Doctoral themes 2023

Schiff base Cobalt Complexes in O₂ Activation and anticancer therapy 

Supervisors

Susanta Hazra, susanta.hazra@tecnico.ulisboa.pt

Isabel Correia, icorreia@tecnico.ulisboa.pt

Registration Institution

Instituto Superior Técnico

Project description

Current strategies in drug design involve the development of small molecules to target biomolecules such as nucleic acids and proteins. The use of metal catalysts as therapeutic agents brings a new strategy for the design of metallodrugs that exhibit a distinct mode of action differing from traditional Pt-drugs.

The interaction of CoII complexes in solution with O₂ has been the subject of extensive studies. Although under certain conditions, oxidation of CoII to CoIII complexes occurs, the intermediate peroxo (O₂²⁻) and superoxo (₂^-) species can be isolated. Schiff base CoII complexes were also found to coordinate/pick up O₂ and the oxygenation reactions {[CoL] + O₂ = [CoL(O₂)]} are reversible at low temperature in some cases. In 1946, Calvin et al. reported that the Co(salen) complex and its analogues can bind the oxygen molecule. They demonstrated that some of these complexes were able to reversibly bind dioxygen, both in the solid state and in suitable organic solvents. These results led to further intensive research on the metal complexes (Co, Fe, Cu, etc.) of salen and its related derivatives, due to both scientific/chemical interest and to possible applications in industry, as well as in biology and medicine. In fact, these kinds of metal complexes that reversibly bind molecular oxygen can mimic the behavior of very important bio-molecules (e.g., haemoglobin).

Cobalt complexes have also been investigated in reduction of O₂, while porous materials with immobilized cobalt complexes were applied in catalysis, gas storage and sensor technology.

The project will aim to synthesize Schiff base cobalt complexes and use them in O₂e activation studies to model protein sites, as well as to evaluate their DNA binding ability and select lead compounds for cytotoxicity studies with cancer cells. Extension to related metal ions and the reduced versions of the Schiff base will also be investigated. 

Part of the work (ca. 6 months) will be carried out at the School of Pharmaceutical Sciences and Health Products, Università di Camerino, Italy, in collaboration with prof. Claudio Pettinari.

Keywords

Oxygen (O₂) activation

DNA binding and cleavage

Cytotoxicity

Catalysis