Why HS⁻ and CN⁻ can be detected by different chemosensors with similar structures: a quantum mechanics and molecular dynamics study

Abstract

Understanding the sensing mechanism is important for evaluating and developing effective chromogenic anion chemosensors. A challenging question in this area is how do you explain the selectivity of one chemosensor to anions that are usually difficult to distinguish. To this end, the sensing mechanisms of two chemosensors (COUMC & HCHI) with similar structures are theoretically investigated by means of quantum mechanics and molecular dynamics simulations. The selectivity of each chemosensor to three common anions that can possibly influence the detection of each other, namely CN⁻, HS⁻ and F⁻, is thereby explained. The result of the quantum mechanics calculation reveals that COUMC_HS⁻, COUMC_CN⁻ and HCHI_CN⁻, are favored both kinetically and thermodynamically. A further analysis based on molecular dynamics simulations reveals that the affinity of anions to the reaction sites of COUMC follow the order of CN⁻ > HS⁻ > F⁻. On the other side, F⁻ and HS⁻ anions are unable to approach the reaction sites of HCHI. These different affinities are explained subsequently by the different strengths of water–anion complexes and different surface electric potentials between COUMC and HCHI. The photochemistry properties indicate excitation and emission on large conjugated planar structures for a single COUMC/HCHI. For the anion-bonded chemosensors, only localized excitation is observed and no obvious differences on absorption and emission spectra are found when adding different anions. Based on our results, we conclude that the reaction selectivity is determined from both the reaction energy and the affinity of anions to the reaction sites. The different selectivity between COUMC and HCHI is attributed to spatial effects and surface electrostatic potential changes caused by the benzyl substituent in COUMC.

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I. Introduction

In order to meet the demand of instant and accurate in vivo anion detection, chromogenic chemosensors have become an important technology that has attracted wide attention due to their sensitivity and cost-effective features.^1–6 The chromogenic anion chemosensors can be applied in many areas, such as detecting pollutants in water, tracing particular molecules in medical care, and measuring important anions in molecular biology research.^7–10 Up to now, a number of chromogenic anion chemosensors containing various fluorescent groups have been synthesized.^3,11–15

Among all kinds of measured anions that potentially need to be sensed, hydrosulfide (HS⁻) and cyanide (CN⁻) are known to play important roles in a wide range of biological, chemical, and environmental processes.^1,16–18 Although the amount of experimental research on HS⁻ and CN⁻ chemosensors is considerable,^3,11,19–22 the detailed mechanism for these anions detected by a specific fluorescent molecule remains to be elucidated. Moreover, one kind of anion may influence the detection of another kind. For example, fluoride, having the smallest ionic radius and the highest charge density, may influence the detection of CN⁻ and HS⁻ due to its widespread existence in living organisms (e.g. bones and teeth), chemical materials, and natural environment.^23,24 CN⁻ and HS⁻ may also influence the detection of each other under certain circumstances.^25–28 As a matter of fact, in some experimental studies, when discussing the selectivity of the synthesized chromogenic anion chemosensors, either the simultaneous response to two kinds of anions (e.g. CN⁻ and F⁻) are reported,^23,24 or the selectivity to these anions is not tested.^29,30

As an important application of chromogenic anion chemosensors, studies have reported that molecular fluorescent probes only respond to one particular kind of anion and can discriminate between CN⁻, HS⁻, or F⁻.^{3,20,29,31–33} However, the reason why these chemosensors have selectivity to one certain kind of anion is not clearly discussed. Recently, two separate studies on two anion chemosensors with similar structures give us the chance to look deeply into the mechanism of the selectivity to anions. In one study, Guo et al.³³ synthesized a CN⁻ chromogenic chemosensor, which is able to discriminate CN⁻ and most other anions. The probe molecule is composed of a hybrid coumarin–hemicyanine and contains an indolium group (HCHI). In the other study, a similar molecule, which is named, according to the authors, as a hybrid fluorophore of coumarin merocyanine (COUMC), is synthesized to solely detect HS⁻ in water solution.²⁰ The only difference between these two molecules is the substituent on the nitrogen atom of the indolium group (Scheme 1, methyl for HCHI and benzyl for COUMC). This difference is the key factor in controlling the selectivity. Elucidating the detailed function of the substituent group in these studies may help us understand and develop more efficient chemosensors.

