Poly (squaramides): Synthesis, Anion Sensing, and Self-Assembly

by

Ali Rostami

A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy

Department of Chemistry University of Toronto

© Copyright by Ali Rostami 2012

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Poly (squaramides): Synthesis, Anion Sensing, and Self-

Assembly

Ali Rostami

Doctor of Philosophy

Department of Chemistry University of Toronto

2012

Abstract

The focus of the research presented in this thesis is the design, synthesis, and anion recognition

properties of a structurally novel class of poly (amides) that incorporates the

diaminocyclobutenedione (squaramide) group into the polymer backbone.

In Chapter 1, a brief overview of different anion-responsive synthetic macromolecules is

presented. Emphasis is placed on the wide structural diversity of the polymers, the mechanisms

of their anion-induced responses, and features such as signal amplification, multivalency, and

cooperative behavior that can be exploited productively in the context of anion recognition and

sensing.

Chapter 2 describes a new method for the regioselective preparation of squaramides, using Lewis

acid-catalyzed condensations of diethyl squarate and different anilines. Zinc

trifluoromethanesulfonate promotes efficient condensations of anilines with squarate esters,

providing access to symmetrical and unsymmetrical squaramides in high yields from readily

available starting materials. Colorimetric anion-sensing behavior and computational studies

illustrating the enhanced hydrogen bond donor ability and acidity of squaramides in comparison

to ureas are presented.

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In Chapter 3, the application of the synthetic method described above to the selective preparation

of polysquaramides composed of 1,2-isomeric repeat units is described. The optical, thermal and

aggregation properties of these materials are also discussed.

Finally, Chapter 4 describes self-assembly properties as well as applications of these materials in

the area of anion recognition and sensing. Incorporating an anion-binding squaramide group into

a polymeric architecture results in drastic alterations in the selectivity and magnitude of its

anion-induced response, resulting in a sensitive and discriminating turn-on fluorescence sensor

for dihydrogenphosphate ions. This unusual behavior is the result of a cooperative, anion-

triggered aggregation process that was further probed by dynamic light scattering (DLS),

transmission electron microscopy (TEM) and laser confocal microscopy.

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Dedicated to my lovely parents, Parvaneh and Abbas

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Acknowledgments

First and foremost I offer my sincerest gratitude to my supervisor, Dr. M. S. Taylor, who has

supported me throughout my thesis with his patience and knowledge whilst allowing me the

room to work in my own way. I attribute the level of my Ph.D. degree to his encouragement and

effort and without him this thesis, too, would not have been completed or written. One simply

could not wish for a better or friendlier supervisor.

My appreciation goes to all the members of Taylor’s group for their continuous help and

friendship. In particular, many thanks go to Sunny Lai, Mike Chudzinski, Corey McClary, Doris

Lee, Elena Dimitrijevic and Gholam Sarwar for our great discussions and shared moments in the

Lab. I would also like to thank members of Winnik’s group especially Mohsen Soliemani and

Dr. Gerald Guerin fantastic scientists and polymer chemists, I learned not only about polymer

chemistry but also about enjoying life. I gratefully thank Chu Jun Wei for her assistance in the

synthesis and sensory properties of squaramide-based model compound required for our second

publication. Also, many thanks go to Xiao Yu Li and Alexis Collin, undergraduate students who

helped me with catalyst screening and UV/vis titration experiments required for our first

publication. I would also like to extend my acknowledgment to all spectral services staff for their

fantastic work and patience.

I gratefully acknowledge the funding sources NSERC and University of Toronto that made my

Ph.D. work possible.

My most sincere gratitude goes to my lovely parents, for constantly supporting my education,

both financially and emotionally. Last but not least; I would like to thank all my friends,

especially Ali Alavi, for his presence, encouragement and motivations throughout this period.

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Table of Contents

ABSTRACT………………………………………………………………………………………ii

ACKNOWLEDGEMENTS………………………………………………………………………iv

LIST OF TABLES………………………………………………………………………………..ix

LIST OF SCHEMES………………………………………………………………………………x

LIST OF FIGURES……………………………………………………………………….……..xii

LIST OF APPENDICES ………………………………………………………………...……...xvi

LIST OF ABBREVIATIONS…………………………………………………………………..xvii

1 CHAPTER1……………………………………………………………………………………..1

1 Polymers for anion recognition and sensing…………………………………………………….1

1.1 Introduction……………………………………………………………………………………1

1.2 Polymer-based chemical sensors: general principles………………………………………….2

1.3 Anion responsive polymers……………………………………………………………………4

1.3.1 Anion responsive chemodosimeters………………………………………………………....4

1.3.2 Lewis acid–base interactions: organoboron, organosilicon, and metal cation-containing

anion-responsive polymers…………………………………………………………………..…....5

1.3.3 Ion-pairing interactions: anion recognition by cationic polyelectrolytes…………………15

1.3.4 Polymers bearing hydrogen bond-donor groups……………………………………….......19

1.4 Conclusions…………………………………………………………………………………..26

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1.5 References……………………………………………………………………………………28

2 CHAPTER 2…………………………………………………………………………………...31

2 N,N!-Diarylsquaramides: Synthesis and applications in colorimetric anion sensing………...31

2.1 Introduction…………………………………………………………………………………..31

2.2 Squaramide preparation……………………………………………………………………...34

2.3 Development of a Lewis-acid-promoted condensation of anilines with squarate Esters…....36

2.4 Hydrogen bonding of N,N!-diarylsquaramides with neutral acceptors: solid-state and

computational studies………………………………………………………………………..40

2.5 Colorimetric anion sensing by nitro-substituted N,N!- diarylsquaramides…………………..42

2.6 Computational investigation of the acidity of squaramides………………………………….51

2.7 Conclusions…………………………………………………………………………………..53

2.8 References……………………………………………………………………………………54

2.9 Experimental procedures……………………………………………………………………..57

3 CHAPTER 3…………………………………………………………………………………...64

3 Polysquaramides: synthesis, thermal and optical properties……………………………….......64

3.2 Aromatic polyamide synthesis…………………………………………………………….....65

3.3 Polysquaramides: synthetic challenges and limitations……………………………………...68

3.4 Monomer synthesis…………………………………………………………………………..70

3.5 Polysquaramide synthesis by Lewis acid catalyzed condensation polymerization………….73

3.6 Thermal properties of polysquaramides……………………………………………………...77

3.7 Aggregation properties of polysquaramides in solution……………………………………..78

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3.8 Computational modeling of oligo(fluorenesquaramides)…………………………………....79

3.8.1 Conformation of oligo(fluorenesquaramides)……………………………………………..79

3.8.2 Bandgap calculations on oligo(fluorenesquaramides)……………………………..………81

3.9 Optical properties of polysquaramides………………………………………………………82

3.10 Conclusions…………………………………………………………………………………85

3.11 References…………………………………………………………………………………..85

3.12 Experimental procedures…………………………………………………………………....87

4 CHAPTER 4………………………………………………………………………………….104

4 Polysquaramides: anion sensing and self-assembly…………………………………………..104

4.1 Introduction……………………………………………………………………………........104

4.2 Synthetic receptors with rigidity and preorganization……………………………………...106

4.3 Self-assembled molecular capsules…………………………………………………………108

4.4 Self-assembled polymers…………………………………………………………………...111

4.4.1 Anion detection by a fluorescent polysquaramide……………………………………......111

4.4.2 Nature and magnitude of emission responses: molecular weight effect………………….114

4.4.3 Selectivity towards different anions…………………………………………………........116

4.4.4 Aggregation properties: microscopy and light scattering studies………………………...118

4.4.5 Anion-induced self-assembly of polymeric chains…………………………………...…..121

4.4.6 Nature and magnitude of emission response: structural effects…………………………..124

4.4.7 Selectivity of structurally different polymers towards different anions……………….…127

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4.4.8 Anion induced self-assembly of different polysquaramides……………………………...128

4.5 Conclusions ………………………………………………………………………………...130

4.6 References…………………………………………………………………………………..132

4.7 Experimental procedures…………………………………………………………………....135

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List of Tables

Table 2.01 Evaluation of Lewis acid catalysts for the condensation of 3,5-bis(trifluoromethyl)-

aniline and diethyl squarate………………………………………………………………………37

Table 2.02 Preparation of symmetrically substituted N,N!-diarylsquaramides by Zn(OTf)2-

catalyzed condensation…………………………………………………………………………..38

Table 2.03 Preparation of unsymmetrically substituted N,N"-diaryl squaramides by Zn(OTf)2-

catalyzed condensation…………………………………………………………………………..39

Table 3.01 Effect of solvent ratio on polymer molecular weight and polydispersity……………74

Table 3.02 Molecular weight and polydispersities for different Polysquaramides determined by

GPC………………………………………………………………………………………………75

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List of Schemes

Scheme 2.01 Applications of squaramide in chemistry, biology and material sciences…………31

Scheme 2.02 Recognition of carboxylate anion with squaramide-based receptor……………....32

Scheme 2.03 A squaramide fluorescent ensemble for monitoring sulfate in water……………...33

Scheme 2.04 Squaramide based chloride ion receptor…………………………………………..33

Scheme 2.05 Traditional methods for the preparation of mono-squaramide and bis-

squaramides………………………………………………………………………………………34

Scheme 2.06 Mechanism for the synthesis of squaramides and squaraines……………………..35

