Theoretical investigation of the self-association of antitumor drug imexon

The dimers resulting from self-association of oxo-imino, oxo-amino, and hydroxyl-imino tautomers of imexon, that present two hydrogen bonds, were fully optimized with the density functional methods B3LYP, M06-2X in conjunction with 6-311++G(d,p) basis set. Additionally, second-order Moller-Plesset (MP2) level in combination with 6-311++G(d,p) basis set was employed for comparison purpose. The thermodynamic stability of the self assembled structures in gaseous phase has been obtained according to the analyses of total electronic energies and hydrogen bonding interactions. The bulk water environment has been simulated using the universal solvation model based on solute electron density (SMD). Stability and structure of homochiral and heterochiral imexon dimers resulting from the three imexon tautomers have been carried out to investigate the chiral discrimination. The imexon dimer with heterochiral configuration resulting from self-assembling oxo-amino tautomer is found to be thermodynamically most stable in both gas and aqueous phases. The interaction energies for these self assembled structures were further evaluated with the basis set superposition error corrections. The so-called seven-point interaction energy which includes corrections for BSSE and deformation was calculated. The intermolecular interactions of the selected dimers have been analyzed by calculation of electron density (rho) and Laplacian ( backward difference (2)rho) at the bond critical points (BCPs) using atoms-in-molecule (AIM) theory.