Progress of 3-aminopyridinium-based synthetic receptors in anion recognition

Abstract

This review describes the overall development on synthetic receptors built on the pyridinium motif with different functionalities at the 3-position in anion recognition. The review covers only the organic systems. In the designs, the pyridinium group along with the other functional motifs plays a crucial role in the binding of various anions of different shapes and sizes. Complexation characteristics are communicated through changes in ¹H NMR, emission, color or gelation behaviours.

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Kumaresh Ghosh

Kumaresh Ghosh received his M.Sc. and Ph.D. in 1994 and 1999, respectively, from the Indian Institute of Technology, Kharagpur. He is currently Associate Professor of Chemistry at the University of Kalyani, India. His research thematics encompass molecular recognition and supramolecular chemistry, with a special emphasis on the design of chemosensors for neutral, cationic, and anionic substrates.

Avik Ranjan Sarkar

Avik Ranjan Sarkar received his M.Sc. (Organic Chemistry) in 2004 from the North Bengal University, India. In 2006, he joined the Ph.D. program in the University of Kalyani, Nadia, India, under the supervision of Dr Kumaresh Ghosh. He obtained his Ph.D. in 2012. In the same year, he joined the research group of Prof. Hwan Myung Kim as a postdoctoral research fellow at Ajou University, Korea. His research interest focuses on the synthesis of two-photon probes for metal ions and organelles and its application in the biomedical field.

Tanmay Sarkar

Tanmay Sarkar received his M.Sc. degree with specialization in organic chemistry from the University of Kalyani in 2008. He earned his Ph.D. in 2013 under the supervision of Dr Kumaresh Ghosh at the University of Kalyani. His research thesis included the design and synthesis of sensors for cations and anions. Currently, he is a postdoctoral fellow in the research group of Prof. David Margulies at the Weizmann Institute of Science, Israel.

Santanu Panja

Santanu Panja received his M.Sc. degree with specialization in organic chemistry in 2011 from the University of Calcutta. He is now pursuing his Ph.D. at University of Kalyani under the guidance of Dr Kumaresh Ghosh. His research interest includes the design and synthesis of stimuli-responsive organogelators and sensors for cations and anions.

Debasis Kar

Debasis Kar received his M.Sc. in Applied Chemistry in 2008 from Bengal Engineering and Science University, Shibpur, specialising in organic chemistry. He has recently submitted his Ph.D. thesis at the University of Kalyani under the supervision of Dr Kumaresh Ghosh. The main focus of his research is to develop fluorogenic and chromogenic receptors for anions and anion-responsive supramolecular gels.

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Introduction

Design and synthesis of artificial receptors for anion recognition is a fertile area of research in supramolecular chemistry.^1–8 Anion recognition chemistry is a rapidly developing discipline in the field of supramolecular chemistry. It began to grow during the late 1960s when Simmons and Park reported the complexation properties of series of positively charged ammonium macrocyclic hosts with halides.⁹ Following their report, exploration in this area began in the mid 1970s, when Lehn and coworkers described the anion-binding properties of a variety of macrobiocyclic and macrotricyclic ammonium-based receptors.^10,11 After that, a tremendous growth in anion recognition chemistry occurred. Receptors for anions can be neutral and charged in nature. In anion recognition, charge receptors are considerably more attractive than neutral receptors due to their efficacy in complexation of anions involving charge–charge interaction along with other noncovalent forces.

In charged receptors, the cationic parts act as hosts for binding anions and must compete with associated counter anions. In comparison, neutral hosts for anions exhibit relatively weak binding of anions and must deal with the associated counter cations. These types are known as ion pair binding hosts. A survey of previous studies reveals that charged receptors based on guanidinium,^12,13 imidazolium,^14–16 benzimidazolium,^17–25 polyammonium^26,27 and thiourenium^28–30 motifs are known and well explored in anion recognition. Similar to these charged systems, the pyridinium motif has been noted as a useful and versatile motif in devising molecular receptors for anions. This motif provides polar C–H bond as hydrogen bond donor to anions and the complex is further stabilized by charge–charge interaction. The easy incorporation of 3-aminopyridine in the desired structures with moderate to good yields and flexibility in tuning the designs are possible factors for pyridinium-based compounds to act as receptors for neutral as well as charged guest molecules. Thus, this review focuses on pyridinium-based receptors (especially 3-aminopyridinium-based) related to the sensing of different anions.

A simple pyridine amine or amide is not a good motif for anion binding. However, judicious placement of this motif with the quaternization of ring nitrogen can lead to a number of structures that are capable of binding anions with considerable efficiency. The binding of anions takes place through hydrogen bonding involving polar C–H bonds and other appended functionalities of the pyridinium motif. The hydrogen bonded complex is stabilized by charge–charge interactions. Fig. 1 highlights the various approaches in using 3-aminopyridine as the building block for various receptor structures.

Fig. 1 Strategies to use 3-aminopyridine in building up receptor structures.

It is established that the C–H group adjacent to neutral or protonated/alkylated nitrogen atoms is often involved in hydrogen bonding in the crystal structure.^31–33 Due to weakness, C–H⋯X (X = O, N, Cl⁻, Br⁻, I⁻ etc.) hydrogen bonds are rarely incorporated into synthetic receptors as determining forces to stabilize the complexes in solution.³⁴ In this regard, receptors combining N-alkylpyridinium and amide groups were first prepared and employed for binding of carboxylate by Jeong et al.³⁵ They reported that although pyridine amide 1 binds benzoate in d₆-DMSO with a K_a of 16 M⁻¹, the alkylated pyridinium motif 2 shows an increase in the K_a value (300 M⁻¹) involving different binding modes (2 and 2a) (Table 1).³⁵ Considering this feature Jeong et al. prepared different bispyridinium salts 3, 4 and 5 for binding of dicarboxylates. Adipate was selectively complexed with a high association constant (K_a > 5 × 10⁵ M⁻¹). The alkylated pyridinium groups attached to amide nitrogen exhibited increased affinities to anions and neutral guests as compared with their neutral counterparts. This result is attributed to the increase in acidities of both NH (amide) and CH (aromatic ring) proton donors induced by the quarternization of pyridine moiety. These interesting features of pyridinium moiety inspired several groups to develop pyridinium amide or urea-based receptors for anions. Of the different architectures, 3-amino or other substituted pyridines with different templates that provide various binding properties towards anions due to various binding pockets generated have been undertaken in the discussion. The introduction of fluorogenic and chromogenic moieties to the receptors enabled easy detection of anionic species, compared with the conventional ¹H NMR titration methods. The recognition affinities of these receptors towards the different anions are briefly summarized in Table 1 (chemical structures can be found in the discussion).

