Multistructural microiteration combined with QM/MM-ONIOM electrostatic embedding.

Multistructural microiteration (MSM) is a method to take account of contributions of multiple surrounding structures in a geometrical optimization or reaction path calculation using the quantum mechanics/molecular mechanics (QM/MM) ONIOM method. In this study, we combined MSM with the electrostatic embedding (EE) scheme of the QM/MM-ONIOM method by extending its original formulation for mechanical embedding (ME). MSM-EE takes account of the polarization in the QM region induced by point charges assigned to atoms in the multiple surrounding structures, where the point charges are scaled by the weight factor of each surrounding structure determined through MSM. The performance of MSM-EE was compared with that of the other methods, i.e., ONIOM-ME, ONIOM-EE, and MSM-ME, by applying them to three chemical processes: (1) chorismate-to-prephenate transformation in aqueous solution, (2) the same transformation as (1) in an enzyme, and (3) hydroxylation in p-hydroxybenzoate hydroxylase. These numerical tests of MSM-EE yielded barriers and reaction energies close to experimental values with computational costs comparable to those of the other three methods.

Chemoselective Cleavage of Si-C(sp3) Bonds in Unactivated Tetraalkylsilanes Using Iodine Tris(trifluoroacetate).

Organosilanes are synthetically useful reagents and precursors in organic chemistry. However, the typical inertness of unactivated Si-C(sp3) bonds under conventional reaction conditions has hampered the application of simple tetraalkylsilanes in organic synthesis. Herein we report the chemoselective cleavage of Si-C(sp3) bonds of unactivated tetraalkylsilanes using iodine tris(trifluoroacetate). The reaction proceeds smoothly under mild conditions (-50 °C to room temperature) and tolerates various polar functional groups, thus enabling subsequent Tamao-Fleming oxidation to provide the corresponding alcohols. NMR experiments and density functional theory calculations on the reaction indicate that the transfer of alkyl groups from Si to the I(III) center and the formation of the Si-O bond proceed concertedly to afford an alkyl-λ3-iodane and silyl trifluoroacetate. The developed method enables the use of unactivated tetraalkylsilanes as highly stable synthetic precursors.

RETRACTED: Asymmetric remote C-H borylation of aliphatic amides and esters with a modular iridium catalyst.

Site selectivity and stereocontrol remain major challenges in C-H bond functionalization chemistry, especially in linear aliphatic saturated hydrocarbon scaffolds. We report the highly enantioselective and site-selective catalytic borylation of remote C(sp3)-H bonds γ to the carbonyl group in aliphatic secondary and tertiary amides and esters. A chiral C-H activation catalyst was modularly assembled from an iridium center, a chiral monophosphite ligand, an achiral urea-pyridine receptor ligand, and pinacolatoboryl groups. Quantum chemical calculations support an enzyme-like structural cavity formed by the catalyst components, which bind the substrate through multiple noncovalent interactions. Versatile synthetic utility of the enantioenriched γ-borylcarboxylic acid derivatives was demonstrated.

Roles of Closed- and Open-Loop Conformations in Large-Scale Structural Transitions of l-Lactate Dehydrogenase.

The mechanism of l-lactate generation from pyruvate by l-lactate dehydrogenase (LDH) from the rabbit muscle was studied theoretically by the multistructural microiteration (MSM) method combined with the quantum mechanics/molecular mechanics (QM/MM)-ONIOM method, where the MSM method describes the MM environment as a weighted average of multiple different structures that are fully relaxed during geometry optimization or a reaction path calculation for the QM part. The results showed that the substrate binding and product states were stabilized only in the open-loop conformation of LDH and the reaction occurred in the closed-loop conformation. In other words, before and after the chemical reaction, a large-scale structural transition from the open-loop conformation to the closed-loop conformation and vice versa occurred. The closed-loop conformation stabilized the transition state of the reaction. In contrast, the open-loop conformation stabilized the substrate binding and final states. In other words, the closed- to open-loop transition at the substrate binding state urges capture of the substrate molecule, the subsequent open- to closed-loop transition promotes the product generation, and the final closed- to open-loop transition at the final state prevents the reverse reaction going back to the substrate binding state. It is thus suggested that the exchange of stability between the closed- and open-loop conformations at different states promotes the catalytic cycle.

