Cl. Waller et Jd. Mckinney, THEORETICAL INVESTIGATION INTO THE POTENTIAL OF HALOGENATED METHANES TO UNDERGO REDUCTIVE METABOLISM, Journal of computational chemistry, 14(12), 1993, pp. 1575-1579
The density-functional theory (DFT)-based computational chemistry soft
ware package DMol was used to provide insight into the reductive poten
tials of a series of halomethanes. It is known that certain members of
this series are readily reduced in vivo via catalysis by cytochrome P
450. DMol was used to calculate the electron affinities of these molec
ules to be used as measures of their reduction potentials. Our results
are consistent with experimental electrochemical reduction potentials
and indicate that electron affinity is dependent upon the number and
type of halogens present in the molecule. Calculated bond lengths and
angles also compared favorably with experimental results and estimates
derived from other ab initio methods of calculation. Concurrent with
this study was the observation of a linear empirical relationship betw
een electron affinity and the lowest unoccupied molecular orbital ener
gy. It is possible that these values could be used as indicators of re
ductive potentials and ultimately of metabolic rates for use in PB-PK
models designed to predict the dose associated with the toxicity of mo
lecules of this and other classes. (C) 1993 by John Wiley & Sons, Inc.