Dynamic Electric Field Complicates Chemical Reactions in Solutions

Letter Cite This: J. Phys. Chem. Lett. 2019, 10, 2991−2997

pubs.acs.org/JPCL

Dynamic Electric Field Complicates Chemical Reactions in Solutions Yao Kun Lei,†,§ Jun Zhang,†,§ Zhen Zhang,‡ and Yi Qin Gao*,† †

Institute of Theoretical and Computational Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China ‡ Department of Physics, Tangshan Normal University, Tangshan 063000, China

Downloaded by BUFFALO STATE at 22:23:46:272 on May 23, 2019 from https://pubs.acs.org/doi/10.1021/acs.jpclett.9b01038.

S Supporting Information *

ABSTRACT: Chemical reactions can be strongly influenced by an external electric field (EEF), but because the EEF is often time-dependent and in case it does not adapt quickly enough to the reaction progress, especially during fast barrier crossing processes, dynamic effects could be important. Here we find that electrostatic interactions can reduce the height of the reaction barrier for a Claissen rearrangement reaction and accelerate the key motions for bonding. Meanwhile, strong electrostatic interactions can modify the barrier into an effective potential well, confining the system into the barrier until solvents adjust themselves to provide an appropriate EEF for charge redistribution. In this case, the otherwise concerted mechanism becomes a stepwise one. Consequently, the motion of solvents modulates the reaction dynamics and leads to heterogeneous reaction paths, even in a seemingly homogeneous aqueous solution. In addition, an excessive stabilization of transition state retards the barrier crossing process, making the thermodynamically favorable pathway less favored dynamically.

A

dependent and may not adjust rapidly enough to charge transport in chemical reactions,14 especially during barrier crossing, so that not only the free energy but also the dynamic effects should be taken into account.15,16 As a result of unfavorable EEF, the charge redistribution will be trapped until solvents adapt themselves to this process, which is called the dynamic polarization cage17 in Grote−Hynes theory.18−20 In our previous article, hereafter referred as Part I,21 we found that in an aqueous solution there are two classes of trajectories for Claisen rearrangement (Scheme 1) with different transition path lengths by machine leaning method36 (Supporting Information, Section III), which we name Type A and Type B, respectively, for convenience. The bond formation occurs in a more concerted way with bond breaking in Type A than in Type B trajectories. Along Type B trajectories, the solute is more likely trapped in a potential well created by the

ll chemical reactions can be viewed as the movement of electrons or nuclei; as such, one expects that their kinetics and thermodynamics could be influenced by external fields. Many theoretical studies predict that electrostatic effects should, in principle, influence the stabilities of chemical species by stabilizing charge-separated resonance contributors.1,2 More specifically, if the transition state (TS) is more polar or can be more polarized by an external field than the reactant, then the reaction barrier can be largely reduced by a favorably oriented external electric field (OEEF). Indeed, the elegant experiment of an OEEF-catalyzed Diels−Alder reaction confirmed these previous theoretic predictions.3 In addition to an artificially applied electric field,4,5 it is important to note that nature has devised chemical species with built-in electric fields that catalyze a variety of reactions by stabilizing ionic resonant structures in their TSs. For example, the catalytic power of enzymes has been attributed6,7 to preorganized polar groups that stabilize transition states and impart electrostatic catalysis on their respective reactions. By mutating different residues in the active site of ketosteroide isomerase, Fried and Boxer found8,9 by vibrational stark spectroscopy that the increment of the activation barrier due to key mutations strongly correlates with the extent of the electric field decrease caused by the mutant.10,11 Two additional problems related to OEEF need to be addressed. First, when it comes to catalytic effects of OEEFs, more attention was paid to the decrease in the height of activation barrier than to the shape of the potential surface and therefore the force. In fact, previous theoretic calculations have predicted that the mechanism of the Diels−Alder reaction (concerted or stepwise) can be changed by the external electric field.12,13 Second, the electric field exerted by solvents is time© XXXX American Chemical Society

Scheme 1. Scheme of Forward and Backward Reactionsa

a

cis-2-Vinylcyclopropanecarboxaldehyde (left) interconverts to 2,5dihydrooxepin (right), with the bond forming/breaking sites indexed in red characters.

