The addition of transition metal centers to organic compounds facilitates interesting changes in the qualities and functions of the original organic drugs, leading to the preparation of compounds known as metallotherapies. Cis-diamminedichloroplatinum (II) (cisplatin) is one such compound and is used as a chemotherapeutic agent. Unfortunately, cisplatin has unwanted side effects, so the search for an alternative is well underway. Investigators have studied the efficacy of gold transition metal complexes as alternatives to cisplatin, and it has been found in our laboratory that the parent organic ligands often have more enhanced anti-cancer activity than the corresponding gold (III) complexes. In order to determine if the organic ligands are the sole source of anti-tumor efficacy, new copper (II) complexes have been made to determine if changing the metal center has an impact on the anti-cancer activity. Four new complexes will be examined: 2-sec-butyl-1,10-phenanthroline-dichloro copper (II) {[mono-sec-butylphen) CuCl2}, 2,9-di-sec-butyl-1,10-phenanthroline dichloro-copper (II) {[di-sec-butylphen) CuCl2}, 2-n-butyl-1,10-phenanthroline-dichloro copper (II) {[mono-n-butylphen) CuCl2}, and 2,9-di-n-butyl-1,10-phenanthroline-dichloro copper (II) {[di-n-butylphen) CuCl2}. The complexes were synthesized by reacting mono and di-substituted 1,10-phenanthroline ligands with cupric chloride. These complexes have been characterized via elemental analysis, ultraviolet-visible spectroscopy, X-ray crystallography, and mass spectrometry. X-ray crystallographic studies indicate that the geometries of the complexes are distorted square pyramidal for the 5-coordinate species and distorted tetrahedral for the 4-coordinate species, and the mass spectrometry data indicate that each complex equilibrates between the monomeric and dimeric forms in solution. In-vitro SRB assays indicate these cupric compounds are more potent inhibitors of lung tumor cell growth than our previously reported gold(III) complexes. Testing with non-cancerous Human Foreskin Fibroblasts (HFF) imply selectivity for cancerous cells over healthy cells. Future studies will aim to provide a more detailed understanding of the dynamic structural interconversion as well as propose mechanisms of anticancer action that the cupric complexes may perform.

Synthesis and biological testing of cupric phenanthroline complexes: An alternative to cisplatin?

251st National Meeting (2016)

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