The biological world of proteins involves recognition processes based on multiple non-covalent interactions. Many proteins contain a metal ion, which may play a structural role, but may also intervene directly in molecular recognition processes, or even act as a catalyst to activate small biological molecules for the selective transformation of organic substrates. The protein active site of metallo-enzymes defines the metal's environment (nature of the ligands, geometry of the coordination site), protects the reactive species formed, selects the nature of the substrate and facilitates its transport to the active site and its evacuation after reaction. One approach to addressing and studying these phenomena of recognition, control and reactivity is the development of model systems, i.e. artificial low-molecular-weight systems that reproduce or mimic one or more prejudiced aspects important in biological activity.
From a fundamental point of view, the aim of such chemical modeling work is manifold:
- to study the behavior of the metal ion thus confined within a macrocyclic structure controlling its first and second coordination spheres, while allowing controlled access for interaction with a molecule exogenous to the system ;
- evaluate the importance and consequences of this supramolecular control on the reactivity of the metal ion ;
- evaluate environmental effects: confinement in an organic protein medium, access to the solventH2O ;
- from an applied point of view, develop new molecular receptors, with the longer-term prospect of developing systems that can act as probes, sensors or catalysts.
The aim of this seminar is to present a biomimetic and supramolecular approach with artificial systems mimicking both the coordination site and the hydrophobic pocket of the active site of a metallo-enzyme. The strategy is based on the synthesis of molecular cavities functionalized by coordinating groups mimicking the imidazole residues of the histidine sites classically present at the active site of enzymes. The role of the cavity is to control both the metal's second sphere of coordination and the approach of exogenous molecules that are candidates for interaction with the metal. Cavity effects modifying and controlling the properties of the metal ion thus confined are highlighted and discussed in the context of biomimicry in general and metallo-enzyme reactivity in particular. Recent developments in heteropolymetallic systems are also presented.
