Yongho Kim

Multiconfiguration molecular mechanics algorithm for potential energy surfaces of chemical reactions

We present an efficient algorithm for generating semiglobal potential energy surfaces of reactive systems. The method takes as input molecular mechanics force fields for reactants and products and a quadratic expansion of the potential energy surface around a small number of geometries whose locations are determined by an iterative process. These Hessian expansions might come, for example, from ab initio electronic structure calculations, density functional theory, or semiempirical molecular orbital theory. A 2×2 electronic diabatic Hamiltonian matrix is constructed from these data such that, by construction, the lowest eigenvalue of this matrix provides a semiglobal approximation to the lowest electronically adiabatic potential energy surface. The theory is illustrated and tested by applications to rate constant calculations for three gas-phase test reactions, namely, the isomerization of 1,3-cis-pentadiene, OH+CH4→H2O+CH3, and CH2Cl+CH3F→CH3Cl+CH2F.

Free-Energy Surfaces for Liquid-Phase Reactions and Their Use To Study the Border Between Concerted and Nonconcerted α,β-Elimination Reactions of Esters and Thioesters

Distinguishing between the concerted second-order mechanism for beta-eliminations and nonconcerted mechanisms with discrete carbanion intermediates is very difficult experimentally, but the ability of quantum chemistry to find stationary points of the free-energy surface in liquid-phase solutions, even for complex reagents, provides a new tool for elucidating such mechanisms. Here we use liquid-phase density functional theory calculations to find transition states and intermediates on the free-energy surfaces of four base-initiated alpha,beta-eliminations of acetoxy and mesyloxy esters and their analogous thioesters. The geometries, free energies, and charge distributions of these structures support a stepwise irreversible first-order elimination from a conjugate base (E1cB(I)) mechanism with acetoxy ester 3, acetoxy thioester 4, and mesyloxy thioester 6. However, mesyloxy ester 5, which has an excellent nucleofuge and a less-acidic proton, follows a concerted but asynchronous E2 mechanism with an E1cB-like transition state. The anti transition state is more favorable than the syn one, even for the poorer nucleofuge and more-acidic thioesters. The article includes a general scheme for describing liquid-phase reactions in terms of free-energy surfaces.

Determination of Spin Inversion Probability, H-Tunneling Correction, and Regioselectivity in the Two-State Reactivity of Nonheme Iron(IV)-Oxo Complexes

We show by experiments that nonheme Fe(IV)O species react with cyclohexene to yield selective hydrogen atom transfer (HAT) reactions with virtually no C═C epoxidation. Straightforward DFT calculations reveal, however, that C═C epoxidation on the S = 2 state possesses a low-energy barrier and should contribute substantially to the oxidation of cyclohexene by the nonheme Fe(IV)O species. By modeling the selectivity of this two-site reactivity, we show that an interplay of tunneling and spin inversion probability (SIP) reverses the apparent barriers and prefers exclusive S = 1 HAT over mixed HAT and C═C epoxidation on S = 2. The model enables us to derive a SIP value by combining experimental and theoretical results.

Steric effects and solvent effects on SN2 reactions

We present quantum mechanical calculations designed to disentangle the influences of solvent effects and substituent effects on ionic nucleophilic substitution reactions. In particular, we compare the SN2 reactions of Cl- with CH3CH(X)Cl and (CH3)3CCH(X)Cl for X = H and CN in the gas phase and aqueous solution. We find that, for all of these reactions, transition state distortion and dielectric descreening effects are quantitatively larger in magnitude than hydrophobic effects or exchange repulsion, but they also roughly cancel one another so that differential solvation contributes little to differences in the free energies of activation associated with a CH3 versus a (CH3)3C group as a substituent at the reacting position. Differential solvation of the transition-state structures relative to the reactants is less unfavorable for X = H than for X = CN because of the greater charge separations in the X = H case, and this separation places more positive charge on the reacting carbon center. The smaller deceleration associated with aqueous solvation for X = H roughly balances the gas-phase acceleration predicted for X = CN so that the aqueous activation free energies for the substrates are predicted to be similar for these two substituents.

