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.
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.
Kobayashi
Shigeki
S
Division of Analytical Chemistry of Medicines, Showa Pharmaceutical University. kobayasi@ac.shoyaku.ac.jp
Takagi
Akihiko
A
Chikuma
Toshiyuki
T
Tamura
Osamu
O
Kotani
Eiichi
E
Katase
Takao
T
D004249:DNA Damage; D058085:Iron Compounds / Q000737:chemistry*; D008954:Models, Biological; D010084:Oxidation-Reduction; D013941:Thymine / Q000031:analogs & derivatives* / Q000737:chemistry*
D058085:Iron Compounds; C029389:thymine glycol; D013941:Thymine