Molecular Electrostatic Potential Studies on Some Nitroimidazolyl and Nitroheterocyclic Compounds

Summary The electronic wave functions of 11 nitroimidazolyl and nitroheterocyclic compounds were computed using the CNDO/2 quantum chemical method. The location of the greatest nucleophilic reactivity for each molecule was predicted to be mostly near or on the nitro group. As in our previous publication (Lin Liming et al. 1985) the maximum values of the superdelocalizability index for nucleophilic reactivity S(N)max and the sum of S(N)r for each of these compounds were discovered to be significantly correlated with the radiosensitivity as indicated by log(1/C1·6), where C1·6 is the concentration of the compound required to achieve an enhancement ratio of 1·6. The electrostatic potential distribution on a plane parallel to the plane of the imidazole or heterocyclic ring was computed for these compounds with the wave functions obtained from CNDO/2 calculations. In order to analyse the steric electrostatic potential maps, the overall electrostatic potential on an imaginary surface surrounding a molecule was calculated using the multicentre multipole expansion method. It was found that a wide and deep negative potential area exists in a compound which had significant radiosensitizing efficiency, while in metronidazole, which is not an efficient radiosensitizer, the corresponding area is narrow. This phenomenon may be related to the interaction between these compounds and certain biological macromolecules. These preliminary quantum chemical results support Adams' electron affinity theory, and might be helpful in searching for new radiosensitizers.