Functionalized Quinoxaline for Chromogenic and Fluorogenic Anion Sensing.

This Review article provides a comprehensive analysis of recent examples reported in the field of quinoxaline-based chromogenic and fluorogenic chemosensors for inorganic anions such as fluoride, cyanide, acetate, and phosphate, as well as their utility in biomolecular science. It commences with a discussion of the various structural motifs such as quinoxaline-based oligopyrroles, polymers, sulfonamides, cationic receptors, and miscellaneous receptors bearing mixed recognition sites in the same receptor. Advances are discussed in depth, where the focus of this review is to tackle mainly solution state anion sensing utilizing quinoxaline-based receptors using different spectroscopic techniques with reference to anion selectivity by colorimetric and fluorescence response. The various examples discussed in this Review illustrate how the integration of anion binding elements with the quinoxaline chromophore could result in anion responsive chemosensors. Over the years, it has been observed that structural modification of the quinoxaline moiety with different sets of signaling unit and recognition sites has resulted in a few anion specific chemosensors.

Introduction

Owing to their remarkable electronic and photophysical properties, quinoxaline and its derivatives have been widely employed as efficient building blocks for the synthesis of numerous organic molecules and polymeric materials appropriate for different applications.1 The electron‐deficient character of the conjugated quinoxaline ring is responsible for some interesting properties, such as distinctive absorption and emission spectra, charge transfer from an electron donor to the quinoxaline ring, high charge‐carrier mobility, and a low reduction potential rendering the compound possible low energy band gap. Because of these interesting inherent properties, several quinoxaline‐based conjugated materials have been synthesized in the past two decades and their applications in the field of light‐emitting diodes (LEDs),2 organic photovoltaics (OPVs),3 dye‐sensitized solar cells (DSSCs),4 organic field‐effect transistors (OFETs),5 nonlinear optics,6 and fluorescent optical chemosensors7 have been widely explored.

The development of chromogenic and fluorogenic molecules for anion sensing has gained considerable research attention, owing to the fundamental roles that anions play in many biological, environmental, and chemical processes.8 Inspired by the recognition tools exploited by nature in anion‐binding proteins,9 researchers have developed numerous synthetic receptors that employ hydrogen bonds offered by specific binding sites from amide, urea, pyrrole, indole, guanidinium, and imidazolium functionalities for the recognition and sensing of anionic species.10 Chemosensors capable of representing an optical response upon receptor‐anion interactions are viable, owing to the low cost and easy detection of anions in solution.

Chemosensors for anions generally involve the covalent linking of a chromophore/fluorophore signaling subunit capable of giving information about the anion binding event with the hydrogen bonding receptor subunit.11 Whereas chemosensors commonly refer to systems that typically employ coordinative forces for anion binding, which in turn change the electronic properties of the receptor molecule, the term chemodosimeter (reactive sensors) is related to the use of specific irreversible reactions involving anions.12 Boronic acid −B(OH)2 functionalized fluorescent anion sensors are well documented in the literature as chemodosimeters for detecting and determining the concentration of fluoride in aqueous/semi‐aqueous media.13 In general, hydrogen‐bond‐induced π‐electron delocalization, or anion‐induced −NH or −OH deprotonation, are believed to be responsible for signaling the binding event in sensors that generally employ polarized −NH and −OH functions.14 The ability to establish hydrogen bonds between the anion and receptors with −NH group(s) is usually determined by the degree of electron deficiency on the interacting −NH proton (or proton acidity) and the electronegativity of the anion (or anion basicity). Intense colorations with emergence of new bands in the optical spectral region can also be attributed to the strong anion–π charge transfer interactions involving π‐acidic receptors, such as triazine, naphthalene diimide, and dinitrophenyl‐functionalized receptors.15 Currently, sensors based on anion‐induced changes in luminescence properties are particularly attractive because of their potential for high selectivity and sensitivity at low substrate concentrations. The binding of anionic species leads to certain modification of the fluorescence emission behavior such as changes in emission intensity, wavelength, or lifetime of the of receptor molecules. Along this line, the design of ratiometric fluorescence chemosensors also provides the basis for the manipulation and advancement of various photophysical processes with the ultimate goal of selective and sensitive signaling of targeted anions.16 The ratio of the emission intensities at two different wavelengths is sufficient to determine the analyte concentration independent of probe concentration or any instrument‐related parameters.

Chromogenic and fluorogenic chemosensors are generally designed to combine the ability to recognize and respond to an external input with mediation of an internal charge transfer (ICT),17 photoinduced electron transfer (PET),18 excimer/exciplex emission,19 excited‐state intramolecular proton transfer (ESIPT),20 enhancement/quenching of luminescence upon anion association,21 or exciton–migration‐induced signal amplification in polymer luminescence,22 as a mode of signaling mechanism. Luminescent signaling of anion recognition has been achieved using a variety of conjugated chromophores including naphthalene, naphthalene (di)imide, anthracene, pyrene, and quinoxaline derivatives,11, 21, 23 and also transition metal complexes such as, rhenium(I) and ruthenium(II) complexes.24

In spite of the large number of chromogenic and fluorogenic chemosensors for anions reported to date, there are only a few examples of highly selective chemosensor for a specific anion.11, 21, 23, 25 The main challenge for supramolecular and organic chemists working in the area of anion sensing and recognition is to achieve anion‐specific chemosensor in aqueous medium. However, achieving both anion selectivity and water solubility of organic receptors may be quite challenging, which has perhaps limited the selective anion sensing studies mostly to organic media. High hydration enthalpy of some of the biologically and environmentally relevant anions like F−, Cl−, AcO−, and PO4 3− represents another obstacle towards anion recognition in water, owing to the formation of a hydration shell around the anions, which significantly limits the receptor anion interaction by hydrogen bonds at low analyte concentration. Several highly acknowledged reviews on chromogenic and/or fluorogenic chemosensors for anions can be noted in literature that have largely highlighted the use of nitrophenyl, naphthalene (di)imide, and polycyclic aromatic hydrocarbon based chemosensors.11, 21, 23, 25 However, functionalized quinoxaline‐based anion sensors have not been well addressed anywhere, in spite of their frequent use in the development of chemosensors over the years.

This Review aims to deliver a comprehensive compilation of the examples reported to date related with the developments of quinoxaline‐based chromogenic and fluorogenic chemosensors for inorganic anions such as, fluoride, cyanide, acetate, and phosphate. In this Review, based on the anion recognition motifs, quinoxaline‐based anion sensors have been categorized into five different types: 1) quinoxaline oligopyrroles, 2) quinoxaline‐based polymers, 3) quinoxaline sulfonamides, 4) quinoxaline‐based cationic receptors, and 5) miscellaneous quinoxaline receptors with mixed recognition sites (e.g. amide and pyrrole in the same receptor). The focus remains primarily on the solution‐state anion sensing properties of quinoxaline‐based receptors using different spectroscopic techniques with reference to anion selectivity by colorimetric and fluorescence response.

Quinoxaline‐Based Anion Sensors

Quinoxaline Oligopyrroles

Most of the quinoxaline‐based receptors developed for the purpose of anion sensing have utilized 2,3‐dipyrrolylquinoxaline (DPQ) derivatives, in which two pyrrole −NH groups could function as anion binding sites and the quinoxaline moiety can serve as a chromogenic and fluorogenic reporter of an anion binding event. The earliest contribution was made by Sessler and co‐workers, who first reported the use of DPQ 1, and nitro‐DPQ 2 as efficient chromogenic and fluorogenic chemosensors for fluoride in dichloromethane (DCM) and dimethyl sulfoxide (DMSO) solutions.26 They proposed that the DPQ system is expected to operate through a combination of electronic and conformational effects (Figure 1). Both the compounds display a remarkable F−‐induced color change from yellow to orange (1+F−) and yellow to purple (2+F−), and their fluorescence emission are quenched to all extents in the presence of F−. Sensing of F− by DPQ was explained by the expected perturbation of the orbital overlap between the pyrrole and quinoxaline subunits, thereby changing the optical characteristics of the later. Owing to the greater electron deficiency, compound 2 displays an association constant (K a=1.18×105  m −1 in DCM) that is significantly higher than that of 1 (K a=1.82×104  m −1 in DCM) for 1:1 receptor–anion interaction, and also shows a remarkable selectivity for F− over Cl− and H2PO4 − [K a (F−/Cl−) >1800, K a (F−/H2PO4 −) >1400]. In contrast, the fluorinated receptor 3 exhibits a sharp color change from yellow to orange in the presence of both F− and H2PO4 − in DCM solutions, and its fluorescence emissions are also quenched in the presence of both F− and H2PO4 −.27 These maiden results of Sessler and co‐workers illustrated how the anion sensing properties of DPQ can effectively be tuned by introducing different electron‐withdrawing substituents on the quinoxaline or on the pyrrole subunits of the parent DPQ (Table 1). Based on these attractive spectroscopic features of DPQ and its derivatives, newer opportunities to synthesize variously substituted DPQs and related classes of motifs to develop anion sensors have been opened up.

