Poster abstracts

Poster number 68 submitted by Sun Jeong Im

Calculations of pKa values for canonical nucleosides and nucleoside analogs

Sun Jeong Im (Department of Chemistry, Wayne State University), Evan L. Jones (Department of Chemistry, Wayne State University), Alan J. Mlotkowski (Department of Chemistry, Wayne State University), H. Bernhard Schlegel (Department of Chemistry, Wayne State University), Christine S. Chow (Department of Chemistry, Wayne State University)

Abstract:
Nucleosides play diverse structural and functional roles in biological systems. Understanding fundamental properties of the nucleosides is important for their applications as chemical probes of nucleic acid structure and function. As the nucleosides are tuned to modify their binding properties, their physical properties such the pKa values may also change. Unlike canonical nucleosides, modified nucleosides are often not well understood in terms of acid-base properties. Previously, theoretical pKa values of canonical and aza-/deaza-modified nucleobases were determined.1, 2 In this study, the theoretical pKa values for canonical nucleosides and nucleoside analogs such as antiviral compounds were calculated by using an ab initio quantum mechanical method and B3LYP density functional with 6-31+G(d,p) basis set along with an implicit-explicit solvation model. The results of these computations will be presented along with comparisons to known experimental pKa values. The ability to estimate theoretical pKa values will be beneficial for further development of modified nucleosides and their applications.

References:
1. 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. The Journal of Physical Chemistry A 2022, 126 (9), 1518-1529.
2. Mlotkowski, A. J.; Schlegel, H. B.; Chow, C. S., Calculated pKa Values for a Series of Aza- and Deaza-Modified Nucleobases. The journal of physical chemistry. A 2023, 127 (15), 3526-3534.

Keywords: pKa calculations, nucleosides, nucleoside analogs