Received: April 12, 2019 Accepted: May 16, 2019 Published: May 16, 2019 2991

DOI: 10.1021/acs.jpclett.9b01038 J. Phys. Chem. Lett. 2019, 10, 2991−2997

Letter

The Journal of Physical Chemistry Letters

Figure 1. (a) Force constants of C3−C8 and C12−O15 for a Type A trajectory. K1 (black line), K2 (blue line). Bond length of C3−C8: d1 (red line). When force constant is less than zero, bonding or bond breaking has been finished. For the Type A trajectory, bond breaking and bonding are very close in time. (b) Same as panel a but for the Type B trajectory. (c) Mulliken charge for C1 (blue line), C12 (green line), and O15 (red line) for the Type A trajectory. (d) Same as panel c but for a Type B trajectory. Charge redistribution is retarded during 2000−2300 fs.

but K2 remains positive until ∼2300 fs, showing that during this trapping period (2000−2300 fs) C3−C8 is broken without C12−O15 being formed (Figure 1b). In fact, potential barriers exist for both bond-making and bond-breaking steps. Therefore, the longer the time the reactant resides in this region, the more likely the potential well is modified by solvents, which retards the barrier crossing.

external interaction, forming an intermediate state. The continuation of the reaction awaits the proper adjustment of solvents. Actually, the analysis in Part I suggests that the hydrogen bonding with the solvent has an important influence on the progression of the reaction. Moreover, the hydrogenbond vibration shows a similar time scale with the reaction coordinate change in the TS region, which implies that this external interaction is “dynamic” and nonequilibrium effects should be considered. In this Letter, we will show the important role dynamic effects play in barrier crossing and explain why there are distinct reaction paths in the Claisen rearrangement reaction in homogeneous solutions. Our results also reveal that an excessive stabilization of TS may retard the barrier crossing process, making the thermodynamically favorable pathway not necessarily favored in the dynamic sense. In Part I, the Claisen rearrangement reaction (Scheme 1) is trapped during the barrier crossing along Type B trajectories (Figure 3d). According to Grote−Hynes theory, the barrier crossing cannot be finished until the environment adapts itself to this process in the polarization cage regime, where the barrier is modified into an effective well by a strong solvent force. On the basis of our previous calculation,21 the system falls well into this regime (Supporting Information, Section IV). Modif ied Ef fective Potential Well. First, we perform a detailed analysis on the effective potential surface for the two types of trajectories. For the convenience of description, we define the bond lengths of C3−C8 and C12−O15 as d1 and d2, respectively, and in all trajectories, the origin of time is realigned, so that the first 2000 fs corresponds to the reactant, the last 2000 fs corresponds to the product, and the reaction takes place at ∼2000 fs. By calculating the force constants (K1, K2, eq 1) of the carbon−carbon bond (C3−C8) and carbon− oxygen bond (C12−O15), it was found that the interval between the critical points (Ki < 0, i = 1,2) for bond breakage and formation is longer in Type B than in Type A trajectories (Figure 1a,b). For Type B trajectories, it is clear that K1 decreases to below zero before being trapped (2000−2300 fs),

