Since Ru(Ⅱ)tri(polypyridyl)complexes can bind DNA in the groove,the chemistry of metallo-groove binders has been extended to many applications such as artificial photonucleases and DNA recognizers.Here we found that ...Since Ru(Ⅱ)tri(polypyridyl)complexes can bind DNA in the groove,the chemistry of metallo-groove binders has been extended to many applications such as artificial photonucleases and DNA recognizers.Here we found that the major product was N-(2-deoxy-β-D-erythro-pentofuranosyl)-spiroiminodihydan toin(dSp)when the nucleoside 2’-deoxyguanosine(dG)was exposed to the visible light irradiation of Ru(Ⅱ)tri(polypyridyl)complexes including Ru(bpy)_(3)^(2+)(bpy=2,2’-bipyridyl),Ru(OP)_(3)^(2+)(OP=1,10-phenan throline)and Ru(DIP)_(3)^(2+)(DIP=4,7-diphenyl-1,10-phenanthroline).Interestingly,we found that in the oxi dation of dsDNA the major oxidation product is 8-oxo-7,8-dihydro-2’-deoxyguanosine(8-oxodG)instead of dSp.The formation of dSp and 8-oxodG increased significantly in^(D)2_(O)and decreased markedly with the addition of NaN_(3).[^(18)O]-Labeled 8-oxodG was also found to be produced more than non labeled 8-oxodG under an^(18)O_(2)atmosphere.The above results clearly indicated that^(1)O_(2)was the major oxidant during the oxidation of both dG and dsDNA by the irradiation of Ru(Ⅱ)complexes,which was further confirmed by both ESR spin-trapping and UV methods.Among the above three Ru(Ⅱ)complexes,Ru(DIP)_(3)^(2+)is the most effcient photosensitized generator of dG oxidation products,while in the oxidation of dsDNA,Ru(bpy)_(3)^(2+)is the most effective.This is thefirst report that the irradiation of Ru(Ⅱ)polypridyl complexes with visible light can induce potent oxidation of dG and ctDNA to the more mutagenic product dSp and 8-oxodG via an^(1)O_(2)-mediated mechanism.Thesefindings should provide new perspec tives for future investigations on whether ubiquitous Ru(Ⅱ)complexes could cause oxidatively generated DNA damage in cellular models.展开更多
基金supported by the“From 0 to 1”Original Innovation Project,the Basic Frontier Scientific Research Program,CAS(ZDBS-LY-SLH027)NSF China Grants(21976200,21836005,22021003,21621064,21377158,and 21976199).
文摘Since Ru(Ⅱ)tri(polypyridyl)complexes can bind DNA in the groove,the chemistry of metallo-groove binders has been extended to many applications such as artificial photonucleases and DNA recognizers.Here we found that the major product was N-(2-deoxy-β-D-erythro-pentofuranosyl)-spiroiminodihydan toin(dSp)when the nucleoside 2’-deoxyguanosine(dG)was exposed to the visible light irradiation of Ru(Ⅱ)tri(polypyridyl)complexes including Ru(bpy)_(3)^(2+)(bpy=2,2’-bipyridyl),Ru(OP)_(3)^(2+)(OP=1,10-phenan throline)and Ru(DIP)_(3)^(2+)(DIP=4,7-diphenyl-1,10-phenanthroline).Interestingly,we found that in the oxi dation of dsDNA the major oxidation product is 8-oxo-7,8-dihydro-2’-deoxyguanosine(8-oxodG)instead of dSp.The formation of dSp and 8-oxodG increased significantly in^(D)2_(O)and decreased markedly with the addition of NaN_(3).[^(18)O]-Labeled 8-oxodG was also found to be produced more than non labeled 8-oxodG under an^(18)O_(2)atmosphere.The above results clearly indicated that^(1)O_(2)was the major oxidant during the oxidation of both dG and dsDNA by the irradiation of Ru(Ⅱ)complexes,which was further confirmed by both ESR spin-trapping and UV methods.Among the above three Ru(Ⅱ)complexes,Ru(DIP)_(3)^(2+)is the most effcient photosensitized generator of dG oxidation products,while in the oxidation of dsDNA,Ru(bpy)_(3)^(2+)is the most effective.This is thefirst report that the irradiation of Ru(Ⅱ)polypridyl complexes with visible light can induce potent oxidation of dG and ctDNA to the more mutagenic product dSp and 8-oxodG via an^(1)O_(2)-mediated mechanism.Thesefindings should provide new perspec tives for future investigations on whether ubiquitous Ru(Ⅱ)complexes could cause oxidatively generated DNA damage in cellular models.