Figure 1

a) Dipyrrolylquinoxaline (DPQ, 1) and its nitro and fluoro derivatives 2 and 3, b) proposed mode of anion binding by DPQ.

Table 1

Association constants (K a [m −1]) of quinoxaline‐based sensors with different anions. The absorption spectral change or fluorescence emission spectral change observed upon titration of a quinoxaline probe with anion was used to calculate the respective binding constants (× indicates that the association constant for the anion was not studied/determined).

Sensors	F−	Cl−	H2PO4 −	H2P2O7 2−	AcO−	CN−
1	18 200	50	60	×	×	×
2	118 000	65	80	×	×	×
3	61 600	180	17 300	×	×	×
4	32 000	550	4 300	×	×	×
5	1 000 000	5 800	300 000	×	×	×
7a	2 100	170	6 800	×	×	×
7b	×	470	20 000	×	×	×
8a	15 531	514	9 933	×	20 602	×
8b	152 535	821	78 845	×	24 452	×
9	8 970 000	10 900	1 130	×	×	×
10a	51 300	<100	<200	93 700	×	×
10b	24 700	<100	<100	58 900	×	×
10c	25 600	<100	<100	57 300	×	×
10d	27 500	<50	<50	39 000	×	×
10e	12 200	<100	<100	30 000	×	×
10f	10 200	<100	<100	24 300	×	×
11	17 300	<100	<100	18 000	×	×
12	19 600	<100	<200	29 500	×	×
13	16 800	×	×	11 200	×	×
14	482 200	×	100	31 6000	1 200	6 630
15	150 700	×	525	62 6000	3 800	16 800
17	60 000	×	×	×	×	×
P3	70 200	×	×	49 300	×	×
P4	520 000	×	×	380 000	×	×
P5	616 000	×	×	×	×	×
19	6 500	×	2 000	×	1 100	×
20	255 000	4 400	70 000	×	30 000	×
21	25 000	120	2 300	×	13 000	230 000
21‐Re	3 100 000	6 500	28 000	×	×	×
22	400 000	210	19 000	×	170 000	×
22‐Ru	1 300 000	1 300	290 000	×	1 800 000	×
23	140 000	170	8 800	×	670 000	×
24	×	4 200	×	×	1 790 000 000	460 000 000
25	500 000	×	×	×	×	×
26	440	×	×	×	×	×
26‐Ru	12 000	10	40	×	×	×
26‐Co	54 000	20	50	×	×	×
27	68 000	500	1 620	×	×	3 450
27‐Ru	640 000	1 700	14 000	×	×	428 000
31b	162 000	×	×	×	187 000	×
31c	×	×	×	×	764 000	×
31d	758 000	×	×	×	396 000	×
32	19 400	13 400	21 500	×	×	×
34	×	×	158 500	5 000	×	×
35a	50 000 000	60	250 000	×	4 000 000	×
35b	×	60	631 000	×	20 000 000	×
36	12 000	110	23 000	×	820 000	×
37	×	×	×	×	2 512 000	×

Sessler and co‐workers have also demonstrated that the inherent selectivity and anion binding affinities of DPQ can be modulated by introducing additional pyrrole groups to the α‐pyrrolic positions of parent DPQ to give quinoxaline‐oligopyrrole receptors 4 and 5,28 or by generating macrocyclic quinoxaline‐bridged porphyrinoids 6 (Figure 2).29 Addition of fluoride to a dichloromethane solution of 4 results in a visible change in color from yellow to red, which can well be correlated with the UV/Vis spectral changes, which shows a decrease in the intensity of the original band (426 nm) and the appearance of a broad peak at higher wavelength (500–580 nm). The fluoride binding affinity of 4 having four pyrrole rings was found to be higher than the parent DPQ 1 (Table 1). On the other hand, receptor 5 with six pyrroles as hydrogen bond donors shows a 50‐fold increase in binding constant value (>106  m −1) in comparison to 1 for the complexation of fluoride under similar conditions (Table 1). Because of the greater number of pyrrole −NH donors, receptor 5 shows a substantial increase in dihydrogenphosphate binding affinity and, from 1H NMR spectral studies, it has been proposed to be hydrogen bonded with the receptor according to binding mode II (Figure 3). Larger fluoride‐induced downfield shifts of the outer pyrrole −NH signals compared to the inner pyrrole −NH (Δδ=3.80 vs. 2.05 ppm, respectively) suggest that the outer “claw‐like” pyrrole subunits bind F− more effectively. Unlike the acyclic derivatives of DPQ (1–5), macrocycle 6 contains two interconnected −NH binding cavities whose inward pointing cores can act as cooperative anion binding sites. Both F− (20 equiv) and H2PO4 − (300 equiv) can induce a colorimetric response from yellow to orange in 10 % DMSO/DCM solutions of 6. However, such color changes are not observed, even upon the addition of more than 300 molar equivalents of Cl−, Br−, NO3 −, or HSO4 − to the individual solutions of 6, likely owing to the lower charge density present on these anions relative to those on F− and H2PO4 −. UV/Vis spectrophotometric titrations showed the origin of two new bands at 329 and 480 nm at the expense of the original bands observed at 367 and 427 nm upon titration with F− and H2PO4 −, respectively, in DCM. The UV/Vis titration curves and ab initio calculations, carried out at the HF/3‐21G level for 6 and its possible fluoride complexes with different binding modes, led to the conclusion of positive homotropic allosteric binding behavior (Figure 4). That is, once a fluoride ion is captured in one cavity, the other cavity “shrinks” to the point where its size is better optimized for fluoride binding. The fluoride complexes, inner (6–F−) and inner (6–2F−) with inward binding modes are more stable by 15.73 and 24.20 kcal mol−1, respectively, than outer (6–F−) and outer (6–2F−), wherein the fluoride anion is bound outside the macrocycle.

Figure 2

Quinoxaline–oligopyrrole receptors 4 and 5, and macrocyclic quinoxaline‐bridged porphyrinoids 6.

Figure 3

Proposed anion binding modes of receptor 5.

Figure 4

Possible anion binding modes of macrocyclic receptor 6.

Sessler and co‐workers have also explored the anion recognition properties of 2,3‐diindolyl quinoxaline (DIQ) 7 a and its mono‐nitro derivative 7 b (nitro‐DIQ) by performing UV/Vis titration experiments in DCM (Figure 5).30 The nitro‐DIQ receptor 7 b displays a significant colorimetric response from yellow to orange when exposed to fluoride and dihydrogenphosphate, and the resulting titrations revealed several isosbestic points expected for a 1:1 binding stoichiometry. For both the receptors, the greatest affinity has been displayed for H2PO4 −, unlike their DPQ analogues, which showed the greatest affinity for F− (Table 1). However, a reliable binding constant could not be determined from the spectrophotometric titration of 7 b with F− anion, owing to the observation of biphasic behavior. The higher H2PO4 − selectivity of DIQs [K a(7 a)/K a(1)=113, and K a(7 b)/K a(2)=250] can be ascribed to the β‐connectivity that links the two indole recognition motifs to the quinoxaline core and, thereby, provides a more open cavity expected to favor the binding of larger anionic substrate like dihydrogenphosphate.