K1 =

∂ 2H ∂ 2H ; K2 = ∂d1∂d1 ∂d 2∂d 2

(1)

where H is the Hamiltonian of entire system. From Figure 1a,b, it is obvious that the reactant resides in this region for a longer time in a Type B than in a Type A trajectory, which is consistent with the existence of a potential well for the reaction along the former, as previously mentioned. The bond-forming and -breaking steps are more concerted in Type A than in Type B trajectories. It is intriguing to understand the reason behind the lingering of the reactant near the transition state. Therefore, we try to identify the processes that are related to the trapping of the reactant. Because the most predominant change for the chemical reaction in the TS region is the redistribution of electrons, we suspect that this trapping could result from the retarded charge redistribution of the reacting species. Figure 1c,d shows that the negative charges (electrons) mainly flow from C12 to O15 and, as the reaction proceeds, further to C1. Comparing these two panels, it is clear that the charge redistribution is very rapid for the Type A trajectory, whereas it becomes significantly hindered during the transition-state trapping (2000−2300 fs) in a Type B trajectory. This difference is a common feature for all trajectories examined. Electrostatic Interaction Aids Reactant in Approaching TS. Next, we investigate the contributions of the solvents to electrostatics during the reaction progress. Specifically, we examine how solvents assist the system in approaching TS by activating the reactant (or rather, imposing work on solute) or altering the reaction barrier. 2992


Letter


Figure 2. (a) Intramolecular potential energy averaging over all reactive trajectories. (b) Interaction between solute and solvents (electrostatic energy plus van der Waals energy) averaging over all reactive trajectories (blue line), only Type A trajectories (black line), and only Type B trajectories (red line). (c) Work done on the stretch motion of C12−O15 by solvents (red line) and solute (black line). Energy change due to vibration−rotation coupling (blue line). (d) O15 charge averaging over all reactive trajectories (blue line), only Type A trajectories (black line), and only Type B trajectories (red line).

First, the electric field induced by water can significantly reduce the reaction barrier.22,23 To elucidate this effect, we investigate the intramolecular potential Eintra and the intermolecular potential Einter following the reaction progression (RC) averaging over all trajectories.

due to the vibration−rotation coupling by applying eq 3 derived from the Poisson bracket.28,29 Wsol(t ) =

∫0

t

Fsolvco dt ; WQM(t ) =

RC = 0.82d1 − 0.18d 2 Wvb(t ) = −0.5*

In the above equation, RC is the reaction coordinate optimized using the Bayesian measure24,25 in Part I. According to Figure 2a,b, the intramolecular barrier is ∼17 kcal/mol, and the electrostatic interaction causes the stabilization of TS as well as the destabilization of the reactant. This change leads to a reduction of the barrier up to ∼10 kcal/mol (Figure 2b). This reduction can be interpreted in terms of the change of charge distribution. In the previous section, we showed that the electron is initially enriched at O15 as the system approaches TS (the first step of charge redistribution, Figure 2d). Therefore, the TS can be effectively stabilized by the electrostatic interaction with nearby water, resulting in a shallow barrier. Such an effect echoes a mechanism called electrostatic catalysis.6,26,27 On the other hand, because of a strong electrostatic interaction between the solute and solvent, work can be done on the solute to accelerate certain specific motions. In addition, because of the rotational motion of the solute, strong coupling between the rotation and stretch motions of C12−O15 due to the large derivative of the moment of inertia with respect to the bond length of C12− O15 will strongly influence the approach of C12 and O15, corresponding to a Coriolis effect. The charge redistribution is prompted by the compression of the C12−O15 distance, which is also promoted by solvents and Coriolis effects. To quantify these effects, we calculate the work (Wsol, WQM, eq 2) done on the stretch motion of C12−O15 by solvents as well as the remaining part of the solute and the energy change Wvb

∑ i=x ,y,z

∫0

t

vco

∫0

t

FQMvco dt

∂Ii 2 ωi dt ∂d 2

(2)

(3)

dd

where vco = dt2 , Fsol and FQM are the forces applied to the stretch motion of C12−O15 by solvents and solute, respectively, Ii is the moment of inertia, and ωi is the angular velocity. As Figure 2c shows, the work contribution from solvents and the Coriolis effect outweighs that of the solute before 2000 fs, showing that solvents and Coriolis effects play an important role in activating the reactant and promoting the reactive modes. Furthermore, Figure 2a,b shows that the interaction between solutes and the solvent can modify the intramolecular potential surface into a well near the TS. More interestingly, this well is deeper in Type B than in Type A trajectories due to the stronger electrostatic interaction. Oriented External Electric Field. The above analysis shows that the reactant could be trapped in a transient potential well induced by improper solvent configurations for a significant period of time near the TS, during which electrostatic interactions play a critical role. Therefore, we calculated the external electric field imposed on C12 projected along the C12−O15 vector and that imposed on O15 projected along the C1−O15 vector by applying eqs 4 and 5. E2 =

