       -4.16492       -1.04428 
78 
 
C          4.49709       -3.98263       -1.51265 
H          4.02348       -4.75542       -2.10340 
C          3.82065       -2.81055       -1.22348 
H          2.81680       -2.66345       -1.60302 
C          6.50213       -5.37893       -1.34047 
C          1.69613       -1.88524        1.49285 
C          0.64469       -2.78840        1.38896 
H         -0.01285       -2.74941        0.53080 
C          0.44143       -3.73291        2.38765 
H         -0.38232       -4.43095        2.30814 
C          1.29730       -3.78013        3.48005 
H          1.14343       -4.52010        4.25539 
C          2.35300       -2.87906        3.58311 
H          3.01798       -2.91732        4.43630 
C          2.55094       -1.92835        2.59314 
H          3.36803       -1.21946        2.67405 
C          6.00897        5.47632       -0.01461 
H          6.65036        4.82286        0.58592 
H          5.97823        5.08342       -1.03618 
C          6.51872        6.89823        0.00350 
H          7.52896        6.93518       -0.40423 
H          6.54128        7.28223        1.02310 
H          5.87721        7.54089       -0.59909 
H          0.70937        0.98002        1.21499 
 
Table A.10. Cartesian coordinates for compound 2f‘·2f‘ (meso-dimer for -OPh analogue) 
Atom        x           y                z 
P          1.92141        0.79131       -0.26147 
O          0.78543        1.51236       -0.92423 
79 
 
O          6.53956       -3.99151       -1.19988 
N          2.02262       -0.82536       -0.62475 
N          4.97709        8.03803        0.16496 
C          3.59102        1.36451       -0.52551 
C          4.57382        0.46252       -0.73510 
H          5.58336        0.84492       -0.86408 
C          4.43734       -0.97249       -0.81836 
C          3.18131       -1.58317       -0.74275 
C          3.09026       -2.97766       -0.82535 
H          2.11643       -3.44875       -0.76712 
C          4.22370       -3.74153       -0.97276 
H          4.15972       -4.82045       -1.03252 
C          5.48901       -3.14105       -1.05234 
C          5.58959       -1.76691       -0.97746 
H          6.54735       -1.26819       -1.03595 
C          3.87197        2.80945       -0.37778 
C          5.03179        3.22763        0.28458 
H          5.69956        2.49146        0.71451 
C          5.32555        4.57143        0.42127 
H          6.22247        4.88754        0.93716 
C          4.44618        5.52323       -0.09631 
C          3.27888        5.12301       -0.74537 
H          2.60112        5.86640       -1.14344 
C          2.99450        3.77540       -0.88166 
H          2.09196        3.46511       -1.39128 
C          4.74073        6.91971        0.04861 
C          7.83932       -3.42380       -1.31227 
H          8.06387       -2.84264       -0.41180 
H          7.86840       -2.74857       -2.17381 
C          8.82206       -4.55834       -1.48203 
H          9.83191       -4.16050       -1.58264 
80 
 
H          8.79387       -5.22113       -0.61745 
H          8.58521       -5.13637       -2.37497 
H          1.13240       -1.32490       -0.52414 
P         -1.83870       -0.83501       -0.24159 
O         -0.58006       -1.54000        0.16537 
O         -6.03526        4.24836        0.94534 
N         -1.79480        0.81008       -0.03092 
N         -4.96926       -7.90305        1.34215 
C         -3.39028       -1.28890        0.51650 
C         -4.28646       -0.31809        0.79650 
H         -5.24232       -0.62508        1.21435 
C         -4.11342        1.10510        0.61877 
C         -2.88448        1.63685        0.21450 
C         -2.74464        3.02402        0.08792 
H         -1.78912        3.43301       -0.21776 
C         -3.81060        3.85580        0.33656 
H         -3.71118        4.92879        0.23273 
C         -5.05144        3.33451        0.73214 
C         -5.19474        1.96973        0.87834 
H         -6.13228        1.53222        1.19349 
C         -3.71128       -2.72292        0.68277 
C         -4.99895       -3.18586        0.38912 
H         -5.74136       -2.49828        0.00330 
C         -5.33121       -4.51660        0.56144 
H         -6.32798       -4.86844        0.33091 
C         -4.36480       -5.41187        1.02114 
C         -3.07251       -4.96965        1.30158 
H         -2.32861       -5.67016        1.65720 
C         -2.74907       -3.63508        1.12870 
H         -1.74774       -3.29074        1.35074 
C         -4.70057       -6.79521        1.19888 
81 
 
C         -7.30470        3.76745        1.37118 
H         -7.69766        3.06517        0.62875 
H         -7.19240        3.23607        2.32210 
C         -8.21923        4.96014        1.52189 
H         -9.20286        4.63183        1.85789 
H         -8.33183        5.47687        0.56903 
H         -7.81697        5.65942        2.25452 
H         -0.90390        1.25228       -0.29356 
O          1.65012        0.93158        1.34869 
O         -2.03326       -1.14197       -1.84182 
C          2.42198        0.19621        2.24001 
C          3.51657        0.80032        2.83895 
C          2.06499       -1.11320        2.52760 
C          4.27398        0.07137        3.74738 
H          3.75515        1.82865        2.59475 
C          2.83279       -1.83172        3.43459 
H          1.19713       -1.54270        2.04046 
C          3.93610       -1.24381        4.04341 
H          5.12751        0.53465        4.22565 
H          2.56580       -2.85461        3.66811 
H          4.52892       -1.80929        4.75059 
C         -3.06789       -0.51671       -2.52823 
C         -4.25761       -1.20300       -2.71875 
C         -2.88728        0.76802       -3.01906 
C         -5.29228       -0.58260       -3.40703 
H         -4.35624       -2.20940       -2.33039 
C         -3.93080        1.38009       -3.70142 
H         -1.94065        1.27030       -2.86233 
C         -5.13323        0.70995       -3.89317 
H         -6.22390       -1.11125       -3.56359 
H         -3.80062        2.38351       -4.08590 
82 
 
H         -5.94271        1.19250       -4.42543 
 
  
83 
 
4. Photophysical Properties in Different Solvents  
 
Figure A.6. Fluorescence decay curve of 2d vs Ludox Prompt sample. 
Solvent effects on fluorescence  
 
Figure A.7. Emission spectra of 2a in various solvents. 
 
 
 
 
84 
 
Table A.11. Photophysical properties of 2a in various solvents  
 Cyclohexane Toluene Chloroform DCM THF Acetonitrile 
λabs 353 351 348 349 358 350 
λem 445 446 452 448 456 456 
Stokes Shift 
(nm) 92 95 104 99 98 106 
 
 
 
 
 
 
 
 
Figure A.8. Emission spectra of 2b in various solvents. 
 
Table A.12. Photophysical properties of 2b in various solvents 
 Cyclohexane Toluene Chloroform DCM THF Acetonitrile 
λabs 346 346 343 344 358 345 
λem 442 442 447 445 453 458 
Stokes Shift 
(nm) 96 96 104 101 95 113 
 
 
 
 
 
 
85 
 
 
Figure A.9. Emission spectra of 2c in various solvents. 
 
Table A.13. Photophysical properties of 2c in various solvents 
 Cyclohexan Toluen Chlorofor Acetonitril
e e m DCM THF e 
λabs 366 365 360 365 367 363 
λem 467 466 474 472 480 486 
Stokes Shift 
(nm) 101 101 114 107 113 123 
 
 
 
 
 
 
 
 
 
 
 
86 
 
 
Figure A.10. Emission spectra of 2d in various solvents. 
 
Table A.14. Photophysical properties of 2d in various solvents 
 Cyclohexan Toluen Chlorofor DCM THF Acetonitrile e m e 
λabs 355 353 352 365 361 357 
λem 458 461 467 465 473 475 
Stokes Shift 
(nm) 103 108 115 100 112 118 
 
 
 
 
 
 
 
 
 
 
 
87 
 
 
Figure A.11. Emission spectra of 2e in various solvents. 
 
Table A.15. Photophysical properties of 2e in various solvents 
 Cyclohexan Toluen Chlorofor DCM THF Acetonitrile e m e 
λabs 365 361 360 362 368 365 
λem 467 469 473 478 488 493 
Stokes Shift 
(nm) 102 108 113 116 120 128 
 
 
 
 
 
 
 
 
 
 
 
88 
 
 
Figure A.12. Emission spectra of 2f in various solvents. 
 
Table A.16. Photophysical properties of 2f in various solvents 
 Cyclohexan Toluen Chlorofor
e e m DCM THF 
Acetonitril
e 
λabs 386 384 381 386 387 386 
λem 504 508 515 518 524 531 
Stokes Shift 
(nm) 118 124 134 132 137 145 
 
 
 
 
Figure A.13. Fluorescent image of 2f in Acetonitrile, THF, DCM, Chloroform, Toluene, 
Cyclohexane (left to right) 
89 
 
 
5. Experimental and Computational Examination of the Dimer 
Solution-state studies of dimer strength 
General procedure for variable concentration (VC) NMR experiments. CDCl3 was added 
in a 1:1 ratio to H2O, shaken vigorously, then allowed to separate. The organic phase was 
then separated and used to prepare ca. 10 mM solutions of heterocycle 2. These solutions 
were then diluted through addition of known amounts of the H2O-saturated CDCl3 solvent, 
with 31P NMR spectra being collected after each addition. The 31P NMR spectra were 
chosen over those of 1H NMR for these experiments since they give comparable results to 
1H NMR signals and the 1H NMR signals become impossible to track at lower 
concentrations due to complex splitting of multiple signals by the phosphorus center. The 
chemical shift of the phosphorus signal was tracked and fitted to generate the dimerization 
values.10 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure A.14. Binding isotherm (red), fit (blue), and residuals (inset) of VC NMR of 2b. 
90 
 
 Table A.17. Experimental and fitting data for VC NMR experiment of 2b 
Concentration Experimental 
(mM) δ (ppm) Fit δ (ppm) 
 
8.60 11.3755 11.37636588  
8.32 11.3583 11.35553759 
8.06 11.3315 11.33535491  
7.48 11.2871 11.28750165 
6.97 11.2465 11.24300097  
6.14 11.1654 11.16255996  
5.49 11.09 11.09160143 
4.96 11.0247 11.02836421  
4.16 10.918 10.92008376 
3.58 10.8299 10.83033275  
2.96 10.7164 10.72063772 
2.53 10.6342 10.6324564  
2.11 10.5421 10.53825939  
1.76 10.4816 10.44649514 
1.46 10.3465 10.36343269  
1.25 10.2875 10.29857999 
1.10 10.2345 10.24644727  
0.877 10.1592 10.16767483 
0.731 10.1191 10.11087501  
0.585 10.0577 10.05013847  
 
 
Figure A.15. Representative 31P NMR spectra for VC NMR of 2b. 
 
 
91 
 
 
 
 
Figure A.16. Binding isotherm (red), fit (blue), and residuals (inset) of VC NMR of 2c. 
 
Table A.18. Experimental and fitting data for VC NMR experiment of 2c 
Concentration Experimental 
(mM) δ (ppm) Fit δ (ppm) 
14.0 11.2039 11.2064793 
13.6 11.1831 11.1885475 
13.2 11.1672 11.1711442 
12.2 11.1341 11.1297717 
11.4 11.0951 11.0911563 
10.0 11.0212 11.0209934 
8.96 10.9617 10.9586984 
8.09 10.9091 10.9028468 
6.79 10.8023 10.8064342 
5.84 10.7176 10.7257245 
4.84 10.6209 10.6260187 
4.12 10.5419 10.5449533 
3.45 10.4777 10.4573812 
2.86 10.4277 10.3710209 
2.39 10.2748 10.2918817 
2.04 10.1932 10.2294034 
1.79 10.1464 10.1787126 
1.43 10.0982 10.1012771 
1.19 10.0425 10.0447712 
0.954 10.0123 9.98368372  
92 
 
 
 
Figure A.17. Representative 31P NMR spectra for VC NMR of 2c. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
93 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure A.18. Binding isotherm (red), fit (blue), and residuals (inset) of VC NMR of 2d. 
 
Table A.19. Experimental and fitting data for VC NMR of 2d  
Concentration Experimental Fit δ 
(mM) δ (ppm) (ppm) 
12.6 10.7014 10.694546 
12.2 10.6799 10.679281 
11.8 10.6658 10.664594 
10.9 10.6234 10.630185 
10.2 10.5926 10.598709 
9.00 10.5362 10.543093 
8.03 10.5069 10.495405 
7.25 10.4546 10.453992 
6.09 10.3830 10.385454 
5.24 10.3280 10.330913 
4.34 10.2696 10.267033 
3.70 10.2173 10.217883 
3.09 10.1697 10.167531 
2.57 10.1452 10.120592 
2.14 10.0711 10.079881 
1.83 10.0379 10.049254 
1.60 10.0143 10.025362 
1.28 9.9839 9.9904767 
1.07 9.9667 9.9662182 
0.856 9.9540 9.9410965 
 
94 
 
 
Figure A.19. Representative 31P NMR spectra for VC NMR of 2d. 
 
 
 
95 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure A.20. Binding isotherm (red), fit (blue), and residuals (inset) of VC NMR of 2e. 
 
Table A.20. Experimental and fitting data for VC NMR of 2e  
Concentration Experimental 
(mM) δ (ppm) Fit δ (ppm) 
11.6 10.7552 10.75070613 
11.2 10.7379 10.73691784 
10.9 10.7255 10.72367435 
10.1 10.6966 10.69273486 
9.39 10.6656 10.66454316 
8.27 10.609 10.61499453 
7.39 10.5668 10.57278564 
6.68 10.5217 10.53634355 
5.60 10.4786 10.47648406 
4.83 10.4291 10.42926445 
3.99 10.3749 10.37444554 
3.41 10.3314 10.33263873 
2.85 10.3066 10.29015441 
2.36 10.2735 10.25087549 
1.97 10.2087 10.21706939 
1.69 10.1835 10.19180097 
1.48 10.1671 10.17218912 
1.18 10.1399 10.14371351 
0.985 10.1185 10.12402601 
0.788 10.109 10.1037383 
 
96 
 
Figure A.21. Representative 31P NMR spectra for VC NMR of 2e. 
97 
 
 
 
 
 
 
 
 
 
 
 
 
Figure A.22. Binding isotherm (red), fit (blue), and residuals (inset) of VC NMR of 2f. 
  