Table 1 Binding characteristics of different pyridinium-based hosts

Receptors	Binding constant (Ka) values with some selected anions (host : guest stoichiometry, solvent and methods used)
1, 2, 3, 4, 5 (Jeong et al. ref. 35)	1 with PhCOO^−: Ka = 16 M^−1 (1 : 1, d6-DMSO, ^1H NMR)
	2 with PhCOO^−: Ka = 300 M^−1 (1 : 1, d6-DMSO, ^1H NMR)
	3, 4 and 5 individually with adipate: Ka > 5 × 10^5 M^−1 (1 : 1, d6-DMSO, ^1H NMR)
	3, 4 and 5 individually with adipate: Ka > 10^3 M^−1 (1 : 1, 10% D2O/DMSO, ^1H NMR)
	Anions were used as N^nBu4^+ salts
6 and 7 (Fabbrizzi et al. ref. 36)	6 with CH3COO^−, F^− and H2PO4^−: log Ka > 6 (1 : 1, DMSO, UV-vis)
	7 with CH3COO^−: log Ka = 5.10 ± 0.05 (1 : 1, DMSO, UV-vis)
	7 with F^−: log Ka = 4.77 ± 0.02 (DMSO, UV-vis)
	7 with H2PO4^−: log Ka = 3.11 ± 0.01 (DMSO, UV-vis)
	Anions were used as N^nBu4^+ salts
8a–g, 9, 10, 11 and 12 (Steed et al. ref. 37a)	8a with Br^−: K11 = 850 M^−1 (1 : 3, CD3CN, ^1H NMR)
	8c with Cl^−: K11 > 100 000 M^−1 (1 : 3, CD3CN, ^1H NMR)
	8c with Br^−: K11 = 13 800 M^−1 (1 : 3, CD3CN, ^1H NMR)
	8c with AcO^−: K11 = 10 500 M^−1 (1 : 3, CD3CN, ^1H NMR)
	8c with Cl^−: K11 = 15 M^−1 (1 : 3, d6-DMSO, ^1H NMR)
	8d with Cl^−: K11 = 8 M^−1 (1 : 3, d6-DMSO, ^1H NMR)
	8c with Cl^−: K11 = ca. 82 000 M^−1 (1 : 3, d6-DMSO/CD3CN 50% v/v, ^1H NMR)
	8d with Cl^−: K11 = ca. 3000 M^−1 (1 : 3, d6-DMSO/CD3CN 50% v/v, ^1H NMR)
	9 with Cl^−: K11 = 17 380 M^−1(1 : 3, CD3CN, ^1H NMR)
	9 with AcO^−: K11 = 3680 M^−1(1 : 3, CD3CN, ^1H NMR)
	10 with CH3COO^−: K11 = 49 000 M^−1(1 : 3, CD3CN, ^1H NMR)
	11 with Br^−: K11 = 17 M^−1(1 : 3, CD3CN, ^1H NMR)
	12 with CH3COO^−: K11 = 7 M^−1 (1 : 3, CD3CN, ^1H NMR)
	Anions were used as N^nBu4^+ salts
13, 14 and 15 (Steed et al. ref. 37b)	13 with Cl^−: log Ka = 9.2 ± 0.3 (2 : 1, CH3CN, UV-vis); log Ka = 4.2 ± 0.1 (1 : 1, CH3CN, UV-vis)
	13 with AcO^−: log Ka = 12.7 ± 0.2 (2 : 1, CH3CN, UV-vis); log Ka = 6.0 ± 0.3 (1 : 1, CH3CN, UV-vis); log Ka = 10.5 ± 0.3 (1 : 2, CH3CN, UV-vis)
	13 with succinate: log Ka = 5.0 ± 0.2 (1 : 1, CH3CN, UV-vis)
	13 with malonate: log Ka = 5.4 ± 0.2 (1 : 1, CH3CN, UV-vis)
	14 with Cl^−: log Ka = 12.1 ± 0.4 (2 : 1, CH3CN, UV-vis); log Ka = 5.7 ± 0.3 (1 : 1, CH3CN, UV-vis)
	14 with AcO^−: log Ka = 11.6 ± 0.3 (2 : 1, CH3CN, UV-vis); log Ka = 5.5 ± 0.2 (1 : 1, CH3CN, UV-vis); log Ka = < 4 (1 : 2, CH3CN, UV-vis)
	14 with succinate: log Ka = 10.5 ± 0.6(1 : 1, CH3CN, UV-vis); log Ka = 5.3 ± 0.3 (1 : 1, CH3CN, UV-vis); log Ka = < 4 (1 : 2, CH3CN, UV-vis)
	14 with malonate: log Ka = 10.0 ± 0.3 (2 : 1, CH3CN, UV-vis); log Ka = 4.7 ± 0.3 (2 : 1, CH3CN, UV-vis)
	15 with Cl^−: log Ka = 4.2 ± 0.2 (1 : 1, CH3CN, UV-vis); log Ka = 7.7 ± 0.4 (1 : 2, CH3CN, UV-vis)
	15 with AcO^−: log Ka = 3.8 ± 0.2 (2 : 1, CH3CN, UV-vis); log Ka = 5.6 ± 0.2 (1 : 1, CH3CN, UV-vis); log Ka = <4 (1 : 2, CH3CN, UV-vis)
	15 with succinate: log Ka = 5.5 ± 0.1 (1 : 1, CH3CN, UV-vis); log Ka = 11.2 ± 0.2(1 : 2, CH3CN, UV-vis)
	15 with malonate: log Ka = 5.2 ± 0.1 (1 : 1, CH3CN, UV-vis); log Ka = 11.2 ± 0.2 (2 : 1, CH3CN, UV-vis)
	Anions were used as N^nBu4^+ salts
16 and 17 (Steed et al. ref. 38)	16 with Cl^−: log K11 = 2.64, log K12 = 2.18, log K13 = 1.40 (1 : 3, d6-DMSO, ^1H NMR)
	16 with Br^−: log K11 = 3.46, log K12 = 2.99, log K13 = 1.21 (1 : 3, d6-DMSO, ^1H NMR)
	16 with I^−: log K11 = 1.61, log K12 = 0.60, log K13 = 1.05 (1 : 3, d6-DMSO, ^1H NMR)
	16 with NO3^−: log K11 = 2.54, log K12 = 2.22, log K13 = 0.68 (1 : 3, d6-DMSO, ^1H NMR)
	16 with AcO^−: log K11 = 3.21, log K12 = 3.70(1 : 1 and 1 : 2, d6-DMSO, ^1H NMR)
	16 with H2PO4^−: log K11 = 3.70, log K12 = 3.68(1 : 1 and 1 : 2, d6-DMSO, ^1H NMR)
	17 with Cl^−: log K11 = 3.85, log K12 = 1.96, log K13 = 2.93 (1 : 3, CD3CN, ^1H NMR)
	17. Br^−: log K11 = 3.62, log K12 = 2.24, log K13 = 1.96 (1 : 3, CD3CN, ^1H NMR)
	17. NO3^−: log K11 = 3.46, log K12 = 2.66, log K13 = 1.89 (1 : 3, CD3CN, ^1H NMR)
	17. AcO^−: log K11 = 4.61, log K12 = 2.30, log K13 = 3.67(1 : 3, CD3CN, ^1H NMR)
	Anions were used as N^nBu4^+ salts
18a and 18b (Steed et al. ref. 39)	18a. Na2ATP: Ka = 70 M^−1 [1 : 1, D2O/CD3CN (1 : 1, v/v), ^1H NMR]
19a–d and 20a–d (Steed et al. ref. 40)	19c. Br^−: K11 = 446 M^−1, K12 = 467 M^−1 (1 : 2, CD3CN, ^1H NMR)
	19c. NO3^−: K11 = 3090 M^−1, K12 = 302 M^−1 (1 : 2, CD3CN, ^1H NMR)
	20c. Br^−: K11 = 24 550 M^−1, K12 = 1990 M^−1 (1 : 2, CD3CN, ^1H NMR)
	20c. NO3^−: K11 = 51 290 M^−1, K12 = 912 M^−1 (1 : 2, CD3CN, ^1H NMR)
	19c. Malonate: K11 = 58 800 M^−1, K12 = 83 M^−1 [1 : 2, CD3CN/d6-DMSO (60/40, v/v), ^1H NMR]
	19c. Malonate: K11 = 2720 M^−1, K12 = 15 M^−1 (1 : 2, d6-DMSO, ^1H NMR)
	19c. Succinate: K11 = 2690 M^−1, K12 = 37 M^−1 (1 : 2, d6-DMSO, ^1H NMR)
	Anions were used as N^nBu4^+ salts
21a–b and 22a–b (Beer et al. ref. 41)	21a. Cl^−: Ka = 40 M^−1 (1 : 1, d6-DMSO, ^1H NMR)
	22b. Cl^−: Ka = 110 M^−1 (1 : 1, d6-DMSO, ^1H NMR)
23 and 24 (Steed et al. ref. 42)	23. Cl^−: log K11 = 3.95, log K12 = 3.21 (1 : 2, CD3CN, ^1H NMR)
	24. Cl^−: log K11 = 3.55, log K12 = 3.39 (1 : 2, CD3CN, ^1H NMR)
	Anions were used as N^nBu4^+ salts
25 (Ghosh et al. ref. 43)	25. F^−: Ka = 1.85 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	25. H2PO4^−: Ka = 1.03 × 10^4 M^−1 (1 : 1, CH3CN, fluorescence)
	25. AcO^−: Ka = 6.99 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	25. Propanoate: Ka = 5.07 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	25. C6H5COO^−: Ka = 4.12 × 10^2 M^−1 (1 : 1, CH3CN, fluorescence)
	Anions were used as N^nBu4^+ salts