Figure 5

Diindolyl quinoxalines (DIQs) 7 a–c and corresponding indolocarbazole quinoxalines 8 a–c.

Yan and co‐workers have further oxidized compounds 7 a and 7 b with DDQ in TFA to afford the corresponding indolocarbazole quinoxalines 8 a and 8 b (Figure 5).31 Both the receptors showed high binding affinity for fluoride, acetate, and dihydrogen phosphate, as determined by UV/Vis–fluorescence titration in DMSO (Table 1). However, 8 a showed selective colorimetric response only in the presence of fluoride, whereas 8 b showed colorimetric response for F− and AcO−. The X‐ray crystal structures of chloride and acetate complexes of 8 b showed that the indolocarbazole quinoxaline has a highly flat rigid conjugated structure and an anion is hydrogen bonded with the −NH groups of the carbazole unit. A similar strategy was utilized by Liu et al. to produce polydentate conjugate molecules based on a rigid quinoxaline plane surrounded by six indole −NH groups, that is, 7 c and 8 c.32 Both 7 c and 8 c (Figure 5) showed selectivity for fluoride ions. The interaction of receptor 7 c and 8 c with F− was investigated by suing UV/Vis and fluorescence spectroscopic titration. Compared to 7 c, receptor 8 c, with the same ligating sites and chemical environment but with structure that is more rigid and no conformational flexibility, resulted in different sensing behavior. The ability of 8 c to detect F− was shown by ratiometric fluorescence measurements, as shown in Figures 6 A and 6 B.

Figure 6

Fluorescence titration of A) receptor 7 c with F− (as a TBAF salt from 0 to 30 equiv) in DMSO (λ ex=420 nm) and B) receptor 8 c with F− (as a TBAF salt from 0 to 100 equiv) in DMSO (λ ex=440 nm); the insets in (A) and (B) show fluorescence emission color changes of the receptor 7 c and 8 c solution upon addition of F−. Reprinted from Ref. 32 with permission. Copyright (2012) Wiley‐VCH.

To further enhance the selectivity and sensitivity of quinoxaline oligopyrroles for inorganic anions, Sessler and co‐workers developed a new class of calix[4]pyrrole receptor 9 (Figure 7) bearing 6‐nitro‐2,3‐dipyrrolylquinoxaline (2) as strapping elements that would allow the anion binding event to be followed rather easily.33 The receptor displays a significant colorimetric response from orange to blue/purple when exposed to fluoride and dihydrogenphosphate in CH3CN/DMSO (97:3 v/v) solutions, and an enhanced anion affinity as compared to 1 and 2 (Table 1). A visible color change can also be observed in the presence of acetate anion. In the 1H NMR titration with fluoride (CD3CN/[D6]DMSO, 9:1 v/v), a significant downfield shift of the calix[4]pyrrole −NH signals (Δδ=4.85 ppm) compared to the pyrrole −NH signals on the nitro‐DPQ (Δδ=0.42 ppm), and a rather unusual downfield shift of the β‐pyrrolic −CH protons on the nitro‐DPQ strap, led to the conclusion that a fluoride ion is hydrogen bonded to the calix[4]pyrrole core and is also involved in anion–π interaction with the pyrrole rings of the nitro‐DPQ strap. The association constants obtained from the UV/Vis titration experiments have further been verified by isothermal calorimetric (ITC) titration experiments performed in CH3CN/DMSO (97:3 v/v).

Figure 7

Quinoxaline calix[4]pyrrole receptor 9 and its proposed binding mode with fluoride.

Towards systematic modulation of electronic density in the quinoxaline chromophore, Anzenbacher and co‐workers introduced a range of aryl substituents to the 5‐ and 8‐positions of the quinoxaline ring of DPQ (Figure 8).34 The extended aryl substituents of varying electronic nature served to enhance the sensor emissivity by expanding the conjugated quinoxaline chromophore, and to tune the output emission wavelength as well as the anion binding affinity of the receptors through substituent effects. When observed under an UV lamp (λ ex=360 nm), sensors 10 a–10 f can well respond to the presence of fluoride and pyrophosphate anions, as observed by a dramatic decrease in their fluorescence emission in aprotic solvents such as acetonitrile, dichloromethane, and DMSO. Fluorescence titration experiments revealed more than 95 % quenching of the emission intensity in all cases upon addition of fluoride and pyrophosphate to the dichloromethane solutions of the receptors. Whereas other anions, such as chloride, bromide, hydrogensulfate/sulfate, cyanide, and dihydrogenphosphate, are unable to induce any observable changes in the fluorescence emission and absorption spectra of the receptor solutions. In UV/Vis experiments, the addition of fluoride and pyrophosphate to the individual dichloromethane solutions of 10 a–10 f results in the decrease of the absorption intensity at 400–450 nm, together with the appearance of a strong band centered at 500–550 nm, which is responsible for the intense color of the solutions. The high affinity of receptors 10 a–10 f for fluoride and pyrophosphate is a result of high surface charge density of fluoride anion and pyrophosphate dianion and is evident from their binding constant values summarized in Table 1. Notably, receptor 10 a show considerably increased affinity for fluoride and pyrophosphate compared to the parent DPQ (1) sensor.

Figure 8

Aryl substituted DPQs 10 a–10 f.

Furthermore, to improve the performance of luminescence‐based anion sensors, Anzenbacher and co‐workers reported two novel ways of upgrading the DPQ sensor by attaching a pyrene antenna capable of resonance energy transfer (RET) to the parent DPQ or by excited‐state delocalization in the conjugated system through acetylene bridges.35 Visual inspection under UV light (λ ex=365 nm) showed remarkably enhanced emission for sensors 11 and 12 (Figure 9) in DCM solutions compared to the parent DPQ. The fluorescence emission of sensor 11 is observed at 495 nm and, for sensor 12, the emission is shifted to 550 nm, and this amplification get even stronger in polar solvents such as DMSO that strongly quench the DPQ emission (λ max=495 nm). Addition of fluoride and pyrophosphate results in significant quenching of their emission intensity and can be observed visibly under a UV lamp. The emission‐data‐derived binding constants revealed that sensor 12 displays a twofold increase in binding affinity for pyrophosphate compared to the parent DPQ (Table 1).

Figure 9

Pyrene functionalized DPQs 11–12.

Motivated by the increasing appreciation of quinoxaline‐based chemosensors, Wu et al. synthesized receptor 13 (Figure 10) to understand the mechanism of anion sensing by DPQ with extended conjugation.36 The absorption spectral changes and fluorescence quenching in DPQ‐based anion sensors was previously attributed to the formation of hydrogen bonding between an anion and pyrrole −NH protons. However, it seems to be unlikely to bring about such large electronic perturbation (typical bathochromic shift of ca. 5000 cm−1 upon addition of fluoride anions) by simple hydrogen bonding interactions. Identical to the majority of DPQ‐based anion sensors, receptor 13 also experienced a colorimetric response and fluorescence quenching upon addition of fluoride and pyrophosphate anions in DCM solutions. The 1H NMR titration experiments in [D6]DMSO solution revealed the deprotonation of one of the pyrrole −NH protons in presence of excess fluoride or pyrophosphate anions (5 equiv), and the formation of a hydrogen‐bonded complex between deprotonated receptor and the anion (Figure 10). The 1H NMR experiments also indicated that the receptor 13 could be fully recovered by adding equivalent amounts of trifluoroacetic acid to the anion‐containing solution.

Figure 10

Formation of H‐bonded fluoride complex and subsequent deprotonation of phenyl conjugated DPQ, 13.

