In order to use endogenous elevated tumor copper as a targeting mechanism for breast cancer therapy, it is necessary that the ligand under consideration be capable of reacting spontaneously with copper to form a new complex. Complex formation reactions, particularly those involving metal, can result in dramatic color changes and/or precipitate formation. To test the reactivity of CQ and PDTC with copper, 50 mM of each was added to a 50 mM solution of Basic Copper Chloride (WSDTY). The reaction of CQ and PDTC with copper, in DMSO, results in a dramatic color change, indicating a chemical reaction has occurred and a metal complex has formed. These results are consistent with previous publications showing that both CQ and PDTC are strong copper chelators. Therefore, these ligands may be capable of combining with endogenous tumor copper and forming a reactive complex.
The CQ-copper mixture has been further examined by the advanced photon source (APS) of Argonne National Laboratories. The result is consistent with formation of a new complex between CQ and copper in solution. Furthermore, samples of a PDTC-copper mixture will be analyzed by the APS to confirm complex formation and the resulting structure. The details of these studies will be presented in a future manuscript.
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