Análise conformacional teórica e espectroscópica do enflurano livre, emsolução e em meio biológico

Abstract

Enflurane is a fluorinated volatile anesthetic, whose biological conformation is still unknown. Previous studies have reported the enflurane conformations of for the gas phase and in non-polar solution. With the aim of studying the conformational stability of the enflurane, this study, performed using computational and spectroscopic (infrared, nuclear magnetic rossonance and microwave) techniques, shows that three pairs of isoenergetic conformations are present in the gas phase, neat liquid, polar and non-polar solutions, while a single conformation is largely preferred in relation to other isoenergetic isomers to complex with the active site of the integrin LFA-1 enzyme (PDB code: 3F78), where the widely used anesthetic isoflurane (a constitutional isomer of enflurane) is known to bind. Contrary to previous reports in the literature, weak hydrogen bonding from an electrostatic interaction between the CHF2 hydrogen and the central CF2 fluorines was not found to govern the conformational isomerism of enflurane. Moreover, intramolecular interactions based on steric, electrostatic and hyperconjugative effects usually invoked to describe the anomeric effect are not responsible for the possible bioactive conformation of enflurane, which is rather regulated by the enzyme induced fit.