Theoretical Investigations of the Anaerobic Reduction of Halogenated Alkanes by Cytochrome P450. 1. Structures, Inversion Barriers, and Heats of Formation of Halomethyl Radicals

Abstract

For understanding the properties of the radicals produced in the anaerobic reduction of halogenated methanes by cytochrome P450, the geometries of all chlorofluoromethyl radicals are optimized with both MNDO and ab initio methods. The ab initio calculations employ unrestricted Hartree-Fock theory with 3-21G and 6-31G* basis sets. In addition, the structures of CH3, CH2F, and CH2C1 are optimized with second-order Moller-Plesset perturbation theory (MP2) with 6-31G*, 6-31G**, and 6-31+G* basis sets. MP2 structures of CH3 and CH2F are also obtained with 6-311G** and 6-311+G** basis sets. The degree of nonplanarity, and the inversion barrier, increases in the order H < Cl < F. An examination of the results shows a correlation between the ab initio equilibrium geometry and the inversion barrier for these radicals. A plot of the inversion barrier vs. the degree of nonplanarity produces a single curve for all levels of calculation. This suggests that the equilibrium geometry of the radical determines the magnitude of the inversion barrier. MP2/6-31G*//HF/3-21G energies and HF/3-21G vibrational frequencies of all chlorofluoromethanes and methyl radicals are used with the available experimental data to calculate theoretical heats of formation for these compounds. These theoretical values are used to determine the strengths of C-H bonds in halogenated methanes, which correlate to the activity of the radicals produced in anaerobic reduction toward abstraction of lipid hydrogens. The theoretical heats of formation serve as a guide in deciding between conflicting experimental values. After a reliable set of experimental heats of formation is determined, these values are used to extend the list of HF/3-21G and HF/6-31G* atom equivalents presented by Ibrahim and Schleyer. In addition, MP2/6-31G*//HF/3-21G atom equivalents are determined. © 1987, American Chemical Society. All rights reserved.