Tracking molecular charge distribution along reaction paths with atomic multipole moments

Abstract

We explore the idea of supplementing partial atomic charges with cumulative multipole moments for modeling electrostatic effects during chemical reactions.To this end, we investigate the first stage of alkaline hydrolysis of O,O-dimethyl phosphorofluoridate and show how changes in atomic moments provide a more detailed description of charge redistribution during the reaction than is possible using charges alone. Furthermore, the electrostatic potential on the solvent-excluded surface for this reaction roughly converges at the quadrupolar level, with a root-mean-square deviation of *1 kcal/mol compared to the ab initio Hartree-Fock expectation value. We arrive at similar conclusions for four other reactions, namely the alkaline hydrolysis of demeton-S and phosalone, carbon dioxide hydration, and hydrogen cyanide isomerization. Employing multipole moments on atoms therefore appears to be a feasible and compact way to derive catalytic fields defining the optimal catalytic environment for chemical reactions.

Bottom-Up Nonempirical Approach To Reducing Search Space in Enzyme Design Guided by Catalytic Fields

“…The essential advantage of the present approach is the use of cumulative atomic multipole moments to describe molecular charge redistribution during the progress of the reaction, capturing the anisotropic character of molecular electrostatic potentials, 64 which may be more significant in neutral systems. 43 It may be still crucial in proper description of the catalytic field, since Δ S has at least dipole character, because of the charge conservation principle. Another important feature of the catalytic field is that, despite special emphasis placed on charged residues in the present analysis, it can provide more general information; by considering its gradient Δ⃗ d , one gains insight into the optimal distribution of catalytic dipoles in a way analogous to that presented above for charges (see Figures S1 and S2 in the Supporting Information).…”

“…Furthermore, DTSS could be partitioned into the electrostatic multipole Δ E EL,MTP , electrostatic penetration Δ E EL,PEN exchange Δ E EX , delocalization (induction) Δ E DEL , and correlation (dispersion) Δ E CORR terms defined within symmetry-adapted perturbation or hybrid variation-perturbation theories of intermolecular interactions. , This provides not only insight into the physical nature of catalytic interactions induced upon mutation, but it also allows one to derive, in a systematic way, more approximate methods based on leading terms. Recent experimental results and ab initio analysis of several enzyme systems ,, indicate clearly the dominant contribution of electrostatic term Δ E EL and, in particular, its long-range multipolar electrostatic component Δ E EL,MTP accurately reflecting, at an atomic level, the molecular charge redistribution during the progress of the reaction . The electrostatic multipolar DTSS term, constituting a more-general approach, represents TSS and, at the same time, ground-state destabilization (GSD) effects, postulated earlier as the important contributions to enzyme catalysis.…”

“…Recent experimental results 30 and ab initio analysis of several enzyme systems 26 , 41 , 42 indicate clearly the dominant contribution of electrostatic term Δ E EL and, in particular, its long-range multipolar electrostatic component Δ E EL,MTP accurately reflecting, at an atomic level, the molecular charge redistribution during the progress of the reaction. 43 The electrostatic multipolar DTSS term, 26 constituting a more-general approach, represents TSS 44 and, at the same time, ground-state destabilization (GSD) 23 effects, postulated earlier as the important contributions to enzyme catalysis. Our recent analysis of several mutants of ketosteroid isomerase 45 validated the utility of simple model, based on cumulative atomic multipole expansion (CAMM), 46 in agreement with recent experimental data, 30 confirming the electrostatic nature of catalytic activity.…”

Electrostatic Potential Fitting Method Using Constrained Spatial Electron Density Expanded with Preorthogonal Natural Atomic Orbitals

“…It is widely believed that the ESP charges are physically or chemically nonintuitive because of overfitting and rank problems. − Moreover, because our method employed spherical approximation in the fitting and is designed to reproduce ESP, it is not necessary that the obtained charges are physically reasonable. To check whether our scheme produces meaningful chemical results, we computed atomic charges in a series of organic and inorganic molecules.…”

Predicting substituent effects on activation energy changes by static catalytic fields

“…One obtains in the single computational step, requiring only the knowledge of superimposed transition state and substrate electrostatic potential maps, the complete characteristics of the molecular environment charge distribution exerting optimal catalytic activity. Molecular electrostatic potentials V i TS and V i S could be efficiently estimated using cumulative atomic multipole moments obtained directly from wavefunctions of reactants [ 13 ].…”