Higher organisms use reactive oxygen/nitrogen species (ROS/RNS) for signaling functions, in the defense mechanism against invaders, and in the regulation of cell and organ functions. The chemistry beyond the regulation of these species is usually dependent on metal cofactors, which also promote dioxygen activation through often complex catalytic processes. Heme is an example of a cofactor that can exert both the role of dioxygen activation and ROS/RNS scavenging depending on the protein environment. In the last decade, the study of heme and its model analogues has developed into the study of contracted and expanded porphyrins: corroles (COR – similar to porphyrins but lacking one methylene carbon) and texaphyrins (TEX – penta-aza Schiff base macrocycles) are examples of these molecules. Metal complexes of these macrocyclic ligands exhibit peculiar redox catalytic properties toward ROS/RNS depending on the geometric nature of the ligand cavity and of the encapsulated metal. Moreover, these complexes share with heme the ability to bind to biological macromolecules by coordination of amino acid residues (e.g. histidine) to the metal axial coordination positions. This project focuses on the synthesis of metal complexes of COR and TEX, and their cellular characterization as ROS modulators/suppressors to devise new therapeutic agents against neurodegeneration and new artificial biocatalysts.

This project has received funding from Ministry of University and Research (MUR) – PRIN 2022