Copper(II) and Palladium(II) Complexes with Cytotoxic and Antibacterial Activity

The synthesis of eight square pyramidal copper complexes with general structure [Cu(I-L)(A(L)) H2O](2+), where I-L represents various methylated 1,10-phenanthrolines, and A(L) represents either 1S, 2S- or 1R,2R-diaminocyclohexane, is reported, with the complexes synthesised as both the perchlorate and chloride salts. The crystal structures of [Cu(1,10-phenanthroline) (1S, 2S- diaminocyclohexane](ClO4)(2)center dot H(2)Oand [Cu(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane](ClO4)(2)center dot 1.5H(2)O are reported. Four square planar palladium complexes with general structure [Pd(I-L)(A(L))]Cl-2 have also been synthesised. These complexes were synthesised in order to investigate the structure-activity relationship against both cancer cell lines and bacterial cultures. The copper complexes display anticancer activity similar to cisplatin and 1,10-phenanthroline (phen) in the L1210 murine leukaemia cell line. Methylation of the phen increased the copper complex cytotoxicity by approximately four-fold, compared with the non-methylated complex. No significant difference in activity was observed by altering the chirality of the diaminocyclohexane ligand. The copper complexes demonstrated antibacterial activity against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli; however, high levels of toxicity (30-60% of death) were observed in the nematode Caenorhabditis elegans. The copper complexes have also been shown to act as DNA nucleases, with the ability to cleave plasmid DNA in the presence of hydrogen peroxide. The palladium complexes all have half maximal inhibitory concentration (IC50) values of similar to 10 mu M in the L1210 cell line, with no significant difference in the cytotoxicity of any of the compounds tested. Minimal antibacterial activity of the palladium complexes was observed.