Table A.21. Experimental and fitting data for VC NMR of 2f 
Concentration Experimental 
(mM) δ (ppm) Fit δ (ppm) 
11.8 10.7356 10.7285531 
11.4 10.7052 10.712116 
11.0 10.689 10.6963319 
10.3 10.6654 10.6594712 
9.59 10.6183 10.6259015 
8.45 10.5703 10.5669423 
7.55 10.5243 10.51676 
6.83 10.4787 10.4734671 
5.72 10.4056 10.4024241 
4.93 10.3464 10.3464462 
4.08 10.2772 10.2815335 
3.48 10.2254 10.2320847 
2.91 10.1666 10.1818864 
2.41 10.1348 10.1355237 
2.01 10.1038 10.0956594 
1.72 10.0768 10.0658868 
1.51 10.0456 10.0427937 
1.21 10.01 10.0092865 
1.01 9.9864 9.98613666 
0.805 9.9561 9.96229545 
98 
 
 
Figure A.23. Representative 31P NMR spectra for VC NMR experiment of 2f. 
 
Computational studies on dimer interactions 
 
The geometries for dimeric complexes of 2f and its -OPh counterpart were fully optimized 
without symmetry constraint by using the functional M06-2X11 (accounting for the 
contributions of H-bond/dispersion forces) and TZVP basis set as implemented in Gaussian 
09. The PCM solvation model was used to account for the effects of the chloroform 
environment. All of the optimized structures were confirmed by frequency calculations to 
be minima using the same level of theory. The solution-phase optimized geometries were 
used in the following calculations. The natural bond order (NBO) analyses were carried 
out using NBO 3.1 embedded in Gaussian 09 package. The NCI plot were performed by 
using the Multiwfn program.12 
 
99 
 
 
Figure A.24. The NCI plots for (a) 2f and (b) its -OPh analogue meso-dimeric motifs at 
the PCM(CHCl3)-M06-2X/TZVP equilibrium geometries. NCI regions are represented as 
solid surfaces and blue−green−red scaling from −0.02 < sign(2)(r) < 0 (in a.u.), where 
red surface indicates strong repulsion, blue surface strong attraction and green surface 
relatively weak interactions. Isosurface cutoff for NCI = 0.5. 
 
100 
 
 
Figure A.25. The NBO charge transfer stabilization energy [second-order perturbation 
energies E(2), in kcal/mol] for the indicated H-bond interactions in (a) 2f and (b) its -OPh 
analogue at PCM(CHCl3)-M06-2X/TZVP equilibrium geometries of the meso-dimeric 
motifs. The indicated H-bond interactions shown by the broken line, and H-bond distances 
in Å. 
 
6. References: 
(1) Sheldrick, G. M. Bruker/Siemens Area Detector Absorption Correction Program, 
Bruker AXS, Madison, WI, 1998. 
(2) Van der Sluis, P.; Spek, A. L. BYPASS: an effective method for the refinement of 
crystal structures containing disordered solvent regions. Acta Cryst., Sect. A 1990, A46, 
194−201. 
(3) Sheldrick, G. M. Crystal structure refinement with SHELXL. Acta Cryst. 2015, C71, 
3−8. 
101 
 
(4) Adamo, C.; Barone, V. Toward reliable density functional methods without adjustable 
parameters: The PBE0 model J. Chem. Phys. 1999, 110, 6158-6169.  
(5) Bremond, E.; Savarese, M.; Su, N. Q.; Perez-Jimenez, A. J.; Xu, X.; Sancho-Garcia, J. 
C.; Adamo, C. Benchmarking density functionals on structural parameters of small-
/medium-sized organic molecules J. Chem. Theory Comput. 2016, 12, 459–465. 
(6) Schuafer, A.; Huber, C.; Ahlrichs, R. Fully optimized contracted Gaussian basis sets of 
triple zeta valence quality for atoms Li to Kr J. Chem. Phys. 1994, 100, 5829–5835. 
(7) Gaussian 09, Revision E.01, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. 
E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. 
A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, 
G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, 
M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; 
Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, 
V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, 
S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; 
Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, 
A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, 
V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, 
Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian, Inc., Wallingford CT, 
2013. 
(8) Miertus, S.; Scrocco, E.; Tomasi, Electrostatic interaction of a solute with a continuum. 
A direct utilizaion of AB initio molecular potentials for the prevision of solvent effects J. 
Chem. Phys. 1981, 55, 117–129.  
(9) Barone, V.; Cossi, M.; Tomasi, J. Geometry optimization of molecular structures in 
solution by the polarizable continuum model J. Comput. Chem. 1998, 19, 404–417. 
(10) Thordarson, P. Determining association constants from titration experiments in 
supramolecular chemistry. Chem. Soc. Rev. 2011, 40, 1305−1323. 
(11) Zhao, Y.; Truhlar, D. G. The M06 suite of density functionals for main group 
thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and 
transition elements: two new functionals and systematic testing of four M06-class 
functionals and 12 other functionals Theor. Chem. Acc. 2008, 120, 215–241. 
(12) Lu, T.; Chen, F. Multiwfn: A multifunctional wavefunction analyzer J. Comput. 
Chem. 2012, 33, 580–592.  
102 
 
7. Copies of NMR Spectra 
 
Figure A.26. 1H NMR spectrum of 2a in DMSO-d6. 
 
 
Figure A.27. 13C NMR spectrum of 2a in DMSO-d6. 
103 
 
 
Figure A.28. 31P NMR spectrum of 2a in DMSO-d6. 
 
 
Figure A.29. 1H NMR spectrum of 2b in DMSO-d6. 
104 
 
 
Figure A.30. 13C NMR spectrum of 2b in DMSO-d6. 
 
 
Figure A.31. 31P NMR spectrum of 2b in DMSO-d6. 
105 
 
 
Figure A.32. 19F NMR spectrum of 2b in DMSO-d6. 
 
 
Figure A.33. 1H NMR spectrum of 2c in DMSO-d6. 
106 
 
 
Figure A.34. 13C NMR spectrum of 2c in DMSO-d6. 
 
 
Figure A.35. 31P NMR spectrum of 2c in DMSO-d6. 
107 
 
 
Figure A.36. 1H NMR spectrum of 2d in CDCl3. 
 
 
Figure A.37. 13C NMR spectrum of 2d in CDCl3. 
108 
 
 
Figure A.38. 31P NMR spectrum of 2d in CDCl3. 
 
 
Figure A.39. 1H NMR spectrum of 2e in CDCl3. 
109 
 
 
Figure A.40. 13C NMR spectrum of 2e in CDCl3. 
 
 
Figure A.41. 31P NMR spectrum of 2e in CDCl3. 
110 
 
 
Figure A.42. 1H NMR spectrum of 2f in CDCl3. 
 
 
Figure A.43. 13C NMR spectrum of 2f in CDCl3. 
111 
 
 
Figure A.44. 31P NMR spectrum of 2f in CDCl3. 
112 
 
 
APPENDIX B 
 
SUPPLEMENTARY CONTENT FOR CHAPTER THREE 
 
Synthesis 
General Methods: All reagents were purchased from conventional commercial sources 
and used as received, unless otherwise noted. All NMR spectra were acquired at room 
temperature on a 1H NMR, 13C NMR, and 19F spectra were obtained using a Bruker 500 
MHz spectrometer (1H 500 MHz, 13C 126 MHz, 19F 471 MHz). All 1H and 13C chemical 
shifts () are reported in ppm relative to the residual CHCl3 (1H: 7.26 ppm, 13C: 77.16 
ppm) or (CH3)2CO (1H: 2.05, 13C: 206.26, 29.84).  
 
 
Scheme B1: The second, more successful, synthetic path for reaching host receptor 1 
 
 
Scheme B2: The original, low yielding, synthetic path for accessing receptor 1 
 
 113   
 
 
2-Iodo-4-Trifluoromethyl Aniline (1.4) 
KI (2.1638g, 13 mmol) and KIO3 (1.5762, 7.4 mmol) were added to a RBF containing DI 
water (60mL) and set stirring. 2-iodo-4-trifluoromethyl aniline (3.0216g, 18.8 mmol) was 
then dissolved in MeOH (10 mL) and added to the aqueous solution dropwise. Once 
everything was dissolved in solution 1M HCl was added dropwise (20.5 mL, 20.5 mmol). 
The reaction was then left to stir overnight. The next day the reaction was worked up via 
extraction with DCM. The organic phase was washed twice with saturated solution of 
NaHCO3, then water and finally brine. The organic phase was then dried with NaSO4, 
filtered and the solvent removed in vacuo to yield 1.4 in quantitative yields (3.73 g). 1H 
NMR (500 MHz, Acetone-d6) δ = 7.87 (s, 1H), 7.42 (d, J=9.8, 1H), 6.94 (d, J=8.5, 1H), 
5.53 (s, 2H). 
 
 
4-(Trifluoromethyl)-2-((trimethylsilyl)ethynyl)aniline (1.1) 
The iodo-aniline (8.899g, 31.0 mmol) was dissolved in 200 mL of a 50/50 mixture of 
THF and DIPA then set outgassing under N2 for ~3.3 hours. After this time Pd(PPh3)2Cl2. 
(1.088g, 1.55 mmol) and CuI (0.118g, 0.62 mmol) was weighed out and added to the air 
free flask. Finally, TMSA (12.95 mL, 186 mmol) was added to the solution dropwise via 
an addition funnel. The solution was run overnight and worked up the next day, assuming 
TLC control showed all of the starting material gone. The crude product was purified by 
 114   
 
column chromatography on silica with EtOAc/Hexanes. The product was produced in 
79% yield (6.30 g).  
 
 
2,2′-(2,6-pyridinediyldi-2,1-ethynediyl)bis[4-(trifluoromethyl)-benzeneamine (1.2) 
The TMS protected aniline was (10.3084g, 40 mmol) was dissolved in a minimal amount 
of a 50/50 mixture of MeOH and THF. K2CO3 (31.295g, 240 mmol) was then added (not 
all of it will dissolve). The reaction was monitored by TLC control and, after completion, 
the reaction was filtered and solvent removed by rotary evaporation. The crude product 
was then redissolved in EtOAc and washed thrice with a saturated aqueous solution of 
ammonium chloride, then water and finally brine. The organic phase was then dried with 
NaSO4 and filtered before the EtOAc was removed by rotary evaporator to give the 
deprotected product in quantitative yields. This was then dissolved in 200 mL of 50/50 
THF and DIPA and set outgassing under N2. In a second flask 2,6-dibromopyridine (5.26 
g, 17.2 mmol) was set sparging in 50 mL of THF and DIPA. After sparging was complete 
Pd(PPh3)4 (1.37g, 1.72 mmol) and CuI (0.09047g, 0.65 mmol) was added to the first 
RBF. Then the solution of “elbow” was then cannulated into the first RBF dropwise. The 
solution was set stirring overnight, and the next day solvent was removed in vacuo and 
then purified over silica by column chromatography to furnish the bis-aniline in 21% 
yield (3.74 g). 
 115   
 
 
Host Receptor (1) 
The bis-aniline (5.53 g, 12.3 mmol) was dissolved in 300 mL of ACN and set stirring in a 
brine and ice bath until it reaches -10 °C. In a separate RBF concentrated HI was diluted 
with 100 mL ACN and then cannulated in dropwise, the solution went from a light 
yellow to a bright orange. Then a 10 mL solution of NaNO2 was added by syringe, 
dropwise, after which the solution was a dark red. The solution was monitored by TLC 
and after ~90 minutes the reaction had run to completion. At this point the reaction was 
cannulated over to a quench solution of KI (5.615g, 30.9 mmol) in water. This solution 
was washed twice with sodium bicarbonate, water and brine before the organic phase was 
then dried with NaSO4. The ACN was then removed by rotary evaporation and the 
product was redissolved in DCM and run through a silica plug. The filtrate was reduced, 
in vacuo to furnish the final receptor in a 30% yield (2.46 g).  
 116   
NMR Spectra 
HJB-Exp4-PC-Acetone.1.fid
NH2
F
I
F
F
A (s) B (d) C (d) D (s)
7.87 7.42 6.94 5.53
8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
f1 (ppm)
Figure C.1. 1H NMR spectrum of 2-Iodo-4-Trifluoromethyl Aniline (1.4) in acetone-d6. 
HJB-Exp12-PF-Acetone.1.fid
2100
2000
1900
NH2
1800
F 1700
CH3 1600
F
F Si 1500
CH3
H3C 1400
1300
1200
1100
C (s)
7.48 1000
B (d) A (d) D (s)
7.37 6.90 0.26 900
800
700
600
500
400
300
200
100
0
-100
-200
-300
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
f1 (ppm)
Figure C.2. 1H NMR spectrum of 4-(Trifluoromethyl)-2-((trimethylsilyl)ethynyl)aniline 
(1.1) in acetone-d6. 
117 
1 00 7.4778. 0.41
7.3757 1.00 1.32 7.86821.05 0.47
7.3575
7.4274
6.9110 1.02 0.99
1.03 1.00 7.4079
6.8966
6.9518
1.04 1.02 6.9349
1.92
1.96 2.13 5.5338
4.0527
2.8488
2.8051 Water
2.0500 CDCl3
1.9635 2.0500 Acetone
2.0500 CDCl3
1.1966
0.2587
8.84 8.17 0.2561
0.1920
 
HJB-Exp14-NPDTspot-Acetone.1.fid 6000
5500
5000
4500
4000
F F
F N F
3500
F F
3000
C (dd) NH2 H2N
7.75
B (dd) A (d)
7.44 6.97 2500
D (m)
7.63 2000
1500
1000
500
0
-500
9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
f1 (ppm)  
Figure C.3. 1H NMR spectrum of 2,2′-(2,6-pyridinediyldi-2,1-ethynediyl)bis[4-
(trifluoromethyl)-benzeneamine (1.2) in acetone-d6. 
 
 
 
 
 
 
 
 
 
 
Figure C.4. 1H NMR spectrum of host receptor (1.3) in acetone-d6. 
 
 118   
7.7814
7.7657
7.7317
7.7169
7.6592
1.92 1.43 7.6548
1.88 1.48 7.6155
1.05 0.96 7.6001
7.4295
6.9798
1.00 1.00 6.9627
6.9445
1.85
2.8383 Water
2.0500 Acetone
 
UV-Vis titrations: 
General Titration Procedure: A stock solution of host receptor 1 (0.1 mM) was prepared 
in CHCl3 and sonicated until dissolved. The stock solution was then used to prep 
experimental host solutions at a concentration of XXX +/- uM of which 1.75 mL was 
transferred to a septum sealed quartz cuvette. To maintain a constant host concentration, 
the remaining experimental host solution was then used to dissolve NBu4Cl salt which 
was prepared in vol. flasks and transferred to a septum sealed vial. Aliquots of NBu4Cl 
were added to the host cuvette with a gas-tight Hamilton syringe, and a spectrum was 
recorded after each addition. Binding constants were determined by non-linear regression 
fit to a 1:1 model using the Bindfit software.  
 
