Sensing Mechanism for Biothiols Chemosensor DCO: Roles of Excited

Article pubs.acs.org/JPCA

Sensing Mechanism for Biothiols Chemosensor DCO: Roles of Excited-State Hydrogen-Bonding and Intramolecular Charge Transfer Jun-Sheng Chen,†,§ Ming-Hu Yuan,† Jia-Pei Wang,† Yang Yang,† and Tian-Shu Chu*,†,‡ †

State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People’s Republic of China ‡ Institute for Computational Sciences and Engineering, Laboratory of New Fiber Materials and Modern Textile, the Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071, People’s Republic of China § Department of Chemical Physics, Lund University, 22100 Lund, Sweden S Supporting Information *

ABSTRACT: The biothiols sensing mechanism of (E)-7-(diethylamino)-3-(2-nitrovinyl)-2H-chromen-2-one (DCO) has been investigated using the density functional theory (DFT) and time-dependent DFT methods. The theoretical results indicate that the excited-state intermolecular hydrogen bonding (H−B) plays an important role for the biothiols sensing mechanism of the fluorescence sensor DCO. Multiple H−B interaction sites exist in DCO and in its Michael addition product DCOT, which then induce the formation of the H−B complexes with water molecules, DCOH2 and DCOTH4. In the first excited state, the intermolecular H−Bs between water molecule and DCO in DCOH2 are cooperatively and generally strengthened and thus induced the weak fluorescence emission of DCO, while the cooperative H−Bs between water molecule and DCOT in DCOTH4 are overall weakened and thus responsible for the enhanced fluorescence emission of DCOT. Moreover, the theoretical results suggest that the blue shift of the UV−Vis absorption spectrum of DCOT can be attributed to the relatively weak excited-state intramolecular charge transfer in DCOT compared to DCO.

1. INTRODUCTION Biothiols like cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) participate in numerous cellular functions and play critical roles in many physiological processes.1 Cys and Hcy are involved in cellular growth, while GSH is involved in redox homestasis.2 Alteration of the intracellular biothiols level is significantly associated with a number of diseases, such as cardiovascular disease, leucocyte loss, psoriasis, liver damage, cancer, and even AIDS. Thus, biothiols detection is of great biological, clinical, and environmental significance. During the past decade, a fluorescent chemosensor for biothiols has attracted broad attention due to its easy operation, low cast, and high sensitivity and selectivity.3,4 There are numbers of investigations being carried out on biothiol-specific fluorescent chemosensors, most of which have largely focused on developing and synthesizing new fluorescent chemosensors. Detailed explorations and explanations for the sensing mechanism of these synthesized chemosensors are still insufficient. Many strategies have been employed in the development of the fluorescent chemosensors for biothiols,5 such as Michael reactions, cyclization with aldehydes, cleavage of sulfonamide and sulfonate esters, cleavage of selenium−nitrogen bonds, cleavage of disulfide bonds, oxidation−reduction processes in metal complexes, metal complexes−displace coordination, and use of nanoparticles.3 Among these strategies, the one based on Michael reactions, first reported by Sippel6,7 in 1981, is actively © XXXX American Chemical Society

adopted in developing biothiols chemosensors in recent years. This sort of chemosensor is based on thiol addition to different kinds of Michael acceptors, such as maleimides, squaraines, 7oxanorbornadiene, quinones, chromenes, propiolates, acrylic acid, α,β-unsaturated aldehydes, ketones, diesters, and malonitrile.4 Employing the Michael reaction is a very simple and straightforward method for the design of chemosensors for biothiols, which can display ratiometric, ON−OFF, OFF−ON and even near-infrared fluorescent behaviors. Through Michael addition reactions, the biothiols react with Michael acceptor type fluorescent chemosensors in the ground state, and the addition reaction products exhibit different photophysical properties with the involvement of the excited states, accompanied by a remarkable change of absorption or emission originating from intramolecular charge transfer (ICT),8−10 photoinduced electron transfer (PET)11 or other mechanisms.3−5,12 Based on the Michael reaction between biothiols and Michael acceptors, a series of structurally simple and high-performance fluorescent chemosensors have been successfully developed.2−5,8−11,13−16 The Michael reaction Special Issue: International Conference on Theoretical and High Performance Computational Chemistry Symposium Received: February 25, 2014 Revised: May 6, 2014

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dx.doi.org/10.1021/jp501946n | J. Phys. Chem. A XXXX, XXX, XXX−XXX

