title: Oxidation of tertiary amines by cytochrome p450-kinetic isotope effect as a spin-state reactivity probe.
abstract: 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 Fe-O 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.
authors.affiliation: State Key Laboratory of Physical Chemistry of Solid Surfaces and Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005 (China), Fax: (+86) 592-2184708.
authors.forename: Chunsen
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Physical Chemistry of Solid Surfaces and Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005 (China), Fax: (+86) 592-2184708.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Organic Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University, Jerusalem, 91904 (Israel), Fax: (+972) 2-658-4680.
authors.forename: Kyung-Bin
authors.initials: KB
authors.lastname: Cho
authors.affiliation: Department of Organic Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University, Jerusalem, 91904 (Israel), Fax: (+972) 2-658-4680.
authors.forename: Sason
authors.initials: S
authors.lastname: Shaik