Calculated pKa Values for a Series of Aza- and Deaza-Modified Nucleobases

A variety of synthetic modified nucleobases have been used to investigate the structure and function of RNA and DNA or act as enzyme inhibitors. A set of these modifications involves the addition or removal of a nitrogen atom in the ring. These aza and deaza modifications have garnered interest as useful biochemical tools, but information on some of their physical characteristics is lacking. In this study, the B3LYP density functional with the 6-31+G(d,p) basis set and an implicit–explicit solvent model was used to perform ab initio quantum mechanical studies to estimate pKa values of aza- and deaza-modified nucleobases. A comparison between theoretical and known experimental pKa values was carried out, and adjustment factors were applied to 57 pKa values in the purine and pyrimidine data sets.