Scheme 2.07 Preparation of bis-squaramides by (a) condensation reaction and (b) copper

catalyzed cross-coupling reaction………………………………………………………………..36

Scheme 2.08 Sequential deprotonations of bis(4-nitrophenyl)urea as the basis for colorimetric

anion sensing……………………………………………………………………………………..43

Scheme 2.09 DFT-Calculated gas-phase acidities for N,N!-diphenylurea and N,N!-diphenyl-

squaramide……………………………………………………………………………………….52

Scheme 3.01 Commercial aromatic polyamides…………………………………………………64

Scheme 3.02 Aromatic polyamide synthesis utilizing diacid and diisocyanates………………...67

Scheme 3.03 Aromatic polyamide synthesis utilizing diamines and diacids…………………....67

Scheme 3.04 Aromatic polyamide synthesis utilizing palladium-catalyzed condensation……...67

Scheme 3.05 Polysquaramide copolymer syntheses by condensation of squaric acid and

diamine…………………………………………………………………………………………...68

Scheme 3.06 Formation of 1,3-diamide isomer in basic media………………………………….69

Scheme 3.07 Polysquaramide synthesis by solid-state thermal condensation protocol…………69

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Scheme 3.08 Synthesis of diaminofluorenes with varied side chains……………………………70

Scheme 3.09 Synthesis of diaminotrifluorene monomer………………………………………...71

Scheme 3.10 Synthesis of aminofluorene monomer with a hydrophilic, flexible spacer………..72

Scheme 3.11 Other aromatic diamine monomers utilized for poly(squaramide) synthesis……...72

Scheme 3.12 Scandium (III) triflate-catalyzed polycondensation of diaminofluorene and diethyl

squarate…………………………………………………………………………………………..73

Scheme 3.13 Preparation of polysquaramides with well-defined end groups…………………...74

Scheme 3.14 Preparation of model compound 3.28 and poly(squaramides) Poly1#Poly5 by

Lewis acid catalyzed condensation………………………………………………………………76

Scheme 3.15 Three calculated structures (B3LYP/6-31G(d)) of difluorenesquaramide………...80

Scheme 3.16 DFT calculations on three different conformers of trifluorenesquaramides………81

Scheme 3.17 Bandgap calculations on oligo(fluorenesquaramides)…………………………….82

Scheme 3.18 Squaramide based receptors with chiral side chains………………………………84

Scheme 4.01 A shape-persistent triazole based macrocycle……………………………………106

Scheme 4.02 Chloride ion templation of a cyclic hexaurea macrocycle……………………….107

Scheme 4.03 Cavitand-based coordination cage via self-assembly approach………………….108

Scheme 4.04 Encapsulation of an anionic guest by a neutral cage……………………………..109

Scheme 4.05 Encapsulation of sulfate anion by crystallization of the bipyridine-urea ligand with

nickel (II) sulfate……………………………………………………………………………..…110

Scheme 4.06 Analyte-induced self-assembly…………………………………………………..122

Scheme 4.07 Sulfate-induced micellization of amphiphilic block copolymer…………………123

Scheme 4.08 Sulfate-induced dimerization of squaramide……………………………………..123

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List of Figures

Figure 1.01 Signal ‘gain’ in fluorescence quenching of conjugated polymers by a paraquat

derivative.………………………………………………………………………………………….3

Figure 1.02 (a) Anion-induced desilylation/cyclization as the basis for fluoride detection. (b) A

polymeric chemodosimeter for fluoride…………………………………………………………...5

Figure 1.03 Representative anion-responsive organoboron polymers…………………………….6

Figure 1.04 Structure of an anion-responsive, fluorescent poly(silane)…………………………10

Figure 1.05 Turn-on fluorescence response of an anionic PPE–Cu2+ adduct to pyrophosphate...11

Figure 1.06 Turn-on fluorescence response of imidazole-functionalized polyacetylene#Cu22+

adduct to cyanide ion…………………………………………………………………………….12

Figure 1.07 Turn-on fluorescence response of imidazole-functionalized polyfluorene#Cu22+

adduct to cyanide ion…………………………………………………………………………….12

Figure 1.08 Benzimidazole-functionalized polyfluorene metal-binding polymer for phosphate

and pyrophosphate detection…………………………………………………………………….13

Figure 1.09 Turn-on fluorescence response of DCPDP#functionalized poly hydroxyethyl

methacrylate#Cu22+ adduct to pyrophosphate ion………………………………………………14

Figure 1.10 Conjugated polypyrrole zwitterionic polymer responsive to alkali metal iodide

salts………………………………………………………………………………………………16

Figure 1.11 Anion responsive cationic polymers.…………………………………………..........17

Figure 1.12 Fluorescent, polymeric anion sensors based on acidic OH groups…………………20

Figure 1.13 Polymeric anion sensors based on acidic NH groups……………………………….24

Figure 2.01 Solid-state structures (ORTEP) of the hydrogen- bonded complexes of 2.20 and

DMSO (top); 2.20b and DMSO (middle) and 2.35 and DMSO (bottom)……………………….41

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Figure 2.02 Structures and DFT-calculated energies of interaction (gas phase, B3LYP/6-

311++G**) of squaramide- DMSO and urea-DMSO hydrogen-bonded complexes……………42

Figure 2.03 (a) Absorption spectrum of squaramide 2.34 as a function of solvent composition. (b)

UV-vis spectra of 2.34 in DMSO as a function of concentration………………………………..44

Figure 2.04 Changes in absorption spectrum of squaramide 2.34 upon addition of tetra-n-

butylammonium fluoride………………………………………………………………………...45

Figure 2.05 Changes in the absorption spectrum of 2.34 upon addition of tetrabutylammonium

fluoride…………………………………………………………………………………………...46

Figure 2.06 (a) Changes in the absorption spectrum of 2.34 upon addition of tetrabutyl-

ammonium acetate. (b) Absorption intensity of 2.34 at 459 nm as a function of added acetate in

acetonitrile……………………………………………………………………………………….47

Figure 2.07 (a) Changes in the absorption spectrum of 2.34 upon addition of tetrabutyl-

ammonium p-toluenesulfonate. (b) Absorption intensity of 2.34 at 395 nm as a function of added

Bu4NOTs in DMSO…………………………………………………………………………….49

Figure 2.08 Changes in the 1H NMR spectrum of 2.34 upon addition of tetrabutylammonium p-

toluenesulfonate………………………………………………………………………………….50

Figure 2.09 Photographs of 2.34 in the presence of (left to right): Bu4NOTs; no analyte;

Bu4NOAc; Bu4NF………………………………………………………………………………..51

Figure 2.10 DFT-calculated highest occupied molecular orbitals for the conjugate bases of (top)

N,N!-diphenylurea and (bottom) N,N! -diphenylsquaramide…………………………………….53

Figure 3.01 GPC profiles for structurally different Polysquaramides…………………………...75

Figure 3.02 1H NMR spectrum of Poly1a in d6-DMF…………………………………………...77

Figure 3.03 (a) TGA data for different Polysquaramides. (b) TGA curve of Poly4 under

nitrogen……………………………………………………………………..................................78

Figure 3.04 GPC profiles of Poly1a in pure NMP and NMP/LiCl (0.2 wt%)…………………..79

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Figure 3.05 Variable temperature UV/Vis spectra in DMF……………………………………79

Figure 3.06 Absorption spectra of different polysquaramides and the model compound in (a)

pure NMP and (b) NMP/H2O (9:1) at a concentration………………………………………….83

Figure 3.07 (a) Effect of molecular weight on the absorption spectra of squaramide based

receptors. (b) Wavelength absorption maxima of different polysquaramides. (c) CD spectrum of

Poly2 in DMF. (d) CD spectrum of model compound 3.29 in DMF…………………………....84

Figure 4.01 (a) Emission and (b) absorption responses of Poly1a to Bu4N+H2PO4# (10% water in

NMP solvent; $ex = 415 nm)……………………………………………………………………112

Figure 4.02 (a) Plots of 1H NMR spectra of polymer Poly1a in d7-DMF after addition of various

quantities of Bu4N+H2PO4# to demonstrate the reversible nature of the interaction between the

receptor and phosphate: (i) polymer Poly1a; (ii, iii, iv) polymer Poly1a/Bu4N+H2PO4# mixture.

