A Mechanistic Comparison between Cytochrome P_(450)- and Chloroperoxidase-Catalyzed N-Dealkylation of N,N-Dialkyl Anilines

摘要

Most peroxidases use histidine as an axial ligand for heme,while Chloroperoxidase (CPO) uses a thiolate,which is similar to the ligand employed by Cytochrome P_(450) (P_(450)).Several studies have also shown that,unlike other peroxidases,CPO is capable of carrying out monooxygenation reactions in a similar manner to P_(450) in addition to typical peroxidase-like reactions.These observations have been attributed to the similarities of the active-site architecture of the two enzymes.Both enzymes have been shown to efficiently catalyze the oxidative N-dealkylation of amines.The similar magnitudes of the kinetic isotope effects determined for P_(450)- and CPO-catalyzed N-dealkylation of N,N-dimethylaniline have been used to propose that these reactions proceed through similar mechanisms.In this study,we have examined the mechanism of CPO-catalyzed N-dealkylation using a series of radical probes,4-chloro-N-cyclopropyl-N-alkylanilines 1-3,which we have recently used in the mechanistic studies of P_(450),and compared the results with those of P_(450)-catalyzed reactions.The results show that P_(450)- and CPO-catalyzed reactions proceed through distinctly different mechanisms.As previously reported,while P_(450)-catalyzed reactions appear to proceed through a C_(alpha)-hydrogen abstraction mechanism,CPO-catalyzed reactions proceed through a single electron/proton transfer (SET/H~+) mechanism,similar to reactions catalyzed by Horseradish peroxidase (HRP).Thus,CPO may not be a good mechanistic model for P_(450)-catalyzed N-dealky-lations.