Dinuclear copper complexes: advances from bioinorganics to medicine – a review

Abstract The knowledge of the essential role of copper in the human body, especially in its involvement in various important metalloenzymes, such as cytochrome c oxidase, copper-zinc superoxide dismutase, tyrosinase, lysyl oxidase and other, has greatly stimulated research interest in copper coordination compounds from both chemical and medicinal perspectives. Dinuclear copper complexes, in particular, have shown considerable therapeutic potential, as the unique combination of copper chemistry and dinuclear structural modifications has given rise to various highly bioactive compounds and new medicinal possibilities. In this paper, biological activities of medicinally attractive homodinuclear and heterodinuclear copper complexes are reviewed and their therapeutic potential and future perspectives are discussed. An in-depth analysis of key elements that impact their structure-activity relationships was performed and through a rational design approach, supported by the available literature, concluding remarks were given, that could possibly lead to more optimal therapeutic dinuclear copper complex structures. Known limitations regarding copper toxicity, bioavailability, metabolism and clearance were analyzed and possible strategies to mitigate them were discussed as well, including the possibe use of dinuclear copper complexes in targeted therapy and stimuli-responsive drug delivery systems. Finally, the prospects of using dinuclear copper complexes in personalized or combination therapy are postulated.