Residue interactions affecting the deprotonation of internal guanine moieties in oligodeoxyribonucleotides, calculated by FMO methods.

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.