Oxidation of guanine by carbonate radicals derived from photolysis of carbonatotetramminecobalt(III) complexes and the pH dependence of intrastrand DNA cross-links mediated by guanine radical reactions.
The carbonate radical anion CO(3)(*-) is a decomposition product of nitrosoperoxycarbonate derived from the combination of carbon dioxide and peroxynitrite, an important biological byproduct of the inflammatory response. The selective oxidation of guanine in DNA by CO(3)(*-) radicals is known to yield spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) products, and also a novel intrastrand cross-linked product: 5'-d(CCATCG*CT*ACC), featuring a linkage between guanine C8 (G*) and thymine N3 (T*) atoms in the oligonucleotide (Crean et al., Nucleic Acids Res. 2008, 36, 742-755). Involvement of the T-N3 (pK(a) of N3-H is 9.67) suggests that the formation of 5'-d(CCATCG*CT*ACC) might be pH-dependent. This hypothesis was tested by generating CO(3)(*-) radicals through the photodissociation of carbonatotetramminecobalt(III) complexes by steady-state UV irradiation, which allowed for studies of product yields in the pH 5.0-10.0 range. The yield of 5'-d(CCATCG*CT*ACC) at pH 10.0 is approximately 45 times greater than at pH 5.0; this is consistent with the proposed mechanism, which requires N3(H) thymine proton dissociation followed by nucleophilic addition to the C8 guanine radical.
Crean
Conor
C
Chemistry Department, New York University, 31 Washington Place, New York, NY 10003-5180, USA.
Lee
Young Ae
YA
Yun
Byeong Hwa
BH
Geacintov
Nicholas E
NE
Shafirovich
Vladimir
V
D000042:Absorption; D001483:Base Sequence; D002254:Carbonates / Q000737:chemistry*; D003035:Cobalt / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D010782:Photolysis; D013057:Spectrum Analysis; D013431:Sulfates / Q000737:chemistry
D002254:Carbonates; D003432:Cross-Linking Reagents; D009841:Oligonucleotides; D009942:Organometallic Compounds; D013431:Sulfates; D003035:Cobalt; D006147:Guanine; D004247:DNA