The chemical nature of the 2'-substituent in the pentose-sugar dictates the pseudoaromatic character of the nucleobase (pKa) in DNA/RNA

Organic & Biomolecular Chemistry
Subhrangsu ChatterjeeJyoti Chattopadhyaya

Abstract

We here show that the pKa (error limit: 0.01 to 0.03 pKa unit) of a nucleobase in a nucleotide can be modulated by the chemical nature of the 2'-substituent at the sugar moiety. This has been evidenced by the measurement of nucleobase pKa in 47 different model nucleoside 3',5'-bis- and 3'-mono-ethylphosphates. The fact that the electronic character of each of the 2'-substituents (Fig. 1) alters the chemical shift of the H2' sugar proton, and also alters the pKa of the nucleobase in the nucleotides has been evidenced by a correlation plot of pKa of N3 of pyrimidine (T/C/U) or pKa of N7 of 9-guaninyl with the corresponding deltaH2' chemical shifts at the neutral pH, which shows linear correlation with high Pearson's correlation coefficients (R = 0.85-0.97). That this modulation of the pKa of the nucleobase by a 2'-substituent is a through-bond as well as through-space effect has been proven by ab initio determined pKa estimation. Interestingly, experimental pKas of nucleobases from NMR titration and the calculated pKas (by ab initio calculations utilizing closed shell HF 6-31G** basis set) are linearly correlated with R = 0.98. It has also been observed that the difference of ground and protonated/de-protonated HOMO orbital energ...Continue Reading

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Citations

Jul 21, 2011·Organic & Biomolecular Chemistry·José A MansoJulio Casado
Aug 9, 2020·Chemistry : a European Journal·Hoang-Ngoan LeAlain Burger
Jun 1, 2014·Physical Review Letters·Maren ReichlDieter Braun
May 1, 2010·Journal of the American Chemical Society·Tomohisa Sawada, Makoto Fujita

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