Gas-phase thermochemical properties of the damaged base O 6-methylguanine versus adenine and guanine

Anna Zhachkina, Min Liu, Xuejun Sun, F. Sedinam Amegayibor, Jeehiun K. Lee

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43 Scopus citations


(Chemical Equation Presented) The gas phase acidity (ΔH acid and ΔGacid) and proton affinity (PA, and gas phase basicity (GB)) of adenine, guanine, and O6-methylguanine (OMG) have been examined using both theoretical (B3LYP/6-31+G*) and experimental (bracketing, Cooks kinetic) methods. We previously measured the acidity of adenine using bracketingmethods; hereinwemeasure the acidity of adenine by the Cooks kineticmethod (ΔHacid= 335 ± 3 kcal mol -1; ΔGacid=329 ± 3 kcalmol-1). We also measured the PA/GB of adenine using both bracketing and Cooks methods (PA = 224 and 225 kcal mol-1;GB = 216 and 217 kcal mol-1). Guanine is calculated to have several stable tautomers in the gas phase, in contrast to in solution, where the canonical tautomer predominates. Experimental measurements of gas phase guanine properties are difficult due to its nonvolatility; using electrospray and the Cooks kineticmethod, we are able tomeasure a ΔHacid of 335 ± 3 kcal mol-1 (ΔGacid=328 ± 3 kcal mol-1). The proton affinity is 227 ± 3 kcal mol-1 (GB=219 ± 3 kcal mol-1). Comparison of these values to calculations indicates that we may have a mixture of the keto and enol tautomers under our conditions in the gas phase, although it is also possible that we only have the canonical form since in the Cooks method, we form the proton-bound dimers via electrospray of an aqueous solution, which should favor guanine in the canonical form. We also examined O 6-methylguanine (OMG), a highly mutagenic damaged base that arises from the alkylation of guanine. Our calculations indicate that OMG may exist as both the "N9" (canonical) and "N7" (proton on N7 rather than N9) tautomers in the gas phase, as both are calculated to be within 3 kcal mol-1 in energy. We have bracketed the acidity and proton affinity of OMG, which were previously unknown. Themore acidic site of OMG has a ΔHacid value of 338 ± 3 kcal mol-1 (ΔGacid=331 ± 3 kcal mol-1). We have also bracketed the less acidic site (ΔHacid=362 ± 3 kcal mol-1, ΔGacid=355 ± 3 kcal mol-1) and the PA (229 ± 4 kcal mol-1 (GB = 222 ± 4 kcal mol-1)). Weconfirmed these results through Cooks kinetic method measurements as well. Our ultimate goal is to understand the intrinsic reactivity of nucleobases; gas phase acidic and basic properties are of interest for chemical reasons and also possibly for biological purposes, since biologicalmedia can be quite nonpolar. We find that OMG is considerably less acidic at N9 than adenine and guanine and less basic at O6 than guanine; the biological implications of these differences are discussed.

Original languageEnglish (US)
Pages (from-to)7429-7440
Number of pages12
JournalJournal of Organic Chemistry
Issue number19
StatePublished - Oct 2 2009

All Science Journal Classification (ASJC) codes

  • Organic Chemistry


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