Mutual Relations between Substituent Effect, Hydrogen Bonding, and Aromaticity in Adenine-Uracil and Adenine-Adenine Base Pairs.

Paweł A Wieczorkiewicz,Halina Szatylowicz,Tadeusz M Krygowski

doi:10.3390/molecules25163688

Paweł A Wieczorkiewicz, Halina Szatylowicz + Show 1 more

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https://doi.org/10.3390/molecules25163688

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Abstract

The electronic structure of substituted molecules is governed, to a significant extent, by the substituent effect (SE). In this paper, SEs in selected nucleic acid base pairs (Watson-Crick, Hoogsteen, adenine-adenine) are analyzed, with special emphasis on their influence on intramolecular interactions, aromaticity, and base pair hydrogen bonding. Quantum chemistry methods—DFT calculations, the natural bond orbital (NBO) approach, the Harmonic Oscillator Model of Aromaticity (HOMA) index, the charge of the substituent active region (cSAR) model, and the quantum theory of atoms in molecules (QTAIM)—are used to compare SEs acting on adenine moiety and H-bonds from various substitution positions. Comparisons of classical SEs in adenine with those observed in para- and meta-substituted benzenes allow for the better interpretation of the obtained results. Hydrogen bond stability and its other characteristics (e.g., covalency) can be significantly changed as a result of the SE, and its consequences are dependent on the substitution position. These changes allow us to investigate specific relations between H-bond parameters, leading to conclusions concerning the nature of hydrogen bonding in adenine dimers—e.g., H-bonds formed by five-membered ring nitrogen acceptor atoms have an inferior, less pronounced covalent nature as compared to those formed by six-membered ring nitrogen. The energies of individual H-bonds (obtained by the NBO method) are analyzed and compared to those predicted by the Espinosa-Molins-Lecomte (EML) model. Moreover, both SE and H-bonds can significantly affect the aromaticity of adenine rings; long-distance SEs on π-electron delocalization are also documented.

Highlights

Fundamental biological importance makes DNA and RNA base pairs important and popular systems for quantum chemical calculations
The obtained values of the substituent effect descriptors and hydrogen bond strength parameters (EHB, dHB, ρBCP, δ(H,A), ∇2 ρBCP, Edef, ESM ) for the substituted WC and HG base pairs as well as the adenine dimers are presented in Tables S1–S7 (Supplementary Materials)
Adenine contains an amino group at the C6 position, which in base pairs is involved in the hydrogen bond, either through the interaction of NH· · · O or through N· · · HN, as shown in Figures 1 and 2

Summary

Introduction

Fundamental biological importance makes DNA and RNA base pairs important and popular systems for quantum chemical calculations. Various quantum chemical methods were used to investigate intermolecular interactions in Watson-Crick [10], non-canonical Hoogsteen [11], and adenine-uracil RNA base pairs, as well as in Molecules 2020, 25, 3688; doi:10.3390/molecules25163688 www.mdpi.com/journal/molecules. 2020, 25,quantum chemical methods were used to investigate intermolecular interactions in Watson-Crick [10], non-canonical Hoogsteen [11], and adenine-uracil RNA base pairs, as well as in mismatched adenine-adenine base pairs [4,5]. The substituent effects (SEs) on hydrogen bonding mismatched adenine-adenine pairs [4,5].modified. The substituent effects base (SEs)pairs on hydrogen bonding were most frequently studied base in structurally. The influence of substituents on the electronic structure of guanine-cytosine)

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