Molecular recognition between DNA and a copper-based anticancer complex

The aim of this work is to describe the specific recognition site between DNA and an anticancer copper complex by means of computational methods. Molecular dynamics were used to find the preferred site of binding between selected DNA chains and [Cu(2,2'-bipyridine)(acetylacetonate)(H(2)O)](+) (Cas). Full DFT optimizations of selected geometries extracted from simulations, followed by a topological analysis of electron density allowed us to define the specific interactions inside the recognition site. Cas links deoxyribose-phosphate by a coordination bond between metal and the phosphate group. There are several C-H···π, O···π(C) and O···π(N) interactions between the sugar group and the aromatic ligand of Cas. The results indicate that the adduct Cas-deoxyribose-phosphate may be an initial step toward the hydrolysis of DNA chains. Overall, this study provides insights into the initial step of the action mechanism of copper complexes as apoptosis-inducing agents and provides guidelines for the design of this kind of drugs.