Predicting the Regioselectivity and Stereoselectivity of Cytochrome P450-Mediated Reactions
Recently an initiative to design safer chemicals was made by the Evironmental Protection Agency (1). The design of safer chemicals must be a multi-discplinary effort merging chemistry and biology. One of the more important areas in this effort is understanding what governs the rate of bioactivation of xenobiotics. This area is of particular importance since many chemicals are protoxins and must be bioactivated to the ultimate toxin (2). This chapter will outline our efforts toward predicting the stereochemistry and regioselectivity of bioactivation reactions, mediated by cytochrome P450, using computational methods. The following chapter will provide some examples of how the electronic factors can be predicted using computational methods. Overall, it is our hope that these methods can be expanded and incorporated into a general program for designing safer chemicals.
KeywordsValproic Acid Safe Chemical Styrene Epoxidation Heterolytic Cleavage Absolute Stereochemistry
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