Theoretical studies of imidazole nitrenium and carbenium ions

Abstract

Ab initio calculations with the split-valence 3-21G basis set and gradient geometry optimization have been carried out with 2-hydroxylaminoimidazole ( 2), 2-hydroxymethylimidazole ( 5), the nitrenium ion ( 3) and carbenium ion ( 6) derived by loss of OH − from these, and the 5-hydroxy non-aromatic isomers of these. The ring geometries of the two cations show significant deviations from the geometry of imidazole itself, being consistent with a major resonance contributor where the positive charge is delocalized into the imidazole ring. An isodesmic calculation on the equilibrium 6 + 2 ⇌ 5 + 3 shows the nitrenium ion side favored by 22 kcal mol −1. This can be attributed in part to a stabilization of the imidazole nitrenium ion by the heterocyclic ring, but relative destabilization of the imidazole hydroxylamine must also play an important role. Imidazole hydroxylamines and nitrenium ions are formed upon biological reduction of nitroimidazole drugs and the charged species may be responsible for some of the biological effects. These calculations shed some light on the reasons why such nitrenium ions are so easily formed.