Theoretical Studies for the Rates and Kinetic Isotope Effects of the Excited-State Double Proton Transfer in the 1:1 7-Azaindole:H2O Complex Using Variational Transition State Theory Including Multidimensional Tunneling

Variational transition state theory calculations including multidimensional tunneling (VTST/MT) for excited-state tautomerization in the 1:1 7-azaindole:H(2)O complex were performed. Electronic structures and energies for reactant, product, transition state, and potential energy curves along the reaction coordinate were computed at the CASSCF(10,9)/6-31G(d,p) level of theory. The potential energies were corrected by second-order multireference perturbation theory to take the dynamic electron correlation into consideration. The final potential energy curves along the reaction coordinate were generated at the MRPT2//CASSCF(10,9)/6-31G(d,p) level. Two protons in the excited-state tautomerization are transferred concertedly, albeit asynchronously. The position of the variational transition state is very different from the conventional transition state, and is highly dependent on isotopic substitution. Rate constants were calculated using VTST/MT, and were on the order of 10(-6) s(-1) at room temperature. The HH/DD kinetic isotope effects are consistent with experimental observations; consideration of both tunneling and variational effects was essential to predict the experimental values correctly.

Solvent effects in the excited-state tautomerization of 7-azaindole: a theoretical study.

The solvent effect often changes the mechanism of a chemical reaction. Experimental studies of the excited-state tautomerization of 7-azaindole (7AI) suggested that the intrinsic reactions occur via the concerted triple and double proton transfer mechanisms in the gas and liquid phases, respectively. Theoretical study is required to understand how the solvent effect changes the mechanism; however, such studies have rarely been performed in the excited-state. In this study, systematic quantum mechanical calculations were performed to study the excited-state tautomerization of 7AI in methanol. Electronic structures and energies for the reactant, transition state, and product were computed at the complete active space self-consistent field levels with the second-order multireference perturbation theory (MRPT2) to consider the dynamic electron correlation. The IEFPCM and SM8 methods were used to include solvent effect in the excited and ground-state calculations, respectively. The excited-state double proton transfer (ESDPT) in 7AI-CH(3)OH and the triple proton transfer (ESTPT) in 7AI-(CH(3)OH)(2) both occur via a concerted but asynchronous mechanism. The ESTPT barrier was smaller than the activation energy of solvent reorganization; however, the amount of 7AI-(CH(3)OH)(2) in methanol is very small because the complex formation is entropically very unfavorable. Therefore, the ESTPT is not an important path. The MRPT2 barrier of ESDPT was 2.8 kcal/mol, which agrees very well with the experimental value. The MRPT2 barrier of deuterium (D) transfer is larger than the activation energy of solvent reorganization; therefore, the intrinsic D transfer is rate-limiting, while the proton transfer must compete with solvent reorganization. The time-dependent density functional theory (TDDFT) was also used for comparison. Most TDDFT methods used in this study failed to predict transition state structures or barriers of the excited-state tautomerization. Additionally, the TDDFT levels failed to predict correct dipole moments in the excited-state, which produced an unreliable solvent effect on barrier heights.

Excited-State Tautomerization in the 7-Azaindole-(H2O)n (n = 1 and 2) Complexes in the Gas Phase and in Solution: A Theoretical Study.

A systematic study of the excited-state tautomerization of 7-azaindole-(H2O)n (n = 1 and 2) complexes in both gas and solution phases were investigated theoretically. Electronic structures and energies for the reactant, transition state (TS), and product were computed using the time-dependent density functional theory (TDDFT) and complete active space self-consistent field (CASSCF) levels with 6-31G (d,p), 6-311G(d,p), and 6-311+G(d,p) basis sets. Barrier heights and tautomerization energies were corrected by the second-order multireference perturbation theory (MRPT2) to consider the dynamic electron correlation. The solvent effect decreased the tautomerization barrier height in the 7-azaindole-H2O complex. In the 7-azaindole-(H2O)2 complex, two transition states were found for two asynchronous but concerted paths: in the first, the pyrole ring proton moved first to water; in the second, the water proton moved first to the pyridine ring. The CASSCF level with the MRPT2 correction clearly showed that the former path was much preferable to the latter. The preferable barrier height was only 1.6 kcal/mol with a zero-point energy correction, which would make the excited-state tautomerization possible. At all TDDFT levels, the TS structures and barrier heights depended on both the basis set used and the solvent effect. Most TDDFT methods failed to reproduce the CASSCF structures and MRPT2 energies. Only two methods, WB97XD/6-31G(d,p) and M062X/6-311+G(d,p), predicted two TSs for the two asynchronous paths in the 7AI-(H2O)2 complex but failed to reproduce the energetics. Further systematic study is necessary to test whether current TDDFT methods, including solvent effects, can be used to understand excited-state proton transfer reactions.

