The Conformational Map of Volatile Anesthetics: Enflurane Revisited.
Previous ambiguities in the conformational and structural landscape of the volatile anesthetic enflurane have been solved combining microwave spectroscopy in a jet expansion and ab initio calculations. The broadband (2-18 GHz) rotational spectra identified three different rotamers, sharing a common trans ether skeleton but differing in the ±gauche/trans position of the terminal chlorine atom. For each chlorine conformation two different gauche orientations were predicted for the opposite difluoromethyl group, but only one is experimentally observable due to collisional relaxation in the jet. The experimental dataset comprised nine different isotopologues ((35) Cl, (37) Cl, (13) C) and a large number (>6500) of rotational transitions. The inertial data provided structural information using the substitution and effective procedures. The structural preferences were rationalized with additional ab initio, natural-bond-orbital and non-covalent-interaction analysis, which suggest that plausible anomeric effects at the difluoromethyl group could be overridden by other intramolecular effects. The difluoromethyl orientation thus reflects a minimization of inter-fluorine repulsions while maximizing F⋅⋅⋅H attractive interactions. A comparison with previous electron diffraction and spectroscopic data in the gas and condensed phases finally resulted in a comprehensive description of this ether, completing a rotational description of the most common multi-halogenated anesthetics.
Department of Chemistry, University of Virginia, McCormick Rd., Charlottesville, Virginia, 22904, USA.|Max-Planck Institute for the Structure and Dynamics of Matter, Luruper Chaussee 149, 22761, Hamburg, Germany.
Cristóbal
http://orcid.org/0000-0001-5248-5212
C
Pérez
Departamento de Química Física y Química Inorgánica, Universidad de Valladolid, 47011, Valladolid, Spain.
Elena
E
Caballero-Mancebo
Departamento de Química Física y Química Inorgánica, Universidad de Valladolid, 47011, Valladolid, Spain. lesarri@qf.uva.es.
Alberto
http://orcid.org/0000-0002-0646-6341
A
Lesarri
Departamento de Química Física, Universidad del País Vasco, Ap. 644, 48080, Bilbao, Spain.
Emilio J
EJ
Cocinero
Instituto de Química Médica, CSIC, Madrid, Spain.
Ibon
http://orcid.org/0000-0001-6876-6211
I
Alkorta
Department of Chemistry, University of Virginia, McCormick Rd., Charlottesville, Virginia, 22904, USA.
Richard D
RD
Suenram
Institut für Physikalische Chemie and Elektrochemie, Lehrgebiet A, Gottfried-Wilhelm-Leibniz-Universität, Callinstrasse 3A, 30167, Hannover, Germany.
Jens-Uwe
JU
Grabow
Department of Chemistry, University of Virginia, McCormick Rd., Charlottesville, Virginia, 22904, USA. brookspate@virginia.edu.
Brooks H
BH
Pate
ab initio calculations; halogenated ethers; rotational spectroscopy; supersonic jets; volatile anesthetics