Theory of chemical bonds in metalloenzymes. VII. Hybrid-density functional theory studies on the electronic structures of P450

Mitsuo Shoji, Hiroshi Isobe, Toru Saito, Hirotaka Yabushita, Kenichi Koizumi, Yasutaka Kitagawa, Shusuke Yamanaka, Takashi Kawakami, Mitsutaka Okumura, Masayuki Hagiwara, Kizashi Yamaguchi

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16 Citations (Scopus)

Abstract

A first principle investigation has been carried out for intermediate states of the catalytic cycle of a cytochrome P450. To elucidate the whole catalytic cycle of P450, the electronic and geometrical structures are investigated not only at each ground state but also at low-lying energy levels. Using the natural orbital analysis, the nature of chemical bonds and magnetic interactions are investigated. The ground state of the Compound 1 (cpd1) is calculated to be a doublet state, which is generated by the antiferromagnetic coupling between a triplet Fe(IV)=O moiety and a doublet ligand radical. We found that an excited doublet state of the cpd1 is composed of a singlet Fe(IV)=O and a doublet ligand radical. This excited state lies 20.8 kcal mol-1 above the ground spin state, which is a non-negligible energy level as compared with the activation energy barrier of ΔE# = 26.6 kcal mol-1. The reaction path of the ground state of cpd1 is investigated on the basis of the model reaction: 3O(3p) + CH4. The computational results suggest that the reactions of P450 at the ground and excited states proceed through abstraction (3O-model) and insertion (1O-model) mechanisms, respectively.

Original languageEnglish
Pages (from-to)631-650
Number of pages20
JournalInternational Journal of Quantum Chemistry
Volume108
Issue number4
DOIs
Publication statusPublished - Mar 15 2008
Externally publishedYes

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Keywords

  • Density-functional theory
  • Electronic structures
  • Natural orbital analysis
  • P450
  • Reaction mechanisms

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

Cite this

Shoji, M., Isobe, H., Saito, T., Yabushita, H., Koizumi, K., Kitagawa, Y., Yamanaka, S., Kawakami, T., Okumura, M., Hagiwara, M., & Yamaguchi, K. (2008). Theory of chemical bonds in metalloenzymes. VII. Hybrid-density functional theory studies on the electronic structures of P450. International Journal of Quantum Chemistry, 108(4), 631-650. https://doi.org/10.1002/qua.21547