Water‐Soluble μ‐oxo triruthenium Compound of Biological Interest: H‐Bonds Network and Interaction with HSA
Bruno F. A. Pinheiro, Nathan C. Fernandes, Otávio Augusto Chaves, Javier Ellena, Mariana S. de Queiroz, Antônio Cláudio Tedesco, João Honorato, Sofia Nikolaou
Abstract
Abstract The water‐soluble compound [Ru 3 O(CH 3 COO) 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 NH 2 substituents of the ancillary ligands, methanol molecules, the Cl − counter‐ion, and a non‐conventional hydrogen bond with the neighboring 4‐ampy molecules′ π‐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 0 C and pH=7.4 (phosphate buffer), compound 1 shows moderate (K sv =2.4 10 4 M −1 ) and spontaneous (ΔG=−26.4 kJ mol −1 ) binding to human serum albumin (HSA) through ground‐state association, which involves formation of hydrogen bonds (ΔH=−35.7 kJ mol −1 and, ΔS=−29.8 J mol −1 K −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.