(v) Addition of TFA to the mixture of Poly1a/Bu4N+H2PO4#. (b) A multiple and reversible

emission response of Poly1a to

H2PO4#………………….………………………………………………………………………113

Figure 4.03 (a) Fluorescence response of polymer Poly1a to Bu4N+H2PO4#. (b) Linear Hill plot

associated with the interactions between polymer Poly1a and Bu4N+H2PO4#…………………114

Figure 4.04 Concentration dependence of the fluorescence response and degree of cooperativity

of squaramide-based receptors with different number of repeat units to Bu4N+H2PO4#……….115

Figure 4.05 (a) Normalized fluorescence response (I/I0) of polymer Poly1a (black bars) and model compound (grey bars) to anions X# (b) Normalized fluorescence response (I/I0) of polymer Poly1a to divalent and multivalent anions Xn#………………………………………..117 Figure 4.06 (a) Fluorescence response (I/I0) of polymer Poly1a to Bu4N+H2PO4# in 20% H2O/NMP mixture. (b) Linear Hill plot associated with the interactions between Poly1a and Bu4N+H2PO4# in 20 % H2O/NMP mixture……………………………………………………...118 Figure 4.07 (a) Autocorrelation functions and (b) normalized CONTIN plots from DLS measurements at 90° of polysquramide Poly1a (2.4 % 10#5 M): in the absence (red ) and the presence (blue ) of Bu4N+H2PO4# (2.4 % 10#3 M) in DMF…………………………119 Figure 4.08 (a) Autocorrelation functions on Poly1a at different times. (b) Effect of F# and HSO4# on the self-assembly process…………………………………………………………....120 Figure 4.09 (a) TEM image of dried films of different polysquaramide Poly1a and Bu4N+H2PO4#

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(sample was cast from a DMF solution of Poly1a (2.4 % 10#5 M) and Bu4N+H2PO4# (2.4 % 10#3 M). Spherical polymer aggregates are clearly visible. The lacy pattern is the copper framework of the carbon-coated copper TEM gird. (b) A laser confocal microscopy image of a solution of Poly1a in DMF (2.4 % 10#5 M) in the presence of Bu4N+H2PO4# (2.4 % 10#3 M)………...……121 Figure 4.10 calculated structures (B3LYP/6-31G(d)) of bis(fluorenyl)squaramides in the (a) absence and (b) presence of dihydrogenphosphate anion………………………………………124 Figure 4.11 Absorption and emission spectra of different polysquaramides and the model compound 3.28 in the presence of Bu4N+H2PO4# in NMP/H2O mixture………………………125 Figure 4.12 (a) Solvent dependent emission spectra of Poly2 upon addition of water in pure NMP. (b) Emission spectra of structurally different polysquaramides in pure NMP……….….126 Figure 4.13 a) Magnitude of fluorescence response (b) Nature of fluorescence response of structurally different squaramide-based receptors to Bu4N+H2PO4#………………………..….126 Figure 4.14 Normalized fluorescence response (I/I0) of structurally different polymers to anions X#……………………………………………………………………………………………….127 Figure 4.15 (a) Hydrodynamic radii and polydispersity indexes of different polysquaramide aggregates in the presence of H2PO4#. (b) Normalized CONTIN plots from DLS measurements at 90 ° on different polysquaramides (2.4 % 10 #5 ) in the presence of Bu4N+H2PO4# (2.4 % 10#3 M) in DMF. Autocorrelation functions of different polysqsuaramides (2.4 % 10#5 M): (c) Poly3, (d) Poly4 in the absence (red ) and the presence (blue ) of Bu4N+H2PO4#. (e) Effect of Bu4N+H2PO4# on the self-assembly process…………………………………………129 Figure 4.16 TEM image of dried films of different polysquaramides ((a) Poly2, (b) Poly3, and (c) Poly4) and Bu4N+H2PO4# (sample was cast from a DMF solution of different polysquaramides (2.4 % 10#5 M) and Bu4N+H2PO4# (2.4 % 10#3 M). Spherical polymer aggregates are clearly visible. The lacy pattern is the copper framework of the carbon-coated copper TEM gird.

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List of Appendices

Appendix I A. Gas-phase acidity caculations………………………………………………..…136

Appendix I B. Calculations of the urea-DMSO and squaramide-DMSO hydrogen-bonded

complexes………………………………………………………………………………………140

Appendix II X-Ray diffraction data of compound 2.37…...........................................................143

Appendix II X-Ray diffraction data of compound 2.20b….........................................................155

Appendix II X-Ray diffraction data of compound 2.20…..........................................................167

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List of Abbreviations

ADP Adenosine diphosphate

AMP Adenosine monophosphate

Anal. Elemental analysis

app Apparent

aq Aqueous

Ar Aryl

ATP Adenosine triphosphate

ATR Attenuated total reflectance

Bn Benzyl

brs Broad singlet

Bu Butyl

Calcd Calculated

CD Circular dichroism

13C NMR Carbon nuclear magnetic resonance spectroscopy

Conc Concentrated

DCPDP Dicyanomethylene-4H-pyran diamino pyridine

dd Doublet of doublets

ddd Doublet of doublets of doublets

DFT Density functional theory

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DLS Dynamic light scattering

DMA N,N-Dimethylacetamide

DME 1,2-Dimethoxyethane

DMF N,N-Dimethylformamide

DMSO Dimethyl sulfoxide

DNA Deoxyribonucleic acid

DPQ dipyrrolyl quinoxaline

EI Electron impact

ESI Electrospray ionization

ESIPT excited-state intramolecular proton transfer

Et Ethyl

!ex Excitation wavelength

FTIR Fourier-transform infrared

GPC Gel permeation chromatography

HAADF High angle annular dark field

HBO 2,5-bis(benzoxazol-2’-yl)benzene-1,4-diol

HEMA 2-hydroxyethyl methacrylate

HMPA Hexamethyl phosphoramide

HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid)

1H NMR Proton nuclear magnetic resonance spectroscopy

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HOMO Highest Occupied Molecular Orbital

HPLC High performance liquid chromatography

hr Hour/hours

HRMS High-resolution mass spectrometry

ICT Intramolecular charge transfer

IPC Isophthaloyl dichloride

ICP-MS Inductively coupled plasma mass spectrometry

IR Infrared spectroscopy

KSV Stern-Volmer constant

LA Lewis acid

LUMO Lowest Unoccupied Molecular Orbital

m Multiplet

Me Methyl

mg Milligrams

min Minute/minutes

mL Milliliters

mmol Millimoles

m.p. Metlting point

MPD m-Phenylenediamine

nm Nanometer

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NMP N-Methyl-2-pyrrolidone

ODA 3,4’-Diaminodiphenyl ether

ORTEP Oak Ridge Thermal-Ellipsoid Plot

PDI Polydispersity index

Ph Phenyl

Pi Inorganic phosphate

PMPI Poly(m-phenylene isophthalamide)

PPBA Poly(p-benzamide)

PPD p-Phenylenediamine

PPi Pyrophosphate

ppm Parts per million

PPPT Poly(p-phenylene terephthalamide)

Py Pyridine

q Quartet

R Generic alkyl groups

Rf Retention factor (in chromatography)

Rh Hydrodynamic radii

RAFT Reversible addition fragmentation chain transfer polymerization

rt Room temperature

s Singlet

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SDBS Sodium dodecyl benzene sulfonic acid

SDP Sodium dodecyl phosphate

SDS Sodium dodecyl sulfate

SDX Sodium dodecyl carboxylate

STEM Scanning transmission electron microscopy

t Triplet

Td Decomposition temperature

TEM Transmission electron microscopy

TFA Trifluoroacetic acid

TGA Thermal gravimetric analysis

THF Tetrahydrofuran

TLC Thin layer chromatography

TPC Terephthaloyl dichloride

TPP Triphenylphosphite

UV/vis Ultraviolet–visible spectroscopy

Chapter 1 Polymers for anion recognition and sensing*

1.1 Introduction Molecules capable of the selective recognition and sensing of anions represent an intriguing class

of targets, with implications in medical diagnostics, environmental monitoring and remediation,

and the discovery of biological probes or potential therapeutic agents. It is assumed that anions

are engaged in 70 % of all enzymatic processes. They are ubiquitous in the environment from

farming to heavy industries and are often hazardous pollutants: phosphates found in agricultural

fertilizers and nerve agents, fluoride is the byproduct of sarin gas, sulfate is directly related to

nuclear-waste remediation and acid rain, and cyanide that is extremely toxic to mammals is

common in gold mining and metallurgy.1, 2

Anions present unique challenges for molecular recognition: they are characterized by diverse

geometries, charge distributions and sizes, and their high enthalpies of hydration present a

significant obstacle to developing receptors able to function in aqueous medium. The range of

potential applications and the challenging nature of the problem have motivated intensive

research efforts in the area of anion recognition in recent years.3

The exceptional affinities and selectivities displayed by naturally occurring anion-binding

proteins serve as a source of inspiration for the development of synthetic systems. For example,

the crystal structure of a sulfate-binding protein indicates that anion binding is achieved without

the direct participation of positively charged moieties, through precisely positioned hydrogen-

bonding interactions between the sulfate anion and the NH groups of the protein backbone,

serine OH, or tryptophan NH groups.4 The principles of complementarity and preorganization

underlie the design of synthetic anion receptors and sensors able to interact with analytes through

hydrogen bonding, Lewis acid–base coordination, Coulombic interactions, and other noncovalent

contacts (anion–arene interactions and halogen bonding, for example).

* Part of this chapter has recently been published: Rostami, A.; Taylor, M. S. Macromol. Rapid Commun 2012, 33,

21!34

1

Research reported over the past few decades has identified a wide variety of functional groups

and molecular architectures for this purpose, and thermodynamic studies have provided insight

into the roles played by such factors as conformational rigidity and solvation. In several

instances, these discoveries have been exploited in the development of sensors for ‘real-life’

monitoring of analyte concentration in complex environments.5 Challenges remaining for the

field include the development of receptors capable of selective and high-affinity anion

recognition in water: in this regard, the performance of Nature’s anion-binding proteins remains

unparalleled by synthetic systems.

