||Theoretical Investigation into the Potential of Halogenated Methanes to Undergo Reductive Metabolism.
Waller, C. L. ;
McKinney, J. D. ;
||Health Effects Research Lab., Research Triangle Park, NC. Pharmacokinetics Branch.
Redox potential ;
Quantum chemistry ;
Molecular orbitals ;
Computer software ;
Electron density(Concentration) ;
Anaerobic conditions ;
Toxic substances ;
Health hazards ;
DMol computer program ;
DFT(Density-functional theory) ;
Density-functional theory ;
||Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy.
The density-functional theory (DFT) based computational chemistry software package DMol was used to provide insight into the reductive potentials of a series of halomethanes. It is known that certain members of this series are readily reduced in vivo via catalysis by cytochrome P450. DMol was used to calculate the electron affinities of these molecules 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. Concurrent with this study was the discovery of a linear empirical relationship between electron affinity and the lowest unoccupied molecular orbital (LUMO) energy. It is possible that these values could be used as indicators of reductive potentials and ultimately of metabolic rates for use in PB-PK models designed to predict the dose associated with the toxicity of molecules of this and other classes.