Organoselenium functionalized oxacycles as ligands in some trans-palladium(II) complexes: biological evaluation and interaction with small biomolecules

In this article, the biological evaluation and interaction of three selenium-based trans-palladium complexes (Pd–Se1, Pd–Se2, and Pd–Se3) with small biomolecules were performed. The UV–Vis kinetic studies on substitution reaction of synthesized complexes with selected biologically important N- and S-bonding ligands (L-Cys, GSH, L-Met, 5′-GMP, L-His) has emphasized greater affinity of sulphur-based ligands for complex-binding, while the general order of the reactivity was L-Cys > GSH > L-Met > 5′-GMP > L-His. The complex reactivity toward small biomolecules is influenced by ligand flexibility, i.e. the steric hindrances of their corresponding ligands near the coordination site (Se–Pd) during the substitution process. The in vitro cytotoxicity of the investigated complexes against colorectal carcinoma HCT-116 and healthy fibroblast MRC-5 cells exhibited moderate prooxidative and significant cytotoxic character against HCT-116 cells, while such effect on MRC-5 was much weaker. Antioxidant activity (DPPH assay) indicated that all three complexes and their ligands have significant antioxidant activity, with Pd–Se2 being significantly stronger than its ligand L2 or the other complexes. Molecular docking simulations on tyrosinase (Tyr) singled out Pd–Se1 as the most compatible to bind to the cavity of Tyr. At all concentrations, the tested compounds demonstrated genotoxic effects (comet assay) compared to negative control.