Scheme 1 Proposed reactions for HS⁻ addition to COUMC and CN⁻ addition to HCHI for the detection of anions.

In the present study, we concentrate on the mechanisms of COUMC and HCHI for detecting anions. CN⁻, HS⁻, and F⁻, which are most likely to influence the fluorescence sensing, are scrutinized with quantum mechanics (QM) and molecular dynamics (MD) simulations. First of all, the potential energy surfaces give activation energies of all the additive reaction between anions and chemosensors (COUMC and HCHI). Frontier molecular orbital (FMO) theory shows HOMO–LUMO energy gaps following the order HS⁻ > CN⁻ > F⁻ for all the reactant states and transition states. Subsequently, MD simulations are performed to further analyze the affinity of anions to the reaction sites and solvent–anion interactions. Our MD results show that the affinity to the reaction sites for each kind of anion is different. The F⁻–water interaction is the most stable, while the CN⁻–water interaction is weak. Finally, the excitation and emission for the chemosensors and anion-bonded chemosensors are calculated. MOs, which are relevant to the excitation and emission process, are thereby displayed. Combining these results, the reason why CN⁻, HS⁻, and F⁻ can be discriminated is finally explained to be due to both the reaction energy and the affinity of anions to the reaction sites. These results may be helpful in designing chemosensors that are sensitive to specific molecules. Further studies are also helpful in validating our method.

II. Methods and calculation details

Quantum mechanics calculation

In the present study, all the quantum mechanics calculations are performed with Gaussian 09 D.01 version.³⁴ Considering the long-range correction and to compensate for the dispersion interaction between two molecules, ωB97XD/6-311++g** has been employed for the calculation of ground state geometries.³⁵ Harmonic vibrational frequencies have been calculated to characterize the optimized reactant complex and a transition state (TS). Intrinsic reaction coordinate (IRC) calculations have been performed to validate the TSs. To analyze the MO changes during reaction process, geometries were chosen from each IRC path at the reactant side (named as reactant state). Then, the chosen geometries of reactant states, the geometries of TSs and the geometries of products are further calculated with natural bond orbitals (NBO). The calculation of excited state properties is performed with time-dependent density function theory (TDDFT). Various DFT methods, including ωB97XD,³⁵ PBE,³⁶ M062X,³⁷ B3LYP,^38,39 LC-BLYP,⁴⁰ and BLYP^38,39 have been tested. Among these methods, the BLYP functional is the most consistent with the experimental result (ESI, Table S1†). Thus, excitation spectra and emission spectra for COUMC and HCHI systems are calculated with the BLYP/6-311G* method. The solvent effect is taken into account by means of the polarizable continuum model (PCM).^41,42 For the COUMC system, the solvent is pure water. However, for the HCHI system, a mixed solvent of water/methanol = 1/1 (v/v) is used. In our calculation, this solvent is obtained by taking the average dielectric constant and the average dynamic dielectric constant from water and methanol. The electrostatic potential surface (EPS), the involved MOs, and the molecular orbital contributions are drawn and analyzed with Multiwfn3.3.7.⁴³

Molecular dynamics simulations

In order to better describe the interaction between COUMC/HCHI and anions, molecular dynamics simulations, containing one chemosensor molecule and three kinds of anions, have been performed. The force field parameters for COUMC/HCHI and anions (HS⁻, CN⁻, and F⁻) are generated from the general AMBER force field (GAFF)⁴⁴ in the Antechamber⁴⁵ module of AMBER12.⁴⁶ To simulate the experimental solvent conditions and to balance the simulation cost and efficiency, a box of 10 × 10 × 10 nm³ is set up initially. One chemosensor molecule, COUMC or HCHI, is placed in the center of the box. After that, 20 anions of each kind (HS⁻, CN⁻, and F⁻) are added with random positions in the box. Finally, sodium ions (Na⁺) are added to balance the total charge of the system to zero. For COUMC systems, the whole box is filled with explicit water solvent of a Tip3p water model.⁴⁷ However, for HCHI systems, according to the experiment,³³ a 1 : 1 (water/methanol v/v) solvent was used. Thus, in our MD simulation, a mixed solvent is designed containing 4000 methanol molecules and 11 000 water molecules, which approximately equals the experimental conditions. The force field parameters of a methanol molecule are also obtained with GAFF.

