Conversion mechanism and isomeric preferences of the cis and trans isomers of anti-cancer medicine carmustine; A double hybrid DFT calculation

Abstract

The conversion mechanism of cis and trans isomeric forms of anti-cancer medicine carmustine have been investigated. The density functional theory calculations were carried out utilizing the double-hybrid method of Grimme’s B2PLYP combined with Grimme’s D3BJ dispersion and with the basis set of def2-QZVP. According to the obtained results, the trans carmustine in the gas phase by acquiring 21.00 kcal mol−1 can overcome the nitrosyl rotation activation barrier and convert to the cis isomer. The resulting cis form by releases 2.77 kcal mol−1 of energy for gas phase is more stable than the trans carmustine. Moreover, by applying water as a solvent field, it is clear that water molecules by forming hydrogen bonds with the drug would stabilize the trans form by about 1.30 kcal mol−1. In this situation, the conversion activation barrier reaches to 17.22 kcal mol−1 which is 3.77 kcal mol−1 lower than this value for the gaseous state.