Ab initio calculation of structures and properties of halogenated general anesthetics: halothane and sevoflurane

To correctly analyze the effects of general anesthetics on their potential targets by large-scale molecular simulation, the structural parameters and partial atomic charges of the anesthetics are of determinant importance. Geometric optimizations using the Hartree–Fock and the B3LYP density functional theory methods with the large 6-311+G(2d,p) basis set were performed to determine the structures and charge distributions of two halogenated anesthetics, 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane) and fluoromethyl-2,2,2,-trifluoro-1-(trifluoromethyl) ethyl ether (sevoflurane). The calculated bond lengths and angles are within 3% of the corresponding experimental values reported for the similar molecular groups. Charges are assigned using the Mulliken population analysis and the electrostatic potential (ESP) based on the Merz–Kollman–Singh scheme. The atoms-in-molecules (AIM) theory is also used to assign the charges in halothane. The dipole moments calculated with the Mulliken population analysis and ESP for the structures optimized by B3LYP/6-311+(2d,p) were respectively 1.355 and 1.430 D for halothane and 2.255 and 2.315 D for sevoflurane. These are in excellent agreement with the experimental values of 1.41 and 2.33 D for halothane and sevoflurane, respectively. The calculated structures and partial charge distributions can be readily parameterized for molecular mechanics and molecular dynamics simulations involving these halogenated agents. c © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 436–444, 2001