Figure C.5. Representative UV-Vis spectroscopic titration of 1 with TBACl in CHCl3 
out to 32 equivalents.  
0.18
0.16 Predicted Abs 274
0.14 Predicted Abs 375
0.12 Experimental Abs 274
0.1 Experimental Abs 375
0.08
0.06
0.04
0.02
0
0 5 10 15 20 25 30 35
[G]/[H]
 
 
 119   
∆ in Abs
0.002
0
0 5 10 15 20 25 30 35
-0.002
274
-0.004
[G]/[H] 375
Figure C.6. The absorption binding isotherm and residuals of TBACl and host 1 at 274 
and 325 nm.  
Table C.1. Calculated association constants (Ka) for 1 in CHCl3 obtained by fitting to a 
1:1 host-guest model in Bindfit.  
Addition # VGuest Equiv. (𝜇L) Guest M Host M Anion 𝛌1: 274.0 𝛌2: 325.0 
1 5 4.8023E-06 2.5216E-05 0.190449 0.13496858 0.13089709 
2 5 9.5834E-06 2.5216E-05 0.38005531 0.13717921 0.13191755 
3 10 1.9082E-05 2.5216E-05 0.75676211 0.13897592 0.13253617 
4 20 3.7831E-05 2.5216E-05 1.50030567 0.14299439 0.13376707 
5 20 5.6256E-05 2.5216E-05 2.23097401 0.1472857 0.1352873 
6 20 7.4364E-05 2.5216E-05 2.94909869 0.15005948 0.13586836 
7 20 9.2164E-05 2.5216E-05 3.65499997 0.1531345 0.13683006 
8 25 0.00011399 2.5216E-05 4.52065786 0.15732685 0.13772386 
9 25 0.00013537 2.5216E-05 5.36828121 0.16341333 0.1397128 
10 50 0.0001768 2.5216E-05 7.0116326 0.17213741 0.14254235 
11 50 0.00021658 2.5216E-05 8.58924994 0.1794094 0.14429528 
12 50 0.00025481 2.5216E-05 10.1049999 0.18651174 0.14666025 
13 50 0.00029156 2.5216E-05 11.5624518 0.19426057 0.14910294 
14 50 0.00032692 2.5216E-05 12.9649056 0.20099705 0.15107825 
15 50 0.00036097 2.5216E-05 14.3154166 0.20796648 0.15375777 
120 
Residuals
 
16 100 0.00042543 2.5216E-05 16.871741 0.22334722 0.15857396 
17 100 0.00048545 2.5216E-05 19.2517671 0.23541191 0.16212441 
18 100 0.00054146 2.5216E-05 21.4731248 0.24931185 0.168189 
19 200 0.00064299 2.5216E-05 25.4993358 0.26696813 0.1726637 
20 400 0.00081219 2.5216E-05 32.2096873 0.30114302 0.18446825 
 
Table C.2. Titration of 1 with TBACl  
 
 121   
 
APPENDIX C 
SUPPLEMENTARY CONTENT FOR CHAPTER FOUR 
 
Experimental Details 
General Methods. 
Unless otherwise noted all reactions were run open to the atmosphere and consequently 
were exposed to air and water. All reagents were used as purchased from commercial 
sources. The 1H NMR, 13C NMR, and 19F  spectra were obtained using a Bruker 500 
MHz spectrometer (1H 500 MHz, 13C 126 MHz, 19F 471 MHz), and the 1H NMR 
titrations were performed on a Varian 500 MHz spectrometer (1H 500.10 MHz) using d3-
ACN. All 1H NMR and 13C NMR chemical shifts (δ) are reported in parts per million and 
referenced to residual solvent peaks (CHCl3: 1H 7.26 ppm, 13C 77.16 ppm; (CH3)2CO: 1H 
2.05ppm, 13C 29.84 and 206.26 ppm; CH3CN 1H 1.94 ppm, 13C 118.26 and 1.32 ppm). 
Masses for novel compounds were determined with a Waters Xevo G2-XS ToF 
spectrometer.  
 
 
 
 
 
 
 
 122  
 
Full Receptor Synthesis. 
 
 
4-(trifluoromethylthio)acetamide.  
4-(trifluoromethylthio)aniline (7.4 mL, 71.8 mmol) was added under N2 to an oven-dried, 
vacuum-cooled round bottom flask. Acetic anhydride (10.2 mL, 108 mmol) was added to 
the flask dropwise and a white precipitate crashed out upon addition. The mixture was 
stirred at room temperature for one hour. Afterwards, the solid was dissolved using ethyl 
acetate and washed with water and brine. The organic layer was dried (Na2SO4), filtered, 
and concentrated to give the crude protected aniline. The white powdered product was 
purified by running the crude product through a plug with dichloromethane. (12 g, 71% 
yield). 1H NMR (500 MHz, Acetone-d6) δ 9.44 (s, 1H), 7.80 (d, J = 8.7 Hz, 2H), 7.63 (d, J 
= 8.7 Hz, 2H), 2.11 (s, 3H). 
 
 
N-[4-[(trifluoromethyl)sulfonyl]phenyl]acetamide. 
In an oven-dried, vacuum-cooled round bottom flask, the 4-(trifluoromethyl)thio phenyl 
acetamide (12 g, 51.0 mmol) was dissolved in 200 mL of dry dichloromethane and cooled 
to 0 ºC. mCPBA (26 g, 153 mmol) was added in 4 portions under a heavy N2 (g) flow. The 
reaction was allowed to warm up to room temperature while stirring overnight. The 
 123  
 
reaction mixture was diluted with more dichloromethane and Na2S2O3 was used to quench 
any excess mCPBA. The mixture was extracted with dichloromethane and the combined 
organic layers were washed with Na2S2O3, NaHCO3, water and brine, then dried (Na2SO4) 
and concentrated to afford a white precipitate (11.4 g, 84% yield). 1H NMR (500 MHz, 
Acetone-d6) δ 9.84 (s, 1H), 8.08 – 8.00 (m, 4H), 2.18 (s, 3H). 
 
 
N-[4-[(trifluoromethyl)sulfonyl]phenyl]aniline.  
N-[4-[(trifluoromethyl)sulfonyl]phenyl]acetamide  (6.2 g, 23.15 mmol) was dissolved in 
200 mL of EtOH; KOH (1.43 g, 25.46 mmol) was added, and the reaction mixture was 
set to 60 ºC and allowed to stir. After 3 hours, the mixture was concentrated to afford a 
crude solid which was then dissolved in water. White precipitate formed and collected via 
vacuum filtration to afford pure product (4.7 g, 90% yield). 1H NMR (500 MHz, 
Chloroform-d) δ 7.75 (d, J = 8.8 Hz, 2H), 6.75 (d, J = 8.8 Hz, 2H), 4.54 (s, 2H). 
 
Iodoaniline derivatives, 1a-d.  
The aniline derivative (20.76 mmol, 1.0 equiv.) was dissolved in 40 mL methanol. In 
another flask, KIO3 (7.27 mmol, 0.35 equiv.) and KI (13.7 mmol, 0.66 equiv.) were 
dissolved in 100 mL water. The aqueous solution was added to the solution containing 
the aniline derivative then 1 M HCl (23 mL, 1.1 equiv.) was added dropwise. After the 
 124  
 
reaction stirred at room temperature overnight, the mixture was extracted with ethyl 
acetate. The combined organic layers were then washed with Na2S2O3, NaHCO3, water, 
and brine, then dried (Na2SO4) and concentrated to afford crude product.  
R= SO2CF3 (red/brown solid, 92% yield). 1H NMR (500 MHz, Chloroform-d) δ 8.22 (d, 
J = 2.1 Hz, 1H), 7.74 (dd, J = 8.6, 2.1 Hz, 1H), 6.81 (d, J = 8.6 Hz, 1H), 4.99 (s, 2H). 13C 
NMR (126 MHz, CDCl3) δ 153.83, 142.11, 132.45, 123.86, 121.27, 118.88, 118.68, 
116.09, 113.44, 81.85, 77.16. 19F NMR (471 MHz, CDCl3) δ -78.79. MASS SPEC 
NEEDED. 
R= CF3 (brown solid, 79% yield). 1H NMR (500 MHz, Chloroform-d) δ 7.87 (s, 1H), 
7.38 (dd, J = 8.5, 2.2 Hz, 1H), 6.74 (d, J = 8.4 Hz, 1H), 4.41 (s, 2H).  
R= H commercially available  
R= tBu (brown solid, 66% yield). 1H NMR (500 MHz, Chloroform-d) δ 7.65 (d, J = 1.7 
Hz, 1H), 7.19 (d, J = 2.0 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H), 3.99 (s, 2H), 1.28 (d, J = 1.7 
Hz, 9H). 
 
 
Iodotriazene derivatives, 2a-d.       
The iodoaniline derivative (8.55 mmol, 1.0 equiv.) was dissolved in 30 mL acetonitrile 
and set to cool at -10 ºC. Concentrated HCl (5.7 mL, 8.0 equiv.) was added to the flask. 
In another flask, a solution of NaNO2 (20.51 mmol, 2.4 equiv.) in 30 mL water was 
prepared. The aqueous NaNO2 solution was added dropwise to the solution of the 
iodoaniline derivative and left to stir at -10 ºC. This reaction mixture was monitored by 
TLC for consumption of starting material. Once consumed, the reaction mixture was 
 125  
 
added to a quench solution of: HNEt2 (85.45 mmol, 10 equiv.) and K2CO3 (49.56 mmol, 
5.8 equiv.) in 50 mL of acetonitrile and 100 mL of water at -10 ºC. This quenched 
reaction mixture was allowed to warm up to room temperature while continuously 
stirring overnight. The reaction was extracted with ether and the combined organic layers 
were washed with Na2S2O3, NaHCO3, water, and brine. The organic layer was collected 
and dried (Na2SO4) and concentrated to afford the crude iodotriazene that was purified by 
column chromatography (gradient from pure hexanes to 1:9, dichloromethane:hexanes) to 
afford pure iodotriazene.  
R= SO2CF3 (orange solid, 25% yield). 1H NMR (500 MHz, Chloroform-d) δ 8.11 (d, J = 
2.2 Hz, 1H), 7.56 (dd, J = 8.6, 1.9 Hz, 1H), 7.27 (d, J = 8.7 Hz, 1H), 3.60 (qd, J = 7.2, 5.1 
Hz, 4H), 1.07 (dt, J = 30.0, 7.2 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 157.06, 141.51, 
131.04, 126.15, 123.75, 121.16, 118.56, 117.34, 115.97, 96.24, 50.42, 43.64, 14.29, 
10.69. 19F NMR (471 MHz, CDCl3) δ -77.75. MASS SPEC NEEDED. 
R= CF3 (orange solid, quant. yield). 1H NMR (500 MHz, Chloroform-d) δ 8.07 (s, 1H), 
7.51 (dd, J = 8.6, 2.0 Hz, 1H), 7.42 (d, 1H), 3.84 (q, J = 7.2 Hz, 4H), 1.34 (dt, J = 24.0, 
7.3 Hz, 6H). 
R= H (orange solid, quant. yield). 1H NMR (500 MHz, Chloroform-d) δ 7.86 (dd, J = 
7.9, 1.4 Hz, 1H), 7.38 (dd, J = 8.1, 1.6 Hz, 1H), 7.29 (ddd, J = 8.3, 7.2, 1.4 Hz, 1H), 6.85 
(td, J = 7.5, 1.6 Hz, 1H), 3.81 (q, J = 7.2 Hz, 4H), 1.34 (t, J = 7.2 Hz, 6H).  
R= tBu (orange solid, 89% yield). 1H NMR (500 MHz, Chloroform-d) δ 7.88 (d, J = 2.0 
Hz, 1H), 7.60 – 7.01 (m, 2H), 3.80 (q, J = 7.2 Hz, 4H), 1.74 – 0.92 (m, 15H). 
 
 126  
 
 
TMS-protected 3-ethynylpyridine.  
After a mixture of 10 mL tetrahydrofuran and 10 mL acetonitrile, 3-bromopyridine (0.31 
mL, 3.16 mmol), Pd(PhCN)2Cl2 (0.16 mmol, 5 mol%) and CuI (0.16 mmol, 5 mol%) was 
outgassed with N2 (g) for at least 20 minutes, the ligand P(tBu)3 (0.316 mmol, 10 mol%) 
was added. The alkyne, TMSA (4.74 mmol, 1.5 equiv.) was then added dropwise. The 
reaction was allowed to stir at room temperature under a steady flow of N2 (g) overnight. 
The reaction mixture was run through a silica/celite plug and washed with DCM to afford 
the crude product that was then purified by column chromatography (gradient from pure 
hexanes to 2:8, ethylacetate:hexanes) to afford a pure brown oil. (0.549 g, quant. yield). 
1H NMR (500 MHz, Chloroform-d) δ 8.59 (s, 1H), 8.41 (dd, J = 4.9, 1.9 Hz, 1H), 7.62 
(dt, J = 7.8, 1.8 Hz, 1H), 7.10 (dd, J = 7.9, 4.8 Hz, 1H), 0.16 (s, 6H). 
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
Triazene receptor intermediate, 3a-d.  
The 3-ethynylpyridine (1.71 mmols, 1.0 equiv.) was dissolved in Et2O and set to stir in a 
flask. Tetrabutylammonium fluoride (TBAF, 2.40 mmols) was then added to the solution 
and left to stir until the starting material had disappeared by TLC (~ 20 min.). The 
reaction mixture was quenched with NH4Cl and extracted with water and brine x2. The 
organic layer was dried (NaSO4), and the solvent was removed in vacuo to furnish 3-
ethynylpyridine in quantitative yields. While this was going on a new flask of 50% THF 
 127  
 
and 50% DIPA (20 mL total) was outgassed with N2(g) for at least twenty minutes. Once 
isolated 3-ethynylpyridine (2.28 mmol, 1.3 equiv.) was dissolved in a minimal amount of 
THF and outgassed for at least 1 min/mL of solvent. After outgassing, the iodotriazene 
compound (1.76 mmol, 1.0 equiv.), Pd(PPh3)4 (0.18 mmol, 0.10 equiv.), and CuI (0.11 
mmol, 0.06 equiv.) were added to the RBF with the THF/DIPA mixture and set to stir. 
The separate solution of 3-ethynylpyridine in THF was then cannulated dropwise to the 
iodotriazene/catalyst mixture and the reaction was left stirring at 45 °C overnight. The 
next day, the reaction was passed through a silica/celite plug, washed with DCM, and 
concentrated to afford the crude product that was purified by column chromatography 
(gradient from 1:9, DCM:hexanes to 100% DCM)  
R= SO2CF3 (yellow solid, 69% yield). 1H NMR (500 MHz, Chloroform-d) δ 8.77 (s, 
1H), 8.58 (s, 1H), 8.17 (d, J = 2.2 Hz, 1H), 7.85 (dd, J = 8.8, 2.2 Hz, 1H), 7.81 (d, J = 7.9 
Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.31 (dd, J = 7.9, 4.8 Hz, 1H), 3.91 (dq, J = 11.1, 7.2 
Hz, 4H), 1.38 (dt, J = 30.4, 7.2 Hz, 6H). CHECKING WITH MIKE IN SUBGROUP 13C 
NMR (126 MHz, CDCl3) δ 159.95, 153.74, 150.39, 139.86, 137.42, 132.52, 126.79, 
125.30, 124.71, 122.71, 120.43, 120.12, 119.17, 117.53, 93.63, 90.41, 51.86, 44.69, 
15.84, 12.24. 19F NMR (471 MHz, CDCl3) δ -78.49. HRMS (TOF-MS-ES+) for 
C18H17N4SO2F3 [M+H] +: calcd 410.10, found 410.1024. 
R= CF3 (76% yield). NEED NMRS. HRMS (TOF-MS-ES+) for C18H17N4F3 [M+H] +: 
calcd 346.14 , found 346.1405. 
R= H (yellow solid, 97% yield). 1H NMR (500 MHz, Chloroform-d) δ 8.77 (s, 1H), 8.53 
(s, 1H), 7.79 (dd, J = 7.8, 1.8 Hz, 1H), 7.54 (dd, J = 7.6, 1.5 Hz, 1H), 7.45 (d, J = 8.4 Hz, 
1H), 7.34 – 7.27 (m, 2H), 7.10 (t, J = 7.5 Hz, 1H), 3.82 (q, J = 7.2 Hz, 4H), 1.33 (t, J = 
 128  
 
