Mechanistic Study on N‐Demethylation Catalyzed with P450 by Quantitative Structure Activity Relationship using Electronic Properties of 4‐Substituted N,N‐Dimethylaniline

The mechanism of N‐demethylation by P‐450 was investigated using MO calculation of 4‐substituted N,N‐dimethylaniline. The reactivities of the compounds and their intermediates were examined using the energies of HOMO and SOMO, and frontier electron densities. QSAR analysis using these electronic parameters indicated that one‐electron first transfers from nitrogen to P‐450 and the resultant cation radical forms α‐amino radical, followed by hydroxylation and N‐demethylation.