All the MD simulations are carried out with GROMACS 4.6.5.^48–50 Periodic boundary conditions and the particle-mesh Ewald (PME)⁵¹ method for long range electrostatics were applied throughout the simulations. Short range interactions were cut off at 10.0 Å. The time step was set to 1 fs. The system was subjected to 5000 steps of conjugate gradient minimization initially. Subsequently, a 20 ns NPT simulation was held at 300 K to equilibrate the system. Finally, a 2 ns NPT simulation was carried out as the so-called production run, and the coordinates of the system were recorded every 1 ps. These coordinates were applied to analyze the MD results (Fig. 4 and 5). The whole MD simulations for COUMC and HCHI were repeated five times to verify the results.

III. Results and discussion

Reaction paths of thermal free energies

The reaction paths for anion (HS⁻/CN⁻/F⁻)-bonded chemosensors (COUMC/HCHI) are calculated. The obtained structures of all the transition states (TSs) are displayed in Fig. 1. All the anions are placed on top of the reaction sites (C18) and similar configurations are observed for all the six complexes. In a single COUMC or HCHI molecule, the coumarin part and the indolium part connected by the alkene part (contain C1, C2, C16, C18 atoms) to form a co-planar structure. The co-planar structure starts to break at TS states with a considerable C16–C19–C18–N38 dihedral decrease (Fig. 1). The dihedrals of HS⁻ and CN⁻ TSs (around 150°) are smaller than those of F⁻ (about 160°), indicating the TS structures of HS⁻ and CN⁻ TSs are more product-like than the TSs of F⁻.

Fig. 1 Structures of all the transition states. The corresponding C16–C19–C18–N38 dihedrals for single COUMC and HCHI are 179.5 degree and 180.0 degree.

The calculated activation free energy (ΔG_a), the reaction free energy (ΔG_rxn), the rate constant (k_r), and the half-life time (t_1/2) are displayed in Table 1. In both COUMC and HCHI related reactions, HS⁻ shows the lowest ΔG (5.9 kcal mol⁻¹ for COUMC and 8.17 kcal mol⁻¹ for HCHI). For CN⁻ reacting with COUMC (7.7 kcal mol⁻¹), ΔG_a is similar to that of F⁻ (7.8 kcal mol⁻¹). ΔG_a of the HCHI_CN⁻ reaction (10.2 kcal mol⁻¹) is slightly higher than that of F⁻ (9.3 kcal mol⁻¹). According to these ΔG_a values, reactions of HS⁻ are the easiest to happen compared to those of CN⁻ and F⁻. On the other hand, according to the results of the reaction free energies (ΔG_rxn) in Table 1, the reactivity of COUMC–anion systems follows the order CN⁻ > HS⁻ > F⁻. While the reactivity of HCHI–anion systems follows CN⁻ > F⁻ > HS⁻. It is also interesting to note that ΔG_rxn of HCHI_HS⁻ (0.0 kcal mol⁻¹), ΔG_rxn of COUMC_F⁻ and HCHI_F⁻ (0.0 kcal mol⁻¹ and −2.3 kcal mol⁻¹) indicate the reactions may not be favored. In the last column of Table 1, the calculated half-life times (t_1/2) are all relatively short, which means a quick response of anions reacting with COUMC and HCHI.

Table 1 The activation energies (ΔG_a), the reaction free energies (ΔG_rxn), the rate constants (k_r) and the corresponding half-life times (t_1/2) for the reaction paths (kcal mol⁻¹) at 298 K. The reaction free energy diagrams are given in the ESI (Fig. S1). For the calculation of the half-life time of the reactions, we take [DET₀] = [X₀] = 50 μM