26 (Ghosh et al. ref. 44)	26. H2PO4^−: Ka = 1.22 × 10^4 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	26. HSO4^−: Ka = 2.36 × 10^3 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	26. Isophthalate: Ka = 2.73 × 10^3 M^−1(1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	26. Phthalate: Ka = 8.37 × 10^2 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	26. Terephthalate: Ka = 5.03 × 10^2 M^−1(1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	26. Glutarate: Ka = 1.71 × 10^2 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	26. Malonate: Ka = 3.52 × 10^2 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	26. Succinate: Ka = 6.95 × 10^2 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	Anions were used as N^nBu4^+ salts
27 (Ghosh et al. ref. 46)	27. Oxalate: Ka = 7.94 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	27. Adipate: Ka = 5.78 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	27. Pimelate: Ka = 2.59 × 10^4 M^−1 (1 : 1, CH3CN, fluorescence)
	27. 1,4-Phenylenediacetate: Ka = 3.34 × 10^5 M^−1 (1 : 1, CH3CN, fluorescence)
	27. Terephthalate: Ka = 8.16 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	Anions were used as N^nBu4^+ salts
28–33 (Yatsimirsky et al. ref. 47)	28. F^−: log Ka = 5.28 (1 : 1, CH3CN, UV-vis)
	28. Cl^−: log Ka = 5.27 (1 : 1, CH3CN, UV-vis)
	28. Br^−: log Ka = 5.24 (1 : 1, CH3CN, UV-vis)
	28. I^−: log Ka = 3.80 (1 : 1, CH3CN, UV-vis)
	28. H2PO4^−: log Ka = 4.20 (1 : 1, CH3CN, UV-vis)
	28. AcO^−: log Ka = 4.40 (1 : 1, CH3CN, UV-vis)
	28. NO3^−: log Ka = 4.11 (1 : 1, CH3CN, UV-vis)
	29. F^−: log Ka = 4.36 (1 : 1, CH3CN, UV-vis)
	29. Cl^−: log Ka = 5.65 (1 : 1, CH3CN, UV-vis)
	29. Br^−: log Ka = 4.29 (1 : 1, CH3CN, UV-vis)
	29. I^−: log Ka = 3.57 (1 : 1, CH3CN, UV-vis)
	29. H2PO4^−: log Ka = 5.18 (1 : 1, CH3CN, UV-vis)
	29. AcO^−: log Ka = 5.38 (1 : 1, CH3CN, UV-vis)
	29. NO3^−: log Ka = 4.34 (1 : 1, CH3CN, UV-vis)
	30. Cl^−: log Ka = 5.85 (1 : 1, CH3CN, UV-vis)
	30. Br^−: log Ka = 5.40 (1 : 1, CH3CN, UV-vis)
	30. I^−: log Ka = 3.80 (1 : 1, CH3CN, UV-vis)
	30. NO3^−: log Ka = 4.40 (1 : 1, CH3CN, UV-vis)
	Neutral analogues 31, 32 and 33 exhibited weak binding
	(Anions were used as N^nBu4^+ salts)
34 (Gong et al. ref. 48)	34. H2PO4^−: log Ka = 4.28 [1 : 1, CH3CN/EtOH (9 : 1, v/v), fluorescence]
	Anions were used as N^nBu4^+ salts
35 (Gong et al. ref. 49)	35. H2PO4^−: Ka = (3.0 ± 0.3) × 10^4 M^−1 (1 : 1, CHCl3, fluorescence); Ka = (5.0 ± 0.2) × 10^4 M^−1 (1 : 2, CHCl3, fluorescence)
	Anions were used as N^nBu4^+ salts
36 (Ghosh et al. ref. 50)	36.C6H5COO^−: Ka = 3.46 × 10^3 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	36. 4-Butoxybenzoate: Ka = 8.69 × 10^2 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	36. Pyridine-3-carboxylate: Ka = 5.48 × 10^2 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	36. HSO4^−: Ka = 1.87 × 10^3 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	Anions were used as N^nBu4^+ salts
37(Ghosh et al. ref. 51)	37. AcO^−: Ka = 1.08 × 10^4 M^−1 (1 : 1, CH3CN, fluorescence)
	37. Propanoate: Ka = 1.25 × 10^4 M^−1 (1 : 1, CH3CN, fluorescence)
	37. AcO^−: Ka = 1.16 × 10^4 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	37. Propanoate: Ka = 1.04 × 10^4 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	37. C6H5COO^−: Ka = 3.02 × 10^3 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	37. H2PO4^−: Ka = 9.56 × 10^3 M^−1 (1 : 1, CHCl3 containing 2% CH3CN, fluorescence)
	Anions were used as N^nBu4^+ salts
38 and 39 (Ghosh et al. ref. 52)	38. Biotin carboxylate: Ka = 5.12 × 10^4 M^−1 (1 : 1, CH3CN containing 1.2% DMSO, fluorescence)
	38. Biotin methyl ester: Ka = 3.69 × 10^3 M^−1 (1 : 1, CH3CN containing 1.2% DMSO, fluorescence)
	38. AcO^−: Ka = 5.14 × 10^4 M^−1 (1 : 1, CH3CN containing 1.2% DMSO, fluorescence)
	38. Biotin carboxylate: Ka = 1.89 × 10^4 M^−1 (1 : 1, DMSO, fluorescence)
	38. Biotin methyl ester: Ka = 6.33 × 10^3 M^−1 (1 : 1, DMSO, fluorescence)
	38. AcO^−: Ka = 1.19 × 10^4 M^−1 (1 : 1, DMSO, fluorescence)
	39. Biotin carboxylate: Ka = 4.22 × 10^4 M^−1 (1 : 1, CH3CN containing 1.2% DMSO, fluorescence)
	39. Biotin methyl ester: Ka = 7.05 × 10^2 M^−1 (1 : 1, CH3CN containing 1.2% DMSO, fluorescence)
	39. AcO^−: Ka = 1.91 × 10^4 M^−1 (1 : 1, CH3CN containing 1.2% DMSO, fluorescence)
	39. Biotin carboxylate: Ka = 9.70 × 10^3 M^−1 (1 : 1, DMSO, fluorescence)
	39. Biotin methyl ester: Ka = 4.17 × 10^3 M^−1 (1 : 1, DMSO, fluorescence)
	39. AcO^−: Ka = 1.95 × 10^4 M^−1 (1 : 1, DMSO, fluorescence)
	Anions were used as N^nBu4^+ salts
40 (Ghosh et al. ref. 54)	40. Malonate: log Ka = 4.28 (1 : 1, DMSO, fluorescence)
	40. Succinate: log Ka = 4.93 (1 : 1, DMSO, fluorescence)
	40. Glutarate: log Ka = 5.73 (1 : 1, DMSO, fluorescence)
	40. Adipate: log Ka = 6.87 (1 : 1, DMSO, fluorescence)
	40. Pimelate: log Ka = 7.32 (1 : 1, DMSO, fluorescence)
	40. 1,4-Phenylenediacetate: log Ka = 8.93 (1 : 1, DMSO, fluorescence)
	40. Benzoate: log Ka = 5.19 (1 : 1, DMSO, fluorescence)
	40. Acetate: log Ka = 5.52 (1 : 1, DMSO, fluorescence)
	Anions were used as N^nBu4^+ salts
41 (Ghosh et al. ref. 55)	41. Malonate: Ka = 2.09 × 10^4 M^−1 (1 : 1, DMSO, fluorescence)
	41. Succinate: Ka = 1.15 × 10^4 M^−1 (1 : 1, DMSO, fluorescence)
	41. Glutarate: Ka = 4.21 × 10^4 M^−1 (1 : 1, DMSO, fluorescence)
	41. Adipate: Ka = 4.68 × 10^4 M^−1 (1 : 1, DMSO, fluorescence)
	41. Pimelate: Ka = 8.60 × 10^3 M^−1 (1 : 1, DMSO, fluorescence)
	41. Suberate: Ka = 7.29 × 10^4 M^−1 (1 : 1, DMSO, fluorescence)
	41. Terephthalate: Ka = 4.75 × 10^4 M (1 : 1, DMSO, fluorescence)
	Anions were used as N^nBu4^+ salts
42 and 43 (Ghosh et al. ref. 56)	42. Malonate: log K1 = 4.44 ± 0.02, log K2 = 3.36 ± 0.03 (1 : 2, DMSO, fluorescence)
	42. Succinate: log K1 = 4.36 ± 0.03, log K2 = 3.36 ± 0.05 (1 : 2, DMSO, fluorescence)
	42. Glutarate: log K1 = 4.40 ± 0.04, log K2 = 3.63 ± 0.05 (1 : 2, DMSO, fluorescence)
	42. Adipate: log Ka = 4.21 ± 0.02 (1 : 1, DMSO, fluorescence)
	42. Pimelate: log Ka = 4.42 ± 0.04 (1 : 1, DMSO, fluorescence)
