MO AB-INITIO STUDY OF THE STRUCTURAL AND ELECTRONIC-PROPERTIES OF THE5-LIPOXYGENASE INHIBITOR ZILEUTON

The conformational space of zileuton was investigated by MO ab initio calculations at the HF/6-31G* level. The computed energies of the thr ee most stable conformers were found to lie in a small range ( < 4.0 k cal/mol), indicating a certain degree of conformational flexibility. T he preferred protonation site in vacuo and in water (simulated within the Onsager reaction field model) was characterised; the cation result ing from carbonyl oxygen protonation was predicted to be the most stab le, both in vacuo and in water. The UV spectrum of zileuton was also r ecorded in different solvents and the experimental results were implem ented by the outcome of a CI-Singles theoretical study of the excited state properties of the model compound benzothiophene, which is the ch romophoric moiety of zileuton. (C) 1998 Elsevier Science B.V.