System	ΔGa^a (kcal mol^−1)	ΔGrxn^b (kcal mol^−1)	kr^c (M^−1 s^−1)	t1/2^d (s)
a ΔGa = GTS − Grea−int.b ΔGrxn = Gproduct − Greactant.c d
COUMC_HS^−	5.9	−5.3	3.1 × 10^8	3.23 × 10^−5
COUMC_CN^−	7.7	−11.4	1.3 × 10^7	7.69 × 10^−4
COUMC_F^−	7.8	0.0	1.2 × 10^7	8.33 × 10^−4
HCHI_HS^−	8.2	0.0	6.2 × 10^6	1.61 × 10^−3
HCHI_CN^−	10.2	−13.8	2.3 × 10^5	4.35 × 10^−2
HCHI_F^−	9.3	−2.3	9.3 × 10^5	1.08 × 10^−2

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Electrostatic potential (ESP) surface analysis

In the calculation of reaction paths, we notice that the relative positions of anions in the reactant complex are different in the COUMC and HCHI systems. These differences may be one reason for the different reaction barriers. In order to address this question, electrostatic potentials on molecular van der Waals surfaces have been displayed for both chemosensors in Fig. 2. It can be seen that COUMC and HCHI show similar ESP surfaces, on which almost all the local ESP extrema are positive due to the overall positive charge. The only negative ESP region is present near the carboxyl group of coumarin (green) because of the relatively strong electronegativity of oxygen. The difference is that the local positive extrema region of COUMC is considerably larger than that of HCHI. In COUMC, a local maximum ESP (81.2 kcal mol⁻¹) is found on top of the reaction site of the indolium group. For the reactant complexes of HCHI and COUMC_F⁻, the anions are located at the maximum ESP (102.3 kcal mol⁻¹ for COUMC and 111.4 kcal mol⁻¹ for HCHI) points. However, for COUMC_HS⁻ and COUMC_CN⁻, the anions are located at the third maximum ESP (81.2 kcal mol⁻¹) on top of indolium group. This difference is probably because HS⁻ and CN⁻ have relatively larger van der Waals volumes than that of F⁻. The steric exclusion effect of the benzyl substituent in COUMC hinders the HS⁻ and CN⁻ movement to the maximum ESP point. This may result in higher absolute energies for COUMC_HS⁻ and COUMC_CN⁻ reactant complexes, lower activation energies (ΔG_a) and higher reaction free energies (ΔG_rxn) (see Table 1).

Fig. 2 ESP mapped surfaces and the configurations of all the reaction intermediates. Surface local minima (green) and maxima (orange) are also displayed to better illustrate the formation of reactant complexes.

Analyzing frontier molecular orbitals (FMOs)

The MOs from anions and COUMC/HCHI involved in the reactions are all displayed in Fig. 3. For the convenience of understanding the MO contribution, a chemosensor molecule is separated into three groups of atoms according to the co-planar atoms before and after the additive reactions, which are the Big Pi (BP), the Small Pi (SP), and the substituent (SB). It can be seen that in a single COUMC or HCHI, atoms on the BP and SP form a co-planar structure with MOs spread all over the molecule.

Fig. 3 Molecular orbitals (MOs) that are involved in the additive reaction between anions and fluorescent probes. Atoms in the probe molecule have been categorized into three parts (e.g. COUMC LUMO).

It is instructive to take a close look at the reaction by analyzing the frontier molecular orbitals (FMOs) in reactants and products.^52,53 A smaller HOMO–LUMO gap usually means that the reaction is more likely to happen. It should be noted that in the present study, the addition reactions can be ascribed as a pair of electrons, which are from the HOMO of an anion in this case, coupling to the LUMO of the chemosensor molecule. Thus, when considering the MO changes during the reaction, the correct MOs in the reactant states, the TSs, and the products need to be recognized. These involved MOs are HOMO in COUMC_HS⁻ and HCHI_HS⁻, HOMO−2 in COUMC_CN⁻ and HCHI_CH⁻, HOMO−6 in COUMC_F⁻ and HOMO−4 in HCHI_F⁻, LUMO of all the six reaction systems. For each reaction system, the corresponding HOMO–LUMO gap is given in Table 2. The smallest HOMO–LUMO gap is in the COUMC_HS⁻/HCHI_HS⁻ system. The gaps of the CN⁻ system are about 0.5 eV smaller than those of the F⁻ system.

