Theoretical Characterization of the H-Bonding and Stacking Potential of Two Nonstandard Nucleobases Expanding the Genetic Alphabet

The Journal of Physical Chemistry. B
Mohit ChawlaLuigi Cavallo

Abstract

We report a quantum chemical characterization of the non-natural (synthetic) H-bonded base pair formed by 6-amino-5-nitro-2(1H)-pyridone (Z) and 2-aminoimidazo[1,2-a]-1,3,5-triazin-4(8H)-one (P). The Z:P base pair, orthogonal to the classical G:C base pair, has been introduced into DNA molecules to expand the genetic code. Our results indicate that the Z:P base pair closely mimics the G:C base pair in terms of both structure and stability. To clarify the role of the NO2 group on the C5 position of the Z base, we compared the stability of the Z:P base pair with that of base pairs having different functional groups at the C5 position of Z. Our results indicate that the electron-donating/-withdrawing properties of the group on C5 have a clear impact on the stability of the Z:P base pair, with the strong electron-withdrawing nitro group achieving the largest stabilizing effect on the H-bonding interaction and the strong electron-donating NH2 group destabilizing the Z:P pair by almost 4 kcal/mol. Finally, our gas-phase and in-water calculations confirm that the Z-nitro group reinforces the stacking interaction with its adjacent purine or pyrimidine ring.

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Citations

Oct 28, 2019·Protein Science : a Publication of the Protein Society·Zahra OuarayNigel G J Richards
Jan 19, 2018·Physical Chemistry Chemical Physics : PCCP·Mohit ChawlaLuigi Cavallo
Dec 6, 2016·Acta Crystallographica. Section C, Structural Chemistry·Mariko F MatsuuraSteven A Benner
Dec 18, 2020·Frontiers in Chemistry·Xixi CuiChangzhe Zhang
May 23, 2021·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Yu ZhaoQingtian Meng
May 24, 2019·Journal of the American Chemical Society·Giacomo PadroniGlenn A Burley

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