8-Hydroxy-2'-deoxyguanosine formation during the catalytic oxidation of hydrazines in the presence of 2'-deoxyguanosine.
The reaction of 2'-deoxyguanosine (1), substituted hydrazines (Hy) and oxygen, in the presence of Cu(II) as catalyst, yields 8-hydroxy-2'-deoxyguanosine (2). The rate of formation of 2 was found to be dependent upon the oxidation potential of the Hy and on structural factors of the Hy. The conversion of 1 to 2 under these conditions suggested that a Haber-Weiss/Fenton type of process was involved with Hy acting as reductant. However, the dependence of the rate of the conversion of 1 to 2 upon the structure of Hy suggested that the Hy substrates studied may be more directly involved in the process than that of a reducing agent. Additional studies of this reaction system, including the oxygen consumption, radical trapping studies and direct ESR measurements suggest that the conversion of 1 to 2, under the conditions used, involves the intermediacy of complex composed of the metal catalyst, 1, Hy and oxygen. The rate data for the conversion of 1 to 2 appear to be correlated with the carcinogenicity of Hy and therefore 2 may be an important DNA adduct in the carcinogenesis of hydrazines.
Gannett
P M
PM
School of Pharmacy, West Virginia University, Morgantown 26506.
Dalal
N S
NS
Shi
X L
XL
Toth
B
B
D000080242:8-Hydroxy-2'-Deoxyguanosine; D002851:Chromatography, High Pressure Liquid; D003497:Cyclic N-Oxides; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006834:Hydrazines / Q000737:chemistry*; D006878:Hydroxides; D017665:Hydroxyl Radical; D009682:Magnetic Resonance Spectroscopy; D013113:Spin Labels
D003497:Cyclic N-Oxides; D005609:Free Radicals; D006834:Hydrazines; D006878:Hydroxides; D013113:Spin Labels; D017665:Hydroxyl Radical; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine