Is nevirapine atropisomeric? Experimental and computational evidence for rapid conformational inversion

Abstract

The non-nucleoside reverse transcriptase inhibitor nevirapine displays in its room temperature ¹H-NMR spectrum signals characteristic of a chiral compound. Following suggestions in the recent literature that nevirapine may display atropisomerism—and therefore be a chiral compound, due to slow interconversion between two enantiomeric conformers—we report the results of an NMR and computational study which reveal that while nevirapine does indeed possess two stable enantiomeric conformations, they interconvert with a barrier of about 76 kJ mol⁻¹ at room temperature. Nevirapine has a half life for enantiomerisation at room temperature of the order of seconds, is not atropisomeric, and cannot exist as separable enantiomers.