The Journal of Physical Chemistry A

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Scheme 1. Structures of DCOH (the H−B complex between DCO and water molecules) and DCOTH (the H−B complex between DCOT (the DCO Michael addition product) and water molecules)

To support the preceding consideration and to clarify the sensing mechanism of the chemosensor DCO, we carried out DFT/TDDFT calculations to study the ground- and excitedstate properties of the involved molecules in the DCO sensing process. The 1H NMR spectra of DCO and its Michael addition product DCOT were calculated and discussed. The frontier molecular orbitals, vertical excitation energies (VEEs), and corresponding oscillator strengths for these different molecular structures were also presented and analyzed, which indicated that the sensing mechanism of the chemosensor DCO is attributed to the combination of Michael reaction, ICT, and excited-state H−B enhancement (see Scheme 1).

process and the different sensing processes associated with ICT, PET, and so on can be studied by using various spectroscopic techniques, such as mass spectra, 1H NMR spectra, time-resolved absorption spectra, and fluorescence spectra. Theoretically, the density functional theory (DFT) and the time-dependent density functional theory (TDDFT) are competent and efficient enough in understanding the sensing mechanism of chemosensors for biothiols, which have been proven effective in studying ICT, excited-state proton transfer (ESPT), PET, and other sensing mechanisms of fluorescent chemosensors.17−21 Via DFT and TDDFT calculations, more direct and more detailed information can be gained about the geometries and the photophysical properties of the investigated chemosensors. Recently, Guo et al. reported a Michael reaction based colorimetric and OFF−ON fluorescent chemosensor, (E)-7(diethylamino)-3-(2-nitrovinyl)-2H-chromen-2-one, (DCO; see Scheme 1),16 with rapid response speed, excellent selectivity, and sensitivity to Cys. Due to the experiments of Guo et al.16 that were carried out in water−organic mixed solvent, the intermolecular hydrogen bonding (H−B) should be formed between chemosensor DCO and water. Therefore, the importance of hydrogen bonding for the fluorescent chemosensor DCO should not be ignored, because it is known that through the regulation of electronic states by H−B interactions, nonirradiative deactivations of fluorescent chemosensors can be dramatically influenced;22 that is, the fluorescence of the fluorescent chemosensors in H−B surroundings is either quenched or enhanced by H−Bs, especially by the excited-state H−B.23,24 Usually, excited-state H−B plays an important role in fluorescence quenching mechanisms including PET, ICT, and metal-to-ligand charge transfer (MLCT), etc., as revealed in systematic studies of Han and co-workers.22−27 In other words, PET, ICT, and MLCT can be tuned by the excited-state H−B dynamics process and thus influence the fluorescence emission. For example, the PET process can be facilitated by H−B to induce fluorescence quenching,22 which was first suggested by Han and co-workers and which has been widely used in explaining sensing mechanisms for various fluorescent probes. A useful rule has also been established where the intermolecular H−B strengthening/weakening corresponds to red shifts/blue shifts in the electronic spectra.27 Based on this rule, one can judge the excited-state H−B strengthening/weakening behaviors and then go further to reveal the role of the H−B interaction in fluorescence quenching. Additionally, a previous study has demonstrated that the intramolecular H−B plays an important role for the probes for biothiols.2 Hence, the H−B may also play an important role in the sensing mechanism of DCO.

2. THEORETICAL METHODS In the present work, all theoretical calculations were accomplished using the Gaussian 09 programs.28 The groundstate (S0) and the first excited state (S1) geometries were optimized without constraint and studied with the DFT and TDDFT methods, respectively, which have been widely used for large molecule systems including the weakly interacting systems.18,29−32 Considering that the experiments were conducted in water/organic solvent, in all calculations solvent effects were included using the integral equation formalism33,34 (IEF) version of the polarizable continuum model35,36 (PCM) with the dielectric constant of water (ε = 78.4). First we employed the hybrid exchange-correlation functional B3LYP,37−39 and the triple-ζ valence quality with one set of polarization functions (TZVP)40,41 was chosen as the basis set, which is appropriate for such ionic organic compound.18 It is widely known that the TDDFT/B3LYP method suffers severe failure when dealing with charge-transfer excited states.21,42,43 We therefore tested the S0 → S1 VEE with M062X44 functional and two long-range-corrected (LRC) ones: cam-B3LYP45 and wB97XD46,47 functionals. For the first excited state, the geometries were optimized from the optimized ground-sate structures without constraint and studied with the TDDFT/ M062X/TZVP method with IEF-PCM (water, ε = 78.4). The gauge-independent atomic orbital (GIAO)48,49 method was employed to compute the 1H NMR spectra of DCO and DCOT. The B3LYP function with the 6-311+G(2d,p) basis set, which has been proved appropriate for calculating the 1H chemical shift, has been used to calculate the 1H NMR spectra.50,51 3. RESULTS AND DISCUSSION 3.1. Optimized Structures. Figure 1 displays the optimized ground-state structures of the fluorescent chemosensor DCO and its Michael reaction product DCOT with biothiol. Both DCO and DCOT have multiple H−B interaction sites which can play an important role in the sensing B



