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.

Calculations of pKa Values for a Series of Naturally Occurring Modified Nucleobases.

Modified nucleobases are found in functionally important regions of RNA and are often responsible for essential structural roles. Many of these nucleobase modifications are dynamically regulated in nature, with each modification having a different biological role in RNA. Despite the high abundance of modifications, many of their characteristics are still poorly understood. One important property of a nucleobase is its pKa value, which has been widely studied for unmodified nucleobases, but not for the modified versions. In this study, the pKa values of modified nucleobases were determined by performing ab initio quantum mechanical calculations using a B3LYP density functional with the 6-31+G(d,p) basis set and a combination of implicit-explicit solvation systems. This method, which was previously employed to determine the pKa values of unmodified nucleobases, is applicable to a variety of modified nucleobases. Comparisons of the pKa values of modified nucleobases give insight into their structural and energetic impacts within nucleic acids.