METABOLITE PREDICTIONS FOR PARASUBSTITUTED ANISOLES BASED ON AB-INITIO COMPLETE ACTIVE SPACE SELF-CONSISTENT-FIELD CALCULATIONS

The cytochrome P450 mediated oxidative metabolism of a series of para- substituted anisoles has been examined using ab initio CASSCF (complet e active space self-consistent field) calculations. On the basis of th ese calculations, oxidative metabolites were rationalized using the co ncept of hydrogen atom abstraction, spin delocalization, and hydroxyl radical recombination, which is believed to govern part of the oxidati on and oxygenation reactions catalyzed by cytochrome P450. Spin distri butions and energy differences between substrates, metabolic intermedi ates, and products were calculated. A comparison of the predictions wi th recent experimental findings from other laboratories supports the a pplicability of the currently used computational model for predicting qualitatively the oxidative metabolism by cytochrome P450.