The development of anion-responsive polymeric systems has recently emerged as an exciting

direction for research in anion recognition. Macromolecules offer unique opportunities for

achieving sensitivity and selectivity by mechanisms that take advantage of their distinct

properties and behaviors;6 however, anion sensory materials have emerged slowly in comparison

to those for cation sensing.

In this chapter recent advances in polymer-based anion-responsive materials will be discussed,

with an emphasis on the wide structural diversity of polymers that can be employed for this

purpose, and the mechanisms of their anion-induced responses. Following an introduction to the

key concepts that form the basis of polymer-based chemical sensing schemes, the application of

these concepts to anion-responsive systems will be covered; the polymers are grouped according

to the nature of their interaction with anionic analytes (Lewis acid–base, Coulombic, hydrogen

bonding, etc.).

1.2 Polymer!based chemical sensors: general principles Polymers possess unique properties that can offer special advantages for the development of

analyte-responsive systems. Several classes of conjugated polymers display optoelectronic

properties that can be harnessed for signal transduction by electrochemical, colorimetric, or

fluorescence techniques; mechanisms for signal transduction include anion-induced changes in

polymer conformation that result in modulation of the effective conjugation length, or the

introduction or destruction of local traps, giving rise to fluorescence quenching or unquenching

events. The ability to process such materials into thin films or membranes facilitates their

integration into functional devices, and the repeating structures of polymers may give rise to

effects such as multivalency or cooperativity in the context of supramolecular interactions.

2

However, the most striking distinctions between small-molecule and polymeric chemical sensors

often arise from the ability of the latter to achieve signal amplification, giving rise to high levels

of sensitivity for the analyte of interest. The ability of fluorescent conjugated polymers to

function as amplifying chemical sensors was elucidated more than 15 years ago and the concept

forms the basis of several high-performance sensory materials for use in trace detection and

biosensing.6 Studies by Swager and Zhou of the fluorescence quenching-based response of

cyclophane-based poly(phenyleneethynylenes) to bis(pyridinium) ions demonstrated that the

incorporation of analyte-binding motifs gave rise to signal gain due to the ‘molecular wire effect’

(Figure 1.01).7 Control experiments using non-polymeric cyclophane receptor 1.01 indicated that

the polymeric system 1.02 exhibited a 65-fold enhancement of sensitivity (as measured by the

Stern–Volmer constants KSV for static quenching), resulting from the ability of excitons to

diffuse along the polymer chain and thus to ‘sample’ the occupancy of multiple analyte-binding

sites. Later studies (particularly in the context of the detection of ultra-trace concentrations of

trinitrotoluene and related nitroaromatics) revealed that harnessing inter- in addition to

intrapolymer exciton diffusion (for example, in thin films) provides a mechanism for increased

levels of signal amplification.8 The concepts emerging from this pioneering work have proved to

be remarkably general, and underlie the application of conjugated polymers for the detection of

diverse analytes in a wide variety of media.

Figure 1.01 Signal ‘gain’ in fluorescence quenching of conjugated polymers by a paraquat derivative.

C12H25O

O

O

O O O O

O O O O

OC12H25

ON

O NC8H17

C8H17

C8H17

C8H17

O

O

O O O O

O O O On

KSV = 1.63 ! 103 M-1

N N

Analyte = paraquat (PQ2+)

1.01

1.02 (Mn = 1.05 ! 105 g/mol)KSV = 1.05 ! 10 5 M"1

Sensitivity enhancement = KSV(1.02)/ KSV(1.01) = 65

3

1.3 Anion responsive polymers Several of the pioneering studies illustrating the ability of analytes to effect changes in the

conformation, bandgap, or aggregation behavior of polymers, and the results of these changes on

photophysical properties or conductivity, were conducted in the context of cation detection.9

Although many of the initially reported polymer-based sensors were designed for the detection

of cationic species, an expanding body of research carried out by several groups illustrates that

anionic analytes also represent interesting targets for these approaches. The wide structural

diversity of the polymers that have been discovered for anion recognition is described in the

following sections: anion-responsive polymers are grouped by structure and according to the

nature of the functional group that is proposed to interact with the anionic species. The principle

of signal amplification outlined in the previous section has played a key role in these efforts: a

number of interesting polymer backbones that enable the transduction of anion-binding events

into measurable signals have been devised. In addition, polymer-based phenomena other than the

‘molecular wire’ effect – including cooperativity and multivalency – have been brought to bear

on the problem of anion sensing. The increased sensitivity or affinity resulting from these effects

enables the application of polymers to solve challenging problems in anion recognition,

including developing sensors that function in aqueous environments.

1.3.1 Anion!responsive chemodosimeters

Although the majority of the anion-responsive polymers developed to date have been designed to

interact reversibly with their analytes (see below), anion-induced, irreversible covalent bond

formation or cleavage represents another viable detection method. An implementation of this

concept in the context of a polymeric anion sensor was reported by Kim and Swager, who

exploited the reactivity of fluoride toward Si–O bonds as a basis for the selective detection of

this anion (Figure 1.02).10 Reaction of polymer 1.04 with fluoride (Bu4N+F–, 1.6 x 10–7 M in

THF) triggered cleavage of the silyl ether group and cyclization to the corresponding coumarin

(Figure 1.02b), accompanied by a significant red-shift of the polymer emission spectrum.

Control experiments with an alkylidenemalonate not appended to a poly(phenyleneethynylene)

indicated that the degree of amplification resulting from exciton migration to the newly

generated fluorophore was approximately 100-fold.

4

Figure 1.02 (a) Anion-induced desilylation/cyclization as the basis for fluoride detection; (b) A polymeric chemodosimeter for fluoride.

1.3.2 Lewis acid–base interactions: organoboron, organosilicon, and metal cation-containing anion-responsive polymers

Diverse strategies for incorporating Lewis acidic main group or metal-based functional groups

into stimulus-responsive polymers have been developed. These include applications of boron-

and silicon-based polymers, as well as materials that incorporate metal cations.

Organoboron-based polymers display interesting optoelectronic properties when the empty

boron-based p orbitals contribute to the conjugated ! system of the polymer backbone.11 The

occupancy of the boron-based p orbital may have a significant influence on the effective

conjugation length, providing a mechanism for transducing anion-binding events into measurable

signals. A pioneering application of anion sensing by organoboron-based conjugated polymers

was reported by Chujo and co-workers:12 A hydroboration polymerization methodology was

used for the synthesis of the polymer containing a tricoordinate aryl borane functionality.

Addition of fluoride ion to a solution of poly(vinylenephenylenevinylene borane) polymer 1.05

in chloroform led to a hypsochromic shift of the UV-vis absorption maximum, resulting in

change in color of the solution from yellow to colorless. This behavior was interpreted as

O

CO2Et

CO2Et

Si(tBu)(CH3)2NH3CH2C

CH2CH3NH3CH2C

CH2CH3O

CO2Et

O

F-

(a)

(b)

C12H25O OC12H25

H3C

S

CO2Et

CO2Et

n

O

F-C12H25O OC12H25

H3C

S

CO2Et

n

O

O

Si(iPr)3

1.04

1.03

Responsive to F! in THF

5

involving coordination of fluoride to the Lewis acidic boron moiety. This polymer displayed a

fluorescence quenching response to fluoride anion in chloroform solvent. The response was

selective for fluoride over the other halide anions such as Cl!, Br!, and I!, and the observation of

complete quenching upon addition of 0.5 equivalents of n-Bu4N+F– (~ 10–6 M in CHCl3)

indicated some degree of signal amplification relative to a non-polymeric borane species.

Figure 1.03 Representative anion-responsive organoboron polymers.

B

n

B

CN

x y

x / y = 9

B

i-Pr

i-Pri-PrHex Hex

n

i-Pri-Pr

i-Pr

1.05Responsive to n-Bu4+F! in CHCl3 1.06

Responsive to n-Bu4+F! / CN! / I! in THF

1.07Responsive to n-Bu4+F! / CN! in THF

B B

Tip

Hex Hex

Tip

n

Hex Hex

n-1

BHB

Tip

Hex Hex

n

Hex Hex

n-1 Tip

[nBu4N]+CN!

B B

Hex Hex

n

Hex Hex

n-1 TipTip

CN CN

CN

Titration of 1.07 with n-Bu4+CN! in THF

[nBu4N]+CN!

(c)

(b)(a)

(d)

6

Figure 1.03 Representative anion-responsive organoboron polymers.

In recent years, several novel anion-responsive polymers bearing Lewis acidic borane functional

groups have been developed.13 A random conjugated dialkylfluorene/dibenzoborole copolymer

was reported by Bonifácio and coworkers.13b In this conjugated polymer the dibenzoborole

moiety was electronically stabilized by incorporation of a cyano group in the para-position of the

9-phenyl substituent, which increased the environmental stability of the polymer. The polymer

was prepared utilizing Yamamoto-type aryl-aryl coupling with a 9:1 molar ratio of the co-

monomers, and displayed a fluorescence quenching-based response to F–, CN– and I– (n-Bu4N+

counterion, THF solvent), both in solution and in thin films: fluoride concentrations as low as 0.1

mM could be detected using a spin-coated film of the polymer. Upon addition of fluoride and

cyanide to a solution of the polymer 1.06, defined anionic complexes were formed with the

boron, the formation of which were manifested by characteristic isosbestic points at 490 nm (for

F!) and 510 nm (for CN!) and a blue shift in absorption maximum. Incomplete fluorescence

quenching upon fluoride and cyanide addition was reasoned in terms of static quenching

mechanism, whereas complete quenching with iodide was attributed to the collisional-quenching

mechanism. The Stern-Volmer quenching constant (KSV) was much higher for iodide (Kiodide =

23.2 " 106) than fluoride (Kfluoride= 0.49 " 106) and cyanide (Kcyanide= 4.78 " 106).

