Parametrization of 2-Bromo-2-Chloro-1,1,1-Trifluoroethane (Halothane) and Hexafluoroethane for Nonbonded Interactions

Abstract

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.

Molecular association in 2-bromo-2-chloro-1,1,1-trifluoroethane (Halothane)

“…That theoretical investigation [3] concluded that access to the H-atom in Halothane is hindered by adjacent voluminous halogens, and no evidence for CHÁ Á Áhalogen bonding was found. More recent theoretical studies suggested that H-donor properties and formation of weak hydrogen bonds between Halothane and methanol, dimethyl ether, and in other complexes are possible [6][7][8][9]. In this study we found that the highly positive H-atom (Fig.…”

“…Medical applications of Halothane were intensively studied, but no structural studies were carried out. It is a liquid with low boiling point of 325 K [2] and only the energy minimization and ab initio calculations were performed to obtain the structure and properties the isolated molecule of this compound [3][4][5][6][7][8][9]. The theoretical studies on the intermolecular interactions and H-donor properties of Halothane and other anesthetics, and their ability to form complexes with other compounds were not conclusive-initially they suggested no H-donor properties for Halothane [3], whereas most recent results showed that weak hydrogen bonds involving the CH group can be formed [6][7][8][9].…”

Anesthetic and non-anesthetic effects on interfacial lipids around an ion channel

“…The halothane and HFE [2,3] concentrations were about 5 mol% in the lipid bilayers. The simulation procedures are the same as previously reported [4,5].…”

State conditions transferability of vapor–liquid equilibria via fluctuation solution theory with correlation function integrals from molecular dynamics simulation

“…The basic setup of the simulations follows previous work [1,9]. After initial minimization, the systems were equilibrated for 1 ns, followed by a production phase of 5 ns with time steps of 1 fs.…”

“…(1-fluoroethane, 1,1-difluoroethane, and 1,1,1-trifluoroethane) [8] and by Liu et al (hexafluoroethane and halothane) [9]. Both groups fitted parameters to liquid density and enthalpy of vaporization data, reporting deviations from experimental data within 2%.…”