Article pubs.acs.org/JPCB
Theoretical Study of Resorufin Reduction Mechanism by NaBH4 Ping Song,†,‡ Mingbo Ruan,†,‡ Xiujuan Sun,†,‡ Yuwei Zhang,†,‡ and Weilin Xu*,†,‡ †
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, People’s Republic of China ‡ Jilin Province Key Laboratory of Low Carbon Chemical Power, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, People’s Republic of China S Supporting Information *
ABSTRACT: In the current work, the whole reduction mechanism of resorufin by sodium borohydride (NaBH4) has been investigated completely using quantum chemical theory for the first time. The possible pathways for each step were considered as much as possible. The calculated results reveal that the reduction mechanism for resorufin undergoes a nucleophilic addition with BH4−, a synchronous proton abstraction from a carbon (C) atom, a protonation in a nitrogen (N) atom, and then a final hydrolysis process to obtain final reduced product dihydroresorufin. Interestingly, it was found that the protonation of N atom could induce a reduced product molecule with a Λ-type structure rather than a planar one, and the large alteration in geometry will induce different optical properties, such as fluorescent or nonfluorescent. More importantly, countercation Na+ and solvation effect of H2O play important roles in reducing the activation energy in elementary steps, and their stabilization effect has been confirmed by NBO analysis. The detailed theoretical investigation for the reduction reaction of resorufin by NaBH4 will support some guidance for the similar reduction reaction for organic compounds like aldehydes and ketones. reveal real-time redox catalysis.11,12 So in the current paper, planar fluorescent resorufin has been chosen as a reactant to investigate the whole reduction process by NaBH4. According to previous knowledge,4,13,14 the reducing process by NaBH4 should first achieve the attacking of BH4− to the carbonyl group, and then the final hydrolysis to product dihydroresorufin. The first step for addition of BH4− may undergo linear-, four-, five- and six-membered cyclic transition states (Scheme 1b), while there is still no consensus as to the reduction mechanism for the hydride-transfer. In this work, we investigate the complete reduction mechanism of resorufin by NaBH4 from the elementary-step level for the first time, and some important transition states above are revealed. This new information will be useful for the design of organic reactions.
1. INTRODUCTION Sodium borohydride (NaBH4) has been widely used as a reducing agent in organic chemistry since its discovery more than half a century ago.1−4 NaBH4 can reduce carbonyl, aldehyde, and imine groups more gently compared to lithium aluminum (LiAlH4). So far, there is still a lack of reasonable verification in theory in the case of NaBH4 reduction in detail,4 leaving only a number of proposed reaction mechanisms for the first nucleophilicity step of borohydride in previous reports.5−9 Previously, regarding the role of metal cation and solvent molecules, Wigfield et al. only considered the effect of the solvent,6 while Glass and Yadav only considered the role of the cation in their research.9 Moreover, Tomoda’s and Eisenstein’s group have confirmed that the sodium cation and the protonic solvent molecule play some role in the proposed reduction mechanism, which is capable of stabilizing the reaction systems.4 So, with a goal of a comprehensive understanding of the reduction process of NaBH4 to organic molecules, it is necessary to clarify the key elementary steps in this type of reduction process. Resorufin is the important intermediate in the organic synthesis, which is the reductant of resazurin.10 Moreover, resorufin could be used as fluorescence sensor due to its strong fluorescence. It has been known that the fluorescent resorufin can be further reduced to nonfluorescent dihydroresorufin by NaBH4 (Scheme 1a); the nonfluorescent dihydroresorufin can easily be oxidized back to resorufin. This fluorescence on−off phenomenon can be used in a single-molecule experiment to © XXXX American Chemical Society
2. COMPUTATIONAL DETAILS All the calculations have employed the Gaussian 09 program.15 Truhlar’s M06-2X functional16 was developed for computations involving main-group thermochemistry, kinetics, and noncovalent interactions, and has been found to give good energetics for these types of reactions.17 So the DFT method at the Received: June 10, 2014 Revised: July 30, 2014
A
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Scheme 1. (a) The Reduction Process for Resorufin. (b) The Geometries of Proposed Transition States for the First Step
Figure 1. Transition states for the first step as well as the corresponding activation energies (kcal/mol). (Insert: The local reaction part of transition state geometries for TS1a and TS1e).