Table 2 Energy gaps for the MOs involved in the reactions

System	HOMOreactant^a	ΔE^b, eV	ΔETS^c, eV
a These HOMOs are on anions.b ΔE = E(LUMO of COUMC/HCHI) − E(HOMO of anion).c ΔETS = ETS(LUMO) − ETS(HOMO of anion).
COUMC_F^−	HOMO−6	8.00	6.80
COUMC_CN^−	HOMO−2	7.48	6.48
COUMC_HS^−	HOMO	6.67	4.71
HCHI_F^−	HOMO−4	8.03	6.69
HCHI_CN^−	HOMO−2	7.66	6.45
HCHI_HS^−	HOMO	5.98	4.68

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To illustrate the changes of relevant MOs during reactions, examples of HOMO and LUMO changes are given in Fig. 4. The full picture of MOs involved in the reaction for all the reactant states, the TSs, and the products are further listed in Fig. S3–S5.† In Fig. 4, the LUMOs in the reactant states of COUMC_HS⁻ and COUMC_F⁻ are both from COUMC molecules. Their shapes and energy levels are nearly the same. However, according to the energy levels of MOs, the involved HOMO of HS⁻ corresponds to the HOMO in COUMC_HS⁻. While the HOMO of F⁻, which participates in the reaction, corresponds to the HOMO−6 in the COUMC_F⁻ system. For the other reactant states of CN⁻ and F⁻ systems, the MOs involved are HOMO−4 (HCHI–F⁻) and HOMO−2 (COUMC_CN⁻ and HCHI_CN⁻) accordingly (see ESI, S3–S5†).

Fig. 4 Examples of the involved MOs of reactant states and products. The rest of the MOs are listed in the ESI (see Fig. S3–S5†).

In the TSs, the MOs that were previously localized on the anions in the reactant states become partially distributed on both anions and the BP of chemosensors. The corresponding HOMO–LUMO gaps have decreased to 4–7 eV at the TS states (Table 2), with the energy gaps still following the order F⁻ > CN⁻ > HS⁻. These MOs are finally mainly distributed on the BP of chemosensors according to the configuration of the products (see Fig. 4 TS states and products). As a result, when the electrons are transmitted from anions to the chemosensors, the electrons in the COUMC_HS⁻ system need to overcome an energy gap of 4.71 eV. While the electrons in COUMC_F⁻ need to overcome a gap of 6.80 eV. These differences lead to a higher activation energy for the reaction of F⁻ adding to COUMC.

MD simulations and binding energies

The reaction selectivity is not only determined by the reaction energy barrier and HOMO–LUMO gap. In these reactions, whether a anion and a chemsoensor is more easily to react can be also determined by the kinetic processes, such as the collision rate. To investigate whether the anions can approach the reaction sites of chemosensors, molecular dynamics (MD) simulations are carried out. The distances between anions and reaction sites of chemosensors are defined (Fig. 5a). By analyzing the accumulated coordinates, each anion appeared in the range 3–10 Å (R-C18 distance) and the corresponding angle θ at 0–90 degrees is recorded.

Fig. 5 (a) Quantities for characterizing anion positions corresponding to the reaction sites. the angle between v_cr and plain C18C28N38 is named as theta (θ). R-C18 distances are counted. (b) Example of a MD simulation system (solvent molecules are not shown). Distribution of anions in the COUMC system and HCHI system (bottom graphs). Theta and R-C18 distances are counted from the production run of MD simulation.

In Fig. 5, different anions exhibit distinct affinities to the chemosensor reaction sites. For the COUMC system, the number of CN⁻ appearances in the defined region is 273, which is considerably larger than that of HS⁻ (61 counts) and F⁻ (34 counts). Furthermore, CN⁻ is capable of reaching a position of 3–5 Å to the reaction site, while HS⁻ and F⁻ only appear in the region of distance >6 Å. For the HCHI system, a more distinct anion distribution is obtained (Fig. 5 bottom right). Since one HS⁻ and no F⁻ is observed in the defined region, almost only CN⁻ can reach the defined region (734 counts). Moreover, a number of the CN⁻ anions are located in the range 3–5 Å. All this information indicates that CN⁻ may approach the reaction sites of chemosensors easily. But HS⁻ and F⁻ are unlikely to get close to the sites.

