The connection between proton-coupled electron transfer reactions in DNA and the formation of oxidatively generated guanine oxidation products is not well understood.  The one-electron oxidation of guanine in DNA gives rise to the guanine radical cation, G.+.  It has been postulated that the hydration of  G.+, followed by a re-arrangement, leads to the formation of 8-oxo-7,8-dihydroguanine (8-oxoG). However, it has also been shown that the deprotonation product, the neutral radical G(-H).  in DNA is formed on microsecond to sub-microsecond time scales, and that this radical embedded in oligonucleotides has a long lifetime in aqueous solutions (up to tenths of seconds). The G(-H).  radical is not a good substrate for hydration and it is not clear whether  G(-H).  plays any role in the formation of 8-oxo-G.  This is clearly shown from the pH dependence of 8-oxo-G formation in the case of the nucleoside dG as a function of pH.  In the case of oligonucleotides, the kinetics of decay of guanine radicals and 8-oxo-G formation depends strongly on the DNA secondary structure.  In double-stranded DNA guanine radicals retain radical cation character by sharing the N1-proton with the N3-site of cytosine. This proton sharing allows for the hydration of guanine radical cations by formation of 8-oxoG.  By contrast, in single-stranded DNA, deprotonation of radical cations occurs via the irreversible escape of the proton into the aqueous phase, forming the G(-H).  radical, thus diminishing the hydration and 8-oxo-G formation.  Supported by NIEHS Grant RO1 ES011589.

Proton-coupled electron/hole transfer in DNA damage induced by one-electron oxidation of guanine

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.