accurate for charged species than other solvent models.21,22 All the reactants, intermediates, and products have been confirmed to be the minimum with no imaginary frequencies, and each transition state had only one imaginary frequency (Supporting Information, SI). Intrinsic reaction coordinate (IRC) calculations at the same level of theory were performed to ensure that
M062X/6-31+G* level has been carried out to calculate the stationary point with frequency computations. The total energy has been corrected by higher accurate second-order Møller− Plesset perturbation theory (MP2) level using 6-311++G** basis set with solvation effect.18,19 The solvent effect in water was employed by using SMD solvent method,20 which can be more B
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Table 1. Main Geometry Parameters for the First and Third Possible Transition States (Units in Å for Bond Length) TS1a TS1b TS1c TS1d TS1e TS1f TS1 IM1 TS3a TS3b TS3c TS3d TS3e TS3
C1H1
C1O1
BH1
1.16 1.14 1.14 1.14 1.13 1.13 1.12 1.11
1.34 1.37 1.37 1.37 1.39 1.40 1.41 1.39
2.05 2.16 2.20 2.11 2.13 2.17 2.19
C1O1
C1O4
1.48 1.52 1.54 1.55 1.47 1.48
1.82 1.68 1.81 1.81 1.88 1.87
BO1 2.77 2.84 3.78 2.84 2.76 2.85 2.83 1.50 BO1 1.59 1.60 1.59 1.59 1.59 1.59
Na1O1
Na1B
1.99
2.90
2.07 2.18 2.16
2.85 2.95 2.91
H2O1
1.41 1.54 1.49
O1H4
O4H4
0.98 0.97 0.97 0.97 1.01 1.01
1.76 2.31 1.95 1.92 1.60 1.59
membered cyclic TS1a, C1H1 bond in TS1b is reduced to 1.14 Å with increasing distance between BH1 (2.16 Å). The attraction between Na1 and O1 induces longer distance between C1O1 (1.37 Å) and BO1 (2.84 Å). The consideration of Na+ cation lowers the activation energy to 32.9 kcal/mol, confirming the essential role in the reaction for the involvement of Na+. The incorporation of the solvent H2O molecule can be divided into two forms, one acts as one of reactants to form six-membered cyclic transition state TS1c, and the other is only coordinated with carbonyl oxygen rather than reacting with it (fourmembered cyclic TS1d). Both of the H2O molecules construct one hydrogen bonding (O···HOR) in transition states. B1 H1 distance in TS1c is lengthened to 2.20 Å, longer than that in TS1d, and the participation of the H2O molecule forming the sixmembered ring in TS1c significantly enlarged the BO1 bond to 3.78 Å. The incorporation of H2O in these two transition states reduces the activation energies to about 35.8 kcal/mol due to stabilization by hydrogen bonding. It is still hard to occur by these pathways above for the net BH4− attack, or considering only Na+ or H2O separately, although the incorporation of cation or solvent molecules plays an important role in reducing the reaction activation energy. Moreover, all the geometry parameters from Table 1 change slightly for the possible transition states in the first step, well in agreement with the previous report for acetone reduction in methanol.4 In other words, the groups excluding active carbonyl group slightly affect the geometry, and the presence of Na+ and solvent molecules also play minor role in geometry. The hydrogen bonding in transition states can stabilize the geometry and then decreases the active energy barrier, which can accelerate the reaction. This is similar to the hydrogen bonding in excited states, which can decrease the energy gap between the ground state and the excited state, and induce the photoexcitation process more easily. What is different is that the hydrogen bonding in the transition state is formed by the collision of ground state, while the hydrogen bonding in excited state is obtained by absorbing photons. The hydrogen bonding in the excited state can greatly change when being excited by lighting, which will be followed by photophysical and photochemical processes, such as electron transition, internal conversion, intersystem crossing, fluorescence quenching, or enhancement.23−25 As known to us, the water stability for salts is confirmed for several decades,26,27 therefore it is necessary to consider the synergetic effect of the two factors in the current paper. First,
each transition state is the right one to link the expected forward and reverse intermediates.