In quest of electro‐optical sensors for inorganic anions, Wong et al.37 and Anzenbacher et al.38 have synthesized a series of sensors 14–16 (Figure 11), which utilize a DPQ‐like moiety for anion binding and a redox‐active quinone moiety to generate strong colorimetric and electrochemical signals. Sensor 16 could be obtained only in trace amount by the condensation of dipyrrolylethane‐1,2‐dione with tetraamino‐1,4‐benzoquinone, owing to polymerization and, thus, its synthesis and anion sensing properties were not pursued further.38 Sensors 14 and 15 showed a dramatic change in color in the presence of fluoride, cyanide, pyrophosphate (HP2O7 3−), and acetate in MeCN solution, whereas the addition of dihydrogenphosphate (H2PO4 −), benzoate, or chloride did not result in any appreciable change in color. Association constants calculated by monitoring the changes in the UV/Vis titration curves of sensors 14 and 15 in presence of anions revealed that sensor 14 has a much higher affinity for fluoride followed by pyrophosphate, whereas sensor 15 has a fourfold higher affinity for pyrophosphate than fluoride (Table 1). The anion affinity of sensors 14 and 15 was also investigated by using cyclic (CV) and square‐wave voltammetry (SWV).38 Both methods confirmed that the anion binding is accompanied by an anion‐specific change in redox potential and decrease in current, a behavior attributed to the formation of the receptor–anion complex with a lower diffusion coefficient. SWV titrations show measurable changes in peak current and reduction potential even in the case of anions that induce only a weak color change that is insufficient for reliable determination by absorption spectroscopy (e.g. H2PO4 −).

Figure 11

Redox active quinone‐based dipyrrolyl pyrazine receptors 14–16.

It is to be noted that the majority of the above discussed DPQ‐based sensors were not anion specific in the sense that they showed optical signaling in the presence of fluoride and also in the presence of acetate or phosphates (dihydrogenphosphate/pyrophosphate). Thus, their selectivity is limited to at least two anions or even more, as observed in the cases of 14 and 15. In our work with DPQ‐based sensors, we have observed that the anion selectivity can be specifically tuned for fluoride only by functionalization of DPQ‐like recognition sites with tetrathiafulvalene (TTF), 17 (Figure 12).39

Figure 12

TTF‐functionalized DPQ, 17 for selective fluoride sensing. Fluoride selective color changes observed for 17 in CH2Cl2. Reprinted from Ref. 39 with permission. Copyright (2012) Royal Society of Chemistry.

The receptor showed optical color changes from orange to pink only in the presence of F−, whereas no color changes have been observed in the presence of Cl−, Br−, AcO−, HSO4 −, or H2PO4 − in DCM solutions (Figure 12). UV/Vis titration of 17 with F− in DCM showed a notable redshift of the original absorption bands with three clear isosbestic points. Furthermore, the emission intensity of 17 was significantly enhanced upon addition of F− and an association constant value of 6×104  m −1 was obtained by fitting the changes in the emission data to a 1:1 binding stoichiometry. Based on H NMR spectroscopy, which showed the disappearance of pyrrole −NH and broadening of pyrrole −CH protons upon addition of F−, we have suggested that anion‐induced deprotonation of −NH is responsible for the selective sensing of fluoride. Finally, the material may be easily electrodeposited from solution by scanning the potential to the second oxidation process, which eventually produces a stable modified electrode that is electrochemically active in contact with aqueous sodium fluoride (NaF) solution.

A deep cavitand 18 bearing four DPQ moieties has been reported by Rebek and co‐workers for anion recognition (Figure 13).40 From NMR spectroscopy, it has been suggested that the cavitand 18 exists as a vase‐like structure in solution. This DPQ‐functionalized cavitand showed a color change from yellow to red in the presence of fluoride and acetate anions in acetone/dichloromethane. UV/Vis spectroscopic analysis showed the disappearance of the original band at 420 nm and the appearance of two new bands at 350 and 490 nm upon addition of fluoride or acetate. Broadening of H NMR signals for all groups of protons were observed upon the addition of fluoride and acetate in [D6]acetone. Interestingly, no anion binding was observed to occur in deuterated aromatic solvents.

Figure 13

Cavitand 18 with DPQ recognition sites.

Quinoxaline‐Based Polymers

Aldakov and Anzenbacher have also presented a materials chemistry approach for anion sensing by employing two DPQ‐based conductive polymers P1 and P2 (Figure 14), which are able to undergo an adjustable degree of p‐doping, owing to the presence of thiophene moieties in the polymeric backbone.41 Thus, two independent modes of signal transduction can be obtained in the chromogenic sensory materials, increasing the overall reliability of the sensing process. Spectroelectrochemical analysis of P1 and P2 films has enabled the investigation of the polymer electronic structure and determination of the polymer band gaps. The anion sensing ability of the polymers were tested by titration of the polymer films at a constant potential of 0.00 V with different anions (5.0 mm, pH ≈6.5) in aqueous solution, whereas Vis–NIR spectra were recorded concurrently. Gradual absorption spectral changes have been observed upon addition of fluoride and pyrophosphate anions into the individual cells containing the sensor films of P1 and P2. Changes were also observed upon addition of phosphate into a cell containing P2 film. The low level of p‐doping at 0.70 V and a corresponding positive charge in the polymers resulted in a dramatic increase of their anion affinity. For example, the association constant of P1 for pyrophosphate recorded at 0.70 V was calculated as K PP(0.70 V)=260 000 m −1, whereas the constant recorded at 0.00 V was K PP(0.0 V)=61 100 m −1. P2 displays a stronger binding and higher association constants compared to P1 due to the increased acidity of −NH protons of the chlorinated pyrrole.

Figure 14

DPQ‐based polymers, P1–P5, the azomethine‐containing conjugated polymers linked with fluorene and/or quinoxaline units P6 and P7, and the poly(ortho‐diaminophenylene) derivatives containing fluorene and/or quinoxaline moieties P8 and P9.

Wu et al. synthesized two alkylated conductive polymers, P3 (n=7) and P4 (n=110) to understand the mechanism of anion sensing by DPQ‐based polymers (Figure 14).36 The absorption and emission spectra are not very sensitive to the degrees of polymerization, but do show some redshift with a higher degree of polymerization. Both polymers exhibited very bright fluorescence, but are sensitive to the presence of proton donors such as water and acetic acid in solution. As expected, colorimetric responses were observed upon addition of fluoride or pyrophosphate anions to P3 and P4 solutions, which could be attributed to the anion‐induced deprotonation of −NH proton(s). Furthermore, the sensitivity of anion‐induced fluorescence quenching of P3 and P4 was significantly enhanced over the corresponding monomeric sensor 13 (Table 1). The anion‐induced deprotonation generates low‐energy, non‐fluorescent trapping sites and is responsible for the signal amplification, where the quenching of the excited state occurs from the deprotonated DPQ site in the network by rapid exciton migration along the polymeric backbone. Again, the fluorescence lifetimes of the polymer solution do not vary with the concentrations of the anion, indicating that a statically quenched polymer–anion complex dominates the fluorescence quenching mechanism in these systems.

Sessler and co‐workers developed a DPQ‐based copolymer P5 (Figure 14), which is responsive to hydrofluoric acid (HF) vapors in the state of polymeric materials, such as films.42 Thin films of P5 on glass slides, which were prepared by both drop‐casting and spin‐coating methods, were examined for their ability to detect HF in vapor form and in solution when used as a dipstick. Upon exposure to vapors of 12.5 % HF solutions, by weight, the initially bright yellow thin films changed to a distinct red color. This color change was both rapidly reversible upon exposure to vapors of concentrated ammonium hydroxide and slowly reversible under ambient conditions. Similarly, a dipstick test that was performed by submerging the end of a slide covered with the thin film into an aqueous solution of HF provided an even stronger response, with a change from yellow to purple. The association constant of P5 for F− in DCM was estimated to be 6.16×105  m −1 for each DPQ unit.