The statistical result of anion distribution is probably because of the interaction between anions and solvent molecules. The results of the radial distribution function (RDF)^54,55 for anion–hydrogen pairs are displayed in Fig. 6. The hydrogen atoms are from either the water molecules or the methanol molecules (in the case of HCHI). Both graph (a) and (d) show that the solvent hydrogen RDFs for F⁻ reach the maximum at 1.6 Å, indicating a strong interaction between F⁻ and solvent molecules. The peaks of the corresponding RDFs for HS⁻ are located at 2.0 Å, and for CN⁻ are at 2.2 Å. Along with the gradually decreased peaks from F⁻ to CN⁻, the interaction between anions and solvent molecules also decreases.

Fig. 6 Optimized structures of one anion and six nearest water molecules (upper) and the binding free energies (ΔG_binding = G_complex − G_separated). G_separated is the sum of single molecule free energies with the same degree of freedom of the complex. RDF distributions of F⁻/HS⁻/CN⁻ and solvent hydrogen pairs in the COUMC system (a–c) and HCHI system (d–f).

To quantitatively understand the interaction between anions and solvent molecules, quantum mechanics computations are performed by selecting a representative model containing one anion and six surrounding water molecules (the number of methanol molecules interacting with anions is low according to our MD simulation result, and thus is not considered in the quantum mechanics calculation). By optimizating the structure and calculating thermochemistry properties, the optimized structure and the binding energies for anions coordinating water molecules are obtained (Fig. 6, upper). The highest binding free energy (ΔG_binding) is from CN⁻ (8.2 kcal mol⁻¹) indicating a relatively hydrophobic property for CN⁻. The HS⁻ exhibits a moderate ΔG_binding (−3.1 kcal mol⁻¹) and the F⁻ has a ΔG_binding of −8.8 kcal mol⁻¹.

The different anion distributions between the COUMC and HCHI systems are because of the different substituents of the SB group. The results of the anion–water binding structure indicate that the water–CN⁻ complex is unstable while HS⁻ and F⁻ are both coordinated to several water molecules. We roughly calculated the volumes of CN⁻ (54.9 ų), the water–HS⁻ complex (157.8 ų), and water–F⁻ complex (153.9 ų). Combining the calculated ΔG_binding of HS⁻ (−3.1 kcal mol⁻¹) and F⁻ (−8.8 kcal mol⁻¹), these results indicate that the HS⁻ and F⁻ may coordinate with water molecules and form relatively stable cluster structures, among which the water–F⁻ complex is particularly stable. These structures may hamper the water molecules from approaching the reaction sites. Compared to HCHI, the benzyl group in COUMC may result in spatial effects and a change of electron distribution. These changes not only affect the binding of CN⁻, but also let HS⁻ and F⁻ somehow approach the reaction site in the COUMC system. This leads to the different distributions in Fig. 5. Considering the reaction activity of CN⁻ and F⁻, while they have similar ΔG_a, CN⁻ has a much lower ΔG_rxn and therefore it is much easier to approach the reaction site. Thus is it easier for CN⁻ to react with the chemosensors. It is also worthy to note that comparing the calculated ΔG_binding, the coordination between HS⁻ and water molecules is much weaker than that of F⁻. However, HS⁻ is still not observed near to the reaction sites of HCHI. Although the HCHI_HS⁻ system has a relatively small ΔG_a and ΔG_rxn, the additive reaction between HS⁻ and HCHI cannot be favored.

Photochemistry properties of COUMC and HCHI

The excitation and emission of chemosensors, as well as anion-bonded chemosensors are studied accordingly (Fig. 7, 8 and Table 3). The computed spectra are in good agreement with the experimental results. In our calculation, chemosensor molecules (COUMC and HCHI) show the absorption bands at 586/580 nm, which correspond to the electron transfer from HOMO → LUMO containing a partial BP → SP charge transfer (CT) state (Table S3†). The corresponding emission processes are ascribed as a LUMO → HOMO electron transition with the bands at 639/634 nm. The partial CT state is also observed. In our calculation, both of the chemosensors have conjugated planar structures. The HOMOs and LUMOs have contributions from both the BP and SP because of the planar configuration, which leads to the considerable decrease of excitation energies compared to the localized MOs in the case of anion-bonded chemosensors (Table 3).