3. RESULTS AND DISCUSSION 3.1. Test of the First Proposed Transition States. Resorufin is the rigid planar structure with three six-membered rings, which includes one carbonyl group as in usual aldehyde and ketone species. Different from organic ones, resorufin is the sodium salt type with one negative charge in solution. According to the previous report, the first step of the NaBH4 reduction should be the addition of the borohydride to carbonyl, which in principle can follow different reaction pathways shown in Scheme 1b. Transition state TS1a with its four-membered ring is the simplest nucleophilic BH4− addition. The other three transition states TS1b, TS1c, and TS1d (five-, six-, and fourmembered cyclic ones) take account of the metal cation and solvent molecule, respectively. Herein, the H2O molecule in TS1c acts as one reactant, whereas that in TS1d only plays the role of ligand to stable the system. For the purpose of seeking the optimal reduction mechanism, these proposed transition states for the first step have been confirmed one by one. C1H1 and BO1 bond formation is synchronized with BH1 cleavage in TS1a, and the C1 atom in carbonyl group turns into sp3 hybridization with an angle of H1C1O1 of 111.7°. The BH3 group changes to nearly flat due to the broken BH1 bond by 2.05 Å. The transition state is product-like geometry with the new C1H1 bond by 1.16 Å, which is similar to that in the following intermediate. BH3 group begins to transfer from BH4 hydride to O1 atom with the BO1 distance of 2.77 Å. All the geometry parameters are consistent with the previous theoretical results by Eisenstein.7 The typical four-membered cyclic TS1a for only BH4− attack induces so large an activation energy (43.8 kcal/mol in Figure 1) that it is hard to occur for the first nucleophilic BH4− addition. When considering the cation effect, the Na+ is assumed to associate with borohydride. However, the Na+ cation tends to locate over the resorufin planar to be the counterion, so the five-membered transition state for resorufin anion cannot be found. In order to fix the Na+ in NaBH4, the other Na+ cation in resorufin is considered to maintain the balance. The transition state TS1b in Scheme 1b also shows a vibration type corresponding to a stretching vibration of breaking BH1 bond and forming BO1 and C1H1 bond, where Na+ is coordinated to BH3 group with carbonyl oxygen to stable the system. Compared to the fourC
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Figure 2. (a) The proposed hydrolysis mechanisms considering the effect of Na+ and solvent H2O molecules (Unit: kcal/mol). (b) The local reaction part for hydrolysis process. (c) The detailed proton abstraction process accompanied by protonation in N atom to form the intermediate IM2.
The IRC calculation reveals that the following intermediate IM1 for TS1 is the product of BH4− adding to C1 atom in carbonyl group, and the protonation in the C1 atom causes the sp3 hybridization followed by O1 out of the resorufin planar in IM1, leaving residual majority still keeping planar structure. The C1H1 and C1O1 bond are 1.11 and 1.39 Å, respectively, similar to those in TS1. The angle of H1C1O1 changes to 108.3°, compared with that of 107.1° in TS1, indicating a product-like geometry for TS1. The addition of BH4− leads the N atom in IM1 to hold more negative charge (−0.292 e) than that of the resorufin reactant (−0.232 e), indicating further possible protonation on N atom. However, the six-membered ring including C1 with sp3 hybridization tends to transfer to a stable phenyl ring. Therefore, there will be two possible pathways for the protonation on N atom. The first pathway is the direct protonation on an N atom by a H2O molecule attacking, and the other one is followed by the proton abstraction process from a C1 atom. Unfortunately, the transition state for the former pathway cannot be found, and the proton in the H2O molecule refused an attack from an N atom. It may be due to the deficient electronegativity in N atom for pulling the proton. The second pathway is the OH− anion in the aqueous solution toward H1 atom, which forms a transition state TS2 with a strong OH1 stretching vibration of 3882 cm−1. The strong electronegativity of O increases C1H1 to 1.23 Å, with O3H1 distance of 1.59 Å. It indicates that the proton has been removed to form unstable intermediate IM2a, leaving the C1 atom with a negative charge. Then the stable intermediate IM2b has been spontaneously constructed via charge rearrangement of IM2a to form stable phenyl ring with more negative charge of −0.50 e for N atoms compared with that in IM1 of −0.29 e. It can be seen by calculation that the spontaneous protonation process on N atom has been confirmed to form the intermediate IM2 due to the more stable transition state than IM2b. In other words, the proton abstraction process from C1 atom is accompanied by spontaneous protonation on N atom with small active energy of 12.0 kcal/mol (Figure 2a). Heretofore, the reduction for N atom was finished, leaving the geometry for IM2 nonplanar, with the dihedral angle of 159.4° between two sides of phenyl rings. At the