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Table 1. Calculated Important H−B Lengths (Å) and Bond Angles (deg) for the Fully Optimized Structure of DCOH1a, DCOH1b, and DCOH2 DCOH1a d(O1···H1) angle (O1···H1O2) d(O3···H2) angle (O3···H2O4) d(O5···H3) angle (O5···H3O4) binding energies/(kcal mol−1)

4.62

2.23 136.9 2.19 140.0 5.13

DCOH2 1.89 177.7 1.93 176.2 3.28 95.4

The basis set superposition error (BSSE) was accounted for by using the counterpoise method of Boys and Bernardi.52 The calculated binding energies are listed in Table1. The binding energy between DCO and water is 4.62 and 5.13 kcal mol−1 for DCOH1a and DCOH1b, respectively. These H−B lengths, angles, and binding energies indicated that DCO can interact with water molecules and form a stable H−B complex. As shown in Figure 1, four groups, in the Michael reaction product DCOT, can interact with water molecule and form H− B. The CO group on the coumarin moiety and the NO2 group can act as H−B acceptors, the COOH group can act as either H−B donor or acceptor, and the NH2 group can act as a H−B donor. Due to these multiple H−B interaction sites in DCOT, here we first investigate the interaction between the DCOT molecule and one water molecule. We study this with eight initial conformations (see Supporting Information (SI) Figure S1) and obtain six optimized DCOT-H2O complexes (DCOTH1a−DCOTH1f) as shown in Figure 3. The H−B lengths have been labeled in Figure 3, and in order to determine the H−B strength, the binding energy (EB) between DCOT and water molecules was calculated according to eq 1. The calculated binding energies have also been shown in Figure 3. In all of these DCOT-H2O complexes, the water molecule interacts with the DCOT molecule through two H−Bs, except for DCOTH1d in which the water molecule forms a single H−B with the OH group of DCOT. The binding energy of DCOTH1d is larger than that of DCOTH1a, DCOTH1e, and DCOTH1f. On the other hand the binding energies of DCOTH1b and DCOTH1c are larger than that of other DCOT-H2O complexes. These indicate that the COOH group is an important H−B interaction site. The H−B lengths between the water molecule and the NO2 group (in DCOTH1a, DCOTH1b, and DCOTH1c; see in Figure 3) and those between water molecule and the NH2 group (in DCOTH1e and DCOTH1f; see in Figure 3) are larger than 2.0 Å. This demonstrates that the H−B interactions with NO2 or NH2 are relatively weak as compared to those formed with COOH and CO groups. Based on the above results, we have constructed the initial configurations for DCOT and multiple water molecules to form the H−B complexes. In view of the relatively strong H−B interactions of COOH and CO groups, we make sure that the initial configurations of these multiple water complexes have the CO−water and COOH−water H−B interactions (see SI Figure S2). Starting from this, we investigated the DCOT molecule interacting with different numbers of water molecules: DCOT with four water molecules (DCOTH4), DCOT with five water molecules (DCOTH5), and DCOT with six water molecules (DCOTH6). These initial structures are corresponding to a, b, and c, respectively, in SI Figure S2. The

Figure 1. Views of the optimized S0 structures for DCO and DCOT at the B3LYP/TZVP calculation level: gray, C; white, H; red, O; blue, N; yellow, S.

mechanism of the chemosenor DCO, like Han and co-workers discussed in that the absorbance and fluorescence emission of chromophore can be facilitated by H−Bs.22−24,27 DCO contains two H−B interaction sites: the CO group on the coumarin moiety and the NO2 group, acting as H−B acceptor. The optimized ground-state structures of the H−B complexes, formed between DCO with one water molecule and with two water molecules, (DCOH1a, DCOH1b, and DCOH2) are shown in Figure 2. One stable H−B, O1···H1O2, exists