B

SS

Hex

n

BO

O S S

OO

OOSi

Si

O

OB

SS

OO

OO

n

1.08Responsive to n-Bu4+F! / CN! in THF

1.09Responsive to amines and Bu4+F! in THF

(e) (f)

N B B

Hex Hex

n

i-Pr

i-Pr

i-Pr

i-Pri-Pr i-Pr

1.10Responsive to n-Bu4+F! / CN! in THF

(g)

7

Jäkle and co-workers developed efficient transmetallation-based protocols for the synthesis of

fluorene-based organoborane polymers, in which bulky mesityl or tris(isopropyl)phenyl groups

provide steric protection from air oxidation.13c Polymer 1.07 showed selective colorimetric and

fluorescence responses to fluoride and cyanide anions in tetrahydrofuran solvent, but were non-

responsive to larger, less basic anions (Cl–, Br–). A two-step binding process was inferred from

the nature of the spectral changes: initial binding (up to ~ 0.5 equivalents of anion) was proposed

to occur at alternating boron sites, resulting in a red-shifted emission maximum consistent with

charge-transfer between adjacent tetracoordinate (electron-rich) and tricoordinate (electron-

deficient) moieties (Figure 1.03d).

Another report from the same group described an emissive donor-#-acceptor polymer with

alternating electron deficient bifunctional triarylborane and electron rich triphenylamine

moieties.11e Addition of an excess amount of fluoride or cyanide to a solution of polymer 1.10 in

THF led to a red shift in the absorption maximum, concomitant with a quench in the emission

band at 459 nm and formation of a weak blue-shifted emission band. The polymer was not

responsive to other anions such as chloride, bromide, and nitrate, suggesting the absence of

coordination of these larger anions. A two-step binding mechanism, similar to that described for

polymer 1.07 was proposed for this polymer (Figure 1.03g)

Although incorporation of the boron-based p orbital into the main chain of a !-conjugated

system has been identified as a useful design principle, a number of anion-responsive boron-

containing materials that do not benefit from this type of conjugation have been developed.14 For

example, functionalization of polystyrene with thiophene-substituted arylboranes was achieved

through a series of organometallic transformations of poly(4-trimethylsilylstyrene).13a The

presence of the tricoordinate boron functionality in the pendent group provided an opportunity

for the recognition of anions. Changes in the absorbance and emission spectra of the resulting

materials signaled the presence of tetrabutylammonium fluoride and cyanide in THF solvent.

Upon addition of fluoride to a solution of polymer 1.08, a gradual decrease in absorption

intensity at 378 nm followed by the formation of a new band at 338 nm was evident by UV-vis

spectroscopy. These changes were assigned to the formation of bithiophene groups with a

tetracoordinated boron moiety. Based on the absorption and emission spectra, it was clear that

fluoride and cyanide bind tightly to the boron polymers where as other anions revealed no major

response. Stern–Volmer quenching constants indicated roughly 8-fold signal amplification for

8

polymer 1.08 relative to a non-polymeric model compound: intrapolymer exciton migration was

proposed as a mechanism for this effect (Figure 1.03e).

The borasiloxane-based polythiophenes synthesized via electropolymerization by Lee and co-

workers are another structurally distinct class of organoboron polymers that have been employed

for chemical sensing. The axial open coordination sites of the boron serves as the recognition

sites for anion binding.13d Red shifts of the absorption and emission spectra of polymer 1.10

relative to model compounds were consistent with some degree of through-space electronic

communication through the borasiloxane cages. Although detection of amine vapors was pursued

as the major sensory application of 1.10, a film of the polymer on an indium tin oxide-coated

glass electrode displayed a green-to-orange colorimetric response to Bu4N+F– in THF solvent

(Figure 1.03f).

Polysilanes display interesting optoelectronic properties that result from the delocalization of "-

conjugated electrons along the polymer backbone. This feature, combined with the high fluoride

affinity of many organosilicon compounds, has been exploited in anion recognition by Fujiki and

co-workers.15 Fluoroalkylated polysilane 1.11, synthesized by the sodium-mediated coupling

reaction of 3,3,3-trifluoropropylmethyldichlorosilane in octane (Figure 1.04), adapted a rodlike

conformation stabilized by weak Si...F-C interactions between the trifluoropropyl side-chains and

the silicon moieties at the main chain. This polymer displayed a sensitive fluorescence

quenching-based response to nanomolar concentrations of fluoride anion (n-Bu4N+ counterion,

THF solvent), with a Stern–Volmer quenching constant of 1.35 " 107 M–1 indicating significant

levels of amplification due to exciton migration in this system. The polymer displayed a high

level of selectivity for fluoride, and was unresponsive to other anions such as bromide and

chloride. The structure of 1.11 was tuned to enhance the fluoride affinity of the polysilane

backbone: replacement of the electron-withdrawing fluoroalkyl groups by nonfluorinated

moieties resulted in a loss of sensitivity of more than three orders of magnitude, while replacing

the methyl substituents with more sterically encumbered alkyl groups led to a loss of the

fluorescence response.

9

Figure 1.04 Structure of an anion-responsive, fluorescent poly(silane).

As alluded to above, metal cations have been pursued for more than a decade as targets of

polymer-based chemical sensors. The polymers obtained upon cation binding may be viewed as

potential anion-responsive hybrid materials, in which interactions between the analyte and

polymer-bound metal ion result in alterations of the optoelectronic properties of the polymer. A

sensory scheme of this type was reduced to practice by Schanze and co-workers, who employed

carboxylate-functionalized poly(phenyleneethynylene) 1.12 as an amplifying fluorescent

indicator (Figure 1.05).16 The conjugated polyelectrolyte was shown to interact strongly with

Cu2+ ions, resulting in a fluorescence quenching response with a KSV of approximately 106 M–1 in

aqueous HEPES buffer. Titration of the polymer–Cu2+ adduct with pyrophosphate (PPi) anion

resulted in a recovery of fluorescence (30-fold enhancement in the presence of 20 mM PPi): an

analytical detection limit of 80 nM was estimated. The system was shown to be selective for

pyrophosphate over other monovalent and divalent anions (F–, Cl–, Br–, I–, HSO4–, NO3–, HCO3–,

H2PO4–, CH3CO2–, SO42–, CO32–, HPO42–), and a control experiment with the metal chelator

EDTA provided support for a mechanistic hypothesis involving sequestration of Cu2+ by the PPi

anion. The system was employed in a real-time assay of the activity of an alkaline phosphatase

enzyme. Bunz, Rotello and co-workers described another efficient sensor for pyrophosphate

based on a carboxylate-functionalized PPE: in their study, interaction of the anion PPE with 10

nm cobalt–iron spinel nanoparticles resulted in quenching of the polymer fluorescence.17

Addition of pyrophosphate to the polymer–nanoparticle adduct effected a fluorescence recovery

10

that enabled the detection of PPi at high nanomolar concentrations, even in the presence of

relatively high concentrations (0.1 mM) of phosphate anion.

Figure 1.05 Turn-on fluorescence response of an anionic PPE–Cu2+ adduct to pyrophosphate

A number of related systems involving anion-induced ‘unquenching’ of metal-bound fluorescent

polymers have been developed: Li and coworkers described the synthesis of light emitting

polyacetylene containing imidazole moieties through a post functionalization strategy.18 The blue

fluorescence of polyacetylene 1.13 was quenched in the presence of Cu 2+ ions, while in the

absence of the imidazole moieties, no change was observed in the emission behavior of the

polymer. Addition of a solution of CN! (7.0 " 10!5 M) led to emission recovery of the

completely quenched polymer: cyanide ion has more affinity towards Cu2+ than imidazole, as

reflected by the high stability constant of the complex of CN! and Cu2+. The alteration of the

interaction between Cu2+ and imidazole by cyanide ion leads to the recovery of the emission.

Other anions were not able to recover the quenched emission except for H2PO4- and PO43-, which

caused a slight increase in fluorescence intensity. Polymer 1.13 was able to detect cyanide in the

solid state by first dipping the film into an aqueous solution of Cu2+ and subsequently to a

solution of CN!.

O

On

Cu2+

PPi

OO

OO

O

On

OO

O

On

OO

OO

Cu2+

OO

P

P

O

O

O

O

O

Cu2+

Responsive to P2O72! in HEPES buffer

1.12

emissive (ON) non-emissive (OFF)

O

O

11

Figure 1.06 Turn-on fluorescence response of imidazole-functionalized polyacetylene!Cu22+ adduct to cyanide ion

In a separate report, Li described a blue emissive imidazole-functionalized polyfluorene

derivative as a fluorescence probe for cyanide ion utilizing Lewis acid-anion coordination

chemistry through turn-off-turn-on cycle (figure 1.07).19 Addition of aliquots of aqueous solution

of Cu2+ ions (3.0 " 10!8 M) to a dilute solution of polymer 1.14 led to a rapid quenching of the

emission with a Stern-Volmer quenching constant (KSV) of 2.1 " 106 M!1 and recovery of the

initial emission intensity in the presence of CN! (1.2 " 10!5 M!1). The present polyfluorene metal

ion chemosensor showed an improved sensitivity (12 µM) towards CN! compared to the

previous work by the same group on the imidazole-functionalized polyacetylene (70 µM).