∑ i ϵsolvents

2993

1 ij 1 y jj rO15, i· rO15 − C1 zzz * j zz 1 1 1 j |rO15, i|2 jjk |rO15 − C1|*|rO15, i| zz{

qi

(4)


Letter

The Journal of Physical Chemistry Letters E1 =

∑ i ϵsolvents

1 ij 1 y jj rC12, i· rC12 − O15 zzz * j zz 1 1 j1 |rC12, i|2 jjk |rC12 − O15|*|rC12, i| zz{

differences among Type A, Type B, and nonreactive trajectories, we plot the specific time series of E1 for these three cases in Figure 3c−e. It is clear from this Figure that for the reactive trajectory, the external electric field preadjusts relatively sharply before d1 starts to increase and then fluctuates slightly at ∼50 MV/cm. In contrast, along the nonreactive trajectory, we do not observe a significant enhancement of E1 prior to the reaction. Instead, E1 becomes more negative during the barrier crossing process (at ∼2000 fs) (Figure 3e), which is unfavorable for keeping C12 and O15 close to each other. Therefore, in the latter case, the system is likely to recross back to the reaction basin, which leads to a transition failure even after it has entered the TS. To understand the molecular origin for the change of external electric field, we decompose it into contributions from individual water molecules. Interestingly, we find that the electrostatic interaction to which the charge redistribution is susceptible is very local, and the change of EEF mainly results from the motion of water molecules H-bonded to O15 (WAT2, WAT3 in Figure 4) and the water molecule nearest to C12 (WAT1 in Figure 4). These two H-bonded water molecules (WAT2, WAT3) can have attractive interactions with both C12 and O15, confining their separation into small distances (positive contribution to E1, as shown in Figure 4a−

qi

1 1 1 1 1 rO15, i = rO15 − ri , rC12, i = rC12 1 1 1 rC12 − O15 = rC12 − rO15. E1 and

1 1

(5) 1

1

− ri , rO15 − C1 = rO15 − rC1, and E2 are sketched in Scheme 2.

Scheme 2. Sketch Map for Electric Field (E2, E1) and Angle θ

From Figure 3a, one observes that E1 gradually increases to 50 MV/cm as the reaction proceeds (along RC), favoring the charge flux from C12 to O15. To understand in more detail the

Figure 3. (a) Change of E1 following reaction progression averaging over all reactive trajectories. (b) Change of E2 following reaction progression averaging over all reactive trajectories, Type A trajectories, and Type B trajectories. Time series of external electric fields (E1, E2) and key bond lengths (d1, d2) for (c) Type A trajectory, (d) Type B trajectory, and (e) unreactive trajectory. 2994


Letter


Figure 4. Decomposition of E1 by water molecules. (a) Type A trajectory, (b) Type B trajectory, and (c) unreactive trajectory. Conformation in TS for (d) Type A trajectory, (e) Type B trajectory, and (f) unreactive trajectory.