different numbers of H2O were tested to evaluate the effect of H2O. Herein, the transition state with one H2O is denoted as TS1e, two as TS1f, and three as TS1. As can be seen from Scheme 1, the activation energy for the first step with one H2O is decreased to 29.8 kcal/mol, and two H2O with 19.2 kcal/mol, indicating that it is more likely to occur under the synergic effect of Na+ and H2O. When considering three H2O molecules (TS1), the activation energy drops to only 10.2 kcal/mol. The results above further confirmed the role of H2O in the first step of the reaction, and each H2O can drop the activation energy by about 10 kcal/mol. From the view of energy, the participation of three H2O molecules evokes a small activation energy, enough to execute the first step in the reduction process. However, three H2O molecules with two hydrogen atoms from BH4− form a quinquidentate ligand form for Na+, meeting the total fivecoordination number of Na+ in solution.28−30 Therefore, we adopt the model with three H2O molecules for the NaBH4 reduction in the current paper. 3.2. Reduction Reaction Mechanism. All the reactions have been initiated from resorufin (reactant, R), and the integral proposed reduction reaction mechanism has been described in Figure 1. When NaBH4 aqueous solution is added to the resorufin, NaBH4 with three H2O molecules coordinates to resorufin to form five-membered cyclic transition state TS1. The BH4− segment moves to the carbonyl group with Na+ cation, leaving H2O molecules coordinating around to form hydrogen bonds to reduce the activation energy. The broken BH1 bond will take place by the formation of C1H1 and BO1 bond via a stretching vibration of breaking of the BH1 bond. The C1H1 bond is shortened to 1.12 Å with a product-like geometry, and the C1O1 bond is lengthened to 1.41 Å due to the coordination of H2O with Na+ cation. Na1B distance (2.90 Å) is longer than that in NaBH4 (2.27 Å), indicating the separation of Na+ from BH4−. In this respect, this kind of transition state coincides with the previous suggestion, which reveals the product-like transition state.4,5 The synergetic effect for Na+ and three H2O molecules induces small activation energy with only 10.2 kcal/mol for the NaBH4 attack. D
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Figure 3. Whole proposed mechanism for the NaBH4 reduction on resorufin (units in kcal/mol).
same time, the protonation induces sp3 hybridization in an N atom. Finally, the hydrolysis process will occur to form the final reduction product dihydroresorufin. Herein, there are two pathways to form reduction product dihydroresorufin and B(OH)H3, which can further participate in the following reduction reaction. One way is by attacking the BO1 bond by H2O molecule, and unfortunately, there is the absence of the transition state with the breaking of BO1 bond. The other way is by attacking the C1O1 bond by H2O in the solution. It can be seen that there is too large an activation energy (60.3 kcal/mol) for the hydrolysis process with the present of only one water reactant (TS3a), so the hydrolysis process seems unlikely to occur. Therefore, the cooperative effect of cationic and protic solvents should be taken into account again in the hydrolysis process. Obviously, about 12 kcal/mol can be decreased in the activation energy after considering the participation of Na+ and one H2O molecule, which confirms the effective enhancement in hydrolysis process for the synergetic cation and protic solvent. On the basis of this, the successive increasing in H2O numbers has been carried out, and the corresponding activation energies have been listed in Figure 2, followed by the transition states considering different numbers of H2O molecule. It can be seen that the more H2O molecules, the lower the activation energy for the hydrolysis process becomes, due to the stable hydrogen bonding. Moreover, the Na+ cation surrounded by more H2O molecules (three and four) begins to locate over the middle of whole molecule rather than at the side of the BH3 group. All these six types of transition states in the hydrolysis process tend to form new C1O4 and O1H4 bonds synchronously by O4H4 bond cleavage in the H2O molecule and C1O1 bond breaking in the COB moiety. Then the BH3(OH)− will be produced. It is obvious that these transition states in the hydrolysis process exhibit the product-like geometries, and the distance of H4O1 is about 1.0 Å, similar to that in the bonding OH distance. The increasing H2O numbers slightly changes the O1H3 and B O1 bonds. When Na+ participated in transition state TS3b, the C1O4 distance is decreased to 1.68 Å due to the interaction
