Products of Thymine Oxygenation by a Non-heme Oxygenation Model, Fe^II(MeCN)₆²⁺–Ac₂O–H₂O₂, and the Transition State Model between Oxoiron and Thymine

Abstract

Oxidative thymine damage was investigated using a new non-heme oxygenation model, Fe(MeCN)₆²⁺–H₂O₂–Ac₂O, based on high-spin Fe(MeCN)₆²⁺ 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)₆²⁺–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.