Molecular electrostatic potential studies on some nitroimidazolyl and nitroheterocyclic compounds

Area of Science:

• Computational chemistry
• Quantum chemistry
• Medicinal chemistry

Background:

• Nitroheterocyclic compounds are investigated for their potential as radiosensitizers.
• Understanding the electronic properties of these compounds is crucial for predicting their biological activity.
• Previous studies have suggested a correlation between electronic structure and radiosensitizing efficacy.

Purpose of the Study:

• To compute electronic wave functions for nitroimidazolyl and nitroheterocyclic compounds using the CNDO/2 method.
• To predict the sites of nucleophilic reactivity within these molecules.
• To correlate electronic properties with radiosensitizing efficiency and explore potential structure-activity relationships.

Main Methods:

• Utilized the CNDO/2 quantum chemical method to compute electronic wave functions.
• Calculated superdelocalizability indices (S(N)max and sum of S(N)r) to assess nucleophilic reactivity.
• Generated electrostatic potential maps using multicentre multipole expansion to analyze molecular surface properties.

Main Results:

• Nucleophilic reactivity was predominantly located near or on the nitro group for most compounds.
• Maximum superdelocalizability values significantly correlated with radiosensitivity (log(1/C1.6)).
• Compounds with high radiosensitizing efficiency exhibited wide and deep negative electrostatic potential areas, unlike less effective compounds such as metronidazole.

Conclusions:

• Quantum chemical parameters, particularly nucleophilic reactivity and electrostatic potential distribution, are indicative of radiosensitizing potential.
• The findings support Adams' electron affinity theory regarding radiosensitization mechanisms.
• These results provide a basis for the rational design and discovery of novel radiosensitizing agents.