Computational Approach to Unravel the Role of Hydrogen Bonding in the Interaction of NAMI‑A with DNA Nucleobases and Nucleotides

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Molecules, spectroscopy, kinetics, environment, & general theory, 2018-10, Vol.122 (42), p.8397-8411
• Main Authors: Das, Dharitri, Khan, Muntazir S, Barik, Gayatree, Avasare, Vidya, Pal, Sourav
• Format: Article
• Language: English
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/acs.jpca.7b12617

Density functional theory method in combination with a continuum solvation model is used to understand the role of hydrogen bonding in the interactions of tertiary nitrogen centers of guanine and adenine with monoaqua and diaqua NAMI-A. In the case of adenine, the interaction of N3 with monoaqua NAMI-A is preferred over that of N7 and N1 whereas, N7 site is the most preferred site over N3 and N1 in the diaqua ruthenium–adenine interaction. In the monoaqua and diaqua NAMI-A–guanine interactions, the N7 site is the most preferred site over the N3 site. Here, the strength and number of H-bonds play important roles in stabilizing intermediates and transition states involved in the interaction of NAMI-A and purine bases. Atoms in molecules and Becke surface analysis confirm that the interactions between monoaqua and diaqua NAMI-A with the base pairs of GC and AT dinucleotides leads to the structural deformation in the geometry of the base pairs of dinucleotides. The diaqua NAMI-A adducts induce more disruption in the base pairs as compared to monoaqua NAMI-A adducts. which suggests that diaqua NAMI-A could be a better anticancer agent than monoaqua NAMI-A. This study can be extended to envisage the potential applications of computational studies in the development of new drugs and targeted drug delivery systems.