Solvent effects on the intramolecular conversion of trimethylsulfonium chloride to dimethyl sulfide and methyl chloride

Abstract

The formation of CH3Cl from (CH3)3SCl in various solvents has been studied based on M05/6-311+G(2d,p) DFT calculations to quantify the influence of the solvent on the stability of sulfonium cations. Four different pathways (one SN1, one backside and two frontside attacks for SN2) as well as the formation of different ion pairs (tripod, seesaw, and linear) are discussed to investigate the origin of the kinetic solvent effect (KSE) and the contribution of ion pairs to the overall reaction. Ion pairs are formed only in solvents with a permittivity ε lower than 28, but the reaction proceeds via a standard SN2 mechanism with a backside attack in all solvents. The formation of ion pairs does not change the order of the rate law, but it strongly influences the KSE, which can distinguish between reactions starting from free ions and those starting from ion pairs, in contrast to standard kinetic analysis.

A Computational Study of the Promiscuity of the SAM-Dependent Methyltransferase AtHTMT1

“…The desolvation of the reactants has been found to be important for the catalysis of the S N 2 methyl transfer. 33 , 35 The difference Δ DS G ° between the Δ TS G env ° values ( eq 4 ) for water and ether is used to quantify the desolvation effect ( Table 2 ) with ether marking the lower end of the effective permittivity range for the interior of an enzyme. 34 …”

“…The quantum chemical analysis 35 of the methyl transfer between a trimethyl sulfonium ion [(CH 3 ) 3 S + ] as stand-in for n SAM + and Cl – shows that the formation of intermediate [(CH 3 ) 3 S + ·Cl – ] ion pairs depends strongly on the permeability of the solvent. Therefore, the partial solvation of the nucleophile in the enzymatic environment also prevents Cl – from binding to the reactive site as observed in MD simulations without spatial constraints.…”

“…The dielectric constant (ϵ) of the interior of enzymes has been estimated to lie between 4 and 20, 34 and model studies with (CH 3 ) 3 S + mimicking SAM show that the methyl transfer is greatly accelerated in environments with low values for ϵ. 35 A change of the value of ϵ in the electrostatic continuum model from 78 (water) to 4.24 (diethyl ether) in the QM calculations provides an estimate of the magnitude of the electrostatic effect on the reaction rate caused by the desolvation of the reactants in the enzyme. The X-ray structure of AtHTMT1 shows the presence of additional H 2 O molecules at the reactive site, indicating chemical interactions of the nucleophile with these molecules.…”

Computational Study of the Degradation of S-Adenosyl Methionine in Water

“…Figure 1 shows the partition scheme for the SAM molecule in ONIOM calculations. Truhlar's M05 25 functional with the 6-311+G(2d,p) basis set was used for the amino acid and the ribose C 5 methylene group (high-level region), based on a previous evaluation 26 highlighting the superiority of this method for analysis of sulfonium ions in solutions. The low-level region (OLYP/6-31G(d,p)) is defined by the remainder of the adenosine nucleoside.…”

Reaction mechanism of an intracluster SN2 reaction induced by electron capture

“…From a theoretical point of view, the potential energy, 21 reaction dynamics, 22–24 steric 25 and solvent effects, 26–28 and quantum scattering 29 have been studied using ab initio calculations by several research groups. For example, the effects of micro-solvation on the OH − + CH 3 I reaction were investigated using the direct dynamics simulation, 30 which demonstrated that while the S N 2 reaction dominated at all reactant collision energies, proton transfer to form CH 2 I − was found to dominate at higher collision energies.…”