Copper(II) complexes of piperazine based ligand: Synthesis, crystal structure, protein binding and evaluation of anti-cancerous therapeutic potential

• Three new copper complexes were synthesized and characterized.
• Interaction of these compounds with bovine serum albumin (BSA) was performed.
• We characterize and assess the anti-proliferative properties of these three Cu(II) complexes in human breast cancer cells.
• All the results indicate potentiality of zwitterionic ligand based Cu(II) complexes in anti-metastatic therapy.

The reaction of tridentate Schiff base {2-[(2-piperazine-1-yl-ethylimino)-methyl]-phenol} ligand (HOPhL) with copper(II) salts resulted three new compounds (i) [Cu(HNL)(NO3)(H2O)](NO3) (1), (ii) [Cu(HNL)(N3)(ClO4)] (2) and (iii) [Cu2(HNL)(μ1,3-NCS)2](ClO4)2·2H2O (3) where the used ligand transforms to its zwitterionic form (HNL) during complexation. The complexes are characterized by elemental analysis, IR and UV–Vis spectroscopy and single crystal X-ray diffraction. The tridentate NNO donor ligand coordinates copper ion in square pyramidal environment where rest of coordination sites around Cu(II) are occupied by water, nitrate, azide or thiocyanate anion. In complexes 1 or 2 the presence of NO3− and N3− ions do not reveal any kind of aggregation reaction whereas in 3 binding of NCS− ions trigger the dimerization reaction. The interaction of these compounds with bovine serum albumin suggests a static quenching mechanism of fluorescence. The quenching constant, binding constant and number of binding sites are calculated using Stern–Volmer and Scatchard equation. The anti-proliferative and anti-migratory properties of these compounds are established in human breast cancer cells. The observed IC50 value by MTT assay is 30 μM after 6 h for the compounds 1–3 irrespective of their chemical structures. The findings indicate the anti-cancerous therapeutic potential of zwitterionic ligand based copper(II) complexes.

Systematic bio-macromolecular evolution of newly synthesized mononuclear and dinuclear copper(II) complexes of a zwitterionic Schiff base ligand has been carried out. The interaction between metal complexes and BSA in buffer solution studied by UV–Vis and fluorescence spectroscopic methods did suggest that these complexes have strong ability to quench the tryptophan fluorescence of BSA mainly through a static quenching process. All of them have displayed cytotoxic activity, anti-proliferative, anti-adhesive and anti-migratory against human breast cancer cell line.Figure optionsDownload as PowerPoint slide