Dinuclear zinc(II) complexes with compartmental ligands: syntheses, structures, and bioactivities as artificial nuclease

Four water-soluble dinuclear Zn(II) complexes (1-4) of compartmental ligand L = 2,6-bis(R-iminomethyl)-4-R'-phenolate (where R = N-ethylpiperidine or R = N-ethylpyrrolidine, R' = methyl or tert-butyl) have been synthesized, characterized, and their DNA cleavage activity and cytotoxicity toward HepG2 cancerous cells are evaluated. The dinuclear complexes are formed by a pentadentate-substituted phenolate ligand chelating the metal ions separated by ca 3.27 angstrom. Each metal is a distorted trigonal bipyramid, completing the coordination sphere through acetate. The X-ray structural determination of 2 shows that the complex is counterbalanced by half Zn(SCN)(4)(2-) (formulation [Zn2L2(CH3CO2)(2)][(Zn(SCN)(4)](0.5)), while in 1 and 3 two crystallographically-independent complexes are present in the unit cell with a Zn(SCN)(4)(2-). Among the four complexes only the 4-tert-butyl-phenolato derivatives (3 and 4) show DNA cleavage activity in in-vivo conditions and appear to be promising toward metal complexes to be used as anticancer agents. The cytotoxicity of the complexes, investigated through MTT assay, suggests that 4 is a better choice as artificial nuclease.