MO ab initio study of the structural and electronic properties of the 5-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 three most stable conformers were found to lie in a small range ( < 4.0 kcal/mol), indicating a certain degree of conformational flexibility. The preferred protonation site in vacuo and in water (simulated within the Onsager reaction field model) was characterised; the cation resulting from carbonyl oxygen protonation was predicted to be the most stable, both in vacuo and in water. The UV spectrum of zileuton was also recorded in different solvents and the experimental results were implemented by the outcome of a CI-Singles theoretical study of the excited state properties of the model compound benzothiophene, which is the chromophoric moiety of zileuton. (C) 1998 Elsevier Science B.V.