In the course of an ongoing project aimed at finding alternatives to the anticancer drug cis-diamminedichloroplatinum(II) (cisplatin), our lab has begun to investigate the potential therapeutic efficacy of copper (II) complexes possessing alky-substituted polypyridyl ligands. Eight complexes in which the copper(II) center is coordinated by a single polypyridyl ligand were synthesized and characterized: [(mono-sec-butylphen) CuCl2], [(di-sec-butylphen) CuCl2], [(mono-n-butylphen) CuCl2], [(di-n-butylphen) CuCl2], [(di-methylphen) CuCl2], [(4,4’-di-methylbipy) CuCl2], [(6,6’-di-methylbipy) CuCl2], and [(mono-sec-butylbipy) CuCl2] (phen = 1,10-phenanthroline; bipy = 2,2’-bipyridine). Six of these complexes were structurally characterized via X-ray crystallography, and these analyses indicate the complexes adopt distorted square pyramidal or distorted tetrahedral geometries. Complexes in which the copper(II) center is coordinated by two polypyridyl ligands were also synthesized and characterized; [(4,4’-di-methylbipy)2Cu][NO3]2 and [(6,6’-di-methylbipy)2Cu][NO3]2. These bis-coordinated complexes were structurally characterized via X-ray crystallography and found to possess distorted tetrahedral geometries in which the copper(II) centers are coordinated by the bipy ligands and the nitrate ions exist as outer sphere counterions. All of the reported copper(II) complexes were tested for in-vitro anticancer activity against human-derived lung cancer cells and murine glioma cells, as well as non-cancerous human foreskin fibroblast cells. These studies revealed this class of compounds generally exhibits quite remarkable antitumor efficacy, however the cytotoxic activity of the copper-based drugs varies significantly with the position of the alkyl-substituent on the polypyridyl ligand. Despite the fact the copper(II) complexes reported here were found to significantly inhibit tumor cell growth, these compounds did not display the same cytotoxic properties against non-cancerous cells. These results suggest this class of metal-based drugs warrant further investigation as potential anticancer agents.

Synthesis, characterization, and in-vitro antitumor activity of copper(II) complexes possessing alky-substituted polypyridyl ligands

253rd National Meeting (2017)

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