between the Na and surrounding atoms. The attachment of solvent H2O molecules to the Na+ cation brings Na+ far away from the O3 atom, and then relaxes the C1O4 distance. Moreover, the solvent H2O number is up to 3 and 4, the cluster of Na+ cation with solvent H2O transfers over the middle of the dye molecule, leaving the reactant H2O molecule exposed completely to relax the C1O4 distance. Then the interaction between the cluster and the dye itself further loosens the C1O4 distance, longer than that without the cluster. By contrast, not only the Na+ cation but the cluster with less than three H2O molecules lengthens the C1O1 bond, followed by its breakage. When the cluster moves over the dye molecule, the exposed C1O1 bond is shortened. It can be seen that the rapid drop in activation energy results from the collaborative effect of the Na+ cation and the solvent H2O molecules, which brings greater geometry changes in the reaction moiety of the transition state than that of the residual part. Depending on the steric hindrance and the previous report of a hydrous sodium cation, the four solvent H2O molecules with Na+ (denoted as TS3) have been considered in the final hydrolysis process. Interestingly, the stabilized transition state TS3 reduces the activation energy to 15.9 kcal/mol, indicating the possibility for hydrolysis. In addition, the former reaction including the proton abstraction and protonation process is greatly exothermic, which is large enough to prompt the hydrolysis to occur easily. In this way, the complete reduction mechanism for resorufin including final hydrolysis is finished. Although the interference of several H2O molecules may not reflect the real solvation effect, it was enough to indicate the major trend of stabilizing the interaction between solvent and solute. It has been confirmed that the intermediates BHx(OR)−4−x (x = 1−3) were more reactive than the starting borohydride,31,32 so one of the products, NaBH3(OH), will take the continuative reduction reaction with another dye molecule to finish the complete hydrolysis process from BH4− to B(OH)4−. Because we only focus on the process from resorufin to dihydroresorufin, the continuative process from BH3(OH)− to B(OH)4− is no longer studied. To sum up, the calculation results reveal that the product E
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Figure 4. Corresponding NBO orbitals for TS1a (left) and TS1e (right) (Units: kcal/mol).
(1)
like transition state, one proton H1 from BH4 is attached to the C1 atom in carbonyl group. The interactions are mainly focused on the bonding (BD) and antibonding (BD*) orbitals interaction between C1O1, C1H1, and BHa, BHb, or BHc. Moreover, the lone electron pair (n) between O1 and B also contributes to the stabilization effect. When considering the Na+ cation and solvent molecules, more considerable interactions between the Na1 or B and H2O, the carbonyl group and H2O have contributed to stabilize the transition state TS1e. Moreover, the similar interaction between nucleophilic BH4 moiety and carbonyl group has been greatly improved. It is obvious that solvent molecule H2O represents many great interactions with B and O1 atoms. Herein, some typical representations have been listed to reveal the stabilized effect in Figure 4. For instance, the σ-orbital of O2H2 displays large value of E(2) of 258.0 kcal/mol with σ*-orbital of BHc, exhibiting larger interaction between them. Moreover, the n of O1 interacts with σ*-orbital of O2H2 by the E(2) of 144.3 kcal/ mol. In addition, the participation of cation can induce the interaction with carbonyl group, which is described as n of O1 to n* of Na with the E(2) by 44.11 kcal/mol. More importantly, the interaction between solvent H2O molecule and cation is described as the σ-orbital of O2H2 and n* of Na (108.7 kcal/mol). All of these interactions stabilize the transition state TS1e, and then increase those original interactions in TS1a. These strong interactions between Na/H2O and the parent reactant may explain the stability of TS1e with lower activation energy. In other words, the participation of cationic Na+ and the solvent molecule H2O indeed play important roles in stabilizing the transition state, which can easily induce the reaction.