	42. Suberate: log Ka = 4.17 ± 0.03 (1 : 1, DMSO, fluorescence)
	43. Malonate: log K1 = 3.74 ± 0.02, log K2 = 4.31 ± 0.04 (1 : 2, DMSO, fluorescence)
	43. Succinate: log K1 = 3.69 ± 0.03, log K2 = 4.37 ± 0.05 (1 : 2, DMSO, fluorescence)
	43. Glutarate: log Ka = 4.14 ± 0.08 (1 : 1, DMSO, fluorescence)
	43. Adipate: log Ka = 4.73 ± 0.02 (1 : 1, DMSO, fluorescence)
	43. Pimelate: log Ka = 5.00 ± 0.01 (1 : 1, DMSO, fluorescence)
	43. Suberate: log Ka = 4.89 ± 0.01 (1 : 1, DMSO, fluorescence)
	Anions were used as N^nBu4^+ salts
44 (Ghosh et al. ref. 57)	44. N^nBu4^+ H2PO4^−: Ka = 9.07 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	44. Na2ATP: Ka = 3.36 × 10^2 M^−1 [1 : 1, H2O/CH3CN (1 : 1, v/v), fluorescence]
	44. Na2ADP: Ka = 1.79 × 10^2 M^−1 [1 : 1, H2O/CH3CN (1 : 1, v/v), fluorescence]
45 and 46 (Ghosh et al. ref. 59)	45. Citrate: Ka = (2.34 ± 0.01) × 10^4 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	45. Pimelate: Ka = (4.05 ± 0.05) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	45. Adipate: Ka = (1.05 ± 0.01) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	45. Glutarate: Ka = (1.17 ± 0.02) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	45. Succinate: Ka = (1.62 ± 0.01) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	45. F^−: Ka = (1.12 ± 0.01) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	45. Cl^−: Ka = (9.94 ± 0.07) × 10^2 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	45. Br^−: Ka = (8.98 ± 0.07) × 10^2 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	45. I^−: Ka = (9.96 ± 0.07) × 10^2 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	45. H2PO4^−: Ka = (1.01 ± 0.03) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	45. AcO^−: Ka = (1.61 ± 0.02) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	46. Citrate: Ka = (7.02 ± 0.7) × 10^4 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	46. Pimelate: Ka = (1.62 ± 0.04) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	46. Adipate: Ka = (1.50 ± 0.02) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	46. Glutarate: Ka = (1.49 ± 0.02) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	46. Succinate: Ka = (1.54 ± 0.01) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	46. F^−: Ka = (1.18 ± 0.01) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	46. Cl^−: Ka = (1.07 ± 0.02) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	46. H2PO4^−: Ka = (1.81 ± 0.03) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	46. AcO^−: Ka = (8.21 ± 0.02) × 10^3 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), UV-vis]
	Anions were used as N^nBu4^+ salts
47 (Ghosh et al. ref. 60)	47. (N^nBu4^+)3HP2O7: Ka = (9.59 ± 1) × 10^4 M^−1 [1 : 1, CH3CN/H2O (4 : 1, v/v), fluorescence]
49 (Ghosh et al. ref. 65)	49. Na-salt of ATP: Ka = 6.80 × 10^2 M^−1 (1 : 1, H2O, UV-vis)
	49. Na-salt of ADP: Ka = 8.85 × 10^2 M^−1 (1 :  1, H2O, UV-vis)
	49. Na-salt of AMP: Ka = 5.96 × 10^3 M^−1 (1 : 1, H2O, UV-vis)
50 and 51 (Ghosh et al. ref. 66a)	50. H2PO4^−: K11 = (2.45 ± 0.1) × 10^4 M^−1, K12 = (2.21 ± 0.1) × 10^4 M^−1 (1 : 2, CH3CN, fluorescence)
	50. F^−: K11 = (1.06 ± 0.08) × 10^4 M^−1, K12 = (8.21 ± 0.8) × 10^3 M^−1 (1 : 2, CH3CN, fluorescence)
	51. H2PO4^−: K11 = (2.09 ± 0.16) × 10^4 M^−1, K12 = (1.40 ± 0.12 × 10^4) M^−1 (1 : 2, CH3CN, fluorescence)
	51. F^−: K11 = (1.84 ± 0.4) × 10^4 M^−1, K12 = (5.19 ± 0.16) × 10^3 M^−1 (1 : 2, CH3CN, fluorescence)
	Anions were used as N^nBu4^+ salts
53 and 54 (Ghosh et al. ref. 68)	53. L-N-Acetylvaline: Ka = 1.87 × 10^4 M^−1 (1 : 1, CH3CN, fluorescence)
	53. L-N-Acetylalanine: Ka = 2.60 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	53. L-N-Acetylproline: Ka = 1.38 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	53. L-N-Acetylphenylglycine: Ka = 1.31 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	53. AcO^−: Ka = 2.20 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	53. (S)-Mandelate: Ka = 1.60 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	54. L-N-Acetylvaline: Ka = 1.30 × 10^4 M^−1 (1 : 1, CH3CN, fluorescence)
	54. L-N-Acetylalanine: Ka = 6.50 × 10^2 M^−1 (1 : 1, CH3CN, fluorescence)
	54. AcO^−: Ka = 1.70 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	Anions were used as N^nBu4^+ salts
55 (Ghosh et al. ref. 69)	55. D-Lactate: Ka = (4.17 ± 0.7) × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	55. L-Lactate: Ka = (1.92 ± 0.33) × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	Anions were used as N^nBu4^+ salts
56 (Ghosh et al. ref. 70)	56. L-Tartrate: Ka = (6.31 ± 0.056) × 10^3 M^−1 (1 : 1, DMSO, fluorescence)
	56. D-Tartrate: Ka = (8.18 ± 0.55) × 10^3 M^−1 (1 : 1, DMSO, fluorescence)
	56. R-Mandelate: Ka = (2.79 ± 0.39) × 10^3 M^−1 (1 : 1, DMSO, fluorescence)
	56. S-Mandelate: Ka = (2.07 ± 0.22) × 10^3 M^−1 (1 : 1, DMSO, fluorescence)
	Anions were used as N^nBu4^+ salts
61 and 62 (Ghosh et al. ref. 76)	61. F^−: Ka = 3.14 × 10^3 M^−1 (1 : 1, CHCl3, UV-vis)
	61. Cl^−: Ka = 4.20 × 10^4 M^−1 (1 : 1, CHCl3, UV-vis)
	62. F^−: Ka = 2.07 × 10^3 M^−1 (1 : 1, CH3CN, fluorescence)
	62. F^−: Ka = 3.21 × 10^3 M^−1 (1 : 1, DMSO, fluorescence)
	Anions were used as N^nBu4^+ salts
63 (Ghosh et al. ref. 77)	77. F^−: Ka = 8.93 × 10^3 M^−1 (1 : 1, DMSO, UV-vis)
	Anions were used as N^nBu4^+ salts
64a (Ghosh et al. ref. 78)	64a. Cl^−: Ka = 1.31 × 10^4 M^−1 (1 : 1, CHCl3 containing 0.2% DMSO, fluorescence)
	64a. F^−: Ka = 3.2 × 10^4 M^−1 (1 : 1, CHCl3 containing 0.2% DMSO, fluorescence)
	64a. Br^−: Ka = 3.38 × 10^3 M^−1 (1 : 1, CHCl3 containing 0.2% DMSO, fluorescence)
	64a. I^−: Ka = 3.30 × 10^4 M^−1 (1 : 1, CHCl3 containing 0.2% DMSO, fluorescence)
	64a. OH: Ka = 2.64 × 10^4 M^−1 (1 : 1, CHCl3 containing 0.2% DMSO, fluorescence)
	Anions were used as N^nBu4^+ salts

