Poster number 7 submitted by Alan Mlotkowski
Computationally determined pKa values of modified nucleobases: more than just a series of numbers
Alan J. Mlotkowski (Department of Chemistry, Wayne State University), Evan L. Jones (Department of Chemistry, Wayne State University), H. Bernhard Schlegel (Department of Chemistry, Wayne State University), Christine S. Chow (Department of Chemistry, Wayne State University)
Modifications play a role in fine tuning structure and function of RNA. Both natural and nonnatural modifications have been studied for their impact on RNA biology, but also used as chemical tools and building blocks for therapeutics. Despite a large amount of information about modifications being available, some details regarding their physical properties are still lacking. Nucleobases and their modifications contain one or more sites of protonation/deprotonation with unique pKa values. Experimentally, these values can be challenging to determine, particularly for cases in which multi-step syntheses of the modified nucleosides are required. In this study, we performed theoretical calculations to obtain the pKa values of a series of natural and nonnatural modified nucleobases. The calculated pKa values of modified nucleobases were compared to their unmodified counterparts to determine the impact of the added chemical functionalities. Differences in the pKa values between modified and unmodified nucleobases range from 0.1 to 9.1, with an average of 1.8. These nucleobase pKa values can provide insight into the structural and energetic impacts of modifications within a wide range of RNAs.
Jones, E. L.; Mlotkowski, A. J.; Hebert, S. P.; Schlegel, H. B.; Chow, C. S. Calculations of pKa Values for a Series of Naturally Occurring Modified Nucleobases. J. Phys. Chem. A 2022, 126, 1518–1529.
Keywords: Nucleobase, Modification, Structure