Figure 2. Views of the optimized S0 structures for H−B complexes between DCO and water molecules, DCOH1a, DCOH1b, and DCOH2, at the B3LYP/TZVP calculation level: gray, C; white, H; red, O; blue, N; yellow, S.

in DCOH1a; two stable H−Bs, O3···H2O4 and O5···H3 O4, exist in DCOH1b; and two stable H−Bs, O1···H1O2 and O3···H2O4, exist in DCOH2. These H−B lengths and bond angles are listed in Table 1. To determine the H−B strength, the binding energy (EB) between DCO and a water molecule was calculated according to the following: E B = (E DCO + Ewater) − Ecomplex

DCOH1b

1.89 177.7

(1) C



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Figure 3. Views of the optimized S0 structures for H−B complexes between DCOT and water molecule, DCOTH1a, DCOTH1b, DCOTH1c, DCOTH1d, DCOTH1e, DCOTH1f, DCOTH4, DCOTH5, and DCOTH6 at the B3LYP/TZVP calculation level: gray, C; white, H; red, O; blue, N; yellow, S.

final optimized structures from these initial ones are shown in Figure 3. Clearly, four water molecules form seven H−Bs with DCOT in DCOTH4, five water molecules form eight H−Bs with DCOT in DCOTH5, and six water molecules form nine H−Bs with DCOT in DCOTH6. These H−B lengths have been listed in Table 2. As can be seen, there is not much

calculation. The B3LYP function with the 6-311+G(2d,P) basis set, which had been proven appropriate for calculating the 1 H chemical shift,50,51 was used to calculate the 1H NMR spectra. The results are shown in Figure S3 and Tables S1 and S2 and discussed in the Supporting Information. 3.2. UV−Vis Absorption Spectra and Molecular Orbital Analysis. In the experiments reported in ref 16, the UV−Vis titration was carried out in H2O and CH3CN mixed solvent. As shown in Figure 4a, the addition of Cys resulted in an obvious blue shift, a gradual decrease in the absorption peak at 483 nm, and the emergence of a new peak at 400 nm.16 The 483 nm absorption band was ascribed to the transition of the chemosensor DCO, and the new band at 400 nm should be assigned to the Michael reaction product DCOT. Here, using the TDDFT method and the DFT/B3LYP/TZVP optimized geometries, we further calculated the VEEs and the corresponding oscillator strengths for DCO, DCOT, and their H−B complexes. For all of these molecules, our theoretical calculations predict the 12 absorbing transitions. Then, absorption profiles are calculated using the Gaussian models and are further compared with the experimental results (see Figure 4 and SI Figures S4 and S5).16 First, we adopted the TDDFT/B3LYP/TZVP method to calculate the VEEs and the corresponding oscillator strengths. As shown in Figure 4a,b and SI Figures S4a and S5a, these theoretical results agree well with the experimental ones. But it is widely known that the TDDFT/B3LYP method suffers severe failure when dealing with charge-transfer excited states21,42,43 which is just the issue we are currently investigating (see Figure 5 and the subsequent relevant discussion). We have found that for DCOT and its H− B complexes (DCOTH4, DCOTH5, and DCOTH6), the first singlet transition (S0 → S1), corresponding to HOMO → LUMO, is a completely charge-separation state (TDDFT/ B3LYP/TZVP level; see Table S7 and Figures 5 and S7 of the

Table 2. Calculated Important H−B Lengths (Å) for the Fully Optimized Structure of DCOTH4, DCOTH5, and DCOTH6 HB1 HB2 HB3 HB4 HB5 HB6 HB7 HB8 HB9

DCOTH4

DCOTH5

DCOTH6.

2.16 1.94 1.97 1.89 1.58 2.01 2.19

2.24 1.94 1.96 1.89 1.58 2.02 2.19 2.03

2.23 1.91 1.92 1.89 1.59 2.01 2.24 2.03 2.14

difference concerning the H−B lengths of HB1−HB7 in DCOTH4, DCOTH5, and DCOTH6. Hence, in DCOTH5 and DCOTH6, the continually added water molecules almost have no distinct influence on the length and the strength of these H−Bs (HB1−HB7). And one can also note that the H−B lengths of HB8 in DCOTH5 and DCOTH6, and HB9 in DCOTH6 are larger than 2.0 Å. This indicates that the strengths of HB8 and HB9 are weaker than strengths of HB1− HB7. To further understand the structural information on the chemosensor DCO, the Michael reaction product DCOT, and their H−B complexes, 1 H NMR was calculated with tetramethylsilane chosen as a standard substance in the D



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Figure 5. Calculated frontier molecular orbitals HOMO and LUMO for DCOH2 and HOMO, LUMO, and LUMO+1 for DCOTH4.