---

Fabbrizzi et al. reported pyridinium-based structure 6, which includes bound anions such as AcO⁻, H₂PO₄⁻, and F⁻ (taken as tetrabutylammonium salt) in DMSO involving both electrostatic- and hydrogen-bonding interactions.³⁶ In comparison, indole-fused pyridinium compound 7, being less acidic, showed only deprotonation with F⁻ and AcO⁻. H₂PO₄⁻ was complexed in 1 : 1 stoichiometric fashion with a log K_a of 3.11.³⁶

Steed and co-workers described the synthesis and anion binding properties of a series of 3-aminopyridinium-based tripodal, tricationic hosts 8–11 for anions.^37a,b The podand hosts were explored in the binding of halides and oxoanions. The alternating substitution around the central benzene ring preorganizes the hosts in cone conformation. Although the unsubstituted tris (pyridinium) species 8a gives K₁₁ 850 M⁻¹ for Br⁻, structure 11 with no ethyl functionality at the core benzene ring shows a binding constant of 17 M⁻¹ for Br⁻ ions in CD₃CN. This implies the effect of preorganization in the tripods for which the significant degree of cooperativity occurs in binding among the three arms. Among the hosts, the ferrocene appended host 9 exhibited strong binding for Cl⁻ (K₁₁ = 17 380 M⁻¹) as determined by ¹H NMR titration in CD₃CN. AcO⁻ was complexed with a moderate binding constant (K₁₁ = 3680 M⁻¹) value. In contrast, the anthracene appended tripodal host 10 bound AcO⁻ with a high binding constant (K₁₁ = 49 000 M⁻¹) value, which was determined in CD₃CN by ¹H NMR titration. Binding was established through the involvement of N–H and C–H hydrogen bond donation from the arms around the central benzene ring. The same result was realised in the solid state. For example, the X-ray crystal structure of the bromide complex of 8c shows chelation of the Br⁻ ion by six fold array of two NH⋯Br⁻ and four CH⋯Br⁻ interactions (Fig. 2a). In absence of Br⁻, the PF₆⁻ salt of 8c assumes non-convergent partial cone conformation, in addition to the engagement of N–H and C–H bonds to fluorine of PF₆⁻ ion (Fig. 2b).

Fig. 2 X-ray crystal structures of the (a) bromide salt of 8c (three-up conformation) and (b) PF₆⁻ salt of 8c (partial-cone conformation). Reprinted with permission from ref. 37b. Copyright 2003 American Chemical Society.

Steed et al. also synthesized a series of di-, tri-, and tetrapodal anion-binding hosts—13, 14 and 15, respectively—based on 3-aminopyridinium units with pyrenyl reporter groups.^37c The conformational and sensing properties of the hosts were dependent on the spacing and disposition of the binding components. The host 15 bound strongly to dicarboxylates, particularly malonate (log β₁ = 5.2 ± 0.1, log β₂ = 11.2 ± 0.2), in a 2 : 1 anion : host ratio in CH₃CN and exhibited fluorescence quenching as a result of pyrene–pyridinium charge-transfer interaction in the excited state. The higher value of the second equilibrium constant than the first indicates that complexation of the first anion favours complexation of the second anion on the opposite side of the calixarene ring through allosteric conformational changes. The host also preferred Cl⁻ ion over the other monovalent anions, but the association constant for dicarboxylate was at least an order of magnitude higher than that for halides despite the fact that a fluorescent response was observed only upon Cl⁻ ion binding. In contrast, host 14 showed the highest association constants (for 1 : 1 and 2 : 1 adducts) for Cl⁻, while 13 bound strongly to AcO⁻ ion.

However, urea-containing tripodal receptors 16 and 17 reported by Steed and coworkers³⁸ proved to be effective anion-binding hosts and represented an improvement over the amine-based systems. The urea motifs were observed for complex anions along with crystallizing solvents as supported by X-ray crystal structures. The X-ray crystal structures of 16 containing different counter anions represent the various geometries of host (Fig. 3). To determine the binding efficacy in solution, the binding constant values were determined from ¹H NMR in d₆-DMSO. Selectivity for H₂PO₄⁻ was observed over a series of anions such as Cl⁻, Br⁻, I⁻, NO₃⁻, AcO⁻, HSO₄⁻, CF₃SO₃⁻ and ReO₄⁻. Log binding constants for the 1 : 1 and 1 : 2 host/guest complexes with H₂PO₄⁻ were found to be 3.70 and 3.68, respectively. The values of binding constants obtained with 16 in d₆-DMSO were modest due to the highly polar nature of the solvent. However, titrations of the more soluble octyl-substituted host 17 in CD₃CN exhibited larger binding constants (Table 1). On the basis of experimental observations, Steed et al., further reported the occurrence of at least two binding processes during the halide titration. The first equivalent of the guest gave rise to a 1 : 1 complex, in which the value of K₁₁ was, in all cases, higher than K₁₂ and K₁₃. This indicated that the initial binding event may be due to chelation of the guest by the three arms, followed by cases in which each anion binds to a separate arm.

Fig. 3 X-ray crystal structures of (a) bromide salt of 16 (three-up conformation), (b) acetone solvate of PF₆⁻ salt of 16 (complexed acetone), and (c) NO₃⁻ complex of 16. Reprinted with permission from ref. 38. Copyright 2006 American Chemical Society.

In continuation, two new tripodal “pinwheel” type anion binding hosts based on a triethylbenzene core and bipyridinium unit 18a–b were also reported by Steed et al.³⁹ These hosts complexed anions only via CH⋯anion interaction, which was established by their crystal structures (Fig. 4a). Packing of the molecules revealed interhost stacking (Fig. 4b). ¹H NMR titration of tripod 18a with disodium salt of ATP in D₂O/CD₃CN (1 : 1, v/v) resulted in significant changes to the pyridyl proton resonances. A good fit to the 1 : 1 binding model gave the binding constant value of 70 M⁻¹. The influence of charge–charge and π-stacking interactions played a crucial role in this recognition process.

Fig. 4 Crystal structures of (a) 18a and 18b (reproduced from ref. 39).

When the triethylbenzene core is replaced by the calixarene unit, pyridinium-based hosts are found to be versatile in anion binding. Two types of calix[4]arene derived pyridinium-based hosts 19a–d and 20a–d were reported by Steed et al.⁴⁰

Interestingly, although the 1,3-alternate system 19 bound dicarboxylate anions in a ditopic manner following a 2 : 1 guest : host ratio, the cone compound 20 was deprotonated by carboxylates. The ditopic 1,3-alternate host 19c binds malonate with K_a = 58 800 M⁻¹ in CH₃CN–DMSO (60 : 40, v/v) with a 1 : 2 (host : guest) ratio. The malonate anions were chelated by a pairs of pyridinium arms via NH⋯O and CH⋯O interactions, as shown in Fig. 5. In contrast, due to lack of cooperativity between the arms, the cone compounds bound small spherical anions. They strongly bind Br⁻ and NO₃⁻ ions.

Fig. 5 Binding structure of 19c with malonate.

In lieu of 3-aminopyridine, quaternary bispyridinium and polypyridinium compounds 21–22 were also employed in anion binding.^{41 1}H NMR studies in d₆-DMSO revealed that the compounds have an affinity for Cl⁻ ions. Of the different structures, tripodal structure 22b showed the strongest affinity for Cl⁻ ions (K_a = 110 M⁻¹). Electrochemical study revealed that due to the presence of redox active 4,4′-bipyridinium moiety, structure 22a exhibited a significant cathodic shift upon the addition of Cl⁻ ions (ΔE = 130 mV).