Kim et al. compared the sensing capabilities azomethine‐containing conjugated polymers linked with fluorene and/or quinoxaline units P6 and P7 (Figure 14).43 These two polymers are highly responsive and reversible to proton in the solid state, making them promising materials for acid gas sensory. Based on this, reversible chromatic switching behavior was accomplished through pH control of the solution. Protonation of P6 and P7 allowed for naked‐eye colorimetric detection of iodide and acetate anions. A structure modification strategy for these two polymers is suggested to tune the ion‐detecting properties by colorimetric change (Figure 15). In another report, Kim et al.44 described the synthesis of poly(ortho‐diaminophenylene) derivatives containing fluorene and/or quinoxaline moieties P8 and P9. They explored the colorimetric and fluorometric anion sensing capabilities of these materials and found that the color of the polymer solution was altered dramatically upon the addition of fluoride anions without noticeable absorption change in UV/Vis spectrum. The fluorescence was ratiometrically quenched with a linear relationship between fluorescence intensity and fluoride anion concentration, implying static quenching mechanism.

Figure 15

Color change of P6 and P7 in chloroform solutions upon addition of 100 equivalents of anions as their tetrabutylammonium salts (from left to right: polymer, polymer+TFA, polymer+TFA+F−, polymer+TFA+Cl−, polymer+TFA+Br−, polymer+TFA+I−, polymer+TFA+AcO−, polymer+TFA +SO4 2−), P8 and P9 in THF solutions gave fluoride selective color and fluorescence change by addition of 100 equivalenta of the anion as compared to other anions in the bottom four rows. Reprinted from Ref. 43 with permission (top). Copyright (2008) Elsevier. Reprinted from Ref. 44 with permission (bottom). Copyright (2007) John Wiley & Sons.

Quinoxaline Sulfonamides

In addition to functionalized DPQs, several quinoxaline bis(sulfonamide)‐based receptors have been synthesized and applied in anion sensing studies by different research groups, including us. In our effort to study the anion binding capabilities of DPQ and quinoxaline bis(sulfonamide), we synthesized a dipyrrole‐bis‐sulfonamide‐based receptor 19 with two sulfonamide groups on the DPQ unit (Figure 16).45 This receptor showed strong colorimetric and fluorescent responses for fluoride, dihydrogen phosphate, and acetate in chloroform [colorless to red (F−)/yellow (H2PO4 −/AcO−)]. The fluorescence intensity of 19 was enhanced upon addition of F−, H2PO4 −, and AcO− in chloroform. 1H NMR titration of 19 with F− revealed that the sulfonamide −NH proton may be deprotonated while the pyrrole −NH protons are engaged in hydrogen bonding interactions with fluoride. Thus, the colorimetric and fluorometric signaling of F−, H2PO4 −, and AcO− by 19 could be assigned, owing to the deprotonation of sulfonamide −NH complemented by pyrrole −NH hydrogen bonds.

Figure 16

Dipyrrolylquinoxaline‐bis(sulfonamide) receptor 19 and quinoxaline‐bridged bis(sulfonamide) porphyrin receptor 20.

Starnes et al. synthesized a quinoxaline‐bridged bis(sulfonamide) porphyrin receptor 20 (Figure 16), whose anion binding capability has been detected from the perturbation of the porphyrin Soret and Q bands in the UV/Vis spectrophotometry.46 The Soret band of 20 at 422 nm was red‐shifted by 12–16 nm and a clean isosbestic point was observed in each spectrophotometric titration with different anions, carried out in dichloromethane. The receptor showed highest binding affinity for F− followed by H2PO4 −, AcO−, and Cl− (Table 1). The recognition properties of 20 were also investigated by using 1H NMR spectroscopy for F− and Cl− binding.

Sun and co‐workers synthesized a series of quinoxaline bis‐ (sulfonamide)‐based receptors 21–23 (Figure 17), capable of recognizing F−, AcO−, CN−, and H2PO4 − with different sensitivities.47 The anion binding properties of 21–23 have been investigated by UV/Vis and fluorescence spectroscopy, and binding constants are calculated from the changes in the UV/Vis spectra (Table 1). The results from 1H NMR spectroscopic experiments provide further evidence for identifying the receptor–anion interaction processes. Sensor 21 has the weakest acidic sulfonamide −NH protons and, therefore, simply forms hydrogen‐bonding complexes with F−, AcO−, CN−, and H2PO4 − in acetonitrile (CH3CN) solutions. Notably, the emission intensity (λ em) of 21 at 530 nm shows an enhancement upon the addition of F−, AcO−, CN−, or H2PO4 −, unlike the DPQ‐based anion sensors that experience fluorescence quenching upon addition of fluoride or pyrophosphate. Sensor 22 undergoes a stepwise process with the addition of F− and AcO− anions, namely formation of hydrogen bonded complex followed by sulfonamide −NH deprotonation in DMSO solutions. Direct sulfonamide −NH deprotonation occurs upon the addition of CN−, but only a hydrogen‐bonded complex forms with H2PO4 − in DMSO solutions of 22. Similar receptor‐to‐anion interactions have also been detected for 23 with the addition of F−, CN−, and H2PO4 −. However, only a genuine hydrogen‐bonded complex forms in the presence of the AcO− in a DMSO solution of 23, because of the subtle difference in the pKa values of sulfonamide −NH protons when probes 22 and 23 are compared. The degrees of receptor–anion interactions can be easily visualized by naked‐eye colorimetric or luminescent responses.

Figure 17

Pyridine, phenanthroline, and phenanthrene functionalized quinoxaline‐bis(sulfonamide) receptors, 21, 22, and 23, respectively.

A dithieno[3,2‐a:2′,3′‐c]phenazine‐based bis(sulfonamide) receptor 24 (Figure 18) for anion detection has been reported by Kaafarani and co‐workers.48 Anion binding studies using fluorescence and 1H NMR titration experiments revealed strong binding of 24 with cyanide, carboxylate (acetate and benzoate), and dihydrogenphosphate. Fluorescence titration of 24 (CHCl3) with any of these anions resulted in an enhancement of the emission intensity of the probe with concomitant blue shift from 620 to 560 nm. In 1H NMR titration (CDCl3), the sulfonamide −NH proton disappeared, owing to hydrogen bonding with anion; however, a significant downfield shift of the thiophene −CH proton has been observed because of the electrostatic interaction of the tetrabutylammonium cation with dithieno moieties coupled with the delocalization of electron density on the extended aromatic systems and the electron withdrawing effect of the sulfur atoms. Halides were unable to induce any significant changes in the fluorescence emission intensity of 24 as compared to cyanide and carboxylates.

Figure 18

Dithienophenazine based bis(sulfonamide) receptor 24.

Unlike the above‐discussed quinoxaline bis(sulfonamide) receptors, which lack selectivity for a specific anion, our work on naphthalene diimide‐functionalized dihydroquinoxaline bis(sulfonamide) receptor 25 (Figure 19) showed selective optical signaling and fluorescence quenching only in the presence of fluoride among other tested anions (Cl−, Br−, I−, AcO−, HSO4 −, and H2PO4 −).49 Receptor 25 showed selective colorimetric response from blue to green for F− in chloroform or in DMSO solution (Figure 19). Significant quenching (ca. 97 %) of the emission intensity of 25 was observed upon addition of three equivalents of fluoride to a chloroform solution, whereas other anions produced negligible quenching under similar conditions. 1H NMR spectroscopy and single‐crystal X‐ray structure analysis confirmed the deprotonation of a sulfonamide −NH group in the presence of fluoride. A distinctive bathochromic shift (ca. 100 nm) of the original absorption bands of 25 with a clear isosbestic point has been observed in the UV/Vis titration with fluoride in DMSO. Based on the UV/Vis titration data, the association constant was calculated to be 0.5×106  m −1, for 1:1 binding.

Figure 19

Naphthalene‐diimide‐functionalized dihydroquinoxaline bis(sulfonamide) receptor 25 and color changes observed in the presence of different anions. Reprinted from Ref. 49 with permission. Copyright (2009) American Chemical Society.

