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

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.