Detailed mechanism of a DNA/RNA nucleobase substituting bridging ligand in diruthenium(ii,iii) and dirhodium(ii,ii) tetraacetato paddlewheel complexes: protonation of the leaving acetate is crucial

Paddlewheel complexes of bimetallic scaffolds are emerging metallic agents in the bioinorganic chemistry landscape. In the most commonly employed construct, these complexes are decorated by the carboxylate moiety, prompting their possible deployment to target either protein or nucleic acid targets. In this study, density functional investigation was performed to assess viable mechanistic routes for the substitution of one acetate ligand with one chelating purine, i.e. adenine or guanine, in diruthenium and dirhodium tetraacetate paddlewheel complexes. This study evidenced the relevant stages of the process at an atomistic scale of resolution and provided for the encompassed rate-determining chemical events. Therefore, calculations indicated that acetate decomplexation as well as the concomitant nucleobase bridging proceeded gradually via a multistep process that included protonation of the leaving acetate. The present picture of the mechanism is envisioned to be relevant to the design and interpretation of experiments focused on the reaction of diruthenium and/or dirhodium tetracarboxylate complexes with nucleobases and eventuating in the formation of either nucleobase bridged-complexes or in the dismantling of the bimetallic construct.