Figure 1.07 Turn-on fluorescence response of imidazole-functionalized polyfluorene!Cu22+ adduct to cyanide ion

Recently Iyer reported a neutral copolymer polyfluorene-alt-1,4-phenylene derivative containing

the benzimidazole moiety as the pendant group and Fe3+ for the detection of phosphates

(H2PO4!, HPO42!).20 Polymer 1.15 was synthesized by Suzuki cross coupling of dibrominated

fluorene and 4-phenylbronic acid in 80% yield. Addition of aqueous solution of Fe3+ metal salts

(chloride and perchlorate) induced fluorescence quenching of the copolymer with a 97%

emissive (ON)

C C C(CH2)3

C(CH2)3NCl

N

x yx = 0.36y = 0.64

N

N

N

N

Cu2+N

N

N

N

N

N

N

N

CN-

Cu2+[Cu(CN)x]n-

emissive (ON) non-emissive (OFF)

1.13

N

C6H13 C6H13

n

N

N

N

C6H13 C6H13

n

N

N

N

C6H13 C6H13

n

N

N

Cu2+ CN-

[Cu(CN)x]n-

emissive (ON) non-emissive (OFF) emissive (ON)

Cu2+

1.14

12

decrease in fluorescence intensity, reflecting the strong affinity of the benzimidazole moiety

towrds Fe3+. The polymer showed a Stern-Volmer quenching constant (KSV) of 7.8 " 105 M!1 and

a detection limit of 3.38 " 10!6 M. A recovery of both emission and absorption spectra were

accomplished after addition of phosphates (H2PO4!, HPO42!) to a quenched solution of polymer

suggesting that phosphate anions were able to displace Fe3+ from the benzimidazole moiety. The

polymer-Fe3 assay was further applied for the detection of phosphate (1.44 mmol/L) in saliva.

Figure 1.08 Benzimidazole-functionalized polyfluorene metal-binding polymer for phosphate and pyrophosphate detection

Recently, the groups of Tian and Zhu reported that a hydrophilic copolymer containing

dicyanomethylene-4H-pyran moiety display a turn-on fluorescence response towards

pyrophosphate anion (P2O74-) both in solution and in thin film.21 The copolymer (HEMA-co-

DCPDP) 1.16 was prepared by free-radical copolymerization of DCPDP functionalized 2-

hydroxyethyl methacrylate. Treatment of the polymer with a solution of Cu(ClO4)2 in methanol

provided a polymer-metal complex as the anion sensory material. An intramolecular charge

transfer (ICT) process was expected due to its donor-#-acceptor (D-#-A) structure. In the

DCPDP moiety, the diaminopyridine groups act as electron-donating substituents whose donor

ability depends on cation coordination. Addition of Cu2+ to a solution of the polymer led to a

decrease in fluorescence intensity (KSV = 1.42 " 105 M-1), and a hypochromic shift in the

absorption spectra was consistent with the coordination of diaminopyridine groups to the Cu2+,

thus reducing the electron donor ability of the amino groups in the ICT process. Addition of a

solution of pyrophosphate anion to the ensemble of polymer-Cu2+ complex recovered the

fluorescence enenhancement (I/I0 = 4.8). The selectivity of the system towards different anions

was evaluated and it was found other anions such as F!, Cl!, Br!, I!, H2PO4!, HSO4!, HCO3!,

NN

NN

n1.15

Responsive to phosphates in THF/water mixture

13

NO3!, SO42!, CO32!, CH3COO!, ADP, ATP and AMP showed almost no interference except for

the little influence of PO43!. The association constant of the polymer-Cu2+ complex was found to

be 3.1 " 104 M!1 by fluorometric titration curve. The emission enhancement was related to the

electrostatic interaction between pyrophosphate and Cu2+ in polymer-copper complex, in which

pyrophosphate two oxygen atoms coordinate to the Cu2+ reducing its electron withdrawing by

partial charge neutralization. A spin-coated thin film of copolymer-Cu2+ showed a turn-on

response in the presence of a solution of pyrophosphate at 590 nm with a slight bathochromic

shift.

Figure 1.09 Turn-on fluorescence response of DCPDP!functionalized poly hydroxyethyl methacrylate!Cu22+ adduct to pyrophosphate ion

In each of the systems described above, the reversibility of the anion-binding process has not

been demonstrated, and it may be that the polymer–metal anion adducts act as dosimeters rather

than sensors. Nonetheless, the versatility of this general approach, in which both the functional

group interacting with the metal ion and the identity of the metal itself may be tuned, are

apparent from the range of anionic analytes that have been successfully targeted in the

applications reported to date.

OON

Ox y

OH N

O

NN

N

NC

CN

OON

Ox y

OH N

O

NN

N

NC

CN

PPi

OON

Ox y

OH N

O

NN

N

NC

CN

Cu2+

Cu2+

emissive (ON) non-emissive (OFF) emissive (ON)

1.16

Cu2 +

P

PO

O

OO

OOO

14

1.3.3 Ion-pairing interactions: anion recognition by cationic polyelectrolytes

Taking advantage of ion-pairing interactions through the use of cationic receptors has been a key

design principle for achieving anion recognition in competitive (aqueous) medium. Indeed, the

majority of ‘small-molecule’ anion receptors that function in water are positively charged

species.22 Likewise, polymers bearing cationic substituents represent interesting candidates for

use as anion-responsive macromolecules. Although sensory applications of cationic

polyelectrolyes have generally been targeted toward DNA, a number of examples illustrate the

utility of such macromolecules in high-affinity detection of mono- or divalent anions in aqueous

medium.

One of the earliest reports of an anion-responsive organic polymer is the work of Tour and co-

workers, who observed that planar conjugated polypyrrole zwitterionic polymer 1.17 displayed a

near-IR colorimetric response to alkali metal iodide salts in methanol solvent.23 The polymer (Mn

= 4980, PDI = 1.54) was synthesized by copper-bronze-promoted polymerization process

coupling reaction of a diiodo pyrrole derivative in DME. A low iodine-doped conductivity of 4.2

" 10!4 $!1 cm!1 was observed. The presence of the carbonyl functionality in the polymer

backbone was proposed to inhibit polaronic/bipolaronic migrations. Dropwise addition of

aqueous NaOH (0.05 M) to a solution of polymer in THF showed a reversible pH-dependent

shift in the absorption spectra with a decrease in absorption maximum (#max = 512 nm) and

formation of a new band at higher wavelength (#max = 881 nm) with a color change from red to

pale orange. This large change in the absorption maximum to the near-IR region was assigned to

the Brønsted base-induced planarization of the conjugated system, and increased delocalization

of the #-electrons. Control experiments indicated that cation binding to the triethylene glycol

moieties was required for the iodochromic response, and that the nucleophilicity of the halide

anion also played an important role. The results were interpreted in terms of a cation-assisted

nucleophilic attack of iodide on the carbonyl ylide functional groups.

More recently, the group of Leclerc has developed a cationic, water-soluble imidazolium-bearing

polythiophene derivative 1.18a that displays highly selective colorimetric and fluorescence

responses to iodide anion in deionized water.24 This polymer was prepared by oxidative

polymerization of an imidazolium-substituted thiophene in chloroform. The red shift of the

15

maximum absorption from its original wavelength towards lower energy values became more

significant upon addition of NaI to the cationic polymer solution and a color change from yellow

to red-violet was observed. This red shift of the absorption spectrum was accompanied by a

significant decrease in emission intensity upon addition of iodide (concentrations as low as 2 x

10–6 M). The absorption spectrum of the polymer in the presence of aqueous NaI was similar to

that of the polymer alone in the solid state, suggesting an anion-induced aggregation mechanism,

whereby iodide induces changes in polymer conformation from a random-coil (yellow emissive)

to planar and aggregated form (quenched).

Figure 1.10 Conjugated polypyrrole zwitterionic polymer responsive to alkali metal iodide salts

The polymer was not responsive towards other anions such as SO42!, CO32!, HCO3!, H2PO4!,

and CH3COO!. Noteworthy aspects of this system include its high selectivity for iodide, its

ability to function in pure aqueous medium, and the dependence of the sensory properties on

subtle structural features of the polymer (for example, polythiophene 1.18b was considerably

less sensitive toward iodide than 1.18a).

N

N

N

NOO O

OO

O

OO

O

O

O

O

O

O

O O

O

O

O

O

n/4 N

N

N

NOO O

OO

O

OO

O

O

O

O

O

O

O O

O

O

O

O

n/4

I!

visible absorption near-IR absorption

Responsive to KI in methanol

1.17

I

K+

K+

K+

K+

16

Figure 1.11 Anion-responsive cationic polymers.