Metal Complexes of Quinoxaline‐Based Sensors

Synthetic modification of DPQs and other quinoxaline‐based anion receptors through the strategic incorporation of cation binding elements onto the receptor backbone to yield metal complexes to be employed as anion sensors has also resulted in significant enhancement in the anion binding affinity particularly towards fluoride and pyrophosphate. The first contribution in this field was made by Sessler and co‐workers, who demonstrated the fluoride recognition properties of the ruthenium(II) and cobalt (III) complexes of a pyrazino‐phenanthroline fused dipyrrolylquinoxaline derivative, 26 (Figure 20). In complexes 26‐Ru and 26‐Co, the electron‐withdrawing effects that would render the pyrrole −NH protons more acidic take place efficiently through the quinoxaline backbone and lead to enhanced anion binding affinities.50 In UV/Vis spectroscopy, the addition of F− to a DMSO solution the cobalt (III) complex resulted in the emergence of a new peak at higher wavelength (650 nm) with a concomitant change in color from pink to purple, whereas the absorbance of the original absorption bands (323 and 525 nm) significantly decreased.

Figure 20

Pyrazine–phenanthroline‐fused dipyrrolylquinoxaline 26 and its RuII and CoIII complexes 26‐Ru and 26‐Co.

The proposal of adding cationic charges to a DPQ‐based sensor can indeed be employed to increase the anion affinities, as evidenced by the evaluated binding constants of 26, 26‐Ru, and 26‐Co with F−, Cl−, and H2PO4 −, based on their absorption spectral changes (Table 1). The 26‐Co complex with greater charge displayed a much higher affinity for F− anion, as compared to 26 and 26‐Ru. The free receptor 26 displayed a rather low F− affinity, presumably because of the additional electron density donated to the DPQ functionality from the phenanthroline moiety. In the differential pulse voltammetry (DPV) studies, the addition of F− to a DMSO solution of 26‐Co resulted in a complete disappearance of the sharp CoIII/CoII reduction signal, suggesting a redox‐inactive nature in the complex formed. Furthermore, the fact that the CoIII/CoII signal can be restored upon the addition of small amount of water indicates that the complexation between 26‐Co and F− is reversible.

Anzenbacher et al. reported an example of luminescence lifetime‐based anion sensing by employing a RuII metal complex of phenanthroline‐fused dipyrrolylpyrazine, 27 (Figure 21). Preliminary investigations revealed that the addition of fluoride, cyanide, and phosphate to the DCM/MeCN (98:2 v/v) solutions of 27 and 27‐Ru caused significant changes in their absorption and emission properties.51 The emission spectrum of 27‐Ru is significantly quenched and red‐shifted (λ ex=493 nm) with increasing CN− concentration, indicating a lowering in energy of the excited state and enhancement of non‐radiative decay. In all cases, the emission‐data‐derived binding constants are substantially enhanced in 27‐Ru relative to 27, owing to the electron‐withdrawing effects caused by the RuII center (Table 1). In absence of an anion, 27‐Ru exhibited a single‐exponential lifetime of τ=377(±20 ns) and, with increasing cyanide concentration, the intensity decays exhibited complex kinetics that adequately fit a sum of two exponentials (long τ=320–370 ns and short τ=13–17 ns). These emission lifetime data suggest that there are at least two distinct luminescent species, consisting of anion‐bound 27‐Ru (short τ) and free 27‐Ru (long τ), the sum of which results in the observed lifetime quenching.

Figure 21

Phenanthroline fused dipyrrolylpyrazine, 27 and its RuII complex 27‐Ru.

In an effort to increase the sensitivity of receptors 21 and 22, metal complex probes 21‐Re and 22‐Ru have been synthesized upon metal coordination with the pyridylquinoxaline moiety of 21 and the phenanthroline moiety of 22, respectively (Figure 22).47, 52 As a consequence of metal coordination, the sulfonamide −NH protons become increasingly acidic, thereby facilitating proton transfer from the probe molecules to basic anions. A two‐step equilibrium phenomenon was observed in the UV/Vis titration of 21‐Re with F− in DMSO solution. The stepwise process observed can be described by the formation of a hydrogen‐bonded complex with sulfonamide −NH protons followed by deprotonation of a sulfonamide −NH proton to form mono‐deprotonated probe 21‐Re and HF2 −. In the cases of CN− and AcO−, the spectrophotometric responses are attributed to a stepwise double deprotonation, which was further confirmed by titration of 21‐Re with OH− ions and 1H NMR experiments. However, spectrophotometric titrations with Cl− and H2PO4 − showed the formation of a 1:1 hydrogen bonding complexes for both anions, further confirmed by 1H NMR experiments. A two‐step process corresponding to the formation of a hydrogen‐bonded complex followed by deprotonation has also been observed in the spectrophotometric titration of 22‐Ru with F− in DMSO solution. Similar spectral responses were also observed for AcO− and H2PO4 −, albeit with less sensitivity. However, the two‐step absorption spectral isotherms obtained with the addition of CN− are ascribed to a double deprotonation process, which is different from the single proton‐transfer process observed in 22. The 1:2 stoichiometry for receptor–anion interactions together with a two‐step process observed in the spectrophotometric titrations of 22‐Ru with basic anions implies that only one sulfonamide ligand is in action with the incoming anions. Thus, it was speculated that the coordination of a RuII metal center to ligand 22 greatly facilitates the sulfonamide −NH proton dissociation in a polar DMSO solution. As a result, 22‐Ru tends to become a neutral molecule with two −NH protons dissociated at two different ligands, leaving only one intact sulfonamide ligand available for anion interaction.

Figure 22

Rhenium(I) complex of pyridine‐functionalized quinoxaline bis(sulfonamide), 21‐Re and ruthenium(II) complex of phenanthroline‐fused quinoxaline bis(sulfonamide) 22‐Ru and 2,2′‐biyridine ruthenium(II) and cobalt(III) complexes of phenanthroline‐fused quinoxaline bis(sulfonamide) 22‐Ru and 22‐Co (BP=bipyridine).

Shang et al. compared ruthenium(II) and cobalt(III) sulfonamide–quinoxaline complexes as electrochemical sensors (Figure 22).53 Spectrophotometric results indicate that 22‐Ru and 23‐Co have strong affinities for F− or AcO−, and moderate affinities for H2PO4 − or OH−. The interaction of these artificial receptors with F− and AcO− causes visible color changes, which make the receptors colorimetric sensors that can be ascribed to the hydrogen‐bond formation with strong effects on the quinoxaline group. By changing the substitution site on the phenyl ring, for example, from para to ortho, the selectivity between fluoride and acetate may be finely tuned. The correlations between the electronic properties of the substituent and the affinity, as well as the selectivity and the configuration of receptor, will be a very useful guide to design more selective chemosensors to recognize F− or AcO−.

Xu et al.54 designed a novel NIR‐emitting cationic IrIII complex with CN ligands containing dimesitylboryl groups and an extended NN ligand, 28‐Ir (Figure 23). Upon photoexcitation, the complex shows NIR phosphorescent emission around 680 nm. Interestingly, the complex can be excited with long wavelength around 610 nm, which can reduce the background emission interference and improve the signal‐to‐noise ratio. Through the selective binding between boron centers and F−, an ON–OFF‐type NIR phosphorescent probe was realized.

Figure 23

The chemical structures of IrIII complex [Ir(Bpq)2(quqo)]PF6 28‐Ir and ferrocene–imidazole–quinoxaline triad 29.

Alfonso et al.55 reported a nitrogen‐rich ferrocene–imidazole–quinoxaline triad 29 decorated with two pyrrole rings (Figure 23), which, owing to its ditopic nature behaves as an ion‐pair receptor for Ni2+/Hg2+ cations and AcO− anions. Although no affinity for acetate has been observed in UV/Vis study, fluorescence spectrophotometric titrations revealed enhancement of the emission spectrum in the presence of AcO− and H2PO4 −. Cyclic voltammetry titration studies also showed selectivity for AcO− and H2PO4 −, where the wave corresponding to the neutral receptor disappears when 2.5 equivalents of AcO− is added in acetonitrile medium. It also displays the rare property consistent with the cooperative and recognition of ion pairs.

