Interações entre Albumina Humana (HSA) e complexos nitrosilos de rutênio do tipo [RuII(tpy)(L)NO](PF6)3: avaliações espectroscópicas e modelagem molecular

Abstract

The nitric oxide (NO) acts in different physiological processes, from antimicrobial and antiparasitic activities, blood coagulation, blood pressure control, neurotransmission and antitumor action. Among all the physiological processes in which NO is possibly involved, the most developed research area is related to its vasodilatory action. Ruthenium nitrosyl complexes of the type [Ru(tpy)(BDQ)(NO]3+ (RuBDQ) and [Ru(tpy)(BD)(NO]3+ (RuBD) – where tpy = 2,2 ': 6', 2 ”-terpyridine; BDQ = 3,4-diaminobenzoic acid; and BD = o-phenylenediamine –, showed up potential candidates for exogenous NO donating agents and, consequently, potential prodrugs. In the meantime, studies have been proposed on the interactions of these NO donor complexes with biomolecules which are responsible for the storage, transport, metabolism and excretion of drugs such as human albumin (HSA). The studies to understand the interactions between HSA and nitrosyl ruthenium complexes were based on HSA fluorescence quenching experiments. The results showed that there is the interaction between SAH and both complexes via dynamic mechanism. The thermodynamic parameters for the HSA–RuBDQ system showed that the species in question interact via hydrophobic interactions, and those for the HSA–RuBD system indicated that the species interact via hydrogen bonds. The center to center distances between the Trp-214 residue and the RuBDQ and RuBD complexes, estimated by the FRET theory, are 3.38 and 3.01 nm, respectively. The HSA synchronous fluorescence quenching experiments demonstrated that there is interaction between HSA and both RuBDQ and RuBD complexes in a protein microenvironment near the amino acid residues of Tyr and Trp-214. Through studies based on molecular docking it was possible to propose that the interaction between HSA and both complexes occurs in a protein microenvironment near to the amino acid residues of Tyr-452 and Trp-214, corroborating the experimental results. Studies by molecular docking also showed that it is possible that both complexes are inserted in a protein microenvironment referring to the HSA Site I subdomain IIA.