Another example of anion detection by an imidazolium-functionalized conjugated polymer was

reported recently by Lee, Yoon and co-workers, who described applications of polydiacetylene

1.19 for the detection of anionic surfactants in aqueous medium.25 The polymer was synthesized

by UV irradiation of suspensions of highly ordered self-assembled imidazolium functionalized

diacetylene and showed a good film forming property due to double hydrogen bonding and

aromatic interactions involved between imidazolium rings. Surfactants are applied extensively

in a variety of industrial settings and are of concern as environmental pollutants. The

imidazolium-bearing poly(diacetylene) displayed a colorimetric response, accompanied by an

increase in emission intensity, upon addition of anionic surfactants such as sodium dodecyl

sulfate (SDS, at concentrations as low as 2 x 10–7 M), sodium dodecyl carboxylate (SDX),

sodium dodceyl phosphate (SDP) and sodium dodecylbenzenesulfonic acid (SDBS) in aqueous

HEPES buffer. The system was selective for anionic surfactants, showing no response to other

anionic species, neutral or cationic surfactants; furthermore, the four anionic surfactants elicited

three different color changes that enabled the differentiation of SDS, SDC/SDP and SDBS: SDS

induced a blue-to-yellow transition, SDC and SDP induced a blue-to-orange transition, and

SDBS produced a blue-to-red transition. Addition of SDS to 10 µM of polymer induced a

S

OH3C (CH2)3 N

NCH3

H3C Cl!

n

1.18a (m = 3), 1.18b (m = 2)

Responsive to NaI in water

C12H21 C12H21 C12H21 C12H21

N

N

N

N

N

N

N

N

n

O O O O

N N N N

H H HH

Responsive to anionic surfactantssuch as SDS in aqueous buffer

1.19

O

O

HNO

NHO

NH3Cl!

NH3Cl!H3NCl!

NH3Cl!

H3N

H3NCl!

Cl!

n

Responsive to pyrophosphatein aqueous MES buffer

1.20

17

decrease in absorption at 620 nm with a concomitant increase at 490 nm and 523 nm. The

fluorescence spectrum of polymer 1.19 showed a 34-fold increase in emission intensity at 565

nm when 4 µM SDS was added to a 10 µM solution of the polymer. The detection limit of the

polymer for SDS was estimated to be 2 " 10!7 M (56 ppb) and similar changes were observed for

the other anionic surfactants. The polymer–surfactant complexation was formulated as

involving ion-pairing interactions between the surfactant head groups and the imidazolium

moieties, as well as contacts between the hydrocarbon regions of the surfactant and polymer,

driven by the hydrophobic effect. Computational studies indicated that binding of this type

could result in distortion of the polydiacetylene !-system in a manner consistent with the

observed spectroscopic changes.

Ammonium-functionalized, conjugated polyelectrolyte 1.20 was employed as a selective,

ratiometric fluorescence-based sensor for pyrophosphate anion in 2-(N-morpolino)ethanesulfonic

acid (MES)-buffered aqueous solution by Schanze and co-workers.26 The polymer was prepared

by Sonogashira polymerization of a diiodobenzene derivative with branched polyamine side

chains and 1,4-diethynylbenzene. The water-soluble polymer was obtained after deprotection

under acidic conditions (4 M HCl). Addition of PPi at pH 6.5 triggered a red-shift in the

absorbance spectrum of the polymer from its original place related to the conversion between the

“ free chain state” and the “aggregate state” of the polymer chains. This spectral change was

parallel with the decrease of a fluorescence emission band at 435 nm and simultaneous increase

of emission intensity at 530 nm; both effects were suitable for determination of PPi concentration

(with a detection limit of approximately 340 nM) using a convenient and robust ratiometric

format. The spectral changes were consistent with backbone planarization and enhanced

interpolymer exciton coupling arising from anion-induced polymer aggregation. The polymer

was insensitive towards halide ions, carbonate, and sulfate, while biologically important anions

such as adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine

triphosphate (ATP) did somewhat interfere with the emission response.

The observed selectivity toward PPi over other inorganic anions such as phosphate was

interpreted as arising from the unique ability of pyrophosphate to cross-link polymer chains,

giving rise to polymer aggregation. In this regard, similarities may be drawn between this system

and the behavior of pyridinium-based polymers, which have been reported to undergo selective,

18

anion-induced self-assembly into micellar aggregates (without an associated fluorescence

response).27

1.3.4 Polymers bearing hydrogen bond-donor groups

The strength and directionality of hydrogen bonding interactions, combined with the ability to

incorporate hydrogen bond donor groups into a range of preorganized scaffolds, have contributed

to the extensive development of anion receptors based on these interactions. Likewise, diverse

approaches for incorporating hydrogen bond donor groups into polymeric scaffolds have been

investigated for the purpose of anion recognition. The polymeric nature of these receptors gives

rise to unique effects, including signal amplification, cooperative binding, and enhanced

selectivity.

Several fluorescent polymers functionalized with acidic OH groups have been found to act as

sensitive materials for anion detection (Figure 1.12). For example, polyquinoline 1.21 was

studied by Wang and co-workers as a fluorescent chemosensor for Bu4N+F– in DMSO solvent.28

The polymer was synthesized by a nickel(0)-catalyzed coupling reaction / deprotection sequence

(Mn = 6000, Mw/Mn = 1.15). A fluoride-induced red-shifted absorption peak at 500 nm and a

color change from colorless to red were accompanied by formation of a new feature in the

emission spectrum at 620 nm. The increased acidity of the phenolic proton due to the strong

electron withdrawing ability of the quinoline moiety resulted in deprotonation of the OH acidic

proton by strong bases such as fluoride, and subsequent development of an intramolecular charge

transfer (ICT) between the phenolate anion and the quinoline moiety. The response was selective

for F– over less basic anions (Cl–, Br–), and only a minimal response toward

dihydrogenphosphate anion was observed. Comparison with a non-polymeric hydroxyquinoline

revealed that the polymer displayed enhanced sensitivity to 100 equivalents of fluoride (147-fold

enhancement, compared to 17-fold for the model compound in DMSO), as well as an improved

F–/H2PO4– selectivity in comparison to its non-polymeric analog. The higher selectivity of the

polymer compared to the small molecule model compound was attributed to the coil structure of

the polymer in which penetration of smaller anions such as fluoride is more facile.

19

Figure 1.12 Fluorescent, polymeric anion sensors based on acidic OH groups.

Another report from the same group demonstrated a series of polyphenylenes composed of

phenol-substituted oxadiazole moieties as fluorescent chemosensors for fluoride ion.29 The

copolymer 1.22 was synthesized by Suzuki copolymerization of phenol-substituted oxadiazole

monomers with 2,5-dibutoxy-1,4-phenylenediboronic acid and 2,7-dibromo-9,9-dioctylfluorene.

Addition of anions such as F! and H2PO4! (10 !3 M) to a solution of polymer (5 µM in

chloroform) led to fluorescence quenching with Stern-Volmer constants of KSV (F!) = 7.1 " 105

and KSV (H2PO4!) = 9.5 "104 and the formation of a longer-wavelength absorption band at 462

nm with a reduction of the main absorption band at 375 nm. Polymers containing two phenol

groups in each oxadiazole repeat unit exhibited higher sensitivities towards fluoride anion over

dihydrogen phosphate anion in comparison to those having only one phenolic group per repeat

unit. The polymer showed quenching up to 380 fold while a small molecule model compound

displayed only a 3-fold reduction of emission intensity, consistent with an amplification effect.

The polymer fluorescence lifetime was independent of fluoride anion concentration, suggesting a

static quenching process rather than a dynamic process. The polymer was unresponsive towards

other anions such as Cl!, Br!, I!, BF4!, PF6!, while H2PO4! only induced a 6-fold decrease in

emission intensity and a color change from colorless to yellow. The selectivity of the polymer

towards fluoride ion over dihydrogen phosphate ion was attributed to the coil conformation of

the polymer in solution, providing steric hindrance for larger anions such as H2PO4! to access the

hydroxyl group.

OC4H9

C4H9O

OC4H9

C4H9O C8H17 C8H17

x y

1.22Responsive to F! and H2PO4! in CHCl3

N

HO

Nn

1.21Responsive to F! in DMSO

OHN

N

O

OH

O

NHO

OHC6H13 C6H13

O

N n

1.23Responsive to F!, OH!, and AcO! in THF

20

Pang reported a fluorene #-conjugated polymer based chemosensor composed of 2,5-

bis(benzoxazol-2$-yl)benzene-1,4-diol (HBO) units synthesized by Suzuki-Miyaura cross

coupling reaction.30 The absorption spectrum of polymer 1.23 showed bands at 332, 400, and

421 nm while the emission spectrum showed a peak at 616 nm with a large Stokes shift (~200

nm), assigned to excited-state intramolecular proton transfer (ESIPT) in the bis(HBO)

chromophore. Upon addition of anions such as OH!, F!, and AcO!, a decrease in absorption

bands at 400 and 421 nm, and evolution of a new absorption band between 510-540 nm (color

change from to red) was observed. Addition of fluoride or acetate anions also induced a

fluorescence enhancement by a factor of ~20. The corresponding excitation spectrum resembled

to the absorption spectrum, indicating that the new emission band originated from their new

absorption band. This observation was assigned to anion-induced perturbation of the hydrogen-

bonding structure in the bis(HBO) unit in the ground state.