Implementation and performance of the artificial force induced reaction method in the GRRM17 program.

This article reports implementation and performance of the artificial force induced reaction (AFIR) method in the upcoming 2017 version of GRRM program (GRRM17). The AFIR method, which is one of automated reaction path search methods, induces geometrical deformations in a system by pushing or pulling fragments defined in the system by an artificial force. In GRRM17, three different algorithms, that is, multicomponent algorithm (MC-AFIR), single-component algorithm (SC-AFIR), and double-sphere algorithm (DS-AFIR), are available, where the MC-AFIR was the only algorithm which has been available in the previous 2014 version. The MC-AFIR does automated sampling of reaction pathways between two or more reactant molecules. The SC-AFIR performs automated generation of global or semiglobal reaction path network. The DS-AFIR finds a single path between given two structures. Exploration of minimum energy structures within the hypersurface in which two different electronic states degenerate, and an interface with the quantum mechanics/molecular mechanics method, are also described. A code termed SAFIRE will also be available, as a visualization software for complicated reaction path networks. © 2017 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

Multistructural microiteration technique for geometry optimization and reaction path calculation in large systems.

We propose a multistructural microiteration (MSM) method for geometry optimization and reaction path calculation in large systems. MSM is a simple extension of the geometrical microiteration technique. In conventional microiteration, the structure of the non-reaction-center (surrounding) part is optimized by fixing atoms in the reaction-center part before displacements of the reaction-center atoms. In this method, the surrounding part is described as the weighted sum of multiple surrounding structures that are independently optimized. Then, geometric displacements of the reaction-center atoms are performed in the mean field generated by the weighted sum of the surrounding parts. MSM was combined with the QM/MM-ONIOM method and applied to chemical reactions in aqueous solution or enzyme. In all three cases, MSM gave lower reaction energy profiles than the QM/MM-ONIOM-microiteration method over the entire reaction paths with comparable computational costs. © 2017 Wiley Periodicals, Inc.

Multicomponent Molecular Orbital-Climbing Image-Nudged Elastic Band Method to Analyze Chemical Reactions Including Nuclear Quantum Effect.

To analyze the H/D isotope effects on hydrogen transfer reactions in XHCHCHCHY↔XCHCHCHYH (X, Y=O, NH, or CH2 ) including the nuclear quantum effect of proton and deuteron, we propose a multicomponent molecular orbital-climbing image-nudged elastic band (MC_MO-CI-NEB) method. We obtain not only transition state structures but also minimum-energy paths (MEPs) on the MC_MO effective potential energy surface by using MC_MO-CI-NEB method. We find that nuclear quantum effect affects not only stationary-point geometries but also MEPs and electronic structures in the reactions. We clearly demonstrate the importance of including nuclear quantum effects for H/D isotope effect on rate constants (kH /kD ).

Ab initio path integral simulations for the fluoride ion-water clusters: competitive nuclear quantum effect between F(-)-water and water-water hydrogen bonds.

Small hydrated fluoride ion complexes, F(-)(H2O)n (n = 1-3), have been studied by ab initio hybrid Monte Carlo (HMC) and ab initio path integral hybrid Monte Carlo (PIHMC) simulations. Because of the quantum effect, our simulation shows that the average hydrogen-bonded F(-)···HO distance in the quantum F(-)(H2O) is shorter than that in the classical one, while the relation inverts at the three water molecular F(-)(H2O)3 cluster. In the case of F(-)(H2O)3, we have found that the nuclear quantum effect enhances the formation of hydrogen bonds between two water molecules. In F(-)(H2O)2 and F(-)(H2O)3, the nuclear quantum effect on two different kinds of hydrogen bonds, F(-)-water and water-water hydrogen bonds, competes against each other. In F(-)(H2O)3, thus, the nuclear quantum effect on the water-water hydrogen bond leads to the elongation of hydrogen-bonded F(-)···HO distance, which we suggest this as the possible origin of the structural inversion from F(-)(H2O) to F(-)(H2O)3.