Balamurugan and Velmathi used a quinoxaline‐based copper complex in a redox process toward the sensing of iodide ions.56 They synthesized quinoxaline‐based azine derivatives 30 a and 30 b, which showed a highly selective color change from orange and yellow to violet and blue, respectively, in the presence of copper ions. The iodide ions selectively regenerated the receptors 30 a and 30 b from their copper complexes. The receptors showed good binding constants and micromolar detection limit with 1:2 stoichiometric ratio of copper(II) and 1:4 of iodide ions (Figure 24).

Figure 24

Chemical structures of 30 a and 30 b ligands (A), UV/Vis titration of 30 a with Cu2+ (B), UV/Vis titration of 30 a‐Cu2+ with I− anion (C), and redox process regenerating 30 a from 30 a‐Cu2+ using iodide anion (D). Reprinted from Ref. 56 with permission. Copyright (2016) Elsevier.

Quinoxaline‐Based Cationic Receptors

A wide variety of hydrogen‐bond donor cationic systems containing ammonium, guanidinium, pyridinium, and imidazolium moieties exist, which can behave as anion sensors through a combined effect of hydrogen bonding and electrostatic interactions.

In their contribution, Kim and co‐workers reported a series of four quinoxaline‐based imidazolium receptors 31 a–31 d (Figure 25), which are able to display an anion‐induced excimer formation or charge‐transfer phenomenon in organic media,57 defining its uniqueness and exclusivity among the quinoxaline‐based anion sensors. The anion binding affinities of these systems have been studied by using fluorescence and 1H NMR titration techniques. In the fluorescence study of the compounds in the presence of excess anions (100 equiv), the anion‐induced excimer formation (ca. 430 nm) has been observed with almost all anions, except HP2O7 3− and AcO−, which induce unique charge‐transfer fluorescent responses in 31 a and 31 b, respectively. The anion‐induced intermolecular π–π stacking between two quinoxaline rings is responsible for the excimer‐state band. Whereas, the deprotonation of 31 a/31 b in the presence of pyrophosphate or acetate can be correlated with the appearance of a distinct fluorescent peak at higher wavelength (500 nm), owing to the rapid charge‐transfer phenomena from quinoxaline to deprotonated imidazolium ring.

Figure 25

Quinoxaline‐based imidazolium receptors 31 a–31 d.

Kruger et al. have shown that the protonation of 2,3‐dipyridylquinoxaline 32 results in a significant change in the absorption and emission properties of the molecule, owing to the alteration (flattening) of the molecular conformation. Protonated 2,3‐dipyridylquinoxaline (Figure 26) behaves as luminescence anion sensor, showing some degree of selectivity for dihydrogenphosphate, chloride, and fluoride over other anions.58 Fluoride and dihydrogenphosphate quenched the emission intensity (at 454 nm) by 50 and 60 %, respectively. However, deprotonation of the protonated receptor was observed at very high concentrations of fluoride and dihydrogenphosphate, providing the parent molecule, as evidenced both by absorption and luminescence spectroscopy.

Figure 26

a) Protonated 2,3‐dipyridylquinoxaline 32 and b) nucleophilic addition of fluoride/acetate at the C2 position of the substituted phenyl quinoxalinium cation 33.

Recently, phenyl quinoxalinium salts 33 (Figure 26) have been recognized as chemosensors for fluoride and acetate, owing to the nucleophilic addition of these anions at the electron deficient C2 position of the quinoxalinium cation.59 Nucleophilic addition of fluoride/acetate leads to the de‐aromatization of the quinoxalinium cation, resulting in fluorescence quenching and decolorization of the quinoxalinium salt solution, as reflected in the absorption spectroscopic studies, where a significant decrease in the intensity of the absorbance bands was observed upon incremental addition of anion solution. In a representative 1H NMR experiment, addition of 1 equivalent of fluoride to 33 (R=F) resulted in the disappearance of a singlet peak for the quinoxaline proton (adjacent to the positively charged N) at δ=9.71 ppm with the concomitant appearance of a new peak at δ=5.99 ppm that confirms the nucleophilic addition of anion. Similar 1H NMR spectral changes were observed upon addition of 5 equivalents of acetate to 33 (R=F). Unlike F− and AcO−, ascorbate (large anion) quenches fluorescence through a photoinduced electron transfer (PET) mechanism, owing to the formation of a host–guest complex, and no peak shifting was observed in 1H NMR spectroscopy.

The selective binding of monophosphate over diphosphate and triphosphate by receptor 34, composed of two [9]aneN3 units separated by a 2,3‐dimethylenequinoxaline spacer (Figure 27), has been studied by means of potentiometric titrations as well as 1H and 31P NMR experiments in aqueous solutions by Bazzicalupi et al.60 In aqueous solution, the amine groups of the macrocycle can easily become protonated to give charged polyammonium receptor 34. The selective binding of monophosphate by 34 is determined by the distance between the two macrocyclic [9]aneN3 units imposed by the dimethylenequinoxaline spacer that gives rise to a cleft of appropriate dimension for H2PO4 − anion. Two similar receptors composed of two [9]aneN3 units separated by 2,6‐dimethylenepyridine and 2,9‐dimethylene‐1,10‐phenanthroline showed preferential binding for diphosphate and triphosphate, respectively. 1H and 31P NMR experiments revealed that the complexes are essentially stabilized by electrostatic and hydrogen bonding interactions between the phosphate anion and the protonated amine groups of the macrocyclic subunits of the receptors.

Figure 27

Dimethylquinoxaline‐bridged macrocyclic polyamine receptor 34.

Miscellaneous Quinoxaline‐Based Sensors

Further towards the development of highly sensitive chromogenic and fluorescent anion sensors with polarized −NH functions, Sun and co‐workers established that quinoxaline‐based receptors 35 a and 35 b (Figure 28) featuring the combination of hydrazine, hydrazone, imine, and hydroxyl functions can serve as efficient optical sensors for F−, AcO−, and H2PO4 − in DMSO solutions.61 The involvement of hydroxyl groups in anion binding resulted in stronger binding affinity of 35 b than 35 a, as established from the 1H NMR titration experiments in [D6]DMSO, and energy‐minimized molecular models derived from semi‐empirical MOPAC/AM1 method. Owing to their structural flexibility, receptors 35 a and 35 b could adopt a conformation to accommodate strongly interacting anions such as F−, AcO−, and H2PO4 − and to compensate the energy required to “twist” the structural framework by forming multiple hydrogen bonds. Two potential anion binding pockets within the receptor structure result in a 1:2 binding stoichiometry with F−, AcO−, and H2PO4 − in case of 35 a; whereas, for 35 b, a 1:2 binding stoichiometry was observed only with AcO− and H2PO4 −, and the binding isotherm with F− was found to be complicated with multiple equilibria occurring in solution. The formation of an aggregated [2+2] supramolecular complex has been proposed to rationalize the observed absorption and emissive responses of 35 b upon addition of F− (both titration spectra exhibited two distinct conversion steps with increasing concentration of F− anion), and is also supported by electrospray ionization (ESI) mass spectrometry and pulsed‐field gradient NMR spectroscopy. The association of a first F− anion to form a dimeric aggregate via a combination of multiple hydrazine/hydrazone/imine/hydroxyl anion hydrogen bonding and π–π stacking interactions allows for the association of a second F− anion within the preorganized hydrogen bonding pocket and could, therefore, exert homotropic cooperativity effect.

Figure 28

a) Hydrazine and hydrazone functionalized quinoxaline derivatives 35 a, b and b) proposed 1:2 receptor–anion binding mode of 35 b.

Sun and co‐workers also reported a biphenyl quinoxaline‐based receptor 36, featuring the dipyrrole–carboxamide anion recognition motifs (Figure 29).62 The compound showed high selectivity for cyanide over a range of common inorganic anions in semi‐aqueous environment (CH3CN/H2O, 9:1, v/v), owing to the formation of cyanohydrin derivative. Selective cyanide sensing is expressed by a colorimetric response from colorless to yellow accompanied through a change in fluorescence from blue to green. In the UV/Vis titration, three new bands appeared at the expense of the original bands and isosbestic points indicated a clean conversion throughout the titration process. Based on absorption spectral changes, the binding constant was calculated to be log K=5.91 m −1 for a 1:2 receptor–cyanide stoichiometry. Based on the 1H NMR spectral changes upon addition of cyanide in [D6]DMSO solution of 36, the formation of a cyanohydrin adduct has been proposed and was also confirmed by ESI mass spectrometry and 13C NMR spectroscopy.

