Products of thymine oxygenation by a non-heme oxygenation model, Fe(II)(MeCN)6(2+)-Ac2O-H2O2, and the transition state model between oxoiron and thymine

Chem Pharm Bull (Tokyo). 2010 Jun;58(6):775-81. doi: 10.1248/cpb.58.775.

Abstract

Oxidative thymine damage was investigated using a new non-heme oxygenation model, Fe(MeCN)6(2+)-H2O2-Ac2O, based on high-spin Fe(MeCN)6(2+) in a non-aqueous solution, Ac2O-MeCN. Thymine and 1,3-dimethylthymine oxidized by the system gave the corresponding trans-thymine glycol derivatives in good yield. Thymineglycol is equivalent to an oxidative product as a measure of oxidative DNA damage in living cells. It is suggested that the activation of Fe(MeCN)6(2+)-H2O2-Ac2O in Ac2O-MeCN forms the oxoiron O=Fe(IV)(AcO)(MeCN)4(+) as an active species via a hetelolytic two-electron mechanism, not a Haber-Weiss-Fenton-type reaction with a one-electron process by treatment with a radical scavenger. In addition, we also demonstrated the transition state (TS) for the interaction between thymine and O=Fe(IV)(AcO)(MeCN)4(+) in the triplet spin (spin multiplicity; M=3). This model of oxidative thymine damage may provide new insight into the oxidative mechanism of thymine glycol production in non-aqueous reactions of thymine.

MeSH terms

  • DNA Damage
  • Iron Compounds / chemistry*
  • Models, Biological
  • Oxidation-Reduction
  • Thymine / analogs & derivatives*
  • Thymine / chemistry*

Substances

  • Iron Compounds
  • thymine glycol
  • Thymine