Theme

We are interested in the roles of metal cations in biology in close connexion with redox balance. On the one hand, we work on the design of metalloprotein mimics with antioxidant activity, which we are studying in a cellular context. On the other hand, we prepare metallic systems, which can be used as probes for unconventional imaging (infrared or X-ray fluorescence) or in specific contexts (protein aggregation phenomena, as in Alzheimer’s disease), or which can be therapeutic (inhibitors of metabolic pathways).

Inorganic complexes are increasingly used for biological applications, as metallodrugs or metalloprobes. In the inorganic cellular and biological chemistry—metals in biology group, we aim at going from chemistry round-flasks to cells. We use the metal complexes, that we design in the round flasks, in cells, for therapeutic applications or as bioprobes.

 

 

 

 

Allegory of bio-inorganic chemistry: mimicking SOD, from Magritte, La clairvoyance, 1936

Most of the metal complexes studied in the literature for their bioactivity are used as anticancer, antibacterial, or antifungal agents. Hitherto, most bioanalyses focus on their toxicity towards cancer cells, or micro-organisms. In contrast, the anti-oxidants we develop must be non-toxic and restore the basal activity in cells under oxidative stress and the probes are meant to minimally affect the cells. Their characterization requires the development of specific non-routine strategies and protocols to evaluate them.

(a) Bio-active metal complexes:

– Antioxidant complexes mimics of antioxidant metalloproteins.

We design metal-complexes showing an antioxidant activity to rescue cells from oxidative stress. We study them in cellular models of oxidative stress. Some are directly bio-inspired from the antioxidant superoxide dismutase (SOD). In a second strategy, we develop a combinatorial approach to design peptide-based complexes screened for their antioxidant activity (SOD mimics or catalase mimics). In a third approach, in collaboration with Vince Pecoraro (Michigan univ.), we use three-helices bundles to design de novo peptide and study their anti-superoxide activity.

– We design and study metal-centered peptidomimetics and metal complexes as secondary structure mimics towards modulation of protein-protein interactions.

(b) Metal-based probes:

Re(CO)3 complexes are developed as multimodal probes to correlate fluorescence, IR-imaging and X-fluorescence imaging. These probes are easy to conjugate to any kind of bio-molecule.

Innovative techniques are used to investigate their speciation, quantify them and determine their cellular-location, leading to key information about their behavior inside cells.

Controlling inorganic complexes inside cells is an emerging field that we called “cellular inorganic chemistry” as it involves translation of knowledge acquired in round-bottom flask into cells.

References: 

Keywords: Bio-inorganic chemistry, Metals in biology, Mn-SOD mimics, metal-based catalytic anti-oxidants, catalytic drugs, enzymes mimics, sub-cellular imaging, metal carbonyles as multimodal probes (SCoMPIs for single core multimodal probes), IR-imaging, modulators of protein-protein interactions