Conformational sampling of S- and R-warfarin in polar solvents: Implications for stereoselective complex formation

Molecular dynamics simulations of the open side chain conformation of ionic and neutral S- and R-warfarin in aqueous solvent and acetonitrile are described. In all cases, warfarin is found to sample a broad conformational ensemble with major and minor states due to torsional degrees of freedom associated with its side chain. Thermodynamics and kinetics of transitions between these states are analyzed from the simulations and interpreted in the context of stereoselective interactions in biological and non-biological complexes.