Tuning of the structural features of polypyridinium compounds introduced new viologen-based receptors 23–24.⁴² The NMR titration results in CD₃CN revealed that the hosts bound to two Cl⁻ ions with log K₁₁ = 3.95 and log K₁₂ = 3.21 for 23, and log K₁₁ = 3.55 and log K₁₂ = 3.39 for 24. Interestingly, binding of carboxylate anions, particularly acetate, malonate and succinate by pyridinium derivative 23 in CH₃CN resulted in an intense purple colouration (Fig. 6a). Theoretical calculation on the representative system 23.malonate revealed that the origin of color was due to charge-transfer from the anion to the bipyridinium unit. In contrast, anion binding by 24 did not initially result in colour change because anions were complexed at the periphery of the receptor. However, the addition of more than two equivalents of acetate, or more than one equivalent of dicarboxylates gave intense pink color (Fig. 6b).

Fig. 6 Change in color of the host solutions (c = 1 × 10⁻⁴ M): (a) host 23 in the presence of one equivalent of tetrabutylammonium succinate, malonate, acetate, chloride, bromide, nitrate and perrhenate (from left to right); (b) host 24 with four equivalents of the same anions (from left to right). Reproduced from ref. 42 with permission from the Centre National de la Recherche Scientifique (CNRS) and The Royal Society of Chemistry.

Our group exhaustively used the pyridinium motif in building up a series of synthetic receptors that showed potentiality in anion binding. Simple design 25 from our group strongly bound basic anions such as AcO⁻, H₂PO₄⁻ and F⁻ with an affinity constant on the order of 10⁴ M⁻¹ in CH₃CN.⁴³ Analysis of the fluorescence behaviour of 25 towards a series of anions interpreted that the cleft of 25 can distinguish aliphatic carboxylates from aromatic carboxylates and is also able to report the selective binding of tetrahedral-shaped H₂PO₄⁻ ions through strong excimer formation between the pendant anthracenes.

The change of isophthaloyl spacers in 25 by biphenyl units led to a new structure 26 that showed selective complexation of isophthalate and H₂PO₄⁻.⁴⁴ The addition of H₂PO₄⁻, HSO₄⁻ and isophthalate to the solution of 26 in CHCl₃ containing 2% CH₃CN caused changes in monomer emission of anthracene followed by the appearance of an excimer. The greater intensity of the excimer emission in the presence of H₂PO₄⁻ distinguished it from the other anions. Analysis of the fluorescence titration results revealed the K_a value of 1.22 × 10⁴ M⁻¹ for H₂PO₄⁻. It is notable that such anthracene-labelled bispyridinium diamide not only showed propensity for dihydrogen phosphate sensing but also exhibited good interaction with DNA. The compounds of this class are cell permeable and useful for cell staining.⁴⁵

The tuning of structure 25 was further done in our laboratory by macrocyclisation. The synergistic effect of hydrogen bonding, weak π-stacking and charge–charge interactions enabled the macrocycle 27 to complex 1,4-phenylenediacetate (K_a = 3.34 × 10⁵ M⁻¹) selectively. During complexation, a considerable increase in anthracene emission was observed.⁴⁶

Referring to our work on 25, Yatsimirsky and co-workers reported a series of known isomeric dicationic N-methylated pyridyl derivatives⁴⁷ (28–30) of three isomers of N,N′-bis(pyridyl)-2,6-pyridine dicarboxamide 31–33.⁴⁷ The binding of the cationic compounds were studied and compared with the neutral analogues. Cationic receptors offered higher affinity and selectivity for anions in CH₃CN (log K in the range 3.5–6.5) than their corresponding neutral versions. Indeed, the dicationic compounds showed pronounced selectivity for Cl⁻ ions and in some cases for AcO⁻.⁴⁷ The stoichiometry of the complexes was established as 1 : 1 and also 1 : 2 (host : guest), which varied with the isomer. The solid-state binding of the three isomers was also highlighted by Yatsimirsky and co-workers. An analysis of four crystal structures of chloride and triflate complexes of the three isomers revealed anion binding in the cleft involving amide NH and CH interactions.

On the other hand, based on the observation of receptor 25, Gong et al. reported a tripodal fluorescent chemosensor 34 with 3-aminopyridinium as a binding motif for H₂PO₄⁻.⁴⁸ Upon complexation of H₂PO₄⁻, the tripodal receptor 34 in CH₃CN/EtOH (9 : 1, v/v) gave a strong excimer, which was diagnostic to distinguish H₂PO₄⁻ from the other anions. In continuation, the same group reported another chemosensor 35 by changing the spacer. The dipodal sensor 35 exhibited solvent polarity-dependant conformational behaviour. They proposed that intramolecular hydrogen bonding of the pyridinium ortho proton with the amide carbonyl oxygen regulated the cleft dimension, and in both CHCl₃ and CH₃CN, the sensor 35 selectively sensed H₂PO₄⁻.^49a

In addition, Gong et al. synthesized dipodal^49b and tripodal^49c receptors for colorimetric sensing of AcO⁻ over a series of other anions based on the utilization of amide–pyridinium as a recognition site, and nitro-benzene as a signalling unit. The addition of AcO⁻ induced clear color change of the receptor solutions from colorless to yellow.

The rational design of unsymmetrical bispyridinium amide is another strategy with which to make an anion-binding host. Furthermore, we reported the hetero bisamide 36 in 2011, which selectively recognised tetrabutylammonium benzoate over a range of aliphatic monocarboxylates in CHCl₃ containing 2% CH₃CN by showing concomitant increase in pyrene emission. The hydrogen bonding, charge–charge interaction and the π-stacking effect as displayed in Fig. 7 corroborated the selective sensing of benzoate (K_a = 3.46 × 10³ M⁻¹). Moreover, the cleft of 36 showed selective sensing of HSO₄⁻ (K_a = 1.87 × 10³ M⁻¹) over the H₂PO₄⁻ ion by exhibiting considerable change in emission of 36.⁵⁰

Fig. 7 Suggested benzoate complex of 36.

In continuation, we addressed another hetero bisamide 37 that contains anthracene in a selective position to create a PET (photoinduced electron transfer) sensor.⁵¹ The fluorescent hetero bisamide 37 exhibited selective binding of monocarboxylates over their conjugate acids in spite of the presence of binding complementarity to both carboxylate and carboxylic acid (Fig. 8).

Fig. 8 Possible modes of complexation of 37 with carboxylates and carboxylic acids.

Binding analysis indicated that AcO⁻ (K_a = 1.16 × 10⁴ M⁻¹) and CH₃CH₂COO⁻ (K_a = 1.04 × 10⁴ M⁻¹) anions were preferred in the cleft over their conjugate acids by giving significant change in emission (Fig. 9).

Fig. 9 Change in fluorescence ratio of 37 (c = 6.27 × 10⁻⁵ M) at 412 nm upon addition of two equivalents of guests in CH₃CN. Reprinted with permission from ref. 51. Copyright 2011 Taylor & Francis.

Of the different solvent combinations, 2% CH₃CN in CHCl₃ was a better choice for improved selectivity in the recognition process. While the emission of 37 upon addition of aliphatic carboxylate guest in CH₃CN was perturbed to a lesser extent, it was found to be significant with a new emission at ∼512 nm in the less polar solvent CHCl₃ containing 2% CH₃CN. Fig. 10 illustrates this aspect. The binding affinity of the cleft of 37 for anions was further realized from the analysis of global electrophilic characters by using the DFT calculation.⁵¹

Fig. 10 Change in emission of 37 (c = ∼10⁻⁵ M) upon addition of (a) propanoate in CH₃CN and (b) acetate in CHCl₃ containing 2% CH₃CN. Reprinted with permission from ref. 51. Copyright 2011 Taylor & Francis.