Figure 5. Decomposition of E2 by water molecules for (a) Type A trajectory, (b) Type B trajectory, and (c) unreactive trajectory. H-bond length and θ of WAT2 for (d) Type A trajectory, (e) Type B trajectory, and (f) unreactive trajectory. H-bond length and θ of WAT3 for (g) Type A trajectory, (h) Type B trajectory, and (i) unreactive trajectory.

ones, as shown in Figure 4d−e, thus restricting C12 from moving away from O15 (repulsive interaction between O15 and the oxygen atom of WAT1). In contrast, in nonreactive trajectories, WAT1 can form a H bond with C12, as shown in Figure 4 f, leading to an inappropriately oriented electric field. These results show that the preadjustment of E1 due to solvent motion plays an important role in the success of the reaction.

c). Moreover, there is another water molecule WAT1 that behaves differently in reactive and nonreactive trajectories. In reactive trajectories, it plays a similar role as WAT2 and WAT3, but in nonreactive trajectories, it functions to pull C12 apart from O15 (negative contribution to E1, as shown in Figure 4c). In reactive trajectories, the oxygen atom in WAT1 is closer to the negatively charged C12 than it is in nonreactive 2995


Letter

The Journal of Physical Chemistry Letters Reaction Dynamics Modified by Motion of Solvent. The preadjustment of E1 mentioned above occurs in both Type A and Type B reactive trajectories. Next, we averaged E2 over all reactive trajectories as a function of RC, which increases from −100 to −25 MV/cm. This change suggests that the solvent’s initial configuration is unfavorable for the charge redistribution (from O15 to C1) but readjusts as the reaction progresses (Figure 3b). More interestingly, E2 is higher in Type A than in Type B trajectories. Such a difference arises because E2 increases rapidly when RC increases from 1 to 1.6 Å in Type A trajectories but stays at around −125 MV/cm in Type B trajectories, implying that solvents can adjust more promptly in Type A trajectories. It can be seen from the time series of E2 that in Type A trajectories E2 sharply increases almost synchronously as d1 decreases (∼2000 fs in Figure 3c), whereas for Type B trajectories, at about the same reaction progress (∼2000 fs in Figure 3d), E2 stays below −100 MV/ cm. In the latter case, the electron flux from O15 to C1 is strongly hindered. Actually, the stronger hydrogen bond in Type B trajectories obstructs the electron flux from O15 to C1. We also decompose E2 into contributions from individual water molecules. The major contributions to the change of E2 again come from H-bonded water molecules (WAT2 and WAT3, Figure 5). Because the greatest contribution to E2 stems from water molecules H-bonded to O15, we use the Hbond length and θ (Scheme 2) to characterize the motion of these water molecules. Because in the current model the charge of water molecules is fixed, the increase in H-bond length and the decrease in θ both increase E2 (Scheme 2). Time evolutions of these two variables reveal that the H-bond length is largely elongated, and θ decreases when E2 increases, as shown in Figure 5. These results together clearly show that although the electronic stabilization plays a significant part in the reaction process, the external electric field is timedependent rather than static and does not necessarily instantly respond to the reaction process, especially during a fast barriercrossing process. The main question we want to address in this study is whether and, if yes, why, there are multiple reaction paths in a seemingly homogeneous reaction such as the Claisen rearrangement in a simple solvent. The current analysis shows that although strong H-bonding results in a reduction of barrier height by stabilizing the TS (Figure 2b, Type B trajectories) with an elevated negative charge on O15 (Figure 2d, Type B trajectories), it may, on the contrary, lead to an inappropriately oriented EEF (E2) that blocks the charge redistribution (from O15 to C1). In other words, the stronger electrostatic interaction can modify the barrier into a deeper transient potential well (Figure 2a,b) so that it takes a longer time for the system to cross the second barrier, transforming the concert mechanism into a stepwise one. Actually, Figure 2a,b shows that the electrostatic interaction can modify the intramolecular potential surface into a well near the barrier, and this well is a few (∼5) kcal/mol deeper for Type B than for Type A pathways. As a result, the reaction becomes halted along Type B trajectories until an appropriate external electric field is generated by the motion of solvents. Moreover, because the adjustment of E2 mainly results from the elongation of the H bond and the decrease in θ, stronger H bonds, in turn, render a slower adjustment of water molecules. We conclude from these observations that: (1) The motion of solvents is coupled to the reaction dynamics, leading to two distinctly different reaction pathways, even in a seemingly homogeneous

