Conformations and structures of desflurane and isoflurane

The geometric structure and conformational properties of the two inhalation anesthetics desflurane (2-difluoromethoxy-1,1,1,2-tetrafluoroethane, CF3-C HF-O-CHF2) and isoflurane (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoroetha ne, CF3-CHCl-O-CHF2) were studied by gas electron diffraction (GED) and qua ntumchemical calculations (HF/3-21G(*), B3PW91/6-311G(2d) and MP2/6-311G(2d )). Both compounds exist in the gas phase as mixtures of two conformers. Th e predominant form (80(8)% in desflurane and 83(11)% in isoflurane) possess es near trans configuration of the C-C-O-C skeleton (phi(C-C-O-C)= -146(4)d egrees in desflurane and -136(5)degrees in isoflurane) and trans orientatio n of the CHF2 group (C-H bond trans to O-C bond). In the minor conformer, t he CHF2 group is oriented gauche. These conformational properties are discu ssed in terms of anomeric effects. According to the theoretical calculation s four or five stable conformers exist and the types and relative energies depend on the computational method. However, the two structures which are p redicted by all three methods to be lowest in energy correspond to the pred ominant and minor conformer observed in the GED experiments. The gas phase structures of the predominant form are in very close agreement with the cry stal structures which have been reported previously. (C) 2000 Elsevier Scie nce S.A. All rights reserved.