The carboxylate binding affinity of the cleft of hetero bis amides as previously discussed was further used in our laboratory in the selective sensing of tetrabutylammonium salt of biotin (K_a varies in between 10² M⁻¹ and 10⁴ M⁻¹) over the biotin ester by naphthyridine-appended pyridinium salts 38 and 39.⁵² Biotin is an essential co-factor for a number of enzymes that have diverse metabolic functions.⁵³ Despite not using fluorophore, the emission feature of naphthyridine was used to assess the binding characteristics. The diamide clefts of the receptors bound carboxylate functionality involving NH⋯O, CH⋯O hydrogen bonds and charge–charge interactions. The bicyclic urea part of biotin was complexed by the pendant naphthyridine motifs due to which emission of naphthyridine was considerably enhanced. The fluorometric titration was conducted in CH₃CN containing 1.2% DMSO. Binding was also determined by ¹H NMR titration. The unsymmetrical receptor 38 gave improved binding over the symmetrical diamide 39. The less steric feature at the naphthyridine site in 38 allowed for comfortable binding of the bicyclic urea part of biotin.

In an effort to recognise dicarboxylates (larger anions), the ureidopyridyl groups were coupled with anthracene units to make chemosensor 40. ¹H NMR, fluorescence and UV-vis studies established the compound 40 as a selective sensor for 1,4-phenylenediacetate (log K = 8.93) over a series of other aliphatic dicarboxylates in DMSO.⁵⁴

Based on this observation, we further moved to another new system 41 where the ureidopyridyl unit is replaced by trans-pyridylcinnamide. The trans-pyridylcinnamide motif was used as an alternative of urea to form a hydrogen-bonded complex with the carboxylate in the mode shown in Fig. 11. However, the sensor 41 showed moderate selectivity for long-chain pimelate over a wide range of dicarboxylates by exhibiting good fluorescence ‘On-Off’ switchability. The switching mode was noted to be the reverse of that in the urea analogue 40. The interplay of N–H⋯O, C–H⋯O hydrogen bonds and charge–charge interactions contribute to selectivity in the recognition process.⁵⁵

Fig. 11 Hydrogen-bonded complexes of carboxylate with (a) cinnamide and (b) urea derivatives.

Rather than anthracene, triphenylamine was used in building up pyridinium-based ditopic receptors 42 for dicarboxylates.⁵⁶ In the design, the triphenylamine acts as a spacer as well as fluorescent probe to illustrate the recognition process. From fluorescence titration, the open cleft of receptor 42 was selective for pimelate (log K = 5.00 ± 0.01). Upon complexation (suggested mode shown in Fig. 12), the emission intensity gradually decreased to the significant extent. Under comparitively similar conditions, the pyridine-N-oxide analogue 43 was less efficient in the recognition process. This experimental fact indicated the greater electrophilic characteristic of the pyridinium amide for the complexation of anion. This was further explained by calculating the global electropilicity by using the DFT calculation.

Fig. 12 Suggested binding mode of dicarboxylate in the cavity of 42.

The variation of the synthetic spacer in the designed-molecule draws attention. The placement of pyridinium motifs on ortho-phenylenediamide core resulted in compound 44,⁵⁷ which selectively bound H₂PO₄⁻ in CH₃CN, giving excimer emission at 456 nm due to π–π stacking between the pendant naphthalene units. The sensor 44 also fluorometrically distinguished ATP from ADP and AMP in CH₃CN–H₂O (1 : 1, v/v) at pH 6.5 by exhibiting a more intense band of exciplex formed due to favorable stacking of the adenine ring in between the pendant naphthalenes (Fig. 13).

Fig. 13 Possible binding structure of 44 with ATP.

The pyridinium-based architectures were also used in the indicator displacement assay (IDA) technique for anion sensing. In this technique, an indicator is first allowed to bind reversibly to a receptor and then a competitive analyte is introduced into the system causing the displacement of the indicator from the host which in turn modulates the optical signal.⁵⁸ Pyridinium-based symmetrical receptors 45 and 46 were first applied in the IDA technique for the selective sensing of carboxylate guests.⁵⁹

Both the receptors responded in CH₃CN/H₂O (4 : 1, v/v) at pH 6.3 for the selective naked-eye detection of citrate over a series of guests. Additionally, receptor 46 (c = 6.29 × 10⁻³ M) formed stable gel selectively with citrate in CH₃CN. It was proposed that conventional N–H⋯O and unconventional C–H⋯O hydrogen bonds, charge–charge interactions and pyrene with large π-surface interplayed together to set up a network in solution in the presence of citrate for which gelation occurred. The non-responsive behaviour of 45 in the formation of the gel indicated the role of pyrene in 46. However, both the receptors gave binding constant values on the order of 10⁴ M⁻¹ with 1 : 1 stoichiometry.

Using the IDA technique, tetrabutylammonium hydrogenpyrophosphate was recognized over a series of other anions in both CH₃CN and aqueous CH₃CN (CH₃CN : H₂O = 4 : 1, v/v, pH = 6.5) by receptor structures 47 and 48.⁶⁰ In the unsymmetrical receptors, pyridinium motifs were manipulated by using 3-picolinic acid. Compound 47 showed a binding constant value of (9.59 ± 1) × 10⁴ M⁻¹ for HP₂O₇³⁻. However, the Merrifield resin-supported bead 48 was of practical use to naked-eye detection of HP₂O₇³⁻ in CH₃CN : H₂O (4 : 1 v/v), as well as in pure water at pH 6.5 via the IDA technique. Moreover, the experiments with blood serum suggest that the sensor bead 48 is capable of sensing HP₂O₇³⁻ selectively in complex biological systems. It is notable that the selective detection of hydrogen pyrophosphate or pyrophosphate (PPi) is an important aspect in supramolecular chemistry research. PPi is a biologically important target that arises from ATP hydrolysis under cellular conditions.⁶¹ It is involved in DNA sequencing/replication⁶² and has physiological relevance in energy storage and signal transduction. Therefore, the detection of PPi has become important in cancer research.^62,63 Patients with calcium pyrophosphate dehydrate (CPPD) crystals and chondrocalcinosis are generally found to have high synovial fluid PPi levels.⁶⁴

Following the IDA technique through the use of uranine dye, a water-soluble tripodal receptor 49 was established from our laboratory as a chemosensor for naked-eye recognition of AMP (K_a = 5.96 × 10³ M⁻¹) over ADP and ATP in aqueous environment.⁶⁵ Complexation of AMP was supported by both experimental and theoretical investigations. Furthermore, the tripod was used to recognise the intercellular AMP as well as the ALP-mediated conversion of ATP/ADP via the IDA technique.

In addition, modification of the substituent of pyridine ring nitrogen by using 1,2,3-triazole ring, which is surrogate of amide, was performed, and the structure 50 was synthesized in our laboratory. The receptor structure 50 selectively recognized H₂PO₄⁻ by exhibiting ratiometric change in emission and formed a stable gel in CHCl₃ containing 10% CH₃CN. This was useful for visually sensing of H₂PO₄⁻.^66a In comparison, receptor 51, which is devoid of a triazole motif, did not form a gel with H₂PO₄⁻ under similar conditions. Upon interaction with H₂PO₄⁻, the intensity of monomer- and excimer-emission peaks of 51 increased markedly without giving any ratiometric nature in the spectra. Moreover, F⁻ ion-induced greater quenching of monomer emissions in both 50 and 51 in a non-ratiometric manner distinguished it from other anions examined. These observations underlined the key role of the triazole ring in 50 in anion recognition. Indeed, a triazole is a well-established motif in anion binding.^66b Job's plot analysis of the flourescence titration spectra gave a 2 : 1 (guest : host) complex between H₂PO₄⁻ and 50. This was also true for F⁻. On the basis of 2 : 1 stoichiometry in the excited state, the association constants of 50 for H₂PO₄⁻ and F⁻ were established to be (K₁₁ = 2.45 ± 0.1 × 10⁴ M⁻¹, K₁₂ = 2.21 ± 0.1 × 10⁴ M⁻¹) and (K₁₁ = 1.06 ± 0.08 × 10⁴ M⁻¹, K₁₂ = 8.21 ± 0.8 × 10³ M⁻¹), respectively. The receptor 51 followed 2 : 1 (guest : host) binding stoichiometries with both H₂PO₄⁻ and F⁻ in an excited state similar to that of 50 and gave relatively lower binding constant values [(K₁₁ = 2.09 ± 0.16 × 10⁴ M⁻¹, K₁₂ = 1.40 ± 0.12 × 10⁴ M⁻¹ for H₂PO₄⁻) and (K₁₁ = 1.84 ± 0.40 × 10⁴ M⁻¹, K₁₂ = 5.19 ± 0.16 × 10³ M⁻¹ for F⁻)].

