Conformational analysis of some new derivatives of 4-nitroimidazolyl-1,4-dihydropyridine-based calcium channel blockers

Molecular mechanic (MM+), semi empirical (AM1) and ab initio (RHF/6-21G) calculations were employed to obtain the optimum 3D structure of some recently synthesized 4-nitroimidazolyl-1,4-dihydropyridine derivatives as calcium channel antagonists. MM+ calculation was conducted in the gas and aqueous phase and the others were used only for gas phase calculations. The conformation of dihydropyridine ring (DHP), position of aryl group with respect to DHP ring, conformation of ester groups and the heat of formation (ΔHf) of these compounds were investigated. In addition, we studied how the protonation of the nitrogen of DHP ring influenced 3D structures. It was found that MM+ and AM1 produced relatively similar results, while the results of ab initio method were very different from the other methods. All the computation methods suggested a flattened boat-like conformation for the DHP ring of the studied molecules. However, a slight deviation from the planarity was observed for some molecules. The calculated heat of formations indicated that the 3D structures obtained by AM1 method were more stable than those resulted from MM+ method. Moreover, it was obtained that addition of a proton to the DHP derivatives decreased the stability of the molecules.