Metal complexes of malonie acid (metal Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Ag(I)) were prepared and only the Ag(I) complex inhibited the growth of Candida albicans. Malonate complexes incorporating the chelating 1,10-phenanthroline (1,10-phen) ligand showed a range of activities: good (Mn(II), Cu(lI), Ag(I)); moderate (Zn(II)); poor (Co(II), Ni(II)). Metal-free 1,10-phen and Ag(CH3CO2) were also highly active. The metal-free non-chelating ligands 1,7-phenanthroline and 4,7-phenanthroline were inactive and the Cu(II), Mn(II) and Zn(II) complexs of 1,7-phen displayed only marginal activity. Whereas the Cu(II) malonate/1,10-phen complex induces significant cellular oxidative stress the Zn(II) analogue does not.

Three, structurally characterised, bis-phen Cu(II) complexes of the phthalate isomers display rapid, low micromolar in vitro cytotoxicity against a range of epithelial tumour cells. The complexes induce relaxation of supercoiled plasmid DNA in the absence of external reducing agents and display efficient CT-DNA, Poly[d(A-T)](2) and Poly[d(G-C)](2) binding.

The complexes [Cu(salH)(2)(H(2)O)] (1), [Cu(dipsH)(2)(H(2)O)] (2), {Cu(3-MeOsal)(H(2)O)(0.75)}(n) (3), [Cu(dipsH)(2)(BZDH)(2)] (4), [Cu(dipsH)(2)(2-MeOHBZDH)(2)]·EtOH (5), [Cu(sal)(phen)] (6), [Cu(dips)(phen)]·H(2)O (7), and [Cu(3-MeOsal)(phen)]·H(2)O (8) (salH(2) = salicylic acid; dipsH(2) = 3,5-diisopropylsalicylic acid; 3-MeOsalH(2) = 3-methoxysalicylic acid; BZDH = benzimidazole; 2-MeOHBZDH = 2 methanolbenzimidazole and phen =1,10-phenanthroline) were prepared and characterized. Structures of 4, 5, and 8 were determined by X-ray crystallography. Compounds 1-8 are potent superoxide dismutase mimetics, and they are inactive as inhibitors of COX-2 activity. Compounds 1, 4, and 5 exhibit moderate inhibition of COX-1. Complexes 6-8 display rapid micromolar cytotoxicity against cisplatin sensitive (breast (MCF-7), prostate (DU145), and colon (HT29)) and cisplatin resistant (ovarian (SK-OV-3)) cell lines compared to 1-5, and they exhibit potent in vitro DNA binding and cleavage capabilities.

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Dinuclear Cu2+ and Mn 2+ bis-phenanthroline octanedioate compounds exhibit rapid, unprecedented nano and picomolar in vitro cytotoxicity against human-derived colorectal cancer lines (HT29, SW480 and SW620) and are less cytotoxic toward non-cancerous normal human keratinocyte cells (HaCaT). Both complexes displayed greater in vivo drug tolerance compared to cisplatin when examined using the insect Galleria mellonella. The compounds are potent generators of intracellular reactive oxygen species within HT29 cells, display avid DNA binding and induce O 2 -dependent cleavage of supercoiled pUC18 DNA. The Cu 2+ complex was found to display self-cleaving nuclease activity and a mechanism of deoxyribose C-H bond activation is proposed, based on interactions with the superoxide anion and hydrogen peroxide along with DNA cleavage observations under anaerobic conditions and with an excess of the metal chelator EDTA.