Previous research in the Tyler and Connelly Labs has demonstrated that small copper complexes exhibit significant biological activity, including potent cytotoxicity. However, the mechanism behind this observed cytotoxicity remains unclear. It has been shown that these complexes interact with DNA in several ways, such as acting as effective artificial nucleases and binding directly to the double helix. Until now, the interaction with DNA has not been connected to the observed cytotoxicity. The current study employs several new approaches to determine whether there is a relationship between DNA perturbation, cleavage, and cell death. An in-depth analysis of circular dichroism has been conducted to reveal how the secondary structure of DNA is altered due to complex binding. Moreover, evaluating mitochondrial membrane potential in cancer cells provides insight into the involvement of the copper complexes in the observed cytotoxicity. These cellular studies aim to further elucidate the cellular interactions of small copper complexes and their potential mechanisms of inducing cell death. This report showcases the circular dichroism results of three new copper-containing complexes alongside ethidium bromide displacement studies and the initial findings from investigations into the mitochondrial-mediated apoptosis pathway as a possible mechanism of cell death.
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