Water‐soluble μ‐oxo triruthenium compound of biological interest: H‐bonds network and interaction with HSA

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.