Spectroscopic studies on interactions of the tetrakis(acetato) chloridodiruthenium(II,III) complex and the Ru-2(II,III)-NSAID-derived metallodrugs of ibuprofen and ketoprofen with human serum albumin

Author(s)

Silva Ribeiro Santos, Rodrigo Luis ; Fernandes Sanches, Rute Nazare ; Silva, Denise De Oliveira

• Document type: Journal article
• Source: Journal of Coordination Chemistry; v. 68, n. 17-18, p. 20-pg., 2015-01-01.

Abstract

Diruthenium paddlewheel-structured complexes bearing a Ru-2(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), [Ru-2(mu-O2CCH3)(4)Cl], and the corresponding Ru-2(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 Ru-2 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 Ru-2 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 Ru-2-NSAID metallodrug/protein interactions. The findings suggest that the HSA protein might be a potential carrier in the blood plasma for the Ru-2(II,III)-NSAID metallodrugs. (AU)

• FAPESP's process: 11/06592-1 - Anti-inflammatory and antitumor metallotherapeutic drugs: reactivity, properties and interactions with biocompatible hosts
• Grantee: Denise de Oliveira Silva
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/23047-5 - Anticancer metallodrugs of ruthenium containing bioactive ligands: synthesis, interaction with biomolecules and preparation of biocompatible nanoparticle drug delivery systems
• Grantee: Denise de Oliveira Silva
• Support Opportunities: Regular Research Grants