A Predictive Pattern of Computed Barriers for C−H Hydroxylation by Compound I of Cytochrome P450

• Published in: Journal of the American Chemical Society Vol. 126; no. 27; pp. 8362 - 8363
• Main Authors: de Visser, Sam P, Kumar, Devesh, Cohen, Shimrit, Shacham, Ronen, Shaik, Sason
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 14.07.2004
• Subjects: Alkanes - chemistry; Alkanes - metabolism; Benzene Derivatives - chemistry; Benzene Derivatives - metabolism; Biological and medical sciences; Camphor 5-Monooxygenase - chemistry; Camphor 5-Monooxygenase - metabolism; Chemistry; Cytochrome P-450 Enzyme System - chemistry; Cytochrome P-450 Enzyme System - metabolism; Exact sciences and technology; Ferric Compounds - chemistry; Ferric Compounds - metabolism; Fundamental and applied biological sciences. Psychology; Hydrogen - chemistry; Hydrogen - metabolism; Hydroxylation; Inorganic chemistry and origins of life; Iron Compounds - chemistry; Iron Compounds - metabolism; Kinetics and mechanism of reactions; Mechanisms. Catalysis. Electron transfer. Models; Molecular biophysics; Phenols - chemistry; Phenols - metabolism; Physical chemistry in biology; Thermodynamics; Iron Complexes; Catalytic reaction; Hydroxylation; Cytochrome P450; Reaction path; Theoretical study; Enzymatic catalysis; Transition metal Complexes; Energy barrier; Oxo complex; Hydrogen abstraction; Transition state; Density functional method; Mercapto complex
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja048528h

The communication presents DFT calculations of 10 different C−H hydroxylation barriers by the active species of the enzyme cytochrome P450. The work demonstrates the existence of an excellent barrier−bond energy correlation. The so-obtained equation of the straight line is demonstrated to be useful for predicting barriers of related C−H activation processes, as well as for assessing barrier heights within the protein environment. This facility is demonstrated be estimating the barrier of camphor hydroxylation by P450cam.