In addition to OH groups, acidic NH groups have been incorporated into conjugated polymers to

give rise to anion-sensory materials; among the functional groups that have been employed are

pyrrolyl (1.24a, 1.24b, 1.25), amido (1.26) and ureido (1.27, 1.28, 1.29, 1.30) groups (Figure

1.13 and Figure 1.14). Important precedent for these efforts is the application of polypyrrole

films in anion-selective electrodes for detection of chloride, bromide, nitrate and perchlorate: a

combination of hydrogen bonding interactions involving the pyrrole NH groups, along with ion-

pairing interactions accompanying oxidation of the polymer, are likely responsible for the

polypyrrole–analyte interactions.31 Pioneering work in the development of new classes of

hydrogen-bonding polymers for anion recognition was carried out by Aldakov and Anzenbacher,

who incorporated anion-binding dipyrrolylquinoxaline (DPQ) moieties into thiophene-based

polymers by electrochemical polymerization.32 In analogy to the polypyrrole sensors mentioned

above, a key feature of this design is the prospect for modulating the level of positive charge in

the polythiophene – and thus the extent of Coulombic interaction with anionic analytes, or,

perhaps, the pKa of acidic NH groups – by applying an electric potential. Polymers 1.24a and

1.24b displayed colorimetric responses to tetrabutylammonium fluoride, pyrophosphate and

phosphate in DMSO/water mixed solvent at a constant potential of !0.12 V (potentials are

referenced to the ferrocene/ferrocenium redox couple), with tetrabutylammonium perchlorate as

the supporting electrolyte. Apparent association constants for 1.24a with these anions ranged

from 1.1 " 104 M–1 for pyrophosphate to 9.0 " 10–4 M–1 for dihydrogenphosphate.

21

Electrochemical oxidation of polymer 1.24a resulted in an increase of the apparent affinity

constant for pyrophosphate from 1.1 x 104 M–1 at !0.12 V to >106 M–1 at +0.58 V, and in situ

conductivity measurements using interdigitated microelectrodes revealed a concentration-

dependent decrease in the conductivity of polymer 1.24b upon addition of tetrabutylammonium

pyrophosphate. The ability to use a single material for colorimetric and/or conductivity-based

anion sensing is a noteworthy aspect of this system from the standpoint of developing robust and

versatile sensory devices.

Sun and coworkers reported a fluorescent poly(phenylene ethynylene) polymer containing

dipyrrolylquinoxaline (DPQ) groups that display changes in color and fluorescence intensity

upon addition of fluoride ion.33 Copolymer 1.25 was synthesized by palladium-catalyzed

Sonogoshira cross-coupling reaction of a dibromodipyrrolylquinoxaline monomer and 1,4-

diethynylbenzene. Addition of fluoride or pyrophosphate anions to a solution of polymer in

CH2Cl2, resulted in a color change, from yellow to red. The quenching of the emission band

at #max = 550 nm was assigned to the anion-induced deprotonation of the pyrrole NH protons in

the DPQ moiety. The sensitivity of the anion-induced quenching was considerably increased (34-

fold) compare to a small molecule model compound due to rapid exciton migration. The

oxidation-induced affinity enhancement was assigned to the higher acidity of the DPQ unit upon

p-doping in the polymeric system. The polymer exhibited a linear Stern-Volmer response with a

Stern-Volmer constant of (KSV) = 5.20 " 105, and the fluorescence lifetimes of the polymer

solution did not vary with the concentrations of the anion, consistent with static quenching.

Recently Tian reported a variety of poly(methylmethacrylate)s composed of naphthalimide

signaling moieties and either thiourea34a or imide34b recognition groups by reversible addition-

fragmentation chain transfer polymerization (RAFT). Upon addition of AcO! and H2PO4! to a

solution of polymer 1.27 containing the thiourea moiety in DMSO (10!5 M), only a slight

modulation of the absorption spectra was observed with a color change from light yellow to

orange, while addition of excess F! led to a decrease of the absorption band intensity at 450 nm

and evolution of a new band at 560 nm. Similar results were seen for polymeric films. The

spectral changes were attributed to the acidity of the thiourea protons and an intramolecular

charge transfer process. Monitoring the two thiourea N!H protons by 1H NMR spectroscopy

upon addition of F! to a solution of polymer in DMSO-d6 revealed the disappearance of these

22

protons and formation of a new triplet signal at 16.1 ppm which was assigned to the bifluoride

[FHF]!anion, suggesting the deprotonation of thiourea N!H.

Another report by the same group demonstrated a naphthaimide polyphenylacetylene which was

synthesized by rhodium [Rh(nbd)Cl]2 catalyzed polymerization of the corresponding acetylenic

monomer and further utilized in fluorescence sensing of fluoride ion.34c The polymer 1.26

showed an absorption peak between 310-400 nm assigned to #!#* transition of the

polyphenylacetylene conjugated backbone and the fluorescence spectra of the polymer showed

an emission band at 460 nm (#ex = 340 nm) with a characteristic shape of the naphthalimide unit,

yet lower quantum yield (%PL = 69%). This lower emission of the polymer was attributed to

photoinduced electron/energy transfer from the polyphenylacetylene backbone to the

naphthalimide moiety. Upon addition of fluoride ion to a solution of polymer in acetonitrile, the

absorption band at 360 nm decreased while a new band at 490 nm developed with concomitant

color changes from yellow to pale red. A significant decrease in emission intensity of the

polymer, with a red shift towards higher energy at 580 nm was also observed. A linear

correlation between intensity ratio of absorbance at 490 nm and 360 nm (A490/A360) and fluoride

concentration in acetonitrile was observed which could be applied for ratiomeric sensing. The

changes in absorption and emission spectra was attributed to the electron donating abilities of the

amide group in the presence and absence of fluoride ion and its influence on the intramolecular

charge transfer process from the amide group to the electron-withdrawing imide moiety. The

selectivity of the polymer towards other anions (Cl!, Br!, and I!) was also investigated and no

substantial responses with respect to these anions were observed. The linear emission intensity

ratio at 580 nm and 460 nm (I580/I460) was used to evaluate the polymer efficiency in detecting

fluoride ions.

Yang reported fluorescence fluorene-based conjugated polymer 1.28 that carries a pendant urea

group for anion detection.35 The copolymer (Mn = 5000 g/mol ) was synthesized by Suzuki

cross-coupling reaction of a dibromo fluorene containing two phenyl urea moieties, 2,7-dibromo-

9,9-dihexyl fluorene and 1,4-phenylenediboronic acid with Mn = 5000 g/mol. The UV-vis

spectrum of the polymer in THF displayed absorption maxima at 367 nm, 236 and 267 nm, of

which the former was ascribed to the #!#* transition and the latter to the diphenyl urea side

chain. Addition of fluoride anion to the solution of polymer in THF resulted in a hyperchromic

shift of the band at 237 nm and a hypochromic shift of that at 269 nm. These spectroscopic

23

changes were attributed to the hydrogen bonding interaction between F! with the urea NH

protons. Addition of F! and AcO! resulted in quenching of the polymer fluorescence, while

dihydrogenphosphate anion (Ka = 5.46 " 104 M!1) led to only a medium quenching and other

anions such as Cl!, Br!, and I! were ineffective. The quenching behavior was assigned to

photoinduced electron transfer triggered upon interaction of the urea protons with the anion.

A conceptually distinct and versatile method for transducing hydrogen-bonding events into

measurable signals using a polymeric architecture is described in a series of publications by

Kakuchi and co-workers: incorporation of acidic NH groups into the side chains of a

poly(phenylacetylene) results in a system in which hydrogen bonding interactions with anions

influence the helical conformation of the polymer.36

24

Figure 1.13 Polymeric anion sensors based on acidic NH groups.

CH

C

O NH

N

O

O

(CH2)7CH3

n

1.26Responsive to F! in CH3CN

CH3

CH3C C

H2

CH3 S

S

O

N OO

NH

NHS

O

O n

1.27Responsive to F!, AcO!, and H2PO4! in DMSO

NNSS

O O O O

HNNH

R R

n

1.24a (R = Cl), 1.24b (R = H)Responsive to H2PO42!, P2O72!, and F!

(Bu4N+ salts, DMSO)

OC12H25

C12H25O N N

HNNH

n

1.25Responsive to n-Bu4+F! (Bu4N+ salts, CH2Cl2)

25

Figure 1.14 Polymeric anion sensors based on acidic NH groups.

Urea-containing poly(phenylacetylenes) were synthesized using rhodium catalyzed

polymerization of a functionalized phenyl acetylene. Polymer 1.29 bearing urea-linked L-leucine

substituents did not show evidence of a defined helical conformation in THF solvent, but

addition of tetrabutylammonium chloride, bromide or acetate resulted in dramatic induction of

Cotton effects in the circular dichroism (CD) spectrum, along with a red-shift of the UV-vis

absorption spectrum and color changes from pale yellow to red. These spectral changes implied

that anion binding was accompanied by an alteration in the polymer conformation, leading to a

biased helical conformation along with a change in the conjugation length of the ! system. The

polymer response was dependent upon the ionic radius (and not, apparently, on the basicity) of

the anions, indicating that the spacing of the urea groups along the polymer backbone gives rise

to a significant level of selectivi