Extrapolating H-atom transfer rate constants via thermochemical kinetics: The effect of tunneling

One of the important applications of chemical kinetics is the attempt to understand complex processes through kinetic modeling. This process frequently requires that rate constants be obtained by extrapolation of data either to higher or lower temperatures than the experimental, or by estimation or correlation with such data. Thermochemical kinetics combined with conventional transition state theory forms a framework from which this may be done. However, rate data for H transfer reactions may have a significant contribution from tunneling. In this work, a one dimensional approach to tunneling, consistent with conventional transition state theory, is taken to show how tunneling affects the extrapolation and correlation of rate constants in thermochemical kinetics. It is concluded that extrapolation and correlation are both quite good even when tunneling comprises 80% of the reaction. However, this is not without limitations, which are discussed. © 1993 John Wiley & Sons, Inc.     

Quantum mechanics/molecular mechanics electrostatic embedding with continuous and discrete functions

A quantum mechanics/molecular mechanics (QM/MM) implementation that uses the Gaussian electrostatic model (GEM) as the MM force field is presented. GEM relies on the reproduction of electronic density by using auxiliary basis sets to calculate each component of the intermolecular interaction. This hybrid method has been used, along with a conventional QM/MM (point charges) method, to determine the polarization on the QM subsystem by the MM environment in QM/MM calculations on 10 individual H(2)O dimers and a Mg(2+)-H(2)O dimer. We observe that GEM gives the correct polarization response in cases when the MM fragment has a small charge, while the point charges produce significant over-polarization of the QM subsystem and in several cases present an opposite sign for the polarization contribution. In the case when a large charge is located in the MM subsystem, for example, the Mg(2+) ion, the opposite is observed at small distances. However, this is overcome by the use of a damped Hermite charge, which provides the correct polarization response.     

Quantum mechanics and mixed quantum mechanics/molecular mechanics simulations of model nerve agents with acetylcholinesterase

 The accurate modeling of biological processes presents major computational difficulties owing to the inherent complexity of the macromolecular systems of interest. Simulations of biochemical reactivity tend to require highly computationally intensive quantum mechanical methods, but localized chemical effects tend to depend significantly on properties of the extended biological environment – a regime far more readily examined with lower-level classical empirical models. Mixed quantum/classical techniques are gaining in popularity as a means of bridging these competing requirements. Here we present results comparing two quantum mechanics/molecular mechanics implementations (the SIMOMM technique of Gordon et al. as implemented in GAMESS, and the ONIOM technique of Morokuma et al. found in Gaussian 98) as performed on the enzyme acetylcholinesterase and model nerve agents. This work represents part of the initial phase of a DoD HPCMP Challenge project in which we are attempting to reliably characterize the biochemical processes responsible for nerve agent activity and inhibition, thereby allowing predictions on compounds unrelated to those already studied. Received: 10 October 2001 / Accepted: 13 November 2002 / Published online: 1 April 2003 Contribution to the Proceedings of the Symposium on Combined QM/MM Methods at the 222nd National Meeting of the American Chemical Society, 2001 Correspondence to: M. M. Hurley e-mail: hurley@arl.army.mil     

Quantum statistical study of O + O2 isotopic exchange reactions: cross sections and rate constants

Using a wave packet based statistical model, we compute cross sections and thermal rate constants for various isotopic variants of the O + O2 exchange reaction on a recently modified ab initio potential energy surface. The calculation predicts a highly excited rotational distribution and relatively cold vibrational distribution for the diatomic product. A small but important threshold effect was identified for the (16)O + 18O2 reaction, which is suggested to contribute to the experimentally observed negative temperature dependence of the rate ratio, k(18O + 16O2)/k(16O + 18O2). Despite reasonable agreement with quasiclassical trajectory results, however, the calculated thermal rate constants are smaller than experimental measurements by a factor from 2 to 5. The experimentally observed negative temperature dependence of the rate constants is not reproduced. Possible reasons for the theory-experiment discrepancies are discussed.     