DCOTH6) and the second transition (S0 → S2, for DCOTH5 and DCOTH 6) are charge-separation states and their corresponding oscillator strengths are approaching zero (as listed in SI Table S7). However, as listed in SI Tables S8−S10, the TDDFT calculations using M062X, Cam-B3LYP, and wB97XD functionals have predicted that the first transition involved both HOMO → LUMO and HOMO → LUMO+1, and the corresponding oscillator strength is large ( f > 0.8), as well as that the first excited states of DCOT and its H−B complexes possess partial ICT character. Hence, the VEEs of those charge-separation states have been underestimated by the B3LYP functional, and we cannot obtain reliable calculated VEEs results for DCOT and its H−B complexes with the TDDFT/B3LYP/TZVP method. Compared with the experimental results, the calculated VEEs with M062X, Cam-B3LYP, and wb97XD functionals are slightly blue-shifted (see Figure 4 and SI Figures S4 and S5 and Tables S4−S6 and S8−S10). Now we discuss the H−B features and the photophysical property. As shown in SI Figure S4 and Tables S3−S6, the calculated VEEs of DCO and its H−B complexes exhibit a blue shift or red shift. The shift of the calculated VEEs can be ascribed to the intermolecular H−B interaction. The existence of the intermolecular H−B can decrease the energy level of all electronic states and influence the VEEs.27 If the H−B is strengthened in the excited state, the intermolecular H−B will decrease the energy level of this excited state more than that of the ground state, and the energy gap between the excited state and ground state will be decreased. As a consequence, the VEE of the excited state will be red-shifted. On the contrary, when the H−B is weakened in the excited state, the intermolecular H−B will decrease the energy level of this excited state less than that of the ground state, and the energy gap between the excited state and the ground state will be increased and the VEE of the excited state will be blue-shifted. Therefore, based on this rule given by Han and co-workers, i.e., the excited-state intermolecular H−B strengthening/weakening corresponds to

Figure 4. Comparison of experimental and calculated UV−Vis absorption spectra: (a) experimental UV−Vis spectra in H2O/ CH3CN mixed solvent with the addition of 3 equiv of Cys (taken from ref 16); (b) calculated absorption bands of DCOH2 (black line) and DCOTH4 (red line), obtained at the TDDFT/B3LYP/TZVP level; (c) calculated absorption bands of DCOH2 (black line) and DCOTH4 (red line), obtained at the TDDFT/M062X/TZVP level; (d) calculated absorption bands of DCOH2 (black line) and DCOTH4 (red line), obtained at the TDDFT/Cam-B3LYP/TZVP level; (e) calculated absorption bands of DCOH2 (black line) and DCOTH4 (red line), obtained at the TDDFT/wB97XD/TZVP level.

SI). Moreover one can note that the second singlet transition (S0 → S2), corresponding to HOMO-1 → LUMO (see SI Table S7), is also a charge-separation state (see SI Figure S7), and its corresponding transition oscillator strengths are approaching zero in DCOTH5 and DCOTH6. Therefore, to validate the ability of the B3LYP functional in describing the present ICT process and the completely chargeseparation states, we further performed M062X44 functional and LRC functional calculation with two LRC functionals (cam-B3LYP45 and wB97XD46,47) to obtain the VEEs for DCO, DCOT and their H−B complexes (see SI Tables S3−S6 and S7−S10, Figure 4c−e and SI Figures S4b−d and S5b−d). For chemosensor DCO, the calculated VEEs agree well with the experimental results.16 As listed in SI Tables S3−S6, for the first singlet transition (S0 → S1) that occurred in DCO and in its H−B complexes, we obtained the same results with B3LYP, M062X, Cam-B3LYP, and wB97XD functionals. This indicates that these funcitonals can describe the excited transitions of the chemosensor DCO and its H−B complexes correctly, except that the VEEs obtained with M062X, cam-B3LYP, and wB97XD functionals are relatively blue-shifted compared with that of the B3LYP functional and the experimental results.16 According to the TDDFT/B3LYP calculation, the first singlet transition (S0 → S1, for DCOT, DCOTH4, DCOTH5, and E



