Lead(II)-Catalyzed Oxidation of Guanine in Solution Studied with Electrospray Ionization Mass Spectrometry.

Summary of "Lead(II)-Catalyzed Oxidation of Guanine in Solution Studied with Electrospray Ionization Mass Spectrometry."

The oxidation of guanine was investigated in water/methanol solution in the absence and presence of Pb(II) with a variable temperature reactor coupled to a tandem mass spectrometer that allowed signature ions of solution reagents and products to be monitored by electrospray ionization (ESI). Two different oxidizing agents were employed, one strong (peroxymonosulfuric acid) and one weaker (hydrogen peroxide). Peroxymonosulfuric acid was observed to oxidize guanine rapidly at room temperature, kapp > 10-2 s-1, both in the absence and presence of Pb(II) to produce spiroiminohydantoin. Guanine did not show measurable oxidation by hydrogen peroxide in the absence of Pb(II) at concentrations of H2O2 up to 1 M at temperatures up to 333 K (kapp < 3x10-8 s-1 at 298 K) but, in the presence of Pb(II), was observed to produce both 5-carboxamido-5-formamido-2-iminohydantoin, (2-Ih), and imidazolone (Iz) in the ratio of 2.3 ± 0.1 with a total rate enhancement of more than 4x103. The activation energy was measured to be 82 ± 11 kJ mol-1 and is more than 120 kJ mol-1 lower than that for the uncatalyzed oxidation with hydrogen peroxide measured to be at least 208 ± 26 kJ mol-1. An activation energy of 113 ± 9 kJ mol-1 has been reported by Bruskov et al. [Nucl. Acids Res. 2002, 30, 1354] for the heat-induced oxidation by hydrogen peroxide of guanine embedded as guanosine in DNA which leads to the production of 8-oxo-7,8-dihydro-guanine (8-oxo-G). The lead dication lowers the activation energy by activating the hydrogen peroxide oxidant, possibly by O-O bond activation, and by directing the oxidation, possibly through coordination to the functional groups adjacent to the carbon C5: the C6 carbonyl group and the N7 nitrogen. The coupling of tandem mass spectrometry (MS2) with a simple variable temperature reactor by ESI proved to be very effective for measuring reaction kinetics and activation energies in solution. Signature ions of both reagents and products, as well as the catalyst, could be identified and the data were acquired in real time. The technique should be suitable for exploring other chemical and biochemical reactions that occur on similar timescales (minutes to hours).

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This article was published in the following journal.

Name: The journal of physical chemistry. B
ISSN: 1520-5207
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• PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22946584
• DOI: http://dx.doi.org/10.1021/jp302720z