Water-Soluble μ-oxo triruthenium Compound of Biological Interest: H-Bonds Network and Interaction with HSA

Author(s)

Pinheiro, Bruno F. A. ; Fernandes, Nathan C. ; Chaves, Otavio A. ; Ellena, Javier A. ; De Queiroz, Mariana S. ; Tedesco, Antonio C. ; De Araujo-Neto, Joao H. ; Nikolaou, Sofia

• Document type: Journal article
• Source: European Journal of Inorganic Chemistry; v. 27, n. 13, p. 11-pg., 2024-04-10.

Abstract

The water-soluble compound [Ru3O(CH3COO)(6)(4-ampy)(3)]Cl (1, 4-ampy=4-aminopyridine) was evaluated in terms of its biologically relevant properties. Compound 1 participates in a hydrogen bonding network which includes the NH2 substituents of the ancillary ligands, methanol molecules, the Cl- counter-ion, and a non-conventional hydrogen bond with the neighboring 4-ampy molecules ' pi-cloud, as determined by X-ray measurements. One protonation equilibrium was observed at pH values below 2.3. Additionally, the compound exhibited a partition coefficient value of -0.86 (+/- 0.07), indicating that it is highly hydrophilic. At 37(degrees)C and pH=7.4 (phosphate buffer), compound 1 shows moderate (K-sv=2.4 10(4) M-1) and spontaneous (Delta G=-26.4 kJ mol(-1)) binding to human serum albumin (HSA) through ground-state association, which involves formation of hydrogen bonds (Delta H=-35.7 kJ mol(-1) and, Delta S=-29.8 J mol-K-1 (-1)). Molecular docking calculations support the formation of hydrogen bonds between 1 and HSA, and suggest subdomain IIA (site I), which contains the Trp-214 residue, as the primary interactive pocket, in agreement with the experimental static fluorescence quenching mechanism. Furthermore, a preliminary assay reveals that 1 has low cytotoxicity towards human glioblastoma U87-MG cells. (AU)

• FAPESP's process: 21/04876-4 - Studies on structure & activity of RuII / arene / mercaptoligants complexes against cancer
• Grantee: João Honorato de Araujo Neto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/04173-3 - Evaluation of the compound [Ru3O(CH3COO)6(4-ampy) 3]CH3COO as a potential candidate for metallopharmaceutical
• Grantee: Bruno Faria Abrantes Pinheiro
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 22/03478-8 - Reactivity of polynuclear ruthenium compounds with potential biological application
• Grantee: Sofia Nikolaou
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/14050-6 - Investigation of the acid-base chemistry and biological properties of water-soluble trinuclear ruthenium carboxylates
• Grantee: Bruno Faria Abrantes Pinheiro
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 23/07614-6 - Study of the interaction of the [Ru3O(CH3COO)6(THIQ)2(CH3OH)]PF6 complex with human serum albumin: the influence of lability and hydrophobicity on the development of ruthenium metallopharmaceuticals
• Grantee: Nathan Campos Fernandes
• Support Opportunities: Scholarships in Brazil - Scientific Initiation