Nuclear magnetic shielding constants of liquid water: insights from hybrid quantum mechanics/molecular mechanics models

We present a gauge-origin independent method for the calculation of nuclear magnetic shielding tensors of molecules in a structured and polarizable environment. The method is based on a combination of density functional theory (DFT) or Hartree-Fock wave functions with molecular mechanics. The method is unique in the sense that it includes three important properties that need to be fulfilled in accurate calculations of nuclear magnetic shielding constants: (i) the model includes electron correlation effects, (ii) the model uses gauge-including atomic orbitals to give gauge-origin independent results, and (iii) the effect of the environment is treated self-consistently using a discrete reaction-field methodology. The authors present sample calculations of the isotropic nuclear magnetic shielding constants of liquid water based on a large number of solute-solvent configurations derived from molecular dynamics simulations employing potentials which treat solvent polarization either explicitly or implicitly. For both the (17)O and (1)H isotropic shielding constants the best predicted results compare fairly well with the experimental data, i.e., they reproduce the experimental solvent shifts to within 4 ppm for the (17)O shielding and 1 ppm for the (1)H shielding.     

Time-resolved and steady-state fluorescence studies of excited-state proton-transfer reactions of proflavine

Time-resolved and steady-state fluorescence studies of proflavine in aqueous solution are presented. The observation of a monoexponential fluorescence decay with a time constant decreasing with increasing pH and the presence of an anomalous red-shift in the fluorescence spectrum as a function of pH indicate the existence of a complex proton-transfer mechanism in the excited state. A reaction scheme is proposed and the corresponding proton-transfer rates are evaluated. An excited-state pK value of 12.85 is obtained for the equilibrium between the cationic form of proflavine and the same form dissociated at an amino group.     

Quantum effects in ab-initio calculations of rate constants for chemical reactions occuring in the condensed phase

An overview of recent advances in the development of methods designed to calculate rate constants for chemical reactions obeying mass action kinetic equations in condensed phases is presented. A general framework addressing mixed quantum-classical systems is elaborated that enables quantum features such as tunneling effects, zero-point vibrations, dynamic quantum coherence, and non-adiabatic effects to be calculated. An efficient Monte Carlo sampling method for performing ab-initio calculations of rate constants and isotope effects in chemical processes in condensed phases is outlined, and the connection of isotope effects to reaction mechanism is explored     

Quantum mechanics/molecular mechanics study of the catalytic cycle of water splitting in photosystem II

This paper investigates the mechanism of water splitting in photosystem II (PSII) as described by chemically sensible models of the oxygen-evolving complex (OEC) in the S0-S4 states. The reaction is the paradigm for engineering direct solar fuel production systems since it is driven by solar light and the catalyst involves inexpensive and abundant metals (calcium and manganese). Molecular models of the OEC Mn3CaO4Mn catalytic cluster are constructed by explicitly considering the perturbational influence of the surrounding protein environment according to state-of-the-art quantum mechanics/molecular mechanics (QM/MM) hybrid methods, in conjunction with the X-ray diffraction (XRD) structure of PSII from the cyanobacterium Thermosynechococcus elongatus. The resulting models are validated through direct comparisons with high-resolution extended X-ray absorption fine structure spectroscopic data. Structures of the S3, S4, and S0 states include an additional mu-oxo bridge between Mn(3) and Mn(4), not present in XRD structures, found to be essential for the deprotonation of substrate water molecules. The structures of reaction intermediates suggest a detailed mechanism of dioxygen evolution based on changes in oxidization and protonation states and structural rearrangements of the oxomanganese cluster and surrounding water molecules. The catalytic reaction is consistent with substrate water molecules coordinated as terminal ligands to Mn(4) and calcium and requires the formation of an oxyl radical by deprotonation of the substrate water molecule ligated to Mn(4) and the accumulation of four oxidizing equivalents. The oxyl radical is susceptible to nucleophilic attack by a substrate water molecule initially coordinated to calcium and activated by two basic species, including CP43-R357 and the mu-oxo bridge between Mn(3) and Mn(4). The reaction is concerted with water ligand exchange, swapping the activated water by a water molecule in the second coordination shell of calcium.     