Fig. 7 Excitation and emission mechanism for COUMC and COUMC_HS⁻. Experimental measured values are given in brackets.

Fig. 8 Excitation and emission mechanism for HCHI and HCHI_CN⁻. Experimental measured values are given in brackets.

Table 3 Vertical excitation and emission information, composition in terms of MOs, the assigned molecular parts, and the oscillator strengths

	Trans. nm (eV)	MOs (CI)	Assignment^a	f
a These definitions are given in Fig. 2.b All the spectra, the MO configurations, and the group contributions are given in the ESI, Fig. S6–S9, Table S3.
Excitation
COUMC	586 (2.12)	H → L (97%)	BP + SP → BP + SP (CT^b)	1.46
COUMC_HS^−	436 (2.84)	H−1 → L (40%)	BP + SP → BP (CT)	0.69
		H → L (56%)	BP + SP → BP (CT)
COUMC_CN^−	447 (2.77)	H → L (95%)	BP → BP	0.72
COUMC_F^−	439 (2.83)	H−1 → L (25%)	SP → BP (CT)	0.62
		H → L (70%)	BP → BP
HCHI	580 (2.14)	H → L (97%)	BP + SP → BP + SP (CT)	1.50
HCHI_HS^−	443 (2.75)	H−1 → L (33%)	SP → BP (CT)	0.80
		H → L (64%)	BP → BP
HCHI_CN^−	442 (2.75)	H → L (82%)	BP → BP	0.77
HCHI_F^−	448 (2.76)	H → L (94%)	BP → BP	0.84
Emission
COUMC	639 (1.94)	L → H (97%)	BP + SP → BP + SP	1.42
COUMC_HS^−	495 (2.50)	L → H−1 (95%)	BP → BP	0.85
COUMC_CN^−	495 (2.50)	L → H−1 (95%)	BP → BP	0.87
COUMC_F^−	494 (2.51)	L → H−1 (95%)	BP → BP	0.91
HCHI	634 (1.95)	L → H (97%)	BP + SP → BP + SP	1.48
HCHI_HS^−	494 (2.51)	L → H−1 (95%)	BP → BP	0.89
HCHI_CN^−	494 (2.51)	L → H−1 (95%)	BP → BP	0.93
HCHI_F^−	491 (2.52)	L → H−1 (95%)	BP → BP	0.87

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The excitation and emission bands for anion-bonded chemosensors involve MOs of different forms. When HS⁻ bonded to COUMC, the bonded chemosensor exhibits the maximum absorption spectra at 436 nm with both HOMO and HOMO−1 taking part in the excitation. The assigned groups are BP + SP → BP. The absorption spectra of the HCHI_HS⁻ system with a band at 443 nm also show similar excitation properties. When CN⁻ and F⁻ bonded to COUMC, the absorption spectra show peaks at 447 nm and 439 nm respectively. The MOs involved are mainly HOMO → LUMO (BP → BP). A fraction of HOMO−1 → LUMO (SP → BP) is also observed in COUMC_F⁻. When CN⁻ and F⁻ bond to HCHI, the corresponding MOs for excitation are only localized excitations (BP → BP). All the emission spectra of anion-bonded COUMC and HCHI correspond to the localized BP → BP electron transition from LUMO to HOMO−1. The localized electron transition of the anion-bonded chemosensors is due to the hybridization of the atomic orbitals of the reaction site (C18) from sp² to sp³ during the addition reaction. The broken conjugated planar structure and the formation of a σ-bond on C18 makes the BP perpendicular to SP. The excitation of electrons is restricted to the BP part.

Based on the descriptions above, we are able to study the fluorescence mechanisms of anions detected by chemosensors. For a single chemosensor, the excitation and emission processes both happen on the conjugated planar π orbitals with partial CT states from the BP to SP. When anions bond to COUMC/HCHI, the partial CT states are also found in COUMC_HS⁻, COUMC_F⁻, and HCHI_HS⁻ systems. However, CT effects in anion-bonded systems are trivial and no obvious difference is found when comparing the spectra of different systems. Due to the similar photochemistry properties of anion-bonded chemosensors, HS⁻/CN⁻/F⁻ cannot be discriminated by the fluorescence spectra. This result further demonstrates that anions are differentiated by the additive reaction to chemosensors and the interactions with solvent molecules.

