Parametrization of 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane) and hexafluoroethane for nonbonded interactions

Ab initio and empirical methods were combined to optimize the partial atomic charges and Lennard-Jones parameters for two halogenated compounds, halothane (CF3CHClBr, a potent volatile anesthetic) and hexafluoroethane (CF3CF3, a nonanesthetic). Charge optimization was achieved using empirical calculations by systematically adjusting the charge assignments to fit minimum interaction energies and geometries between a TIP3 water molecule and the halogenated compounds to the corresponding values from the ab initio calculations, which were carried out at the HF/6-311+G(2d,p) and HF/6-31G(d) levels for halothane and hexafluoroethane, respectively. To optimize the Lennard-Jones parameters, the initial estimates were obtained from scaling the values from the ab initio minimum interaction energies and geometries between neon and the halogenated compounds calculated at the MP3/6-311++G(3d,3p) level. The Lennard-Jones parameters were further refined by fitting the empirical interaction energies to the corresponding ab initio values. The refined parameters were finalized by reproducing experimental values of the heats of vaporization and densities for liquid halothane and hexafluoroethane, using molecular dynamics simulations. The calculated heats of vaporization and liquid densities using the optimized parameters are in excellent agreement with the experimental values. The results indicate that the combination of ab initio and empirical approaches works well for obtaining the nonbonded parameters of molecules with heavy halogen atoms, such as Cl and Br. The refined nonbonded parameters are readily applicable in molecular dynamics simulations involving these halogenated compounds.