7.2 Hz, 6H). NEED DRY HNMR. NEED CARBON. HRMS (TOF-MS-ES+) for 
C17H18N4 [M+H] +: calcd 278.15, found 278.1531. 
R= tBu (light brown oil, quant. yield). 1H NMR (500 MHz, Chloroform-d) δ 7.88 (d, J = 
2.0 Hz, 1H), 7.60 – 7.01 (m, 2H), 3.80 (q, J = 7.2 Hz, 4H), 1.74 – 0.92 (m, 15H). 13C 
NMR (126 MHz, CDCl3) δ 207.02, 152.31, 150.42, 148.14, 147.85, 147.66, 138.25, 
129.58, 127.08, 123.10, 116.83, 116.79, 92.40, 89.24, 34.52, 31.41, 31.04. HRMS (TOF-
MS-ES+) for C21H26N4 [M+H] +: calcd 334.22, found 334.2157. 
 
 
Neutral ethynyl pyridine receptor, 4a-d. 
HI (0.54 mmol, 3.0 equiv.) and I2 (0.54 mmol, 3.0 equiv.) were dissolved in ACN (5 mL) 
then set to stir at 60 °C. While the first solution was coming up to temperature the 
triazene (0.18 mmol, 1.0 equiv.) was dissolved in ACN (5 mL), which was then added 
dropwise into the first flask and stirred at 60 °C while monitoring via TLC. After the 
starting material was consumed (~40 min), the mixture was extracted with EtOAc and 
washed with NaHCO3, Na2S2O3, and water x2 each. The organic layer was then dried 
with Na2SO4 and concentrated to form an oil which was purified on silica via column 
chromatography (gradient from 100% hexanes to 3:7 ethylacetate:hexanes).  
R= SO2CF3 (tan solid, 40% yield). 1H NMR (500 MHz, Acetone-d6) δ 8.88 (s, 1H), 8.66 
(d, J = 3.9 Hz, 1H), 8.50 (d, J = 8.4 Hz, 1H), 8.23 (d, J = 2.3 Hz, 1H), 8.06 (dt, J = 7.8, 
1.9 Hz, 1H), 7.83 (dd, J = 8.4, 2.3 Hz, 1H), 7.50 (dd, J = 8.0, 4.8 Hz, 1H). NEED TO 
 129  
 
CHECK CARBON WITH MIKE IN SUBGROUP.13C NMR (126 MHz, Acetone) δ 
152.99, 150.93, 142.45, 139.48, 134.12, 132.75, 132.13, 131.48, 124.46, 121.88, 119.78, 
119.29, 116.70, 113.65, 93.60, 92.97. 19F NMR (471 MHz, CDCl3) δ -79.33. HRMS 
(TOF-MS-ES+) for C14H7INSO2F3 [M+H]+: calcd 436.92, found 436.9194. 
R= CF3 (yellow solid, 31% yield). 1H NMR (500 MHz, Chloroform-d) δ 8.62 (d, J = 2.5 
Hz, 1H), 8.42 (dd, J = 4.9, 1.7 Hz, 1H), 8.01 (d, J = 8.3 Hz, 1H), 7.89 – 7.75 (m, 1H), 
7.70 (d, J = 2.2 Hz, 1H), 7.35 – 7.13 (m, 2H). NEED TO CHECK CARBON WITH 
MIKE IN SUBGROUP. 19F NMR (471 MHz, CDCl3) δ -58.44. HRMS (TOF-MS-ES+) 
for C14H7INF3 [M+H] +: calcd 372.96, found 372.9575. HRMS (TOF-MS-ES+) for 
C13H8IN [M+H] +: calcd 304.97, found 304.970. 
R= H (tan solid, 20% yield). 1H NMR (500 MHz, Chloroform-d) δ 8.83 (d, J = 2.1 Hz, 
1H), 8.58 (dd, J = 5.0, 1.7 Hz, 1H), 7.92 – 7.85 (m, 2H), 7.54 (dd, J = 7.7, 1.7 Hz, 1H), 
7.35 (td, J = 7.6, 1.2 Hz, 1H), 7.31 (ddd, J = 7.8, 4.9, 0.8 Hz, 1H), 7.05 (td, J = 7.8, 1.7 
Hz, 1H).  
R= tBu (yellow solid, 87% yield). 1H NMR (500 MHz, Chloroform-d) δ 8.84 (s, 1H), 
8.57 (d, J = 3.3 Hz, 1H), 7.89 (dt, J = 7.9, 2.0 Hz, 1H), 7.79 (d, J = 8.4 Hz, 1H), 7.57 (d, J 
= 2.4 Hz, 1H), 7.31 (dd, J = 7.9, 4.9 Hz, 1H), 7.09 (dd, J = 8.4, 2.4 Hz, 1H), 1.32 (s, 9H). 
13C NMR (126 MHz, CDCl3) δ 152.49, 151.68, 149.09, 138.75, 138.72, 130.16, 128.84, 
127.96, 123.36, 120.54, 97.64, 95.49, 89.14, 34.89, 31.34. HRMS (TOF-MS-ES+) for 
C17H16IN [M+H] +: calcd 361.03, found 361.0327. 
 
 130  
 
Methylated ethynyl pyridine. 
The neutral receptor (0.067 mmol) was added to a bomb flask followed by an excess of 
MeI (5 mL). The reaction vessel was then sealed and set to stir at 110 °C overnight. Over 
the next 24 hours, the product would precipitate out of solution. The yellow precipitate 
was collected and washed with minimal DCM to afford pure product.  
R= SO2CF3 (yellow solid, quant. yield). 1H NMR (500 MHz, Acetone-d6) δ 9.65 (s, 1H), 
9.30 (d, J = 6.1 Hz, 1H), 8.94 (d, J = 8.1 Hz, 1H), 8.53 (d, J = 8.4 Hz, 1H), 8.42 – 8.32 
(m, 1H), 8.26 (d, J = 2.4 Hz, 1H), 7.91 (dd, J = 8.4, 2.3 Hz, 1H). NEED CARBON. 19F 
NMR (471 MHz, Acetone) δ -79.27. HRMS (TOF-MS-ES+) for C14H7I2NSO2F3 [M+H] 
+: calcd 451.94, found 451.9429. 
R= CF3 (yellow solid, quant. yield). 1H NMR (500 MHz, Acetone-d6) δ 9.62 (s, 1H), 
9.30 (d, J = 6.2 Hz, 1H), 8.89 (d, J = 8.1 Hz, 1H), 8.38 (t, J = 7.2 Hz, 1H), 8.29 (d, J = 
8.3 Hz, 1H), 8.00 (d, J = 2.2 Hz, 1H), 7.60 (d, J = 8.2 Hz, 1H), 4.76 (s, 3H). NEED 
CARBON. 19F NMR (471 MHz, Acetone-d6) δ -63.70. HRMS (TOF-MS-ES+) for 
C14H7I2NF3 [M+H] +: calcd 387.98, found 387.9810. 
R= H (yellow solid, quant. yield). 1H NMR (500 MHz, Acetone-d6) δ 9.40 (s, 1H), 9.16 
(d, J = 6.1 Hz, 1H), 8.84 (d, J = 8.1 Hz, 1H), 8.38 – 8.31 (m, 1H), 8.05 (d, J = 8.0 Hz, 
1H), 7.71 (dd, J = 7.9, 1.7 Hz, 1H), 7.59 – 7.52 (m, 1H), 7.30 (td, J = 7.7, 1.5 Hz, 1H), 
4.71 (s, 3H). NEED CARBON. NEED FLUORINE. HRMS (TOF-MS-ES+) for 
C13H8I2N [M+H] +: calcd 319.99, found 319.9936. 
R= tBu (yellow solid, quant. yield). 1H NMR (500 MHz, Acetone-d6) δ 9.48 (s, 1H), 9.23 
(d, J = 6.1 Hz, 1H), 8.84 (d, J = 8.0 Hz, 1H), 8.39 – 8.32 (m, 1H), 7.94 (d, J = 8.5 Hz, 
1H), 7.73 (d, J = 2.4 Hz, 1H), 7.37 (dd, J = 8.5, 2.5 Hz, 1H), 4.74 (s, 3H), 1.34 (s, 9H). 
 131  
 
NEED CARBON. No peaks shown on 19F NMR. HRMS (TOF-MS-ES+) for C17H16I2N 
[M+H] +: calcd 376.06, found 376.0562. 
 
 
Methylated PF6 pyridine receptor, 5a-d.  
The methylated receptor (0.423 mmol, 1.0 equiv.) was dissolved in 10 mL of acetone and 
40 mL of water and set to stir. To this flask, AgPF6 (1.068 mmol, 2.5 equiv.) was added 
and stirred for about 40 minutes during which time gray precipitate (AgI) formed. This 
precipitate was filtered off and the filtrate solvent mixture was removed in vacuo until 
only water remained. At this point white precipitate (final product) began to crash out of 
the water and was collected via filtration and washed with minimal water to give the final 
pure product.  
R= SO2CF3 (white solid, quant. yield). 1H NMR (500 MHz, Acetone-d6) δ 9.52 (s, 1H), 
9.24 (d, J = 6.2 Hz, 1H), 8.95 (d, J = 8.2 Hz, 1H), 8.57 (d, J = 8.4 Hz, 1H), 8.41 (t, 1H), 
8.27 (d, J = 2.3 Hz, 1H), 7.94 (dd, J = 8.4, 2.3 Hz, 1H), 4.74 (s, 3H). NEED CARBON. 
19F NMR (471 MHz, Acetone) δ -71.74, -73.24, -79.32. 
R= CF3 (white solid, quant. yield). NEED PROTON AND CARBON IN ACETONE. 19F 
NMR (471 MHz, Acetone-d6) δ -63.79, -71.90, -73.41. 
R= H (white solid, quant. yield). 1H NMR (500 MHz, Acetone-d6) δ 9.32 (s, 1H), 9.07 
(d, J = 6.1 Hz, 1H), 8.80 (d, J = 8.1 Hz, 1H), 8.29 (dd, J = 8.2, 6.2 Hz, 1H), 8.02 (d, J = 
8.0 Hz, 1H), 7.71 (dd, J = 7.8, 1.6 Hz, 1H), 7.54 (t, J = 7.6 Hz, 1H), 7.28 (td, J = 7.7, 1.6 
 132  
 
Hz, 1H), 4.65 (s, 3H). 13C NMR (126 MHz, Acetone) δ 148.34, 147.55, 145.97, 140.09, 
134.29, 132.54, 129.45, 129.12, 128.23, 124.80, 101.12, 99.26, 85.80, 49.52. 19F NMR 
(471 MHz, Acetone) δ -71.64, -73.14. 
R= tBu (white solid, quant. yield). 1H NMR (500 MHz, Acetone-d6) δ 9.34 (s, 1H), 9.09 
(d, J = 6.1 Hz, 1H), 8.81 (d, J = 8.1 Hz, 1H), 8.33 – 8.25 (m, 1H), 7.93 (d, J = 8.4 Hz, 
1H), 7.73 (d, J = 2.5 Hz, 1H), 7.36 (dd, J = 8.5, 2.5 Hz, 1H), 4.67 (s, 3H), 1.33 (s, 9H) ). 
CHECKING CARBON WITH MIKE IN SUBGROUP. 13C NMR (126 MHz, 
Chloroform-d) δ 152.88, 148.35, 147.55 (d, J = 14.2 Hz), 145.94 (d, J = 18.2 Hz), 139.80 
(d, J = 22.4 Hz), 131.42 (d, J = 24.9 Hz), 130.25 (d, J = 8.7 Hz), 129.15 (d, J = 21.9 Hz), 
127.90, 124.96, 99.75, 97.42, 85.31, 49.54, 35.28, 31.13. 19F NMR (471 MHz, Acetone) 
δ -71.91, -73.41. 
 
Titrations 
 
General Methods. 1H NMR spectra were acquired at room temperature on a Varian Inova 
500 MHz spectrometer (500.11 MHz). 1H chemical shifts (δ) are expressed in ppm 
relative to residual CH3CN (calibrated to 1.94 ppm) shifts. 
 
General Procedure. A 4.0 mL host solution (0.9-1.5 mM in CD3CN) was prepared. Of 
this, 500 μL was added to a septum-sealed NMR tube. A 19-30 mM host/guest (TBAX, 
where X = I, Br, or Cl) stock solution was prepared using the remaining 3.5 mL of host 
solution. Aliquots of the host/guest solution were added to the NMR tube using Hamilton 
gas-tight syringes, and 1H NMR spectra were recorded at 25 °C after each addition of 
 133  
 
guest. The Δδ of the CHaryl and CHmethyl protons were used to follow the progress of the 
titration, and association constants were determined using the Thordarson method. 
 
 
Figure C.1. Representative 1H NMR titration done in CD3CN with 5a where 
participating protons can be seen shifting with increasing chloride concentration. 
 