Figure 29

a) Formation of cyanohydrin derivative upon addition of cyanide to a solution of 36 and b) deprotonation of 36 upon addition of acetate.

However, F− and AcO− anion‐induced deprotonation of receptor 36 has been proposed from 1H NMR experiments. The amide and pyrrole −NH signals of 36 shifted downfield and became broad upon addition of even less than 1 equivalent of AcO−, indicative of a dynamic process occurring at a rate comparable to the 1H NMR spectroscopic timescale.63 The quinoxaline −CH proton signal also shifted downfield and the rest of the aromatic proton signals displayed upfield shifts. These observations suggest the initial formation of a hydrogen‐bonding complex between 36 and AcO−, followed by an intramolecular proton transfer from one of the amide −NH protons to an acetate anion (Figure 29). The titration of F− against a [D6]DMSO solution of 36 resulted in a downfield shift and peak broadening of the amide and pyrrole −NH signals, indicating the formation of a typical hydrogen‐bonding complex upon addition of 1 equivalent of F−. The amide −NH signals gradually disappeared upon further addition of F− and the quinoxaline −CH peak get slightly upfield shifted, suggesting the neat deprotonation of an amide ‐NH group to form the HF2 − anion.62

Duke and Gunnlaugsson reported a bis‐quinoxaline amidothiourea‐based supramolecular cleft, 37 (Figure 30), for the fluorescent sensing of anions in organic media.64 Both the ground and excited states of 37 were considerably affected upon recognition of acetate by the individual amidothiourea functions. The emission intensity at 464 nm was quenched by approximately 62 % after the addition of 2 equivalents of AcO− in acetonitrile (MeCN) solution. The absorption spectral changes upon titration with AcO− were best fitted to a three‐component binding model using the non‐linear regression analysis programme SPECFIT, and two binding constants were determined for the 1:1 and 1:2 receptor–anion interactions (log K 1:1=log K 1:2=6.4). This clearly indicates that both amidothiourea functions are acting independently and a mixture of both the 1:1 and 1:2 complexes are formed in an almost equal amounts. Similar changes in the absorption and emission spectra were observed in the presence of hydroxide ions, indicating the anion‐induced deprotonation of the receptor is responsible for the sensing of acetate anion and were also confirmed by carrying out 1H NMR titrations in [D6]DMSO.

Figure 30

Bis‐quinoxaline amidothiourea based supramolecular cleft 37.

Conclusions

In this Review, we have given a comprehensive account of quinoxaline‐based chromogenic and fluorogenic chemosensors and reagents for inorganic anions. The concept of anion coordination chemistry coupled with optical signal generation by hydrogen‐bond‐induced changes in the electronic properties or deprotonation of the sensory probe is the primary approach employed in most of the reports. The examples discussed in this Review illustrate how the integration of anion binding elements with the quinoxaline chromophore could result in anion responsive chemosensors. One aspect that has been observed in common for these chemosensors is that they all showed colorimetric response for fluoride, and very often for acetate and phosphate as well, owing to their high basicity as compared to other halides and oxyanions. Only quinoxaline receptors 7 c, 8 a, 8 c, 17, and 24 as well as polymers P8 and P9 showed highly selective colorimetric and fluorescence response towards fluoride, and 35 showed optical selectivity only for cyanide by cyanohydrin formation. Thus, over the years we see that structural modification of the quinoxaline moiety with different sets of signaling unit and recognition sites has resulted in a few anion selective receptors. Based on the reports on several functionalized DPQ systems, it is evident that the anion binding affinities can be significantly enhanced by incorporation of electron‐withdrawing functions on DPQ or by introducing aromatic functions on to the quinoxaline ring or by metal complexation.

However, there are very few single‐crystal X‐ray structures showing the receptor anion hydrogen bonding interactions for quinoxaline‐based receptors. Amongst the neutral receptors, dihydrogenphosphate complex of 7 b and chloride/acetate complexes of 8 b are the only three examples where hydrogen bonding between pyrrole −NH and anion (spherical chloride, trigonal acetate and tetrahedral dihydrogenphosphate) can be observed in the respective crystal structures. Then again, no deprotonated receptor molecule (with tetrabutylammonium counter cation) has been structurally characterized although pyrrole −NH deprotonation in the presence of basic anions suggested being responsible for colorimetric sensing in several receptors based on spectroscopy results. Amongst the cationic receptors, hydrogen bonding between a chloride anion with the imidazolium −CH protons of receptors 30 a and 30 d has been established by crystallography.

Thus, it can be concluded that the anion sensing by quinoxaline‐based receptors are limited to only basic anions in organic medium, and no effort has been made to date towards the sensing of some other environmentally and biologically toxic anions such as arsenate or selenate. It is important to mention here that the detection and determination of anions in real wastewater samples have not been pursued with any of these quinoxaline‐based receptors, possibly owing to their poor solubility in water. However, innovative design and synthesis of quinoxaline‐based molecules and materials by considering their stabilities, optimal geometries for hydrogen bonding interactions, optoelectronic properties, and water solubility should make it possible to obtain attractive sensory systems for anions in aqueous medium, which will contribute greatly to the academic foundation and practical applications of anion recognition chemistry.

We hope that this Review article will help new researchers to take up research in the emerging field of anion sensing and develop highly selective and sensitive anion sensors in water, which could find practical applications in chemical science and technology.

Conflict of interest

The authors declare no conflict of interest.

Biographical Information

Sandeep Kumar Dey received his Ph.D. in Chemistry from Indian Institute of Technology Guwahati (India) in 2013 under the supervision of Prof. Gopal Das. After a one‐year post‐doctoral stay in the group of Prof. Shih‐Sheng Sun at Academia Sinica (Taiwan) during 2013–2014, he joined the group of Prof. Christoph Janiak at Heinrich‐Heine‐University in Dusseldorf (Germany) as an Alexander von Humboldt (AvH) Postdoctoral Fellow (2014–2016). He is currently a DST‐INSPIRE faculty at the Department of Chemistry of Goa University (India). His research interests are mainly in the field of supramolecular chemistry and functional porous materials for adsorption and catalysis applications.

Mohammad Al Kobaisi received his Ph.D. under the supervision of Prof. Colin Rix and Prof. David Mainwaring from RMIT University (Australia) in 2007, investigating the design of selective adsorbent polymers for sensing applications. Currently, he is a Senior Researcher at Swinburne University of Technology (Australia). His main interest is in materials engineering, especially biopolymer hydrogels in drug delivery and vaccine formulation. He also collaborates in the field of functional organic materials in photonic sensing and supramolecular self‐assembly.

Sheshanath V. Bhosale completed his M.Sc. in Chemistry at Udgiri College Udgir of Swami Ramanand Teerth Marathwada University Nanded (India) in 1999. He worked as a Project Assistant at the National Chemical Lab, Pune (India) before moving to Freie University Berlin (Germany), where he received his Ph.D. (Magna Cum Lauda) in Supramolecular Chemistry under the supervision of Prof. J. H. Fuhrhop in 2004. Dr. Bhosale pursued postdoctoral studies with Prof. S. Matile at University of Geneva (Switzerland) under the auspices of a Roche Foundation Fellowship. This was followed by a stay at Monash University (Australia) for five years as an Australian Research Council (ARC)–Australian Postdoctoral Fellow. He worked at RMIT University Melbourne (Australia) for six years under an ARC Future Fellowship. Currently, Prof. Bhosale is working in the Department of Chemistry at Goa University (India) as a Professor under the University Grants Commission–Faculty Recharge Programme. His research interests include design and synthesis of π‐functional materials, especially small molecules, for sensing, biomaterials, and supramolecular chemistry applications.