Temperature dependence on the structure of Zundel cation and its isotopomers.

Temperature dependence on the structural fluctuations of Zundel cation, H5O2(+), and its isotopomers, D5O2(+) and T5O2(+), have been studied using path integral molecular dynamics simulations in which nuclear quantum effect is fully taken into account. It has been found that the fluctuations of hydrogen-oxygen and oxygen-oxygen distances, which are relevant to the hydrogen bonded structure, grow drastically as the temperature increases within the range of investigation between 100 K and 900 K. The fluctuation with respect to the position of non-bonded hydrogen also increases substantially as the temperature increases. The temperature dependence on the fluctuation is greater for D5O2(+) or T5O2(+) than that of H5O2(+), since the zero-point effect of the former is less than the latter.

Communication: A concerted mechanism between proton transfer of Zundel anion and displacement of counter cation.

Ab initio path integral molecular dynamics simulation of M(+)(H(3)O(2)(-)) (M = Li, Na, and K) has been carried out to analyze how the structure and dynamics of a low-barrier hydrogen-bonded Zundel anion, H(3)O(2)(-), can be affected by the counter alkali metal cation, M(+). Our simulation predicts that the quantum proton transfer in Zundel anion can be strongly coupled to the motion of counter cation located nearby. A smaller cation can induce larger structural distortion of the Zundel anion fragment making the proton transfer barrier higher, and hence, lower the vibrational excitation energy. It is also argued that a large H∕D isotope effect is present.

Efficient ab initio path integral hybrid Monte Carlo based on the fourth-order Trotter expansion: Application to fluoride ion-water cluster.

We propose an efficient path integral hybrid Monte Carlo (PIHMC) method based on fourth-order Trotter expansion. Here, the second-order effective force is employed to generate short trial trajectories to avoid computationally expensive Hessian matrix, while the final acceptance is judged based on fourth-order effective potential. The computational performance of our PIHMC scheme is compared with that of conventional PIHMC and PIMD methods based on second- and fourth-order Trotter expansions. Our method is applied to on-the-fly ab initio PIHMC calculation of fluoride ion-water complexes, F(-)(H(2)O) and F(-)(D(2)O), at ambient temperature, particularly focusing on the geometrical isotope effect.

The chemical shift of deprotonated water dimer: ab initio path integral simulation.

The (1)H NMR chemical shift in deprotonated water dimer H(3)O(2)(-) has been studied by ab initio path integral simulation. The simulation predicts that the isotropic shielding of hydrogen-bonded proton increases as a function of temperature by about 0.003 ppm/K. This change is about an order of magnitude larger than that of the nonhydrogen-bonded proton. It is concluded that this is caused by the significant difference in the quantum distribution of proton at high and low temperatures in the low barrier hydrogen bond.

Temperature and isotope effects on water cluster ions with path integral molecular dynamics based on the fourth order Trotter expansion.

Path integral molecular dynamics simulation based on the fourth order Trotter expansion has been performed to elucidate the geometrical isotope effect of water dimer anions, H(3)O(2)(-), D(3)O(2)(-), and T(3)O(2)(-), at different temperatures from 50 to 600 K. At low temperatures below 200 K the hydrogen-bonded hydrogen nucleus is near the center of two oxygen atoms with mostly O...X...O geometry (where X = H, D, or T), while at high temperatures above 400 K, hydrogen becomes more delocalized, showing the coexistence between O...X-O and O-X...O. The OO distance tends to be shorter as the isotopomer is heavier at low temperatures, while this ordering becomes opposite at high temperatures. It is concluded that the coupling between the OO stretching mode and proton transfer modes is a key to understand such a temperature dependence of a hydrogen-bonded structure.