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Oxidation of Tertiary Amines by Cytochrome P450—Kinetic Isotope Effect as a Spin‐State Reactivity Probe
Author(s) -
Li Chunsen,
Wu Wei,
Cho KyungBin,
Shaik Sason
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200802215
Subject(s) - chemistry , kinetic isotope effect , trimethylamine , reactivity (psychology) , photochemistry , amine gas treating , hydrogen atom abstraction , kinetic energy , tertiary amine , oxygen , alkylation , computational chemistry , medicinal chemistry , hydrogen , deuterium , organic chemistry , catalysis , medicine , physics , alternative medicine , quantum mechanics , pathology
Two types of tertiary amine oxidation processes, namely, N ‐dealkylation and N ‐oxygenation, by compound I (Cpd I) of cytochrome P450 are studied theoretically using hybrid DFT calculations. All the calculations show that both N ‐dealkylation and N ‐oxygenation of trimethylamine (TMA) proceed preferentially from the low‐spin (LS) state of Cpd I. Indeed, the computed kinetic isotope effects (KIEs) for the rate‐controlling hydrogen abstraction step of dealkylation show that only the KIE LS fits the experimental datum, whereas the corresponding value for the high‐spin (HS) process is much higher. These results second those published before for N,N‐ dimethylaniline (DMA), and as such, they further confirm the conclusion drawn then that KIEs can be a sensitive probe of spin state reactivity. The ferric‐carbinolamine of TMA decomposes most likely in a non‐enzymatic reaction since the FeO bond dissociation energy (BDE) is negative. The computational results reveal that in the reverse reaction of N ‐oxygenation, the N ‐oxide of aromatic amine can serve as a better oxygen donor than that of aliphatic amine to generate Cpd I. This capability of the N ‐oxo derivatives of aromatic amines to transfer oxygen to the heme, and thereby generate Cpd I, is in good accord with experimental data previously reported.