Following modification, pyridinium-based receptor modules have been used to bind zwitterionic α-amino acids. In this context, Jeong et al. made a new simple compound 52 that is composed of two components, namely benzo-18-crown-6 and a urea functionality for binding the ammonium and carboxylate groups of zwitterionic α-amino acids (52a), respectively.⁶⁷ They examined the amino acid-binding property by solid–liquid and liquid–liquid extractions at 24 ± 1 °C and also applied it in the transportation of amino acids across a CHCl₃ liquid membrane. The transport efficiency was established as Phe > Trp > Ile > Leu > Val ≫ Ala > Ser ≫ Asp, His.

For fluorometric sensing of a particular α-amino acid derivative, pyridinium amide was used in conjunction with the urea motif by our group using the PET sensor 53.⁶⁸ Fluorescence studies of 53 in CH₃CN (λ_ex = 370 nm) revealed a moderate quenching of the emission at 415 nm upon addition of L-N-acetylproline, (S)-mandelate, pyruvate, and L-N-acetylglycine, whereas L-N-acetylalanine and L-N-acetylvaline resulted in an increase of emissions, including the appearance of a broad emission of moderate intensity at 492 nm. The peak at 492 nm, which was more significant in presence of L-N-acetylvaline than L-N-acetylalanine, was attributed to the formation of a charge-transfer complex between the excited state of anthracene and the electron-deficient nitrophenyl urea. This was confirmed by considering the amide–amide analogue 54. Fluorometric titrations revealed 1 : 1 binding of L-N-acetylvaline (K_a = 2.60 × 10³ M⁻¹) with receptor 53 in CH₃CN.

The attachment of a chiral amide or urea segment to the side chain of the 3-aminopyridinium unit resulted in chiral sensors such as 55 and 56. The chiral receptors were found to be useful in chiral recognition of hydroxyl carboxylates such as lactate and tartrate.

A synthetic fluorescent chemosensor that discriminates the enantiomers of a particular chiral guest by exhibiting different fluorescence behaviors draws attention in the area of molecular recognition. The simple pyridinium-based chiral receptor 55 containing L-valine as the chiral source fluorometrically recognizes D-lactate [(K_a = 4.17 ± 0.7) × 10³ M⁻¹] over L-lactate in CH₃CN with enantiomeric fluorescence ratio (ef) of 5.32.⁶⁹ While upon gradual addition of D-lactate to the solution of 55 the monomer emission at ∼400 nm increases significantly, a small emission increase with the addition of L-lactate was observed. Similarly, by using L-valine as a chiral source, an anthracene-based chiral chemosensor 56 was established as an efficient enantioselective sensor for L-tartrate (ef = 29.38) over D-tartrate in DMSO.⁷⁰ In the presence of tetrabutylammonium salt of L-tartaric acid, the monomer emission of 56 at 432 nm was considerably enhanced giving a binding constant value of (6.31 ± 0.05) × 10³ M⁻¹.

The versatility of pyridinium motifs in molecular recognition is commendable. It cannot be completed if its use in gel chemistry is not discussed. Gels are considered as viscoelastic solid- or liquid-like materials (called gelators), comprised of cross-linked networks and a solvent, which was the major component. Multiple non-covalent interactions among the gelators are critical to establish the network in solution. For this, several functional groups are identified in gelator molecules. Amide, hydroxyl and urea groups are generally incorporated into the structures of gelators for the formation of self-associated chains that contribute to the gelation of solvent molecules.⁷¹ In 2003, Kato et al. reported some pyridyl ureas that acted as gelators and produced fibrous self-assembly.⁷² Dostidar and co-workers investigated the gelation properties of the pyridyl ureas such as 57, 58 and 59.⁷³ Among the three, only compound 57 exhibited gelation ability in pure water. The isomeric compounds 58 and 59 are non-gelators. A theoretical calculation on this aspect was recently performed by Xie et al.⁷⁴ They studied the conformational and hydrogen-bonding behaviours of the three isomers (57, 58 and 59) in detail.

Bispyridyl ureas 60 with flexible linkers generally did not show any gelation property. However, upon interaction with both Ag⁺ and Cu²⁺ salts, they exhibited gelation tendency. Metal-induced cross linking introduced gelation of the systems.⁷⁵

Besides the metal ions, the introduction of the cholesteryl unit onto the pyridine ring nitrogen in the dipyridyl urea 58 modified its gelation property. In relation to this, the compound 61 exhibited gelation in CHCl₃;⁷⁶ the gel was anion responsive. In the presence of F⁻, the gel state was transformed into the sol and validated the visual sensing of F⁻. Conversely, unsymmetrical pyridyl urea salt 62 fluorimetrically distinguished F⁻ from the other anions in both CH₃CN and DMSO with appreciable binding constant values.⁷⁶ It is noteworthy that the compound 62 formed gel in DMSO in the presence of F⁻, whereas the compound 61 underwent a transition from gel to sol state in CHCl₃ in the presence of same anion. Generally, anions are gel breakers, but the appearance of the gel in the presence of F⁻ in the case of 62 is noteworthy. We explained this due to the effective aggregation of gelators. The dianionic species obtained from fluoride-induced deprotonation of urea motifs in 62, and the resulting HF₂⁻ are involved in intermolecular contacts to set up a network in solution. The stabilization of the network is influenced by a large hydrophobic surface of the cholesterol moiety. The replacement of the coumarin substituent in 62 by nitrophenyl motif resulted in a similar type of compound 63, which acted as low-molecular weight gelator in DMSO : H₂O (1 : 1, v/v) in the presence of F⁻ (Fluoride source: KF, NaF, CsF and tetrabutylammonium fluoride).⁷⁷ During gelation, the color change was useful in naked-eye detection of F⁻. The deprotonation of urea protons and subsequent delocalization of the charge to the nitrophenyl motif introduced the color change. Furthermore, the gel state was reported to be a good semiconductor, in addition to a medium to detect Cu²⁺ and Pb²⁺ ions by showing a transition from gel to sol.

Like pyridinium ureas, cholesterol appended pyridinium amides were found to be noteworthy as low molecular weight gelators. Recently, we have demonstrated that cholesterol-appended pyridinium diamide 64 gives instant gel from chloroform.⁷⁸ The gel is pH-responsive and exhibits ionic conductivity due to the movement of unrestricted Cl⁻ ions within the network. The gel acted as a media to recognize Ag⁺ ion over a series of other cations by exhibiting gel-to-sol transformation. The gel state reappeared in the presence of chloride salt and indicated reversibility in the process. It was further observed that hexafluorophosphate analogue 64a which was obtained from 64 on anion exchange, allowed the selective recognition of Cl⁻ over other halides by forming transparent yellow-colored gel in CHCl₃.

Conclusion

Significant progress in the design and synthesis of receptors (both non fluorescent and fluorescent) of various architectures based on pyridinium motif has been made during the past several years. The use of 3-aminopyridine and related derivatives has provided various strategies for the design of chemosensors for the recognition of anions, including halides, phosphate derivatives, phosphate-based nucleotides, DNA, and dicarboxylates. In addition, the enantioselective sensing of hydroxyl carboxylates by pyridinium-based chiral fluororeceptors has been explored. Further, it has been observed that the incorporation of hydrophobic surfaces into pyridinium-based urea or amide receptors draws considerable attention as the compounds of this class are useful in gel chemistry. Gels are stimuli-responsive and highly appealing in anion recognition. Although an increasing number of receptors/probes have been developed on the basis of a 3-aminopyridine unit, further developments in the fabrication of new sensing systems, including chiral receptors, stimuli-responsive gelators, and nano particle-hooked sensors, with high sensitivity and selectivity are still in demand. Moreover, in continuation of our work on the systems 47 and 48, there is sufficient scope to use 3-aminopyridine to develop solid-supported receptor beads that are useful for detecting anions in an aqueous environment.

Acknowledgements

We thank DST [Project no. SR/S1/OC-76/2010(G); Date: 23.08.2011] New Delhi, India, for financial support. T.S., S.P. and D.K. thank CSIR, New Delhi, India, for a fellowship.

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