title: Conformational Exploration of Enflurane in Solution and in a Biological Environment.
abstract: Enflurane is a fluorinated volatile anesthetic, whose bioactive conformation is not known. Actually, a few studies have reported on the conformations of enflurane in nonpolar solution and gas phase. The present computational and spectroscopic (infrared and NMR) work shows that three pairs of isoenergetic conformers take place in the gas phase, neat liquid, polar, and nonpolar solutions. According to docking studies, a single conformation is largely preferred over its isoenergetic isomers to complex with the active site of Integrin LFA-1 enzyme (PDB code: 3F78 ), where the widely used anesthetic isoflurane (a constitutional isomer of enflurane) is known to bind. Weak hydrogen bonding from an electrostatic interaction between the CHF2 hydrogen and the central CF2 fluorines was not found to rule 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 governed by the enzyme induced fit.
authors.affiliation: Department of Chemistry, Federal University of Lavras , 37200-000, Lavras, MG, Brazil.
authors.forename: Laize A F
authors.initials: LA
authors.lastname: Andrade
authors.affiliation: Department of Chemistry, Federal University of Lavras , 37200-000, Lavras, MG, Brazil.
authors.forename: Josué M
authors.initials: JM
authors.lastname: Silla
authors.affiliation: Department of Chemistry, University of Manitoba , Winnipeg, MB R3T 2N2, Canada.
authors.forename: Susanna L
authors.initials: SL
authors.lastname: Stephens
authors.affiliation: Department of Chemistry, University of Manitoba , Winnipeg, MB R3T 2N2, Canada.
authors.forename: Kirk
authors.initials: K
authors.lastname: Marat
authors.affiliation: Department of Chemistry, Federal University of Lavras , 37200-000, Lavras, MG, Brazil.
authors.forename: Elaine F F
authors.initials: EF
authors.lastname: da Cunha
authors.affiliation: Department of Chemistry, Federal University of Lavras , 37200-000, Lavras, MG, Brazil.
authors.forename: Teodorico C
authors.initials: TC
authors.lastname: Ramalho
authors.affiliation: Department of Chemistry, University of Manitoba , Winnipeg, MB R3T 2N2, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: van Wijngaarden
authors.affiliation: Department of Chemistry, Federal University of Lavras , 37200-000, Lavras, MG, Brazil.
authors.forename: Matheus P
authors.initials: MP
authors.lastname: Freitas
mesh_terms: D020134:Catalytic Domain; D004737:Enflurane / Q000737:chemistry*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000378:metabolism*; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011789:Quantum Theory; D012996:Solutions; D013816:Thermodynamics
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D012996:Solutions; D004737:Enflurane