Exploring the structure of a ruthenium acetate cluster for biological purposes

Author(s)

Silva, Camila F. N. ^[1] ; Barbosa Ramos, Loyanne Carla ^[2] ; Rohrabaugh, Thomas N. ^[3] ; Vandevord, Jessica M. ^[3] ; da Silva, Roberto Santana ^[2] ; Turro, Claudia ^[3] ; Nikolaou, Sofia ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 - USA

• Document type: Journal article
• Source: Inorganic Chemistry Communications; v. 114, APR 2020.
• Web of Science Citations: 0

Abstract

This work evaluates the cytotoxicity of {[}Ru-3(mu(3)-O)(mu-OAc)(5)[mu-eta(1)(C),eta(2)(N,N)-phen](Py)(2)](PF6 ) (1), a triruthenium acetate cluster combined with an ortho-metallated 1,10-phenanthroline (phen) ligand, along with its interactions with biomolecules. In vitro cytotoxicity tests against the B16F10 (murine melanoma) and L929 (fibroblast) cell lines showed that 1 decreased cancer cell viability by 50% at 25 mu M, while it requires 50 mu M of free phen ligand to achieve the same effect. Importantly, 1 is not active against non-tumor cell model L929 up to 100 pM. Spectrophotometric titrations suggest that 1 and DNA interacted weakly through electrostatic attraction and semi-intercalation. Despite the presence of a planar and aromatic ligand, relative viscosity measurements are not consistent with the DNA intercalation of 1, presumably due to the small size of phenanthroline. The proteinbinding ability of compound 1 was evaluated using human serum albumin (HSA) as a model and monitored by spectroscopic techniques, including steady-state emission and absorption, time-resolved luminescence, and circular dichroism, CD. Compound 1 quenches the HSA emission efficiently (K-ap = 4.72 x 10(8) M-1, 298 K) mostly by static quenching, consistent with its relatively strong binding to HSA (K-b = 3.70 x 10 6 M-1, 298 K). Analysis of AH and AS values (604 kJ/mol and 2162 J/mol K, respectively) suggest the contribution of hydrophobic interactions. CD measurements demonstrated that the protein a-helical structure decreased in the presence of I, indicating a partial conformation change of HSA. Although the interaction of 1 with DNA is weak, its binding to the model protein HSA is strong, such that the cytotoxicity of the complex may be attributed to protein-complex interactions. This work provides a framework to design new triruthenium acetates to achieve stronger and more selective binding to biomolecules. Importantly, the selective activity of 1 towards a cancer cell line, while remaining inactive against healthy cells, represents a critical finding for the design of new cancer therapeutics based on triruthenium acetate clusters. (AU)

• FAPESP's process: 17/15202-9 - Photochemical research and systematic in vitro study of the interaction mechanisms in novel trinuclear ruthenium complexes with DNA using different techniques
• Grantee: Camila Fontes Neves da Silva
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 14/25561-8 - Trinuclear ruthenium carboxylates with functional ligands CO, NO and intercalators: chemical study and interactions with biomolecules target
• Grantee: Camila Fontes Neves da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/18060-3 - Use of inorganic supramolecular structures for the development of functional molecules and controlled release of bioactive species
• Grantee: Sofia Nikolaou
• Support Opportunities: Regular Research Grants