Quantum tunneling of magnetization and related phenomena in molecular materials

Molecules comprising a large number of coupled paramagnetic centers are attracting much interest because they may show properties which are intermediate between those of simple paramagnets and classical bulk magnets and provide unambiguous evidence of quantum size effects in magnets. To date, two cluster families, usually referred to as Mn12 and Fe8, have been used to test theories. However, it is reasonable to predict that other classes of molecules will be discovered which have similar or superior properties. To do this it is necessary that synthetic chemists have a good understanding of the correlation between the structure and properties of the molecules, for this it is necessary that concepts such as quantum tunneling, quantum coherence, quantum oscillations are understood. The goal of this article is to review the fundamental concepts needed to understand quantum size effects in molecular magnets and to critically report what has been done in the field to date.     

Theoretical studies and rate constants calculation for the reactions of acetone with fluorine and bromine atoms

Theoretical investigations are carried out on the multichannel reactions CH₃COCH₃ + F (R1) and CH₃COCH₃ + Br (R2) by means of direct dynamics methods. The minimum energy path (MEP) is obtained at the MP2/6-31 + G(d,p) level, and energetic information is further refined at the MC-QCISD (single-point) level. The rate constants are calculated by the improved canonical variational transition-state theory (ICVT) with the small-curvature tunneling (SCT) contributions in a wide temperature range 200–1,500 K for the title reactions, H-abstraction channel is favored for the two reactions. The theoretical overall rate constants are in good agreement with the available experimental data and are found to be k _1a  = 3.22 × 10⁻¹⁵ T ^1.51exp(1,190.91/T) cm³ molecule⁻¹ s⁻¹, k ₂  = 5.95 × 10⁻¹⁸ T ^1.98exp(−4,622.45/T) cm³ molecule⁻¹ s⁻¹. Furthermore, the rate constants of reaction Cl + CH₃COCH₃ (R3) calculated in the other paper are added to discuss the reactivity trend of different halogen reaction with acetone on the rate constants of this class of hydrogen abstraction reactions.     

Quantum mechanics/molecular mechanics strategies for docking pose refinement: distinguishing between binders and decoys in cytochrome C peroxidase

We investigate the effect of systematically applying molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) to docked poses in an attempt to improve the correspondence between theoretical prediction and experimental observation. The proposed scheme involves running a short time scale MD simulation on a docked ligand pose (and any known structurally important crystal structure waters in the active site), followed by QM/MM minimization. Both of these steps are relatively fast for moderately sized ligands; longer time scale MD involving the protein is not found to improve the results. The final binding energy is given in terms of the QM/MM total energy, a van der Waals correction, and a term to account for desolvation effects. This methodology is first tested with a trypsin inhibitor, for which we establish the importance of running MD before reoptimizing with QM/MM. The method is then applied to cytochrome c peroxidase using a set of binders and decoys. In this example, the proposed methodology affords much better discrimination between binders and decoys than the traditional docking approach used. For both systems presented, application of this protocol results in a significantly better energetic ranking and a smaller root mean squared deviation from known crystallographic ligand poses. This work highlights the importance of including polarization effects through QM/MM and of sampling with MD to refine a set of initial docked poses.     

Stereochemical studies on germacrenes: an application of molecular mechanics calculations

Molecular mechanics calculations are successfully carried out to evaluate relative stabilities of each conformation of germacrene-A ($\text{1}$), germacrene-B ($\text{2}$) and hedycaryol ($\text{3}$) in their ground states and transition states. Thus, the calculation results on each transition state model indicate that the elements are formed from the corresponding germacrenes through the most stable transition states (CC), regardless of the most stable conformers in each ground state.     

Determination of the elementary rate constants of autoacceleration reactions on polymers

Equations describing the course of an autoacceleration reaction on a polymer in the low conversion region were derived and used to obtain relationships between the curvature of the conversion curve at the beginning and the elementary rate constants k₁ and k′₂. Calculations carried out by using our relationships are compared with the procedure suggested by Kawabe and Yanagita, and the applicability of the individual methods for the determination of the elementary rate constants is discussed.     

Comparison between hydrogen-transfer and fluoro-transfer reactions on the microcanonical unimolecular rate constants

The microcanonical rate constants for the hydrogen-transfer process of HCCF (reaction 7) and the fluoro-transfer process of FCCF (reaction 8) are carried out with tunneling correction and curvature correction. The results show that the tunneling effects and curvature effects on the rate constant of reaction 7 is quite different from that of reaction 8. The rate constants for different rotational states are also studied for these reactions.