Theoretical study of molecular interaction between tirapazamine enzymatic catalysis metabolites and water

The weakly hydrogen-bonded complexes, between tirapazamine enzymatic catalysis metabolites and water, have been investigated by density functional theory (DFT), using the B3LYP hybrid functional. The geometries of these complexes have been fully optimized at the B3LYP/6-31G(d) and B3LYP/6-311+G(d) levels. The stabilization energies and charge changes of some atoms have been calculated and analyzed. The results indicate that the catalysis metabolites and water can form stable hydrogen-bonded complexes. Nine complexes are identified. It is important and necessary to add zero-point vibrational energy (ZPVE) and basis set superposition error (BSSE) corrections for calculating stabilization energy. The results also reveal an important relationship between the relative stabilities of hydrogen-bonded complexes and the final products of tirapazamine medication.