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Figure 6. Views of the optimized S0 and S1 structures for DCOH2 and DCOTH4 at the TDDFT/M062X/TZVP level: gray, C; white, H; red, O; blue, N; yellow, S.

red shifts/blue shifts in the electronic spectra,27 we can predict that the H−B between the CO group and the water molecule in DCOH1a is weakened in the excited state because the calculated VEEs of DCOH1a are blue-shifted compared to those of DCO. However, the intermolecular H−B between the NO2 group and the water molecule in DCOH1b is strengthened in the excited state since the calculated VEEs of DCOH1b are red-shifted compared to those of DCO. The coexistence of the H−B strengthening and weakening in the excited state can be inferred from the calculated VEEs of DCOH2 being red-shifted compared to those of DCO and DCOH1a but blue-shifted compared to that of DCOH1b. But overall, the general trend for the cooperative H−Bs in DCOH2 should be a strengthened one due to the spectral red shift between DCOH2 and DCO. This overall trend is further confirmed by the calculated infrared spectra (see section 3.3). The overall H−B strengthening can influence the excited-state dynamic process of chemosensor DCO and induce the weak fluorescence emission of DCO, as we discussed subsequently. The product of Michael reaction DCOT has multiple H−B interactions and can form multiple H−Bs. Shown in Figure 3 and Table 2, we have obtained the stable configurations of DCOT-(H2O)n (n = 4, 5, and 6) complexes, which are DCOTH4, DCOTH5, and DCOTH6, respectively. Since the TDDFT/B3LYP/TZVP method failed to deal with the chargetransfer states of DCOT and its H−B complexes as discussed above, here we focused on the VEEs calculated with M062X, Cam-B3LYP, and wB97XD functionalS (note that the VEEs do not show much difference between these functionals). From these results, one can also note that with the increasing of the number of water molecules (form 4 to 6), the VEEs almost remain unchanged except for a slightly red shift, and the transition orbitals almost keep consistent as shown in SI Figure S7. These indicate that we can employ DCOTH4 to simulate the real experimental case and to discuss the photophysical property of the chemosensor in subsequent sections. We calculated the frontier molecular orbitals involved in the first transition for DCOH2 and DCOTH4, which are shown in Figure 5. Here, the results are from calculation with B3LYP functional, and there are no significant differences in these results between the B3LYP functional and other functionals. The frontier molecular orbitals have also been calculated for

DCO, DCOT, and their other H−B complexes (see Figures S6 and S7, Supporting Information). For DCOH2, the first transition is the HOMO → LUMO transition (see SI Tables S3−S6). It is evident that the CO group and the two ethyl groups contribute a lot to HOMO, but their contributions to LUMO are largely decreased. Thus, the S1 state of DCOH2 owns an ICT character. The first singlet transition of DCOTH4 corresponds to the orbital transitions of both HOMO → LUMO and HOMO → LUMO+1. As seen, the HOMO orbital is localized on the coumarin group and the two ethyl groups, and the LUMO orbitals are localized on the NO2 group, while the LUMO+1 orbital is completely localized on the coumarin group. Thus, the S1 state of DCOTH4 owns an ICT character as well. But one can note that the ICT character of the S1 state of DCOTH4 is relatively weak compared to that of DCOH2. This relatively weak ICT character induced the blue shift of the UV−Vis absorbance of the Michael reaction product DCOT as compared with DCO. 3.3. First Excited-State Geometries and Excited-State H−B. As shown above, both the chemosensor DCO and its Michael reaction product DCOT can interact with water molecules and form H−B complexes, and the H−Bs induced the spectral shift of their UV−Vis absorption spectra. In this section, we investigated the excited-state properties of DCOH2 and DCOTH4, particularly the excited-state H−Bs. The optimized geometries of the first singlet excited states S1 of DCOH2 and DCOTH4 are shown in Figure 6, obtained from the TDDFT/M062X/TZVP calculation. For a reasonable comparison with the ground-state geometries, we also optimized the ground-state geometries of DCOH2 and DCOTH4 with the DFT/M062X/TZVP method and displayed these ground-state structures in Figure 6 as well. The vibrational frequency analysis results confirmed that these optimized structures correspond to the local minimal on the excited states energy surfaces. From Figure 6, one can note that overall DCOH2 remained similar in structure in the first excited state with that in the ground state, but the H−Bs changed from the ground state to the first excited state. As labeled in Figure 6, the length of H−B (O1···H1) enlarged from 1.89 Å (S0) to 1.94 Å (S1) and the length of H−B (O3···H2) shortened from 1.98 Å (S0) to 1.88 Å (S1). Hence the H−B (O1···H1) is weakened and the H−B (O3···H2) is strengthened in the F