Table C.1. Representative 1H NMR Titration of 5a • PF6– with I– in CD3CN at 25 ºC. 
VGuest [Host] 
Entry [I– ] (M) Equiv. δ CHaryl δ CHmethyl 
(μL) (M) 
0 0 1.32E-03 0.00E+00 0.00 8.888 4.322 
1 5 1.32E-03 2.08E-04 0.16 8.892 4.324 
2 5 1.32E-03 4.11E-04 0.31 8.897 4.326 
3 10 1.32E-03 8.06E-04 0.61 8.905 4.329 
4 10 1.32E-03 1.19E-03 0.90 8.912 4.332 
5 10 1.32E-03 1.55E-03 1.18 8.918 4.334 
6 15 1.32E-03 2.08E-03 1.58 8.928 4.339 
7 15 1.32E-03 2.57E-03 1.95 8.934 4.340 
8 15 1.32E-03 3.05E-03 2.31 8.940 4.343 
9 20 1.32E-03 3.64E-03 2.76 8.947 4.346 
10 20 1.32E-03 4.19E-03 3.18 8.954 4.349 
 134  
 
11 20 1.32E-03 4.71E-03 3.57 8.960 4.351 
12 30 1.32E-03 5.44E-03 4.12 8.967 4.354 
13 50 1.32E-03 6.51E-03 4.93 8.978 4.359 
14 100 1.32E-03 8.26E-03 6.26 8.992 4.364 
15 200 1.32E-03 1.07E-02 8.14 9.008 4.371 
16 500 1.32E-03 1.41E-02 10.68 9.016 4.375 
17 500 1.32E-03 1.58E-02 11.97 9.028 4.379 
18 500 1.32E-03 1.68E-02 12.75 9.035 4.381 
 
Binding Isotherm of I– with 5a • PF – 0.0066 CH (aryl) Residuals0.2
CH (methyl) Residuals
CH (aryl) Predicted
CH (methyl) Predicted
0.15 CH (aryl) ExperimentalCH (methyl) Experimental
0.1 0
0 2 4 6 8 10 12 14
0.05
0
0 2 4 6 8 10 12 14
[G]/[H]       -0.006 [G]/[H]  
Figure C.2. Representative binding isotherm and residuals for I– titration of receptor 5a • 
PF6– in CD3CN at 25 °C determined by 1H NMR spectroscopy. 
 
Table C.2. Representative 1H NMR Titration of 5a • PF6– with Br– in CD3CN at 25 ºC. 
VGuest [Host] 
Entry [Br– ] (M) Equiv. δ CHaryl δ CHmethyl 
(μL) (M) 
0 0 1.25E-03 0.00E+00 0.00 8.888 4.323 
1 5 1.25E-03 2.34E-04 0.19 8.896 4.326 
2 5 1.25E-03 4.64E-04 0.37 8.905 4.329 
3 10 1.25E-03 9.10E-04 0.73 8.922 4.335 
4 10 1.25E-03 1.34E-03 1.07 8.938 4.341 
5 10 1.25E-03 1.75E-03 1.40 8.951 4.345 
6 15 1.25E-03 2.35E-03 1.87 8.967 4.351 
7 15 1.25E-03 2.91E-03 2.32 8.982 4.357 
 135  
δ (ppm)
Residuals
 
8 15 1.25E-03 3.44E-03 2.75 8.994 4.361 
9 20 1.25E-03 4.11E-03 3.28 9.008 4.366 
10 20 1.25E-03 4.73E-03 3.78 9.022 4.371 
11 20 1.25E-03 5.32E-03 4.25 9.033 4.375 
12 30 1.25E-03 6.14E-03 4.90 9.047 4.381 
13 50 1.25E-03 7.35E-03 5.87 9.065 4.387 
14 100 1.25E-03 9.32E-03 7.45 9.093 4.398 
15 200 1.25E-03 1.21E-02 9.68 9.124 4.408 
16 500 1.25E-03 1.59E-02 12.71 9.157 4.420 
17 500 1.25E-03 1.78E-02 14.24 9.160 4.422 
       
 
Binding Isotherm of I– with 5a • PF – 0.0066 CH (aryl) Residuals
0.2
CH (methyl) Residuals
CH (aryl) Predicted
CH (methyl) Predicted
0.15 CH (aryl) Experimental
CH (methyl) Experimental
0.1 0
0 2 4 6 8 10 12 14
0.05
0
0 2 4 6 8 10 12 14
[G]/[H]       -0.006 [G]/[H]  
Figure C.3. Representative binding isotherm and residuals for Br– titration of receptor 5a 
• PF6– in CD3CN at 25 °C determined by 1H NMR spectroscopy. 
 
Table C.3. Representative 1H NMR Titration of 5a • PF6– with Cl– in CD3CN at 25 ºC. 
VGuest [Host] δ 
Entry [Cl– ] (M) Equiv. δ CHaryl 
(μL) (M) CHmethyl 
0 0 9.58E-04 0.00E+00 0.00 8.887 4.322 
1 5 9.58E-04 1.99E-04 0.21 8.905 4.328 
2 5 9.58E-04 3.93E-04 0.41 8.911 4.330 
3 10 9.58E-04 7.72E-04 0.81 8.941 4.340 
 136  
δ (ppm)
Residuals
 
4 10 9.58E-04 1.14E-03 1.19 8.957 4.346 
5 10 9.58E-04 1.49E-03 1.55 8.972 4.351 
6 15 9.58E-04 1.99E-03 2.08 9.006 4.362 
7 15 9.58E-04 2.46E-03 2.57 9.019 4.367 
8 15 9.58E-04 2.91E-03 3.04 9.037 4.372 
9 20 9.58E-04 3.48E-03 3.63 9.057 4.380 
10 20 9.58E-04 4.01E-03 4.19 9.079 4.386 
11 20 9.58E-04 4.51E-03 4.71 9.090 4.390 
12 30 9.58E-04 5.20E-03 5.43 9.108 4.396 
13 50 9.58E-04 6.23E-03 6.50 9.134 4.405 
14 100 9.58E-04 7.90E-03 8.25 9.170 4.417 
15 200 9.58E-04 1.03E-02 10.73 9.205 4.429 
16 500 9.58E-04 1.35E-02 14.08 9.262 4.449 
17 500 9.58E-04 1.51E-02 15.77 9.263 4.448 
 
Binding Isotherm of Cl– with 5a • PF – 0.0126 CH(aryl) Residuals
0.4
CH(methyl) Residuals
0.35
0.3
0.25 CH(aryl) Predicted
CH(methyl) Predicted
0.2 CH(aryl) Experimental 0
0 5 10 15
CH(methyl) Experimental
0.15
0.1
0.05
0
0 2 4 6 8 10 12 14 16
[G]/[H]       -0.012 [G]/[H]  
Figure C.4. Representative binding isotherm and residuals for Cl– titration of receptor 5a 
• PF6– in CD3CN at 25 °C determined by 1H NMR spectroscopy. 
 
 
Table C.4. Representative 1H NMR Titration of 5b • PF6– with Cl– in CD3CN at 25 ºC. 
VGuest [Host] 
Entry [Cl– ] (M) Equiv. δ CHaryl δ CHmethyl 
(μL) (M) 
 137  
δ (ppm)
Residuals
 
0 0 1.35E-03 0.00E+00 0.00 8.864 4.318 
1 5 1.35E-03 2.46E-04 0.18 8.874 4.322 
2 5 1.35E-03 4.88E-04 0.36 8.888 4.327 
3 10 1.35E-03 9.57E-04 0.71 8.911 4.335 
4 10 1.35E-03 1.41E-03 1.04 8.932 4.342 
5 10 1.35E-03 1.84E-03 1.37 8.951 4.349 
6 15 1.35E-03 2.47E-03 1.83 8.974 4.357 
7 15 1.35E-03 3.06E-03 2.26 8.993 4.364 
8 15 1.35E-03 3.62E-03 2.68 9.010 4.370 
9 20 1.35E-03 4.32E-03 3.20 9.029 4.376 
10 20 1.35E-03 4.98E-03 3.69 9.045 4.382 
11 20 1.35E-03 5.59E-03 4.14 9.060 4.387 
12 30 1.35E-03 6.45E-03 4.78 9.079 4.394 
13 50 1.35E-03 7.72E-03 5.72 9.106 4.403 
14 100 1.35E-03 9.80E-03 7.26 9.140 4.415 
15 200 1.35E-03 1.27E-02 9.44 9.176 4.428 
16 500 1.35E-03 1.67E-02 12.39 9.192 4.434 
17 500 1.35E-03 1.87E-02 13.88 9.217 4.442 
 
Binding Isotherm of Cl– with 5b • PF – 0.0126 CH(aryl) Residuals
0.4
CH(methyl) Residuals
CH(aryl) Predicted
CH(methyl) Predicted
CH(aryl) Experimental
0.3 CH(methyl) Experimental
0.2 0
0 2 4 6 8 10 12 14
0.1
0
0 2 4 6 8 10 12 14
[G]/[H]       -0.012 [G]/[H]  
Figure C.5. Representative binding isotherm and residuals for Cl– titration of receptor 5b 
• PF6– in CD3CN at 25 °C determined by 1H NMR spectroscopy. 
 
 138  
δ (ppm)
Residuals
 
Table C.5. Representative 1H NMR Titration of 5c • PF6– with Cl– in CD3CN at 25 ºC. 
VGuest [Host] 
Entry [Cl– ] (M) Equiv. δ CHaryl δ CHmethyl 
(μL) (M) 
0 0 1.36E-03 0.00E+00 0.00 8.838 4.309 
1 5 1.36E-03 2.45E-04 0.18 8.847 4.312 
2 5 1.36E-03 4.85E-04 0.36 8.857 4.316 
3 10 1.36E-03 9.52E-04 0.70 8.877 4.324 
4 10 1.36E-03 1.40E-03 1.03 8.891 4.330 
5 10 1.36E-03 1.83E-03 1.35 8.907 4.336 
6 15 1.36E-03 2.45E-03 1.80 8.918 4.340 
7 15 1.36E-03 3.04E-03 2.23 8.941 4.348 
8 15 1.36E-03 3.60E-03 2.64 8.954 4.354 
9 20 1.36E-03 4.29E-03 3.16 8.969 4.359 
10 20 1.36E-03 4.95E-03 3.64 8.982 4.363 
11 20 1.36E-03 5.56E-03 4.09 8.997 4.371 
12 30 1.36E-03 6.41E-03 4.72 9.013 4.377 
13 50 1.36E-03 7.68E-03 5.65 9.034 4.384 
14 100 1.36E-03 9.75E-03 7.17 9.064 4.397 
15 200 1.36E-03 1.27E-02 9.32 9.094 4.405 
16 500 1.36E-03 1.66E-02 12.23 9.138 4.424 
17 500 1.36E-03 1.86E-02 13.70 9.142 4.425 
 
 139  
 
Binding Isotherm of Cl– with 5c • PF – 0.0126 CH(aryl) Residuals0.4
CH(aryl) Predicted CH(methyl) Residuals
0.35 CH(methyl) Predicted
CH(aryl) Experimental
0.3 CH(methyl) Experimental
0.25
0.2 0
0 2 4 6 8 10 12 14
0.15
0.1
0.05
0
0 2 4 6 8 10 12 14
[G]/[H]       -0.012 [G]/[H]  
Figure C.6. Representative binding isotherm and residuals for Cl– titration of receptor 5c 
• PF6– in CD3CN at 25 °C determined by 1H NMR spectroscopy. 
 
Table C.6. Representative 1H NMR Titration of 5d • PF6– with Cl– in CD3CN at 25 ºC. 
VGuest [Host] 
Entry [Cl– ] (M) Equiv. δ CHaryl δ CHmethyl 
(μL) (M) 
0 0 1.73E-03 0.00E+00 0.00 8.828 4.310 
1 5 1.73E-03 2.33E-04 0.14 8.834 4.312 
2 5 1.73E-03 4.62E-04 0.27 8.843 4.316 
3 10 1.73E-03 9.07E-04 0.53 8.859 4.322 
4 10 1.73E-03 1.33E-03 0.77 8.873 4.328 
5 10 1.73E-03 1.75E-03 1.01 8.885 4.333 
6 15 1.73E-03 2.34E-03 1.35 8.903 4.340 
7 15 1.73E-03 2.90E-03 1.68 8.917 4.345 
8 15 1.73E-03 3.43E-03 1.98 8.929 4.350 
9 20 1.73E-03 4.09E-03 2.37 8.944 4.356 
10 20 1.73E-03 4.72E-03 2.73 8.958 4.361 
11 20 1.73E-03 5.30E-03 3.07 8.970 4.366 
12 30 1.73E-03 6.11E-03 3.54 8.985 4.372 
13 50 1.73E-03 7.32E-03 4.24 9.006 4.380 
14 100 1.73E-03 9.29E-03 5.38 9.037 4.392 
15 200 1.73E-03 1.21E-02 6.99 9.078 4.407 
16 500 1.73E-03 1.58E-02 9.18 9.106 4.418 
 140  
δ (ppm)
Residuals
 
17 500 1.73E-03 1.78E-02 10.28 9.110 4.419 
 
Binding Isotherm of Cl– with 5d • PF – 0.0086 CH(aryl) Residuals
0.35
CH(methyl) Residuals
CH(aryl) Predicted
0.3 CH(methyl) Predicted
CH(aryl) Experimental
0.25 CH(methyl) Experimental
0.2
0
0.15 0 2 4 6 8 10 12 14 16
0.1
0.05
0
0 2 4 6 8 10 12 14
[G]/[H]       -0.008 [G]/[H]  
Figure C.7. Representative binding isotherm and residuals for Cl– titration of receptor 5d 
• PF6– in CD3CN at 25 °C determined by 1H NMR spectroscopy. 
 
 
 
Linear Regression Fitting and Statistics of log(KaR/KaH) and σp 
 
 
 
Figure C.8. Linear regression residuals of log(KaR/KaH) of Cl– and σp. 
 
 
 
 141  
δ (ppm)
Residuals
 
X-Ray Crystallography 
 
Waiting on Lev for crystal data 
 
 
 
Computational Details 
 
General. Gas phase optimization and frequency analyses were performed for structures 
4a-d and 5a-d via Gaussian 09.1 All computations were ran using B97-D3 density 
functional theory2 with a Def2-TZVP basis set.3 This work utilized the resources of the 
University of Oregon’s high-performance computer, Talapas. Electrostatic potential 
surface (ESP) maps and figures were generated using Gaussian 09. The −hole values 
(VS,max) were assessed using Multiwfn, an open-source software.4 
 
 
Table C.7. Cartesian coordinates for 5a. 
 