aqueous solution, due to the existence of different transient solvation configurations. Such an effect was recognized as temporal heterogeneity.30,31 (2) The thermodynamically favored pathway is not necessarily favored in the dynamic sense. In fact, these phenomena correlate with nonequilibrium reaction dynamics that appear when there are mismatched time scales for the chemical transition and the motion of solvents, with the former being so rapid that the latter cannot instantly follow to reach an equilibrium state. In such a case, the dynamical effects of the reaction environment should be considered. The nonequilibrium reaction dynamics can result in the existence of different transient solvation configurations with distinctly different strengths of interaction between solutes and solvents. Because the dominant interaction between solvents and solute is due to the local H bond, the transition paths can be separated into two rather distinctive types, one with and another without H bonding to the oxygen atom (O15 in Scheme 2). We speculate that when the interaction between the solute and solvents becomes less local (as in the ionic liquid and the enzymatic active site), the media may provide a more continuously distributed electrostatic environment and less distinctive transition path types. Therefore, we expect that similar effects will be generally present in many other condensed-phase reactions and might be even more pronounced in heterogeneous reaction media such as enzymes and interfaces. Actually, previous studies32,33 have found that fast motions of enzyme lead to an increase in the electric field by preparing an enzymatic configuration that is electrostatically favorable, and a single enzyme is able to sample different active configurations with different catalytic efficiencies.34 Therefore, these effects should be considered in the design of efficient enzymes and other catalysts.

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EXPERIMENTAL METHODS QM/MM simulations were performed on the AMBER 10 MD platform. Simulation details are included in the Supporting Information, Section I. For configurational and reactive trajectory sampling, the MD simulations were carried out under an NPT ensemble (300 K, 1 atm). Transition path shootings were executed under an NVE ensemble. To increase the efficiency of configurational and reactive trajectory sampling, the multilevel integrated tempering sampling (MITS,21 Supporting Information, Section II) and enhanced sampling of reactive trajectories (ESoRT35) protocols were adopted. The clustering of reactive trajectories was performed with spectral clustering (Supporting Information, Section III)

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jpclett.9b01038.

■

Simulation details, MITS, spectral clustering of transitions paths, and Grote−Hynes theory (PDF)

