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.