IV. Concluding remarks

In the present study, the mechanisms of two anion chemosensors (COUMC & HCHI) detecting specific anions are studied by means of quantum mechanics and molecular dynamics simulations. The reason why these anions can be differentiated is addressed and discussed as follows.

According to our calculations, in the addition reactions between anions and COUMC/HCHI, the activation free energy (ΔG_a) follow the sequence HS⁻ < F⁻ < CN⁻, in which ΔG_a values of CN⁻ and F⁻ are similar. The order of the corresponding HOMO–LUMO gaps related to the reaction is HS⁻ < CN⁻ < F⁻, in which the values of CN⁻ and F⁻ are also similar. Considering the reaction free energies (ΔG_rxn), only the COUMC_HS⁻, COUMC_CN⁻, and HCHI_CN⁻ show stable products and exergonic reactions.

With molecular dynamics simulations, the distribution of distances between anions and reaction sites are analyzed. The interactions between anions and water molecules are also analyzed. The result shows that CN⁻ is able to approach the reaction site of COUMC/HCHI easily. It is difficult for F⁻ to reach the reaction site because it can form a stable complex with water molecules. The interaction between water molecules and HS⁻ is relatively moderate. The different anion distributions in COUMC and HCHI are attributed to the change of surface electron distribution and the spatial effects caused by the benzyl group in COUMC.

Based on the results above, we are able to explain the selectivity of COUMC and HCHI to specific anions. For COUMC_F⁻ and HCHI_F⁻, the ΔG_a and the HOMO–LUMO gap are both similar to those of CN⁻. However, the ΔG_rxn values indicate the reaction may not be thermodynamically favorable. More importantly, the stable water–F⁻ complex prevents F⁻ from entering the nearby area of reaction sites. Thus, F⁻ is not likely to influence the anion detection of COUMC and HCHI. When detecting HS⁻ with COUMC, the solvent has pH = 7.4. Considering the pK_a of H₂S (7.0) and HCN (9.2), the [CN⁻]/[HS⁻] is estimated to be 0.02. HS⁻ also has the lowest ΔG_a. It should also be noted that unlike HCHI, a considerable amount of HS⁻ is found near to the reaction sites of COUMC. Thus, CN⁻ is not likely to influence the HS⁻ detection by COUMC. In the system of HCHI, according to the result of molecular dynamics simulations, CN⁻ is able to approach the reaction sites easily while HS⁻ can not. Considering ΔG_a and ΔG_rxn of CN⁻ and HS⁻, the CN⁻ reacting with HCHI can be more stable.

Finally, the photochemical properties of chemosensors and the anion-bonded chemosensors are studied. The excitation of a single chemosensor and HS⁻-bonded chemosensors show partial CT effects, while localized excitations are observed in the excitation of other anion-bonded chemosensors. According to our calculations, when different anions bond to chemosensors, similar absorption and emission spectra are obtained. This indicates that it is difficult to discriminate selectivity of anions with the spectra of anion-bonded chemosensors. The selectivity is solely controlled by the reaction activity between anions and chemosensors.

To sum up, both quantum mechanics and the molecular dynamics calculations have been applied for understanding the selectivity of COUMC detecting HS⁻ and HCHI detecting CN⁻. Based on our calculations, the selectivity of chemosensors to anions is evaluated both by the thermodynamics properties of anion–chemosensor interactions and by the affinities of anions to the reaction sites. Besides, considering the experimental²⁰ and the simulation results, the addition reaction of CN⁻ to COUMC is prevented from happening by controlling the solution pH. Thus, it is also possible for CN⁻ to react and be detected by COUMC in a different environment (e.g. changing pH). As a result, further experimental and theoretical studies may be interesting for the possibility of sensing CN⁻ with COUMC and testing the reliability of our method.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 21303068, 81300724), the China Postdoctoral Science Foundation (Grant No. 2014M561284), and Doctoral Fund of Ministry of Education of China (No. 20130061120025).

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra12684g

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