W. Adam*, S. Andler, W. Nau
Apr 4, 1998
Citations
0
Influential Citations
10
Citations
Journal
Journal of the American Chemical Society
Abstract
The 3-(hydroxymethyl)-3,4,4-trimethyl-1,2-dioxetane (HTMD) highly efficiently damages DNA compared to the merely alkyl-substituted derivative 3,3,4,4-tetramethyl-1,2-dioxetane (TMD). To elucidate this difference in oxidative reactivity, two additional hydroxymethyl-substituted 1,2-dioxetanes, namely cis/trans-3-(hydroxymethyl)-3,4-dimethyl-4-(phenylmethyl)- (1α/1β) and 3-(hydroxymethyl)-4,4-dimethyl-3-(phenylmethyl)-1,2-dioxetane (2), were investigated in regard to their photochemical and photobiological properties. The high genotoxic effects of the hydroxymethyl-substituted 1,2-dioxetanes, which are reflected in the significant formation of single-strand breaks in plasmid pBR 322 DNA and the efficient oxidation of guanine in calf thymus DNA and the nucleoside 2'-deoxyguanosine (dGuo), are for the first time understood in terms of radical chemistry. The reactivity order of the dioxetanes 1α/1β > HTMD > 2 ≫ TMD to damage DNA parallels the propensity of these dioxetanes to generate radicals. These reactive ...