Theoretical Chemistry Accounts

, Volume 128, Issue 2, pp 191–206

Theoretical studies on model reaction pathways of prostaglandin H2 isomerization to prostaglandin D2/E2

Authors

  • Naoto Yamaguchi
    • Graduate School of Science and EngineeringIbaraki University
    • VALWAY Technology CenterNEC Soft, Ltd
    • National Security Solutions DivisionNEC Corporation
  • Tatsuya Naiki
    • Graduate School of Science and EngineeringIbaraki University
    • Faculty of ScienceIbaraki University
  • Takamitsu Kohzuma
    • Graduate School of Science and EngineeringIbaraki University
    • Frontier Research Center for Applied Atomic SciencesIbaraki University
  • Toshikazu Takada
    • NEC Corporation
    • Research and Development Program for Next-Generation Computational ResearchRIKEN
  • Fumihiko Sakata
    • Graduate School of Science and EngineeringIbaraki University
    • Graduate School of Science and EngineeringIbaraki University
    • Faculty of ScienceIbaraki University
    • Frontier Research Center for Applied Atomic SciencesIbaraki University
Regular Article

DOI: 10.1007/s00214-010-0814-7

Cite this article as:
Yamaguchi, N., Naiki, T., Kohzuma, T. et al. Theor Chem Acc (2011) 128: 191. doi:10.1007/s00214-010-0814-7

Abstract

Model reaction mechanisms in the biosynthesis of prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2) from prostaglandin H2 with PGD2/E2 synthase were examined using the ab initio second-order Møller–Plesset perturbation method and density functional theory. The reaction was modeled similar to the isomerization of 2,3-dioxabicyclo[2.2.1]heptane to 3-hydroxycyclopentanone in the presence of MeS. An explicit solvation of two H2O molecules was also considered, and two probable types of reaction mechanisms were demonstrated. One mechanism starts with proton abstraction from an oxygen-bound carbon at the endoperoxide by a thiolate ion and the other is stepwise and involves attack of a thiolate anion on an oxygen of the endoperoxide group in the first step with protonation of the other oxygen, followed by deprotonation from a carbon-attached oxygen to break an O–S bond to yield PGD2 or PGE2. We also found that the mPW1LYP hybrid method was superior to the B3LYP functional for systems with respect to the state-of-the-art CCSD(T) energetics.

Keywords

Prostaglandin H2Prostaglandin D2Prostaglandin E2Prostaglandin D2 synthaseProstaglandin E2 synthaseModel reaction mechanismsmPW1LYP hybrid functional

Supplementary material

214_2010_814_MOESM1_ESM.doc (225 kb)
Supplementary material 1 (DOC 225 kb)

Copyright information

© Springer-Verlag 2010