Accurate micro- and macro- gas phase basicities of hydroxyl-radical-modified pyrimidines estimated by advanced quantum chemistry methods

Abstract

The gas phase basicities (GPB) of 16 hydroxyl-radical-derived analogues of model pyrimidine nucleosides were analysed at B3LYP/aug-cc-pVDZ and G3MP2B3 levels of theory. All possible tautomeric equilibriums of neutral and protonated forms of pyrimidine analogues were taken into account. The oxidation of pyrimidines usually reduces the GPB values with respect to canonical values. The only exception was observed in the case of 5,6-dihydroxycytidine, which is more basic than model cytidine if both macro- and micro-scopic measures of basicities are used for comparison. In addition, 6-hydroxycytidine is characterised more by the basic character of the O2 atom compared to the more basic centre of cytidine, despite the fact that the GPB values of both these compounds are almost identical. Although the B3LYP/aug-cc-pVDZ approach seems to be an accurate and robust method for GPB estimation, the microscopic protonation properties are much more sensitive to this method since the difference in energy between some tautomers is often less than 1 kcal/mol with method-dependent succession. In such cases, G3MP2B3 is recommended.