where Fij is the off-diagonal element in the NBO Fock matrix, qi is the donor orbital occupancy, and εi and εj are diagonal elements (orbital energies). According to the NBO analysis, the stabilized effect for the cation Na+ and the solvent molecule H2O have been investigated by second-order perturbation energy E(2), which is listed in Figure 4 with corresponding NBO orbital interactions. It can be seen that there is a great overlap between the nucleophilic BH4 moiety and the carbonyl group in resorufin. Due to the product-
4. CONCLUSIONS In the current paper, the whole reduction mechanism in resorufin by NaBH4 has been investigated completely using quantum chemical theory for the first time. It has been confirmed that it underwent nucleophilic addition for BH4−, synchronous proton abstraction from the C atom and protonation in the N atom, and then the final hydrolysis process to obtain the final reduced product dihydroresorufin. The transition state for the first
dihydroresorufin shows a significant difference in geometry from the reactant resorufin, and the protonation of the N atom evokes itself to be sp3 hybridization, which induces the nonplanar Λshaped structure for dihydroresorufin. The dihedral angle besides the line of ON changes to 156° rather than 180°, and the dramatic change in the geometry may result in different optical properties, which can be used in a single-molecule experiment.11,12 After all, the proposed reduction mechanism on resorufin has been described in Figure 3, which underwent nucleophilic addition for BH4−, synchronous proton abstraction, and protonation, as well as a hydrolysis process. It is validated that the Na+ cation and solvent H2O molecule play a much important role in the whole reduction process, and they can stabilize the transition state to reduce the activation energies. 3.3. The Stabilized Effect for Na+ Cation and Solvent H 2 O Molecule. The whole investigation in reduction mechanism indicated the important role for Na+ cation and solvent effect. So it is necessary to gain insight into the interaction between Na+ or H2O and dye molecule. For simplicity, we only focus on transition states in the first step of the NaBH4 reduction, i.e., the nucleophilic BH4− addition. TS1e has been taken for an example to compare with TS1a, which includes one Na+ and one H2O molecule. To explain higher stability for TS1e than TS1a when cation and solvent molecule coexist, the second-order perturbation energy E(2) has been performed by natural bond orbital (NBO) analysis on the transition states. E(2) can be expressed by eq 1 below: E(2) = E ij = qiFij2/(εj − εi)
F
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Table 2. Second-Order Perturbation Energy E(2) (kcal/mol) of Donor−Acceptor Interaction with Respect to TS1a and TS1e TS
donor
acceptor
interaction
E(2)
TS1a
BD(1)C1O1 BD(1)C1H1 BD(1)BHa LP(2)O1 BD(1)C1O1 BD(1)C1H1 LP(3)O1 BD(1)O2H2 LP(3)O1 LP(2)O2 LP(1)O1 BD(1)O2H2
BD*(1) BHa LP(1)B BD*(1)C1H1 LP(1)B BD*(1)BHc LP*(1)B BD*(1)BHc BD*(1)BHc BD*(1)O2H2 BD*(1)C1O1 LP*(1)Na1 LP*(1)Na1
σ−σ* σ−n σ−σ* n−n σ−σ* σ−n* n-σ* σ−σ* n−σ* n−σ* n−n* σ−n*
8.11 24.99 138.0 3.33 20.47 12.46 124.8 258.0 144.3 52.09 44.11 108.7
TS1e
ASSOCIATED CONTENT
* Supporting Information S
The coordination of all transition state and intermediates structures. This material is available free of charge via the Internet at http://pubs.acs.org.
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nucleophilic BH4− addition is product-like type, good agreement with the previous report. Compared with other transition states, the five-membered ring transition state including Na+ and H2O is the more reasonable one in the first step. In the final hydrolysis process, the solvent H2O molecule attacks the CO bond rather than the OB bond. It confirmed that the countercation Na+ and the solvation effect play important roles in reducing the activation energy in the whole reduction reaction. In other words, the coexistence of countercation and solvent molecules is crucial in the whole reaction process, and their stabilization effect has been confirmed by NBO analysis. The stabilization interactions mainly exist between the parent reactant and the cation or solvent molecule, as well as that between the cation and solvent. In addition, the calculation results reveal that the protonation process in the N atom induces the reduced product with a Λ-type structure, dramatically different from the reactant resorufin with rigid planar structure, and the large alteration in geometry will induce different optical properties. The detailed theoretical investigation for the reduction reaction in resorufin by NaBH4 is valid and effective to guide the similar reduction reaction for organic compounds like aldehydes and ketones.
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ACKNOWLEDGMENTS This work was funded by the National Basic Research Program of China (973 Program, 2012CB932800, and 2014CB932700), National Natural Science Foundation of China (21273220, 21303180), and “the Recruitment Program of Global Youth Experts” of China. The computational support from Dr. Ke-Li Han of the Dalian Institute of Chemical Physics, Chinese Academy of Sciences, is appreciated. G
dx.doi.org/10.1021/jp505739p | J. Phys. Chem. B XXXX, XXX, XXX−XXX
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