Copper has a prominent biological role participating in numerous biological processes, most of them related to dioxygen management and electron transfer. Among these functions, copper is involved as the electroactive metal in the active site of protective SOD1 and SOD3 enzymes, which along with the Mn enzyme SOD2, are in charge of regulating superoxide radical concentration in mammals, getting rid of excess amounts of superoxide anions through their dismutation into hydrogen peroxide and dioxygen. Superoxide is the first product coming out from the reduction of dioxygen to give water. Imbalances between generation and clearance of superoxide anions give rise to the formation of all other reactive oxygen species (ROS) causing oxidative stress. Oxidative stress is related to a variety of health issues that include neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease (AD).[1] Administration of SODs is however not useful for therapeutic treatment due to the drawbacks that they present -such as the absence of oral activity. In this respect, it has been reported that several copper complexes of aza-macrocyclic ligands have SOD activities in vitro which rank among the highest ones so far reported for synthetic systems.[2,3] A step forward to improve the activity, the likely-cell uptake and bio-distribution of these low molecular weight mimetics might be their incorporation in non-toxic nanoparticles (NPs). The grafting of the molecules to the surface of the nanoparticles may yield pre-concentration and amplification of the signal.<br/>Here we discuss the chemistry of new Cu<sup>2+</sup> aza-macrocyclic complexes appropriately functionalized to permit their covalent anchorage to oxidic nanoparticles,[4] and we examine the parameters regulating the general SOD activity enhancement observed.

Synthesis and study of SOD mimetics: From aza-macrocyclic complexes to nano-structured systems

ACS Spring Meeting 2021

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