 X Y Z 
H 0.56677 3.82829 -1.70301 
C 0.47593 2.87918 -1.18175 
C 0.35303 0.46906 0.15123 
C -0.729 2.18606 -1.13094 
C -0.7917 0.97061 -0.45739 
C 1.5382 1.19649 0.07591 
 142  
 
H -1.61602 2.58904 -1.61598 
H -1.73203 0.42135 -0.415 
C 0.3235 -0.77869 0.84392 
C 0.32554 -1.82742 1.43 
C 0.34676 -3.08209 2.12455 
C 0.31521 -5.58703 3.40306 
C -0.70468 -3.97748 1.89278 
C 1.37881 -3.44364 3.00595 
C 1.36104 -4.69326 3.64051 
C -0.71983 -5.21743 2.54135 
H -1.50099 -3.71063 1.19888 
H 2.16216 -4.9904 4.31555 
H 0.32672 -6.56422 3.88476 
I 3.00298 -2.17607 3.42256 
S -2.03813 -6.37912 2.20256 
O -2.68494 -5.90191 0.98831 
O -1.41507 -7.69345 2.21649 
C -3.12485 -6.14675 3.64653 
F -4.24422 -6.91894 3.59412 
F -2.49414 -6.44563 4.81836 
F -3.54626 -4.85335 3.76174 
N 1.57981 2.38196 -0.57785 
C 2.85121 3.122 -0.65002 
H 3.38779 2.99487 0.29388 
H 2.64531 4.18346 -0.80889 
H 3.42333 2.70879 -1.4843 
H 2.46056 0.84427 0.53021 
 
 143  
 
Table C.8. Cartesian coordinates for 5b. 
 
 X Y Z 
H -1.53275 3.76493 -1.78037 
C -1.38771 2.79981 -1.30259 
C -1.01487 0.40151 0.00457 
C -1.15997 1.64474 -2.04358 
C -0.97322 0.43414 -1.38441 
C -1.24573 1.58185 0.70669 
H -1.12618 1.68659 -3.13058 
H -0.79381 -0.47476 -1.9582 
C -0.82222 -0.8228 0.71243 
C -0.66365 -1.83578 1.33849 
C -0.47692 -3.03151 2.10796 
C -0.10428 -5.43182 3.51025 
C -0.25728 -4.23164 1.41783 
C -0.50752 -3.04179 3.50985 
C -0.32245 -4.24067 4.2072 
C -0.06163 -5.43967 2.10936 
H -0.23499 -4.23489 0.32754 
H -0.34636 -4.26692 5.29513 
H 0.03456 -6.35798 4.06876 
I -0.82882 -1.30413 4.64765 
N -1.43308 2.75067 0.04866 
C -1.66487 3.9834 0.82046 
H -2.27816 3.74318 1.69296 
H -2.19203 4.70953 0.19661 
 144  
 
H -0.688 4.36885 1.12262 
C 0.15158 -6.72706 1.34718 
F 0.87956 -6.54656 0.21043 
F -1.02302 -7.28983 0.95554 
F 0.80825 -7.67594 2.06716 
H -1.2821 1.60883 1.7926 
 
Table C.9. Cartesian coordinates for 5c. 
 
 X Y Z 
H -0.50817 4.43527 -1.02704 
C -0.48071 3.41393 -0.65688 
C -0.29988 0.84185 0.31428 
C -1.55026 2.54177 -0.82891 
C -1.45968 1.24356 -0.33803 
C 0.74749 1.74798 0.46379 
H -2.45066 2.87027 -1.3443 
H -2.29234 0.553 -0.46944 
C -0.17051 -0.48405 0.82552 
C -0.01911 -1.59256 1.26293 
C 0.19677 -2.90886 1.78928 
C 0.50705 -5.50189 2.8093 
C -0.91261 -3.75041 1.94049 
C 1.46802 -3.37775 2.155 
C 1.62015 -4.67304 2.66367 
C -0.75745 -5.0417 2.44871 
H -1.90818 -3.40942 1.66417 
 145  
 
H 2.59794 -5.05314 2.9514 
H 0.62686 -6.50848 3.20466 
I 3.20272 -2.2032 1.9755 
N 0.64043 3.00945 -0.01598 
C 1.75685 3.95646 0.14343 
H 2.49346 3.55124 0.84114 
H 1.35543 4.89386 0.53772 
H 2.20639 4.10522 -0.84168 
H -1.62362 -5.68993 2.56328 
H 1.67384 1.47574 0.96261 
 
 
Table C.10. Cartesian coordinates for 5d. 
 
 X Y Z 
H -0.54887 4.16441 -0.7044 
C -0.51057 3.13011 -0.3736 
C -0.31151 0.52189 0.49514 
C -1.654 2.34004 -0.31213 
C -1.55373 1.02329 0.12489 
C 0.80703 1.34771 0.41795 
H -2.62042 2.74803 -0.6018 
H -2.44459 0.39789 0.17638 
C -0.17184 -0.8223 0.9528 
C -0.01105 -1.94687 1.34322 
C 0.21552 -3.28282 1.81312 
C 0.52861 -5.91198 2.71504 
 146  
 
C -0.88599 -4.14825 1.90275 
C 1.48227 -3.74708 2.18082 
C 1.63549 -5.05929 2.63044 
C -0.75653 -5.47874 2.35418 
H -1.86683 -3.77401 1.61326 
H 2.61127 -5.44248 2.92192 
H 0.7066 -6.9238 3.07203 
I 3.20389 -2.5473 2.09002 
N 0.69275 2.6251 -0.01688 
C 1.89375 3.47511 -0.07706 
H 2.06597 3.87004 0.9272 
H 1.73022 4.28734 -0.78969 
H 2.73915 2.86676 -0.40925 
C -1.9942 -6.39185 2.43575 
C -2.62474 -6.53738 1.03391 
H -1.90222 -6.94502 0.31692 
H -2.97777 -5.57963 0.63624 
H -3.48855 -7.21207 1.05718 
C -3.03161 -5.77468 3.39845 
H -2.6044 -5.62872 4.39768 
H -3.90929 -6.42335 3.50238 
H -3.39314 -4.801 3.05015 
C -1.6871 -7.81715 2.94834 
H -1.26652 -7.80011 3.96056 
H -0.97955 -8.33808 2.29277 
H -2.59754 -8.42723 2.98847 
H 1.79828 1.0032 0.70098 
 
 147  
 
Table C.11. Cartesian coordinates for 4a. 
 
 X Y Z 
H 0.12833 4.06952 -1.50739 
C 0.09491 3.1812 -0.8827 
C 0.03654 0.8788 0.59272 
C -0.17191 3.27212 0.47482 
C -0.20114 2.0976 1.22376 
C 0.29564 0.89081 -0.77145 
H -0.3525 4.23526 0.93901 
H -0.40727 2.13987 2.28997 
N 0.32942 2.01632 -1.52557 
C 0.01373 -0.34359 1.33028 
C -0.00662 -1.36417 1.96397 
C -0.03199 -2.58061 2.72196 
C -0.07289 -5.02761 4.1081 
C -0.0645 -3.79005 2.01574 
C -0.0238 -2.60209 4.12583 
C -0.04077 -3.82364 4.81352 
C -0.09988 -5.0029 2.71216 
H -0.05583 -3.77896 0.92616 
H -0.02193 -3.8516 5.90152 
H -0.06927 -5.96817 4.65676 
I 0.02064 -0.85142 5.2863 
S -0.11451 -6.54016 1.8013 
O 0.52307 -6.25747 0.52367 
O 0.46727 -7.53929 2.68596 
C -1.8991 -6.82928 1.58524 
 148  
F -2.16671 -7.97659 0.90112 
F -2.55334 -6.92652 2.7788 
F -2.50587 -5.81711 0.90043 
H 0.48998 -0.02813 -1.31777
Table C.12. Cartesian coordinates for 4b. 
X Y Z 
H -0.61441 3.63972 -1.96172
C -0.53895 2.79105 -1.28756
C -0.36464 0.58185 0.31563 
C -0.33555 2.97446 0.07163 
C -0.24718 1.84722 0.88575 
C -0.56718 0.50125 -1.05576
H -0.24789 3.97198 0.48754 
H -0.08809 1.96166 1.95474 
N -0.65718 1.57898 -1.87258
C -0.27887 -0.59429 1.12059 
C -0.20507 -1.57517 1.81055 
C -0.11666 -2.74377 2.63628 
C 0.05041 -5.10381 4.14315 
C -0.18469 -3.99616 2.00876 
C 0.03487 -2.68174 4.02822 
C 0.11909 -3.86099 4.7776 
C -0.11009 -5.18559 2.7531 
H -0.29901 -4.04976 0.92543 
H 0.24008 -3.82845 5.85847 
H 0.12133 -6.01176 4.74169 
149 
I 0.14907 -0.86677 5.07889 
C -0.16172 -6.5257 2.05983 
F -0.94596 -6.51885 0.94655 
F 1.06761 -6.94205 1.65112 
F -0.65058 -7.51908 2.853 
H -0.66647 -0.45794 -1.55648
Table C.13. Cartesian coordinates for 4c. 
X Y Z 
H -0.25865 3.86017 -1.8606
C -0.23302 2.99815 -1.19981
C -0.15813 0.75799 0.3676 
C -0.31725 3.15014 0.17583 
C -0.27884 2.00716 0.97164 
C -0.08068 0.70888 -1.01796
H -0.41053 4.1356 0.61829 
H -0.34277 2.0964 2.05291 
N -0.11545 1.80251 -1.81792
C -0.11516 -0.43375 1.15264 
C -0.07923 -1.42898 1.82488 
C -0.03577 -2.6154 2.6287 
C 0.05698 -5.00698 4.09191 
C 0.0479 -3.8504 1.97172 
C -0.07296 -2.58755 4.03035 
C -0.02645 -3.78348 4.75821 
C 0.09408 -5.04084 2.70004 
150 
H 0.07779 -3.89261 0.88475 
H -0.0543 -3.77786 5.84527 
H 0.093 -5.93357 4.65986 
I -0.19811 -0.80048 5.12778 
H 0.15904 -5.9935 2.17987 
H 0.01453 -0.23682 -1.54442
Table C.14. Cartesian coordinates for 4d. 
X Y Z 
H -0.03841 3.62563 -1.89212
C -0.03046 2.78586 -1.20288
C -0.04513 0.60119 0.44255 
C 0.31885 2.95765 0.12793 
C 0.31043 1.84289 0.96365 
C -0.37971 0.53078 -0.90328
H 0.59119 3.93671 0.50593 
H 0.57942 1.94808 2.01141 
N -0.3803 1.59676 -1.74051
C -0.06423 -0.56177 1.27045 
C -0.07811 -1.53237 1.97848 
C -0.09364 -2.6899 2.82471 
C -0.13067 -5.03315 4.35472 
C -0.15686 -3.95149 2.21089 
C -0.0484 -2.6109 4.21911 
C -0.06724 -3.78194 4.97962 
C -0.17676 -5.1487 2.95721 
151 
 
H -0.19087 -3.99424 1.12298 
H -0.033 -3.74219 6.06609 
H -0.1425 -5.90975 4.9973 
I 0.04936 -0.78885 5.25586 
C -0.24619 -6.5068 2.23602 
C -1.534 -6.57894 1.38733 
H -1.5567 -5.8155 0.60201 
H -2.4252 -6.43685 2.0101 
H -1.62591 -7.55187 0.89045 
C 0.98089 -6.66774 1.31281 
H 1.01089 -5.90612 0.52599 
H 0.97446 -7.64367 0.81337 
H 1.91516 -6.59015 1.88152 
C -0.26077 -7.7213 3.19174 
H 0.64495 -7.7607 3.80811 
H -0.3107 -8.66344 2.63263 
H -1.12885 -7.69792 3.86082 
H -0.66609 -0.41026 -1.36486 
 
References 
 
(1)  Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; 
Cheeseman, R. J.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; et al. 
Gaussian 09, Revision E.01. Wallingford, CT 2013. 
(2)  Grimme, S.; Ehrlich, S.; Goerigk, L. Effect of the Damping Function in Dispersion 
Corrected Density Functional Theory. J. Comput. Chem. 2011, 32, 1456–1465. 
(3)  Weigend, F.; Ahlrichs, R. Balanced Basis Sets of Split Valence, Triple Zeta 
Valence and Quadruple Zeta Valence Quality for H to Rn: Design and Assessment 
of Accuracy. Phys. Chem. Chem. Phys. 2005, 7, 3297–3305. 
(4)  Lu, T.; Chen, F. Multiwfn: A Multifunctional Wavefunction Analyzer. J. Comput. 
Chem. 2012, 33, 580–592. 
 152  
 
 
NMR Spectra 
N
TMS
 
Figure C.9. 1H NMR spectrum of TMS-protected 3-ethynylpyridine. 
 
S
F3C O
N
H
 
Figure C.10. 1H NMR spectrum of 4-(trifluoromethylthio)acetamide. Wet with water and 
ethyl acetate. 
 153  
 
O O
S
F3C O
N
H
 
Figure C.11. 1H NMR spectrum of N-[4-[(trifluoromethyl)sulfonyl]phenyl]acetamide. 
 
 
O O
S
F3C
NH2
 
Figure C.12. 1H NMR spectrum of N-[4-[(Trifluoromethyl)sulfonyl]phenyl]aniline. 
 
 154  
 
O O
F C S
I
3
NH2
 
Figure C.13. 1H NMR spectrum of 1a. 
 
O O
S IF3C
NH2
 
Figure C.14. 13C NMR spectrum of 1a. 
 
 155  
 
 
Figure C.15. 19F NMR spectrum of 1a. 
 
O O
S I
F3C
N3Et2
 
Figure C.16. 1H NMR spectrum of 2a. 
 
 
 156  
 
O O
S I
F3C
N3Et2
 
Figure C.17. 13C NMR spectrum of 2a. 
 
 
 
Figure C.18. 19F NMR spectrum of 2a. 
 
 157  
 
N
O O
S
CF3
Et2N3
 
Figure C.19. 1H NMR spectrum of 3a. Wet with water and grease. 
 
 
N
O O
S
CF3
Et2N3
questionable carbon
 
Figure C.20. 13C NMR spectrum of 3a. Contains grease. 
 
 158  
 
 
Figure C.21. 19F NMR spectrum of 3a. 
N
O O
S
CF3
I
 
Figure C.22. 1H NMR spectrum of 4a. Wet with water and grease. 
 159  
 
N
O O
S
CF3
I
questionable carbon
 
Figure C.23. 13C NMR spectrum of 4a.  
 
 
Figure C.24. 19F NMR spectrum of 4a. 
 
 160  
N I
O O
S
CF3
I
Figure C.25. 1H NMR spectrum of 5a • I–. Wet with water. 
Figure C.26. 13C NMR spectrum of 5a • I–. 
161 
 
 
Figure C.27. 19F NMR spectrum of 5a • I–. 
 
N PF6
O O
S
CF3
I
 
Figure C.28. 1H NMR spectrum of 5a • PF6 –. 
 
