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

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' 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 370C and pH = 7.4 (phosphate buffer), compound 1 shows moderate (Ksv = 2.4 104 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.