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groups.23,25,27 Hence in order to investigate the H−B strengths in the excited state, we calculated the ground-state and the excited-state vibrational spectra of DCOH2 and DOCTH4 and displayed the vibrational regions of the O−H stretching modes in Figure 7. For DCOH2, in the ground state the O−H stretching modes of the H−Bs of O1···H1O2 and O3··· H2O4 are located at 3702 and 3775 cm−1, respectively. In the excited state, the O−H stretching mode of O1···H1O2 is slightly blue-shifted to 3747 cm−1 and the O−H stretching mode of O3···H2O4 is strongly red-shifted to 3666 cm−1 (see Figure 7a). This indicates that the intermolecular H−B (O1···H1O2) is slightly weakened while the intermolecular H−B (O3···H2O4) is significantly strengthened in the S1 state. For DCOTH4, the O−H stretching modes of the H−Bs did not show much difference between S0 and S1 states, except for the O−H stretching mode of H−B5 (see Figure 7b). It blue-shifted from 2592 cm−1 (S0) to 2653 cm−1 (S1); this indicates that H−B5 (and thus the overall trend of the H−Bs) is weakened in the S1 state. In total, in DCOH2, the excited-state H−Bs are overall strengthened and the excited-state H−B strengthening enhanced the interaction between the excited-state DCO and its surrounding water molecules, which then tuned the energy level of the excited state and the ground state. Eventually, the energy gap between the two states of the H−B system (DCOH2) will be decreased more than that of the non-H−B system (DCO). Hence, the rate of the internal conversion (IC) from the excited state to the ground state is enhanced for DCOH2, as discussed by Han and co-workers.22−25,27 This is to say, the excited-state H−B strengthening will enhance the nonradiative processes more to induce the weak fluorescence emission of DCOH2. Contrary to this, in DCOTH4, the excited-state H−Bs are overall weakened and therefore weakened the interaction between the excited-state DCOT and its surrounding water molecules. Thus, the rate of the IC from the excited state to the ground state is decreased, and this

excited state, further confirming the predictions, in section 3.2, from our calculated UV−Vis absorption spectra with the rule of Zhao and Han.27 The H−B lengths of DCOTH4 in the ground and first excited states are listed in Table 3. Compared to Table 3. Calculated Important H−B Lengths (Å) for the Fully Optimized Structure of DCOTH4 in Ground State (S0) and First Excited State (S1) with TDDFT/M062X/TZVP Method S0 S1

HB1

HB2

HB3

HB4

HB5

HB6

HB7

2.22 2.14

1.92 1.86

1.92 1.92

1.88 1.88

1.52 1.53

1.96 1.96

2.14 2.15

DCOH2, there are no obvious changes in the H−B lengths in DCOTH4, except that the HB1 and HB2 are strengthened in the excited state. However, this kind of H−B strengthening with the HB1 and HB2 is, in nature, quite different from that of H−B strengthening with the H−B (O3···H2) in DCOH2. This is because, first, as evidenced by the calculated infrared spectra (see the following portion), the H−Bs in DCOTH4 are overall weakened; second, HB1 together with HB4, and HB2 together with HB3, are connecting the COOH group with the coumarin part and with the NO2 group, respectively. Thus, the excitedstate H−B strengthening may only ensure a tighter connection between different groups and may therefore generate a negligible (or even a reversible) effect on the interaction of DCOT with its surrounding environment. The H−B strength can also be monitored by the spectral shifts of some characteristic vibrational modes involved in the formation of H−Bs.23 The CO group, NO2 group, and COOH group in DCO and DCOT and the OH group in the water molecule are all involved in the H−B formation. It is therefore rather complex to monitor the vibrational spectra of all of these groups. Fortunately, it has been founded that the stretching mode of the O−H group is much more sensitive to the intermolecular H−B interaction than the other

Figure 7. Calculated infrared spectra for (a) DCOH2 and (b) DCOTH4. The vibrational frequencies of the O−H group’s stretching modes in S0 and S1 states are shown. G



