Reduction Potential of RuIII-Based Complexes with Potential Antitumor Activity and Thermodynamics of their Hydrolysis Reactions and Interactions with Possible Biological Targets: a Theoretical Investigation

• Autor(a) principal: Pereira,Eufrásia S.
• Data de Publicação: 2019
• Outros Autores: Chagas,Marcelo A., Rocha,Willian R.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532019000300571
• topic: density functional theory calculations; ruthenium-based metallodrugs; reduction potential; competitive biological reactions; solvent effects; electronic structure calculations

In this article density functional theory (DFT)-based calculations were employed to investigate the electrochemistry of the antitumor ruthenium complexes trans-tetrachloro(dimethylsulfoxide)imidazole ruthenate(III) (NAMI-A) and trans-[tetrachlorobis(1.-indazole)ruthenate(III)] (KP1019), their hydrolysis products as well as their interactions with biological S-donors and N-donors targets as cysteine, glutathione and guanine nucleobase. The compounds exhibit different electrochemical behavior upon hydrolysis. While the reduction potential of NAMI-A increases up to 0.8 V upon hydrolysis, the reduction potential of KP1019 remains almost constant after the first hydrolysis. NAMI-A and KP1019 complexes have thermodynamic preference to be reduced prior to undergoing hydrolysis and, strong preference to undergo successive hydrolysis instead of interacting with the S-donor and N-donor ligands. Interaction with S-donor ligands in the unprotonated form is highly unfavorable, with the free energy in solution (ΔGsol) ≥ 18 kcal mol-1. For both complexes, the interaction with the guanine and glutathione are of the same magnitude (ΔGsol ca. –0.6 kcal mol-1) meaning that these ligands can compete for binding to the metallodrug.