The multi-coefficient correlated quantum mechanical calculations for structures, energies, and harmonic frequencies of HF and H2O dimers

The accurate determination of interaction energies and structures of hydrogen-bonded complexes has been an important issue of ab initio theory for a long time. Extensive theoretical studies have been performed to correct electronic correlation and the basis set truncation error (BSTE) that is a consequence of the incompleteness of the one-electron basis set. We have used recently developed multilevel methods to calculate the structures, harmonic frequencies and the dissociation energies of the HF and water dimers. The seven multilevel methods, namely SAC-MP2/cc-pVDZ, SAC-MP4SDQ/cc-pVDZ, MC-QCISD, MCCM-CO-MP2, MCCM-UT-MP4SDQ, MCCM-UT-CCSD, and MCG3, have been tested. The MC-QCISD, MCCM-UT-MP4SDQ, MCCM-UT-CCSD, and MCG3 method predict the structures and harmonic frequencies of HF and H2O dimers reasonably well compared with experiments and high level ab initio results. Particularly, the MCCM-UT-MP4SDQ and MCCM-UT-CCSD methods show very good agreement of both the interfragment distances and the dissociation ...

Large tunneling effect on the hydrogen transfer in bis(μ-oxo)dicopper enzyme: a theoretical study.

Type-III copper-containing enzymes have dicopper centers in their active sites and exhibit a novel capacity for activating aliphatic C-H bonds in various substrates by taking molecular oxygen. Dicopper enzyme models developed by Tolman and co-workers reveal exceptionally large kinetic isotope effects (KIEs) for the hydrogen transfer process, indicating a significant tunneling effect. In this work, we demonstrate that variational transition state theory allows accurate prediction of the KIEs and Arrhenius parameters for such model systems. This includes multidimensional tunneling based on state-of-the-art quantum-mechanical calculations of the minimum-energy path (MEP). The computational model of bis(μ-oxo)dicopper enzyme consists of 70 atoms, resulting in a 204-dimensional potential energy surface. The calculated values of E(a)(H) - E(a)(D), A(H)/A(D), and the KIE at 233 K are -1.86 kcal/mol, 0.51, and 28.1, respectively, for the isopropyl ligand system. These values agree very well with experimental values within the limits of experimental error. For the representative tunneling path (RTP) at 233 K, the pre- and post-tunneling configurations are 3.3 kcal/mol below the adiabatic energy maximum, where the hydrogen travels 0.54 Å by tunneling. We found that tunneling is very efficient for hydrogen transfer and that the RTP is very different from the MEP. It is mainly heavy atoms that move as the reaction proceeds from the reactant complex to the pretunneling configuration, and the hydrogen atom suddenly hops at that point.

MC-QCISD calculations for proton affinities of molecules and geometries

Abstract Multi-coefficient QCISD (MC-QCISD) calculations have been performed to calculate the geometries and energies for neutral and protonated molecules to reproduce the absolute proton affinity scale. The calculated structures at the MC-QCISD//ML level agree very well with experiment and with highly correlated post-Hartree–Fock calculations. The mean absolute deviations from the experimental results of the results at the MC-QCISD//ML and the MC-QCISD//MP2/6-31G(d,p) levels are 4.4 kJ/mol and 4.2 kJ/mol, respectively. We conclude that the MC-QCISD level of theory can provide good accuracy of the proton affinity scale with less cost.