AUTHOR INFORMATION

Corresponding Author

*Phone: 86-10-6275-2431. E-mail: [email protected]. ORCID

Yi Qin Gao: 0000-0002-4309-9376 2996


Letter

The Journal of Physical Chemistry Letters Author Contributions

(18) Northrup, S. H.; Hynes, J. T. The Stable States Picture of Chemical Reactions. I. Formulation for Rate Constants and Initial Condition Effects. J. Chem. Phys. 1980, 73 (6), 2700−2714. (19) Ruiz-Pernía, J. J.; Tuñoń , I.; Moliner, V.; Hynes, J. T.; Roca, M. Dynamic Effects on Reaction Rates in a Michael Addition Catalyzed by Chalcone Isomerase. Beyond the Frozen Environment Approach. J. Am. Chem. Soc. 2008, 130 (23), 7477−7488. (20) Grote, R. F.; Hynes, J. T. The Stable States Picture of Chemical Reactions. II. Rate Constants for Condensed and Gas Phase Reaction Models. J. Chem. Phys. 1980, 73 (6), 2715−2732. (21) Zhang, J.; Zhang, Z.; Yang, Y. I.; Liu, S.; Yang, L.; Gao, Y. Q. Rich Dynamics Underlying Solution Reactions Revealed by Sampling and Data Mining of Reactive Trajectories. ACS Cent. Sci. 2017, 3 (5), 407−414. (22) Blake, J. F.; Jorgensen, W. L. Solvent Effects on a Diels-Alder Reaction from Computer Simulations. J. Am. Chem. Soc. 1991, 113 (19), 7430−7432. (23) Blake, J. F.; Lim, D.; Jorgensen, W. L. Enhanced Hydrogen Bonding of Water to Diels-Alder Transition States. Ab Initio Evidence. J. Org. Chem. 1994, 59 (4), 803−805. (24) Hummer, G. From Transition Paths to Transition States and Rate Coefficients. J. Chem. Phys. 2004, 120 (2), 516−523. (25) Best, R. B.; Hummer, G. Reaction Coordinates and Rates from Transition Paths. Proc. Natl. Acad. Sci. U. S. A. 2005, 102 (19), 6732− 6737. (26) Lai, W.; Chen, H.; Cho, K.-B.; Shaik, S. External Electric Field Can Control the Catalytic Cycle of Cytochrome P450cam: A QM/ MM Study. J. Phys. Chem. Lett. 2010, 1 (14), 2082−2087. (27) Hirao, H.; Chen, H.; Carvajal, M. A.; Wang, Y.; Shaik, S. Effect of External Electric Fields on the C-H Bond Activation Reactivity of Nonheme Iron-Oxo Reagents. J. Am. Chem. Soc. 2008, 130 (11), 3319−3327. (28) Ingrosso, F.; Rey, R.; Elsaesser, T.; Hynes, J. T. Ultrafast Energy Transfer from the Intramolecular Bending Vibration to Librations in Liquid Water. J. Phys. Chem. A 2009, 113 (24), 6657−6665. (29) Rey, R.; Hynes, J. T. Tracking Energy Transfer from Excited to Accepting Modes: Application to Water Bend Vibrational Relaxation. Phys. Chem. Chem. Phys. 2012, 14 (18), 6332−6342. (30) Laage, D.; Elsaesser, T.; Hynes, J. T. Water Dynamics in the Hydration Shells of Biomolecules. Chem. Rev. 2017, 117 (16), 10694−10725. (31) Duboué-Dijon, E.; Fogarty, A. C.; Hynes, J. T.; Laage, D. Dynamical Disorder in the DNA Hydration Shell. J. Am. Chem. Soc. 2016, 138 (24), 7610−7620. (32) Zoi, I.; Antoniou, D.; Schwartz, S. D. Electric Fields and Fast Protein Dynamics in Enzymes. J. Phys. Chem. Lett. 2017, 8 (24), 6165−6170. (33) Harijan, R. K.; Zoi, I.; Antoniou, D.; Schwartz, S. D.; Schramm, V. L. Inverse Enzyme Isotope Effects in Human Purine Nucleoside Phosphorylase with Heavy Asparagine Labels. Proc. Natl. Acad. Sci. U. S. A. 2018, 115 (27), E6209−E6216. (34) Hong, N. S.; Petrović, D.; Lee, R.; Gryn’ova, G.; Purg, M.; Saunders, J.; Bauer, P.; Carr, P. D.; Lin, C. Y.; Mabbitt, P. D.; et al. The Evolution of Multiple Active Site Configurations in a Designed Enzyme. Nat. Commun. 2018, 9 (1), 3900. (35) Fu, X.; Yang, L.; Gao, Y. Q. Selective Sampling of Transition Paths. J. Chem. Phys. 2007, 127 (15), 154106. (36) Wang, F.; Zhang, C. Spectral Clustering for Time Series. In International Conference on Pattern Recognition and Image Analysis; Springer: Berlin Heidelberg, 2005; pp 345−354.

§

Y.K.L. and J.Z. contributed equally to this work. Y.K.L., J.Z., Z.Z., and Y.Q.G. designed the research; Y.K.L., J.Z., Z.Z., and Y.Q.G. performed the research; Y.K.L., J.Z., Z.Z., and Y.Q.G. analyzed the data; and Y.K.L., J.Z., and Y.Q.G. wrote the paper. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the Beijing Computing Center for providing the computational resources. This research is financially supported by National Natural Science Foundation of China (21573006, 21821004, 21873007) and National Key R&D Program of China (2017YFA0204702).

