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

Abstract

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 Å. 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 (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 . 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.

Keywords:

• Schiff-bases
• Zinc complexes
• Compartmental ligands
• DNA cleavage
• cytotoxicity

Acknowledgments

The authors wish to thank the University Grants Commission, New Delhi, [UGC Major Research Project, F. No. 34-308\2008 (SR) Dated: 31.12.2008 (DD)] for financial support. We also thank the Department of Science and Technology (DST), New Delhi, for providing single-crystal diffractometer facility at the Department of Chemistry, University of Calcutta, through DST–FIST program. We are also thankful to Dr (Mrs.) Krishna Das Saha, Indian Institute of Chemical Biology, for her help on MTT assays. The generous help of Mr. Bijan Pal, Research Scholar, Department of Chemistry, University of Calcutta, India, to determine the DNA binding constant is also duly acknowledged.