H-atom abstraction by thiyl radicals from peptides and cyclic dipeptides. A theoretical study of reaction rates

Abstract

The reactions of methanethiyl radicals (CH3S˙) with the cyclic anhydrides of glycine (1a), alanine (L,L-1b and D,L-1b), and sarcosine (1c), and the acyclic peptides, N-formylglycinamide (3a) and N-formylalaninamide (3b), were studied by means of theoretical calculations at the B3LYP/6-311+G(d,p) level of theory. Free energies in the gas phase were determined in the classical harmonic oscillator-rigid rotator model, and used to estimate rates of H-transfer reactions at the αC-site of the peptides. The effects of aqueous solution were estimated by the SCIPCM procedure in combination with modified experimental Arrhenius A-factors to calculate solution phase rate constants. The reactions are discussed in terms of the charge and spin polarisation in the transition state, as determined by AIM analysis. Rate constants calculated by this semiempirical Arrhenius approach are in very good agreement with available experimental data on the reaction of D3N+CH2CH2S˙ with 1a and 1c but not 1b in D2O. The rate constants for the reaction of CH3S˙ with 3a and 3b are also in very good agreement with experimental data on the N-acetyl analogues. Contrary to experiment, the cyclic alanine anhydrides, L,L-1b and D,L-1b, were predicted to react more than an order of magnitude more quickly than any of the other dipeptides.