Spectroscopic studies on interactions of the tetrakis(acetato)chloridodiruthenium(II,III) complex and the Ru₂(II,III)-NSAID-derived metallodrugs of ibuprofen and ketoprofen with human serum albumin

Abstract

Diruthenium paddlewheel-structured complexes bearing a Ru2(II,III) multiply bonded core show promising potential in medicinal chemistry. This work reports studies on the interactions of the tetrakis(acetato)chloridodiruthenium(II,III) complex (RuAc), [Ru2(μ-O2CCH3)4Cl], and the corresponding Ru2(II,III)-non-steroidal anti-inflammatory drug (NSAID) metallodrugs of the NSAIDs ibuprofen (RuIbp) and ketoprofen (RuKet) with the human serum albumin (HSA). Circular dichroism (CD) studies showed that the three Ru2 complexes interact with the HSA and induce conformational changes on the secondary structure of the protein. The reaction of the RuAc complex with the protein was monitored and the RuAc/HSA binding constant was estimated on the basis of electronic absorption spectroscopy data. Fluorescence emission spectroscopy studies were performed for all the Ru2 complex/HSA systems and the Stern–Volmer constants and the thermodynamic parameters were determined for the RuAc/HSA binding. Mass spectrometry data confirmed the presence of the Ru2 complexes in the protein phase after ultrafiltration. The studies suggest that the nature of the RuAc binding to the HSA is distinct from that of the derived RuIbp and RuKet metallodrugs. Electrostatic forces, accompanied by coordination of the metal to the amino acid side chains of the protein, seem to be the main forces acting in the RuAc/HSA binding, while non-covalent/hydrophobic forces might be predominant in the Ru2-NSAID metallodrug/protein interactions. The findings suggest that the HSA protein might be a potential carrier in the blood plasma for the Ru2(II,III)-NSAID metallodrugs.