Abstract
The effect of vicinal molecular groups on the intrinsic acidity of a central guanine residue in short single-stranded DNA models and the potentials exerted by the backbone and the nucleobases on the leaving proton were determined by the fragment molecular orbital (FMO) method, in terms of quantum descriptors (QDs) and pair interaction interfragment decomposition analysis (PIEDA). The acidity of the central guanine moiety decreased with increasing oligonucleotide length, in response to changes by less than 1 eV in the ionization potential, global softness, electrophilicity index, and electronegativity descriptors. The differences in these descriptors were majorly interpreted in terms of the electrostatic influence of the negative charges residing on the backbone of the molecule. Additionally, this electric-field effect was determined explicitly for the displacement of the test hydronium ion to a distance of 250 Å from its original position, resulting in good agreement with calculations of the variation in Gibbs free energies, obtained from physical experiments conducted on the identical oligonucleotide sequences. The reported results are useful for biophysical applications of deoxyriboligonucleotides containing guanine residues in order to induce local negative charges at specific positions in the DNA chain.
Highlights
Under physiological conditions, DNA molecules are long polyanionic chains, due to the negative charges residing on the internucleotidic phosphate groups
In RNA trinucleotides modeled by the density functional theory (DFT) algorithm, it was found that electrostatic interactions between the sugar-phosphate backbone and the base have the largest effect, rather than the traditionally studied interbase stacking [6]
This geometrical difference leads to a higher linear density of negative charges in the backbone of the A-rich heptanucleotide, strengthening the influence of the electric field produced by the phosphate groups on the N1-H of the central guanine residue, making the withdrawal of the proton to the solvent more difficult
Summary
DNA molecules are long polyanionic chains, due to the negative charges residing on the internucleotidic phosphate groups. Regarding acid/base ionization, electrostatic considerations dictate that the formation of a new local negative charge on a nucleobase should be more difficult in the polynucleotidic context than in the simple nucleoside, whereas for the installation of a new positive charge the reverse should be true. The structure and properties of DNA have been widely studied over the past decades, due to its central role in biology In this regard, semi- and empirical methods and molecular mechanics (MM) approaches have been widely used to study the molecular interactions between nucleic acids and other molecules [3, 4]. In the case of base-to-base interactions in single chains of DNA of different sizes, the delocalization of orbitals arises in spite of strong stacking interactions [9]
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