 162  
Figure C29. 13C NMR spectrum of 5a • PF6 –. 
Figure C.30. 19F NMR spectrum of 5a • PF6 –. 
163 
 
F3C I
NH2
 
Figure C.31. 1H NMR spectrum of 1b. 
F3C I
N3Et2
 
Figure C.32. 1H NMR spectrum of 2b. 
 164  
 
 
Figure C.33. 1H NMR spectrum of 3b. 
 
N
CF3
I
 
Figure C.34. 1H NMR spectrum of 4b. 
 165  
 
N
CF3
I
questionable carbon 
here need another in 
chloroform or if good, 
need to retake proton 
and fluorine in 
acetone
 
Figure C.35. 13C NMR spectrum of 4b. 
 
Figure C.36. 19F NMR spectrum of 4b. 
 
 166  
 
N I
CF3
I
 
Figure C.37. 1H NMR spectrum of 5b • I–. 
 
Figure C.38. 13C NMR spectrum of 5b • I–. 
 
 167  
 
 
Figure C.39. 19F NMR spectrum of 5b • I–. 
N PF6
CF3
I
need in acetone
 
Figure C.40. 1H NMR spectrum of 5b • PF6 –. 
 168  
Figure C.41. 13C NMR spectrum of 5b • PF6 –. 
Figure C.42. 19F NMR spectrum of 5b • PF6 –. 
169 
 
I
N3Et2
 
Figure C.43. 1H NMR spectrum of 2c. 
 
N
Et2N3
need dried proton
 
Figure C.44. 1H NMR spectrum of 3c. 
 
 170  
 
 
Figure C.45. 13C NMR spectrum of 3c. 
 
N
I
 
Figure C.46. 1H NMR spectrum of 4c. 
 
 171  
 
N I
I
 
Figure C.47. 1H NMR spectrum of 5c • I–. 
 
 
 
Figure C.48. 13C NMR spectrum of 5c • I–. 
 172  
 
N PF6
I
 
Figure C.49. 1H NMR spectrum of 5c • PF6 –. 
 
 
N PF6
I
 
Figure C.50. 13C NMR spectrum of 5c • PF6 –. 
 173  
 
 
Figure C.51. 19F NMR spectrum of 5c • PF6 –. 
 
tBu I
NH2
 
Figure C.52. 1H NMR spectrum of 1d. Wet with DCM and water. 
 
 174  
 
tBu I
N3Et2
 
Figure C.53. 1H NMR spectrum of 2d. 
 
N
tBu
Et2N3
 
Figure C.54. 1H NMR spectrum of 3d. Wet with water and ethyl acetate. 
 
 175  
 
N
tBu
Et2N3
 
Figure C.55. 13C NMR spectrum of 3d. 
 
N
tBu
I
 
Figure C.56. 1H NMR spectrum of 4d. Wet with water and ethyl acetate. 
 
 176  
 
N
tBu
I
 
Figure C.57. 13C NMR spectrum of 4d. 
 
 
 
N I
tBu
I
 
Figure C.58. 1H NMR spectrum of 5d • I–. Wet with water. 
 
 177  
Figure C.59. 13C NMR spectrum of 5d • I–. 
Figure C.60. 19F NMR spectrum of 5d • I–. 
178 
 
N PF6
tBu
I
 
Figure C.61. 1H NMR spectrum of 5d • PF6 –. 
 
N PF6
tBu
I
checking this with Mike
 
Figure C.62. 13C NMR spectrum of 5d • PF6 –. 
 
 
 179  
Figure C.63. 19F NMR spectrum of 5d • PF6 –. 
180 
APPENDIX D 
SUPPLEMENTARY CONTENT FOR CHAPTER FIVE 
Synthesis 
General Methods: All reagents were purchased from conventional commercial sources and used 
as received, unless otherwise noted. All NMR spectra were acquired at room temperature on a 
Bruker Avance-III-HD 600 MHz (1H 600 MHz, 13C 151 MHz, 19F 565 MHz) spectrometer with 
a Prodigy multinuclear broadband BBO CryoProbe. 1H and 13C chemical shifts () are reported 
in ppm relative to the residual CHCl3 (1H: 7.26 ppm, 13C: 77.16 ppm) or CH3CN (1H: 1.94, 13C: 
118.26).  
Methylated Urea and Iodo-Pyridine (1.6) 
The receptor (0.030g, 0.0518 mmol) was weighed out into a narrow bomb flask and a small stir 
bar was added. Then ~1 to 2 mL of MeI was carefully pipetted over the scaffold until it was fully 
submerged. The bomb flask was then sealed and placed in a metal bead bath at room 
temperature. This bath was then set to heat to 110 °C and watched carefully. As soon as there 
was visible precipitation of the methylated receptor, as an orange-brown solid, the flask was 
removed from heat. This typically happened as soon as the flask had reached temperature, if not 
slightly before. The solution was let to cool down to room temperature and, upon chilling, was 
181 
carefully filtered. The precipitate was then washed with cold DCM before being scraped off of 
the filter paper into a massed scintillation vial to yield 0.026g of product (70%). 1H NMR (500 
MHz, Acetone-d6) δ = 9.25 (s, 1H), 9.05 (s, 1H), 8.62 (d, J=4.9, 1H), 8.50 – 8.47 (m, 2H), 8.22 
(d, J=2.1, 1H), 8.09 (dd, J=8.9, 2.1, 1H), 7.77 (d, J=8.5, 3H), 7.73 (d, J=4.9, 1H), 7.65 (d, J=8.5, 
3H), 4.37 (q, J=7.1, 3H), 2.84 (s, 3H), 1.38 (t, J=7.1, 3H). 13C NMR (126 MHz, Acetone-d6) δ = 
165.53, 157.96, 152.30, 149.66, 145.41, 143.81, 137.04, 134.49, 132.66, 127.59, 126.97 (q, 
J=3.9), 125.31, 124.49, 124.43, 119.55, 119.38, 111.02, 99.94, 96.49, 92.09, 61.62, 54.96, 14.58. 
19F NMR (471 MHz, Acetone-d6) δ = -62.32. 
Tridentate Host Receptor (1) 
The methylated scaffold (0.026g, 0.03605 mmol) was dissolved in ~6 mL of acetone (sonicating 
as needed to help solubilize it). Then ~3 mL of water was added to the scintillation vial which 
was set stirring. AgPF6 was then added and the reaction was left to stir for 1-2 hours. Upon 
visible precipitation the solution was filtered until translucent (ppt is not product) the filtrate is 
then subjected to reduced pressure to remove the acetone, at which point the receptor will crash 
out of the water. This aqueous solution was then filtered a second time to yield the receptor as a 
white solid (0.025g, 94%). 1H NMR (500 MHz, Acetone-d6) δ = 9.14 (s, 1H), 9.08 (s, 1H), 8.66 
182 
(d, J=4.9, 1H), 8.49 (d, J=8.9, 1H), 8.47 (s, 1H), 8.23 (d, J=2.1, 1H), 8.13 – 8.09 (m, 1H), 7.75 (t, 
J=7.5, 3H), 7.66 (d, J=8.5, 2H), 4.37 (q, J=7.1, 2H), 1.38 (t, J=7.1, 3H). 19F NMR (471 MHz, 
Chloroform-d) δ = -57.14, -66.70, -68.20. 31P NMR (202 MHz, Acetone-d6) δ = -134.68 – -
153.89 (m). 
 
 
Protected Quinoline (2.1) 
Aminoquinoline (1.00g, 6.9 mmols) was dissolved in DCM and set stirring in an ice bath. Once 
the reaction mixture reached 0 °C TEA (.91 mL, 7.6 mmols) was added to the flask followed by 
pivaloyl chloride (1.2 mL, 8.7mmols). After stirring for 15 minutes the ice bath was removed 
and the reaction was monitored by TLC. After completion the reaction mixture was washed with 
three times with NaHCO3 and dried over Na2SO4. Finally, solvent was removed in vacuo to 
afford a pale-yellow oil (1.56 g, 6.83 mmols, 99% yield). If needed the product was purified by 
column chromatography over ethyl acetate and hexanes, though this could typically be avoided 
by running the reaction overnight. 1H NMR (500 MHz, Chloroform-d) δ 8.46 (d, J = 9.0 Hz, 
1H), 8.27 (s, 1H), 8.17 (d, J = 9.0 Hz, 1H), 7.82 (dq, J = 8.4, 0.9 Hz, 1H), 7.78 (dd, J = 8.0, 1.5 
Hz, 1H), 7.66 (ddd, J = 8.4, 6.9, 1.5 Hz, 1H), 7.45 (ddd, J = 8.1, 6.9, 1.2 Hz, 1H), 1.38 (s, 7H). 
13C NMR (126 MHz, Chloroform-d) δ = 177.67, 151.38, 146.70, 138.69, 130.12, 127.72, 127.32, 
126.50, 125.24, 114.42, 40.14, 27.65. 
 183 
Protected Iodo-Quinoline (2.2)  
Three round bottoms and two stir bars were left in a 150 °C oven to dry overnight. Dry Et2O was 
procured from a solvent still, transferred into one of the dry round bottom flasks with a dry stir 
bar in it and set under N2. Some of this Dry Et2O was cannulated over to a second RBF, that has 
a stir bar and I2 (1.24 equiv.) already in it. This second flask was set stirring, so the I2 can fully 
dissolve before it is needed. The protected quinoline was then added to the first flask and set this 
stirring in a salted ice bath until it reached -20 °C. After that 2.2M nBuLi in hexanes was added 
dropwise via syringe at which point the pale yellow solution grew brighter before changing to a 
lime green color. After 3 hours of stirring at -20 °C the reaction mixture was a solid brown and is 
cooled to -80 °C in an acetone and dry ice bath. Once the desired temperature had been reached 
the solution of I2 was cannulated in dropwise at which point the mixture changed back to a 
warmer yellow. The reaction mixture was left to stir overnight, slowly coming back up to room 
temperature. The next day the mixture was washed with saturated aqueous solution of Na2S2O3, 
then dried and solvent removed. 1H NMR (500 MHz, Chloroform-d) δ = 8.61 (s, 1H), 8.27 (s, 
1H), 8.03 (d, J=8.5, 1.0, 1H), 7.69 (ddd, J=8.4, 6.9, 1.4, 1H), 7.65 (d, J=8.2, 1.4, 1H), 7.48 (ddd, 
J=8.1, 6.9, 1.2, 1H), 1.42 (s, 9H). 13C NMR (126 MHz, Chloroform-d) δ = 176.29, 148.40, 
148.01, 146.52, 130.66, 128.87, 127.62, 126.56, 126.32, 85.86, 40.52, 27.75. 
184 
3-Iodo-2-Amino-Quinoline (2.3)
 Iodoaminoquinoline (1.5 mmols, 0.55g, 1 equiv) was dissolved in a minimal amount of dioxane 
and set stirring in a round bottom flask. Then a solution of 4 N HCl (9.3 mmols, 2.39 mL, 6 
equiv.) was added and let stir at room temperature for about an hour and a half. Then the solution 
was heated to reflux and left stirring overnight. The next day the reaction mixture has 
transitioned from a translucent pale yellow to a dark blue. The reaction mixture was then 
quenched with saturated aqueous solution of NaHCO3 until a basic pH was reached and washed 
in ether with brine. Finally, the organic phase was dried with Na2SO4, filtered and the solvent 
was removed in vacuo to give a crude product. This was purified by an ethyl acetate/hexanes 
plug to give pure product in an 83% yield. 1H NMR (500 MHz, Chloroform-d) δ = 8.40 (s, 1H), 
7.63 (dd, J=8.5, 1.1, 1H), 7.57 (ddd, J=8.4, 6.8, 1.5, 1H), 7.52 (dd, J=8.0, 1.4, 1H), 7.25 (ddd, 
J=8.1, 6.8, 1.2, 1H), 5.40 (s, 2H). 13C NMR (126 MHz, CDCl3) δ 155.01, 147.37, 147.25, 
130.41, 126.42, 125.92, 125.21, 123.15, 80.51, 77.04, 0.03. 
TMS Protected Diyne Quinoline (2.4)  
TMS-protected buta-1,3-diyne was selectively deprotected according to known literature 
procedures with MeLiLiBr. Iodoaminoquinoline was dissolved in a 75 mL of a 50/50 mixture of 
THF and TEA and set stirring under N2 sparging until completely outgassed. The CuI (0.02 
185 
equiv.) and Pd(PPh3)2Cl2 (0.05 mol) were added and the solution stirred at room temperature 
overnight. The next day, after verifying that the reaction ran to completion by TLC, the solvent 
was removed in vacuo and the product purified by column chromatography on silica gel with 
EtOAc and hexanes. 1H NMR (500 MHz, Chloroform-d) δ = 8.07 (s, 1H), 7.60 (dt, J=8.8, 1.0, 
1H), 7.56 (dtd, J=8.8, 3.7, 3.2, 1.5, 2H), 7.26 – 7.22 (m, 1H), 5.39 (s, 2H), 0.26 (s, 10H). 13C 
NMR (126 MHz, Chloroform-d) δ = 156.86, 147.40, 142.69, 1313C NMR (126 MHz, 
Chloroform-d) δ = 156.86, 147.40, 142.69, 131.35, 127.58, 126.05, 123.36, 122.97, 104.74, 
93.49, 87.32, 80.30, 72.02, -0.33.1.35, 127.58, 126.05, 123.36, 122.97, 104.74, 93.49, 87.32, 
80.30, 72.02, -0.33. 
Iodo Diyne Quinoline (2.5)  
The diyne quinoline (1.00 equiv) was dissolved in ACN and set stirring under N2 to outgas. The 
round bottom flask was then wrapped in aluminum foil, to ensure dark conditions, and AgF (1.00 
equiv.) was added and let stir for 20 minutes. After 20 minutes NIS (1.20 equiv.) was added, and 
the reaction was monitored by TLC until done. Upon the disappearance of all starting material 
the reaction was rotovapped down and then washed in water and EtOAc three times before 
drying over Na2SO4 and removing the solvent to yield the product as a brown solid. This product 
was collected and used as is for the next step without further purification.  
186 
Cyclized Quinoline (2.6Bn)   
The iodo-diyne (1 equiv.) was dissolved in a minimal amount of DMF and set stirring under N2. 
Following outgassing lutidine (4 mol%), the azide (1 equiv.), and CuI(PPh3)3 (10 mol%) are 
added. These are left stirring at room temperature overnight. After completion the reaction 
mixture was diluted with EtOAc and washed with a saturated aqueous solution of NH4Cl three 
times. The organic layer was then dried with Na2SO4 and concentrated under reduced pressure to 
yield the crude product as an oil. This was purified by column chromatography over silica gel 
using a EtOAc and Hexanes mixture (3:1) to yield the product. 
Quinoline Host Receptor (2Bn) 
 The newly cyclized compound (0.0429 g, 0.0951 mmol) was dissolved in a minimal amount of a 
50/50 mixture of water and 1,4 dioxane and set stirring. Cyanamide (0.0048 g, 0.1141 mmol) and 
Sc(OTf)3 catalyst (0.0047g, 0.0095 mmol) were added to the reaction. This was then heated to 
100 °C and left stirring for 2 days. The crude mixture was then taken up in EtOAc and washed 
with a saturated solution of NaCO3H, to crash the product out as its carbonate salt analog. While 
187 
the final product was never able to be isolated alone its existence in the crude reaction mixture 
was confirmed by mass spec. HRMS (TOF-MS-ES+) for C21H16IN7 [M+H] +: calcd 493.05, 
found 493.0512.  
 
