Photooxidative damage of guanine in DG and DNA by the radicals derived from the alpha cleavage of the electronically excited carbonyl products generated in the thermolysis of alkoxymethyl-substituted dioxetanes and the photolysis of alkoxyacetones.
On thermolysis of the methoxy (MeO-TMD), tert-butoxy (tBuO-TMD), and hydroxy (HO-TMD) derivatives of 3,3,4,4-tetramethyl-1,2-dioxetane (TMD) in the presence of dG and calf-thymus DNA, the guanine is oxidized considerably more efficiently than the parent TMD. The same trend in the oxidative reactivity is observed for the photolysis of the corresponding oxy-substituted ketones versus acetone. The oxidative reactivity order in the dioxetane thermolysis, as well as in the ketone photolysis, parallels the ability of the excited ketones to release radicals (determined by spin trapping with DMPO and EPR spectroscopy) upon alpha cleavage (Norrish-type-I reaction). In the presence of molecular oxygen, the carbon-centered radicals are scavenged to produce peroxyl radicals, which are proposed as the reactive species in the oxidation of the guanine in dG and calf-thymus DNA.
Adam
W
W
Institut für Organische Chemie, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany. adam@chemie.uni-wuerzburg.de
Arnold
M A
MA
Saha-Möller
C R
CR
D000096:Acetone / Q000031:analogs & derivatives* / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000737:chemistry / Q000528:radiation effects*; D005609:Free Radicals; D006147:Guanine / Q000737:chemistry* / Q000528:radiation effects; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006358:Hot Temperature; D007659:Ketones / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010777:Photochemistry; D010782:Photolysis; D013950:Thymus Gland
D005609:Free Radicals; D006571:Heterocyclic Compounds; D007659:Ketones; D000096:Acetone; D006147:Guanine; D004247:DNA; D003849:Deoxyguanosine