A refreshing approach to understanding the action on DNA of vanadium (IV) and (V) complexes derived from the anticancer VCp2Cl2

A computational study based on derivatives of the anticancer ${\mathrm{VCp}}_2{\mathrm{Cl}}_2$ compound and their interaction with representative models of deoxyribonucleic acid (DNA) is presented. The derivatives were obtained by substituting the cyclopentadienes of ${\mathrm{VCp}}_2{\mathrm{Cl}}_2$ with $H_{2}O$, ${\mathrm{NH}}_3$, ${\mathrm{OH}}^{-}$, ${\mathrm{Cl}}^{-}$, $O^{2-}$ and $C_2{O}_4^{2-}$ ligands. The oxidation states IV and V of vanadium were considered, so a total of 20 derivative complexes are included. The complexes interactions with DNA were studied using two different models, the first model considers the interactions of the complexes with the pair Guanine-Cytosine (G-C) and the second involves the interaction of the complexes with adjacent pairs, that is, d(GG). This study compares methodologies based on density functional theory with coupled cluster like calculations (DLPNO-CCSD(T)), the gold standard of electronic structure methods. Furthermore, the change in the electron density of the hydrogen bonds that keep bonded the G-C pair and d(GG) pairs, due to the presence of vanadium (IV) and (V) complexes is rationalize. To this aim, quantities obtained from the topology of the electron densities are inspected, particularly the value of the electron density at the hydrogen bond critical points. The approach allowed to identify vanadium complexes that lead to significant changes in the hydrogen bonds indicated above, a key aspect in the understanding, development, and proposal of mechanisms of action between metal complexes and DNA.