Theoretical investigation of isotopic scrambling mechanisms in 2-chloroethyl methyl sulfide

Abstract

Ab initio and semiempirical molecular orbital calculations have been applied to study the concerted and stepwise isotopic scrambling mechanisms of 2-chloroethyl methyl sulfide in the gas phase and in aqueous solution. The calculations reveal the structural details of the reactants, transition structures, and intermediates involved in this reaction and provide relative energy estimates. The concerted mechanism is found to be competitive with the stepwise mechanism in the gas phase, but the stepwise mechanism is favored in aqueous solution as no true transition structure for the concerted mechanism could be found using the solvation models. A combined approach of evaluating solvation energies with the generalized-Born-plus-surface-tensions SMx solvation models of Cramer and Truhlar at ab initio optimized geometries is found to deliver the best agreement with experimentally determined reaction barriers. Together with the recent experimental results of McManus and co-workers, the present study provides insights into the controlling factors involved in the elementary reaction steps of sulfur mustards and a solid foundation for investigations into more complex reactions of related compounds.

Ab initio GB study of chemical intermediates in solution; Ethylenesulfonium ion in hydrolysis of 2-chloroethyl methyl sulfide

“…Our GB model does not consider the specific solute-solvent interaction in an SSIP but mimics the SSIP through the steric factor that is involved in C AB and accounts for the exclusion of the solvent shell volume of two species when they approach each other and enter each other's solvent shell. The nonexistence of a CIP for the interaction between 1 and Cl ‫מ‬ has also been suggested by SCRF calculations [13]. …”

“…Donovan [13] calculated the parameters of the 2 r 1 ‫ם‬ Cl ‫מ‬ reaction in solution by ab initio 6-31G* SCRF theory; the energy of 1 plus Cl ‫מ‬ is higher than that of 2 by 31.1 kcal/mol, and the activation energy is 31.8 kcal/mol for the 2 r 1 ‫ם‬ Cl ‫מ‬ reaction [13], suggesting that the cyclic sulfonium ion 1 can hardly exist in aqueous solution, which is against the experimental evidence. In order to reproduce the experimental barrier correctly, an appropriate mixing of energy components was required [13].…”

“…In order to reproduce the experimental barrier correctly, an appropriate mixing of energy components was required [13]. These energetic properties are reflected at the transition state structure; the SCRF transition state is located on the sulfonium side (the SC 2 C 1 angle is 82.5Њ, and the C 1 -Cl distance is 2.601 Å ) [13].…”

“…Donovan calculated the parameters of the isotope scrambling mechanism in 2-chloroethyl methyl sulfide via the cyclic sulfonium ion 1. However, the molecular structure of the sulfonium cation 1 in aqueous solution was not calculated [13]. The SCRF solvation model provided in the MO package they used may be unfavorable for the calculation of ionic species such as the sulfonium cation.…”

“…Politzer and Habibollahzadeh [11] calculated the bonding properties of sulfur mustard in solution using ab initio SCRF theory with Onsager's reaction field model. Donovan analyzed the mechanism of isotopic scrambling in CEMS (2) in the gas phase and in aqueous solution, and the stepwise mechanism, in which the cyclic sulfonium cation 1 is involved, was proposed [13]. In these studies, however, the structure of the cyclic sulfonium cation was not calculated in solution.…”