Mechanisms and structure-activity relationships of cobalt complexes-bovine serum albumin interactions

Three forms of cobalt, including cobalt chloride (CoCl 2 ), cobalt (II) acetylacetonate (Co(acac) 2 ) and cobalt (III) acetylacetonate (Co(acac) 3 ), were evaluated for their interactions with bovine serum albumin (BSA). Results reveal distinct binding mechanisms among cobalt compounds. CoCl 2 bound to negatively charged residues on the BSA surface via electrostatic interactions, exhibiting weak binding affinity ( K b  = (0.09–2.3) × 10 3  L·mol −1 ) and high temperature sensitivity (Δ G ° decreased significantly with increasing temperature). Co(acac) 2 partially penetrated the hydrophobic microenvironment of BSA through its hydrophobic ligands, achieving moderate binding strength ( K b  = (3.24–6.84) × 10 3  L·mol −1 ) with synergistic contributions from hydrogen bonding and van der Waals forces (Δ H ° = −48.80 ± 0.01 kJ·mol −1 , Δ S ° = −89.87 ± 0.01 J·mol −1 ·K −1 ). Co(acac) 3 demonstrated the strongest binding capacity ( K b  = (9.27–32.3) × 10 4  L·mol −1 ), attributed to multimodal interactions (hydrophobic embedding, coordination bonds, and hydrogen bonding) facilitated by its three hydrophobic ligands. The binding affinity of cobalt compounds to BSA increases with ligand complexity and hydrophobicity (CoCl 2  → Co(acac) 2  → Co(acac) 3 ). UV–Vis, three-dimensional fluorescence, and circular dichroism spectra further revealed that organic acetylacetonate ligands enhanced BSA structure perturbation, intensifying with ligand number. Co(acac) 3 induced significant conformational changes in BSA (19.98 % reduction in α -helix content), increased microenvironmental polarity (5 nm fluorescence redshift), and optimized spectral overlap between donor and acceptor (34.6 % increase in J value) by shortening the binding distance ( r  = 2.83 ± 0.01 nm), thereby elevating energy transfer efficiency ( E  = 34.65 %). This study provides molecular-level insights into the biocompatibility and toxicity assessment of cobalt-based compounds.