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

Abstract

Density functional theory method in combination with a continuum solvation model is used to understand the role of hydrogen bonding in theinteractions of tertiary nitrogen centers of guanine and adenine with monoaqua and diaqua NAMI-A. In the case of adenine, theinteraction of N3 with monoaqua NAMI-A is preferred over that of N7 and N1 whereas, N7 siteis themostpreferred siteover N3 and N1 in the diaqua ruthenium-adenine interaction. In the monoaqua and diaqua NAMI-A-guanine interactions, the N7 site is the mostpreferred 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 thebase pairs of GC and AT dinucleotides leads to thestructural deformation in the geometry of thebase pairs ofdinucleotides. Thediaqua NAMI-Aadducts induce more disruption in the base pairs as compared to monoaqua NAMI-Aadducts.whichsuggests 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.