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REFERENCES

(1) Shaik, S.; Mandal, D.; Ramanan, R. Oriented Electric Fields as Future Smart Reagents in Chemistry. Nat. Chem. 2016, 8 (12), 1091− 1098. (2) Hiberty, P. C.; Megret, C.; Song, L.; Wu, W.; Shaik, S. Barriers of Hydrogen Abstraction vs Halogen Exchange: An Experimental Manifestation of Charge-Shift Bonding. J. Am. Chem. Soc. 2006, 128 (9), 2836−2843. (3) Wallace, G. G.; Diez-Perez, I.; Ciampi, S.; Coote, M. L.; Aragonès, A. C.; Darwish, N.; Haworth, N. L.; Bloomfield, N. J. Electrostatic Catalysis of a Diels−Alder Reaction. Nature 2016, 531 (7592), 88−91. (4) Alemani, M.; Peters, M. V.; Hecht, S.; Rieder, K. H.; Moresco, F.; Grill, L. Electric Field-Induced Isomerization of Azobenzene by STM. J. Am. Chem. Soc. 2006, 128 (45), 14446−14447. (5) Darwish, N.; Aragonès, A. C.; Darwish, T.; Ciampi, S.; DíezPérez, I. Multi-Responsive Photo- and Chemo-Electrical SingleMolecule Switches. Nano Lett. 2014, 14 (12), 7064−7070. (6) Warshel, A.; Sharma, P. K.; Kato, M.; Xiang, Y.; Liu, H.; Olsson, M. H. M. Electrostatic Basis for Enzyme Catalysis. Chem. Rev. 2006, 106 (8), 3210−3235. (7) Warshel, A. Electrostatic Basis of Structure-Function Correlation in Proteins. Acc. Chem. Res. 1981, 14 (9), 284−290. (8) Fried, S. D.; Bagchi, S.; Boxer, S. G. Extreme Electric Fields Power Catalysis in the Active Site of Ketosteroid Isomerase. Science (Washington, DC, U. S.) 2014, 346 (6216), 1510−1514. (9) Fried, S. D.; Boxer, S. G. Electric Fields and Enzyme Catalysis. Annu. Rev. Biochem. 2017, 86 (1), 387−415. (10) Chattopadhyay, A.; Boxer, S. G. Vibrational Stark Effect Spectroscopy. J. Am. Chem. Soc. 1995, 117 (4), 1449−1450. (11) Andrews, S. S.; Boxer, S. G. Vibrational Stark Effects of Nitriles II. Physical Origins of Stark Effects from Experiment and Perturbation Models. J. Phys. Chem. A 2002, 106 (3), 469−477. (12) Meir, R.; Chen, H.; Lai, W.; Shaik, S. Oriented Electric Fields Accelerate Diels−Alder Reactions and Control the Endo/Exo Selectivity. ChemPhysChem 2010, 11 (1), 301−310. (13) Shaik, S. S. What Happens to Molecules as They React? A Valence Bond Approach to Reactivity. J. Am. Chem. Soc. 1981, 103 (13), 3692−3701. (14) Shaik, S.; Mandal, D.; Ramanan, R. Oriented Electric Fields as Future Smart Reagents in Chemistry. Nat. Chem. 2016, 8 (12), 1091− 1098. (15) Tuñoń , I.; Laage, D.; Hynes, J. T. Are There Dynamical Effects in Enzyme Catalysis? Some Thoughts Concerning the Enzymatic Chemical Step. Arch. Biochem. Biophys. 2015, 582, 42−55. (16) Gertner, B. J.; Wilson, K. R.; Hynes, J. T. Nonequilibrium Solvation Effects on Reaction Rates for Model SN2 Reactions in Water. J. Chem. Phys. 1989, 90 (7), 3537−3558. (17) Van Der Zwan, G.; Hynes, J. T. Dynamical Polar Solvent Effects on Solution Reactions: A Simple Continuum Model. J. Chem. Phys. 1982, 76 (6), 2993−3001. 2997


Dynamic Electric Field Complicates Chemical Reactions in Solutions

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