  
 188 
NMRs 
 
Figure D.1. 1H NMR spectrum of protected quinoline 
 
Figure D.2. 13C NMR spectrum of protected quinoline 
 189 
Exp37-Product-CDCl3.1.fid
I
O
CH3
N N
CH3
H CH3
8.7 8.6 8.5 8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1
f1 (ppm)
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
f1 (ppm)  
Figure D.3. 1H NMR spectrum of protected iodo-quinoline 
Exp37-Carbon-CDCl3.1.fid
I
O
CH3
N N
CH3
H CH3
220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
f1 (ppm)  
Figure D.4. 13C NMR spectrum of protected iodo-quinoline  
 190 
0.97 8.6134
0.97
0.90
0.96
0.96
1.03
176.2920 1.00
0.90 8.2677 7.2600 CDCl3
148.4029
148.0058 8.03600.96
146.5197 8.0191
130.6637
128.8700
127.6196 7.7090
126.5621 7.7062
126.3186 7.6923
7.6782
0.96
7.6754
1.03 7.6590
7.6428
7.4936
1.00 7.4776
85.8587 7.4635
77.1600 CDCl3
7.2600 CDCl3
40.5184 8.66
27.7478
Exp6-HJB-Acetone.1.fid
I
N NH2
11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
f1 (ppm)
Figure D.5. 1H NMR spectrum of 3-Iodo-2-Amino-Quinoline 
Figure D.6. 13C NMR spectrum of 3-Iodo-2-Amino-Quinoline 
191 
1.00 8.5682
7.6476
1.08 7.6334
2.01 7.5426
1.07 7.2325
1.68 6.0163
2.8435 Water
2.0500 Acetone
Exp33.2-F5-HJB-CDCl3.1.fid
H3C
CH3
Si
CH3
N NH2
8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 5.5 5.4 5.3
f1 (ppm)
8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)  
Figure D.7. 1H NMR spectrum of TMS protected diyne quinoline 
Exp33-F5-Carbon-CDCl3.1.fid
H3C
CH3
Si
CH3
N NH2
160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
f1 (ppm)  
Figure D.8. 13C NMR spectrum of TMS protected diyne quinoline  
 192 
156.8645
1.00 1.00 8.0749
147.3993
142.6889 1.02
2.09
0.87 7.2600 CDCl3
131.3534
127.5785
126.0489
123.3629 7.6129
122.9708 7.5956
1.02 7.5718
7.5627
2.09
7.5582
104.7448 7.5501
1.81 7.5471
93.4887 7.2600 CDCl3
7.2470
87.3176
0.87 7.2443
7.2310
80.3007 7.2285 4.1110 EtOAc
77.1600 CDCl3
72.0243
1.81
2.0416 Acetone
1.2547 EtOAc
0.8801 EtOAc
8.80 0.2551
-0.3333
Exp13-HJB-PT-RC-CDCl3.1.fid
N
N
N
I
N NH2
8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1
f1 (ppm)
8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
f1 (ppm)
Figure D.9. 1H NMR spectrum of cyclized quinoline  
TPD_3_12_ppt_acetone.1.fid
F
F F
O NH
NH
H3C O I
O
N
9.3 9.2 9.1 9.0 8.9 8.8 8.7 8.6 8.5 8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5
f1 (ppm)
10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0
f1 (ppm)
Figure D.10. 1H NMR spectrum of precursor 1.5 
193 
1.00 9.1289 1.00 8.1622
1.02 9.0629 2.04
1.14 7.6369
3 00 7.5807.
1.00 2 23 7.3690.
1.02 0 81 7.2600 CDCl3.
0.93
1.03 8.63950.93
0.88 8.6305
0.92 8.49951.03
1.05 8.48180.88
2.16 8.4578
0.99
1.95 0.92 8.2278 2.01 5.6366
8.2238 2.04 5.4135
5.2994 DCM
1.05 8.1101
8.0884
7.7706
2 16 7.7535.
0 99 7.7141
1.00
.
1.95 7.7044
7.6660
7.6488
3.4850 Et2O
2.35 4.3758
4.3616
2.04
1.14
2.8108 3.00 1.2078 Et2O
2.23
0.81 7.2600 CDCl3
2.0500 Acetone
3.14 1.3811
  
 Figure D.11. 19F NMR spectrum of precursor 1.5  
Exp56-Methylated-Acetone.1.fid
F
F
F
O
H NH3C
O
NH
O
I
9.3 9.2 9.1 9.0 8.9 8.8 8.7 8.6 8.5 8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5
I-
f1 (ppm) N+
CH3
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0
f1 (ppm)  
Figure D.12. 1H NMR spectrum of precursor 1.6 
 194 
1.05 9.2515
0.96 9.0520
1.05
0.96 8.6281
8.6182
1.00 8.4949
1.74 1.00 8.4842
0.93 8.4773
1.02 1.74 8.2259
1.87 8.2218
1.01 8.1051
1.97 0.93 8.1011
1.02 8.0874
8.0833
7.7750
7.7578
1.87 7.7331
1.01 7.7232
1.97 7.6628
7.6454
5.6212 DCM
4.3869
4.3726
2.15
4.3584
4.3442
2.8766 H2O
3.38 2.8434
2.0500 Acetone
2.99 1.3786
 
Figure D.13. 13C NMR spectrum of precursor 1.6 
 
Figure D.14. 19F NMR spectrum of precursor 1.6 
 195 
Exp59-moredilute-acetone.2.fid
9.4 9.3 9.2 9.1 9.0 8.9 8.8 8.7 8.6 8.5 8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4
f1 (ppm)
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
f1 (ppm)  
Figure D.15. 1H NMR spectrum of Host Receptor 1PF6   
 
Figure D.16. 19F NMR spectrum of Host Receptor 1PF6   
 196 
0.75
0.93 0.75 9.1446
0.93 9.0836
1.00
0.60
0.96
0.94
1.00
3.10
2.00 8.66211.00 8.6523
8.4990
0.60
8.4813
0.96
8.4681
0.94 8.2307
8.2270
1.00 8.1128
8.0987 5.6231 DCM
7.7705
3.10 7.7517
7.7406
2.14 2.00 7.6688
7.6516
2.8365 Water
2.0500 Acetone
3.27
Figure D.17. 31P NMR spectrum of Host Receptor 1PF6  
197 
1H NMR Titrations.  
General Methods. 1H NMR spectra were acquired at room temperature on a Varian Inova 500 
MHz spectrometer (1H: 500.11 MHz). 1H chemical shifts () are expressed in ppm relative to 
residual CH3CN (1H: 1.94 ppm) shifts. A solution of host in 10% DMSO-d6/CD3CN (0.73-1.9 
mM) was prep in 3 or 4 mL volumetric flasks. 500 L of this host solution was added to a 
septum-sealed NMR tube. The remaining host solution was used to prepare a host/guest 
(NBu4Cl, NBu4Br, or NBu4I) stock solution in 2 or 3 mL volumetric flasks, respectively. 
Aliquots of the host/guest solution were incrementally added to the NMR tube using gas-tight 
Hamilton syringes, and 1H NMR spectra were recorded, at 25 °C, after each addition of guest. 
The ∆ of the NH protons were tracked to follow the progress of the titration and association 
constants were determined using Thordarson’s Bindfit software.  
Table D.1. Representative titration of receptor 1 with Cl- in 10% DMSO-d6/CD3CN.  
Entry VGuest (𝜇L) [Guest] (M) [Host] (M) Equiv. Anion 𝛅1 (ppm) 𝛅2 (ppm) 
0 0 0 0.000946816 0.00 9.66250 8.515 
1 5 0.000275384 0.000946816 0.29 9.70870 8.531 
2 5 0.000545368 0.000946816 0.58 9.87850 8.5806 
3 10 0.00106976 0.000946816 1.13 10.28150 8.8036 
4 10 0.001574364 0.000946816 1.66 10.56070 8.933 
5 10 0.002060278 0.000946816 2.18 10.77210 9.0358 
6 15 0.002756318 0.000946816 2.91 10.99810 9.1398 
7 15 0.003415725 0.000946816 3.61 11.15700 9.2183 
8 15 0.004041315 0.000946816 4.27 11.27180 9.2709 
9 20 0.004827181 0.000946816 5.10 11.38460 9.3212 
10 20 0.005562752 0.000946816 5.88 11.47290 9.3645 
11 20 0.006252706 0.000946816 6.60 11.53340 9.3942 
12 30 0.007210975 0.000946816 7.62 11.60970 9.4305 
13 50 0.008631856 0.000946816 9.12 11.68670 9.4651 
14 100 0.010956936 0.000946816 11.57 11.78640 9.5129 
15 200 0.014246072 0.000946816 15.05 11.87130 9.5539 
16 500 0.018694494 0.000946816 19.74 11.92860 9.5814 
17 500 0.020946164 0.000946816 22.12 11.9434 9.5876 
 198 
2.5
Predicted N(H)1
2
Predicted N(H)2
Experimental
1.5 N(H)1
Experimental
N(H)2
1
0.5
0
0 5 10 15 20 25
[G]/[H]
0.2 N(H)1
N(H)2
0
0 5 10 15 20
-0.2
[G]/[H]
Figure D.19. Representative binding isotherm for Cl- titration of receptor 1 in 10% DMSO-
d6/CD3CN as determined by 1H NMR spectroscopy.  
Table D.2. Representative titration of receptor 1 with Br- in 10% DMSO-d6/CD3CN. 
Entry Vguest (𝜇L) [Guest] (M) [Host] (M) 
Equiv. 
Anion 𝛅1 (ppm_ 𝛅2 (ppm) 
Host Alone 0 0 0.00132554 0 9.66550 8.51620 
1 2.5 0.00024569 0.00132554 0.19 9.66700 8.51720 
2 2.5 0.00048896 0.00132554 0.37 9.68070 8.52180 
3 5 0.00096832 0.00132554 0.73 9.70790 8.53520 
4 5 0.00143839 0.00132554 1.09 9.76420 8.56010 
5 10 0.00235165 0.00132554 1.77 9.85890 8.60300 
6 10 0.00323077 0.00132554 2.44 9.93740 8.63740 
199 
Residuals 𝜹 - 𝜹 0
7 10 0.00407762 0.00132554 3.08 10.00420 8.66780 
8 10 0.00489396 0.00132554 3.69 10.06420 8.69550 
9 15 0.00606477 0.00132554 4.58 File Corrupted 
10 15 0.00717553 0.00132554 5.41 10.20370 8.75910 
11 15 0.00823076 0.00132554 6.21 10.25520 8.78090 
12 20 0.0095583 0.00132554 7.21 10.31050 8.80530 
13 30 0.01139644 0.00132554 8.60 10.38580 8.83800 
14 50 0.01410987 0.00132554 10.64 10.47160 8.87870 
15 100 0.01851921 0.00132554 13.97 10.58820 8.92280 
16 200 0.02469228 0.00132554 18.63 10.70940 8.98500 
17 300 0.03039049 0.00132554 22.93 10.79140 9.02320 
18 500 0.03566662 0.00132554 26.91 10.84980 9.04790 
19 500 0.03864878 0.00132554 29.16 10.86270 9.05340 
1.2
1
0.8
0.6
0.4
Predicted N(H)1
0.2 Predicted N(H)2
Experimental
0 N(H)1
0 2 4 6 8 10 12 14 16
[G]/[H]
 
0.2 N(H)1
0.1 N(H)2
0
0 5 10 15 20
-0.1
[G]/[H]
Figure D.20. Representative binding isotherm for Br- titration of receptor 1 in 10% DMSO-
d6/CD3CN as determined by 1H NMR spectroscopy.  
 200 
Residuals
𝜹 - 𝜹 0
Table D.3. Representative titration of receptor 1 with I- in 10% DMSO-d6/CD3CN. 
Vguest Equiv. 
Entry (𝜇L) [Guest] (M) [Host] (M) Anion 𝛅1 (ppm_ 𝛅2 (ppm) 
Host Alone 0 0 0.0010415 0 9.6622 8.5159 
1 5 0.00025483 0.0010415 0.24467354 9.6641 8.517 
2 5 0.00050466 0.0010415 0.48454956 9.6884 8.5273 
3 10 0.0009899 0.0010415 0.95046259 9.6947 8.5326 
4 10 0.00145684 0.0010415 1.398794 9.7042 8.5358 
5 10 0.00190648 0.0010415 1.83052055 9.7095 8.5385 
6 15 0.00255056 0.0010415 2.44893965 9.7131 8.5405 
7 15 0.00316075 0.0010415 3.03481038 9.7168 8.5418 
8 15 0.00373964 0.0010415 3.59063646 9.7211 8.544 
9 20 0.00446684 0.0010415 4.28886426 9.7292 8.547 
10 20 0.0051475 0.0010415 4.94240548 9.7317 8.5472 
11 20 0.00578595 0.0010415 5.55541701 9.7327 8.5487 
12 30 0.00667269 0.0010415 6.40682192 9.738 8.5506 
13 50 0.00798751 0.0010415 7.66924988 9.7437 8.5537 
14 100 0.01013902 0.0010415 9.73504109 9.755 8.5587 
15 200 0.01318263 0.0010415 12.6573799 9.7683 8.5667 
16 500 0.01729899 0.0010415 16.6097233 9.7885 8.5841 
17 500 0.01938257 0.0010415 18.6102922 9.7969 8.5769 
18 500 0.02064098 0.0010415 19.8185566 9.8006 8.5802 
201 
 
0.16
0.14
0.12
0.1
0.08
0.06
Predicted N(H) 1
0.04 Predicted N(H) 2
0.02 Experimental N(H) 1
Experimental N(H) 2
0
0 5 10 15 20 25
[G]/[H]
 
0.02 N(H) 1
N(H) 2
0
0 5 10 15 20 25
-0.02
[G]/[H}
 
Figure D.21. Representative binding isotherm for I- titration of receptor 1 in 10% DMSO-
d6/CD3CN as determined by 1H NMR spectroscopy.  
 
 202 
Residuals 𝜹 - 𝜹 0
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