Article

DCO. Our present theoretical prediction is further confirmed by the experimental phenomenon where the fluorescence quantum yield of DCO in pure acetonitrile (CH3CN) solvent is larger than that in water−CH3CN mixed solvent.53

ensures that the Michael reaction product DCOT has strong fluorescence emission. According to our calculation, the sensing mechanism of the chemosensor DCO can be depicted as follows. First, the addition of the biothiols (Cys, Hcy, and GSH) initiated the Michael addition reaction and formed the product DCOT. Second, the multiple H−B interaction sites in DCO and DCOT induced the formation of the H−B complexes with water molecules. In the H−B complex between DCO and water molecules (DCOH2), the H−B is overall strengthened in the S1 state and enhanced the interaction between DCO and water molecules in the solute environment. Meanwhile, the first excited state of DCOH2 showed an obvious ICT character. The combination of the excited-state H−B strengthening and the ICT process induced the weak fluorescence emission of DCO.22−24 In the H−B complex between Michael reaction product DCOT and water molecules (DCOTH4), the intermolecular H−B is overall weakened in the S1 states and thus weakened the interaction between DCOT and the surrounding water molecules. The overall weakened H−Bs and the relatively weak ICT character of the excited state are thus responsible for the enhanced fluorescence emission of the Michael reaction product. Thus, DCO can serve as an excellent candidate for colorimetric and fluorescent chemosensor for biothiols.

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ASSOCIATED CONTENT

S Supporting Information *

Figures showing eight initial conformations of DCOT-H2O H− B complexes, the initial configurations of the H−B complexes DCOTH4, DCOTH5, and DCOTH6, calculated 1H NMR spectrum, calculated absorption bands for DCO and DCOT and their H−B complexes, and calculated frontier molecular orbitals for DCO and its H−B complexes (DCOH1a, DCOH1b, and DCOH2) and for DCOT and its H−B complexes (DCOTH4, DCOTH5, and DCOTH6), text describing 1H NMR spectra calculations and an accompanying reference, and tables listing calculated absorption bands of DCO and DCOT and their H−B complexes with different functionals, the calculated electronic transition energies and corresponding oscillator strengths of the low-lying singlet excited states of DCO, DCOH1a, DCOH1b, and DCOH2 and of DCOT, DCOTH4, DCOTH5 and DCOTH6 with different functionals. This material is available free of charge via the Internet at http://pubs.acs.org.

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4. CONCLUSION We investigated the biothiols sensing mechanism of the colorimetric and fluorescent chemosensor DCO using the DFT and TDDFT methods. The theoretical study indicated that the excited state H−B plays an important role for the sensing mechanism and suggested a sensing mechanism for DCO biothiols. In the ground state, the added biothiols induced the Michael addition reaction between the chemosensor DCO and biothiols and the formation of the product DCOT. Compared to DCO, the S1 state of product DCOT processes relatively weak ICT character, which induces the blue shift of the absorbance spectrum of DCOT. And the relatively weak ICT character also ensures DCOT with a strong fluorescence emission compared to DCO. Meanwhile, DCO and DCOT have multiple H−B interaction sites, interacting with water molecules to form the H−B complexes, DCOH2 and DCOTH4. The formed H−Bs regulated the orbital energy levels and resulted in the blue shift or red shift of the UV−Vis absorption spectra of DCO, DCOT, and their H−B complexes, which agree well with the experimental results.16 The blueshifted or red-shifted UV−Vis absorption spectra indicated the cooperative H−Bs are generally weakened or strengthened in the excited state of DCO and its H−B complexes.23 In order to further understand the excited-state H−B dynamic process, we investigated the excited-state properties of the H−B complexes. For DCOH2, the H−Bs between water molecule and DCO are overall strengthened in the first excited state; thus the interaction between the fluorescence chemosensor DCO and the solute molecules is enhanced in the first excited state. This induced the weak fluorescence emission of DCO.22 For DCOTH4, the H−Bs between water molecule and DCOT are overall weakened in the first excited state; the weakened excited-state H−B resulted in the enhanced fluorescence emission.23 The different excited-state H−B dynamic processes induced different fluorescence emission and made DCO able to act as a fluorescent sensor for biothiols. Hence, the excited-state H−B plays an important role for the biothiols chemosensor

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]; [email protected]. Tel.: +86-41184379029. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work is supported by National Natural Science Foundation of China (NSFC Grant Nos. 21273234, 20833008, and 21103096). We thank Prof. Wei Guo for insightful discussion on the experimental results in ref 16.

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