Blanc SIMI 7 - Sciences de l'information, de la matière et de l'ingénierie : Chimie moléculaire, organique, de coordination, catalyse et chimie biologique

Supramolecular redox control of a biomimetic metallo-site (Cu) embedded in a cavity – cavity-zyme(Cu)

Supramolecular redox control of a biomimetic Cu embedded in a cavity

Enzymes are fascinating biological green catalysts <br />A need for small chemical models<br />Supramolecular redox control and reactivity. <br />Our focus: cavity-controlled mono-copper sites, modeling mono-copper enzyme active sites

Supramolecular control of a redox metal ion

Widen the field of exploitation of the cavity-zyme concept: new ligands, new caps, new platforms, new cavities, maintaining the possible comparison with the classical ligands, and thus biomimetic systems (organic and inorganic synthesis, spectroscopy, electrochemistry…).<br />- Reactivity with O2: preliminary results relative to the oxygenation of guest substrates are promising (vide infra): this must be obviously further explored.<br />- Reactivity with PROS.<br />- Effect of the control of solvent and proton access to the {CuI/(O2 or PROS)/substrate} onto the guest, redox and reactivity properties.<br />- Catalysis: our ambition is to evidence some catalytic processes, the functioning of which is subordinated to the presence of the half-open pocket surrounding the metal center and explore their specificities and particularities.<br />- Open our studies to other media and conditions of studies: grafted electrodes, SECM.<br />

- synthesis of cavity-ligands presenting a biomimetic coordination core
- explore the coordination chemistry of Cu in various solvents (aquous vs organic) using various spectroscopies
- evaluate their redox properties through electrochemistry
- evaluate their reactivity in solution vs O2 and Pros
- grafting of the complexes onto a surface
...

- First water-soluble cavity-complexes
=> complexation of primary amines at physiological pH (Chem Science)
=> stabilisation of both redox states, Cu(I) and Cu(II), in water, in spite of an open coordination sphere. Drastic potential shift associated
(Org Lett, OR, YLM)

- Reductive electrografting of calix[4]arenediazonium salts to form covalently-bound monolayers onto surfaces: Anchoring of versatile platforms for spatially-controlled functionalization (PH,IJ,OR): 1 patent + 1article at Nature com.

- « self-induced electroclick » (Chem. Eur. J., YLM OR)

- « Bowl Complexes » with Cu (EurJIC + 3 articles en prep., YLM, OR) => comparison of the « Bowl vs. Funnel » concepts

- New methodologies for the selective functionalization of cavities through the « covalent capture » startegy.
- « cup and bowl » complexes (2 Chem. Eur. J., Tet. Lett. YLM OR)

Reactivity with O2 and PROS.
- Effect of the control of solvent and proton access to the {CuI/(O2 or PROS)/substrate} onto the guest, redox and reactivity properties.
- Catalysis: our ambition is to evidence some catalytic processes, the functioning of which is subordinated to the presence of the half-open pocket surrounding the metal center and explore their specificities and particularities.
- Open our studies to other media and conditions of studies: grafted electrodes, SECM.

Multipartenaire:
8 articles, 1 chapitre d'ouvrage, 1 brevet
Monopartenaire:
12 articles, 2 chapitre d'ouvrage

17 conférences à l'étranger et 18 en France

An emerging field: Supramolecular bioinorganic redox chemistry
Enzymes are fascinating biological green catalysts endowed with efficiency, selectivity, specificity but also fragility. Copper-enzymes functionality is based on CuII/CuI redox processes. In mammals, they catalyze a variety of oxidative transformations and have key roles, particularly in the central nervous system. They are non-heme and for all of them, amino-acid residues define the first coordination sphere.

A need for small chemical models and for specific electrochemical methods. The elaboration of model compounds offers many advantages: they are more robust, tuneable and thus allow molecular characterizations of putative intermediates that can be probed for their reactivity. The classical strategy to constrain a metallo-site in mononuclear environment relies on the use of steric hindrance. One important drawback is their decreased reactivity towards external substrates. As a result, most studies have been devoted to the spectroscopic characterization of oxo, peroxo or superoxo species and the elucidation of their intrinsic oxidative properties and reactivity remains a real challenge. This is due to the very difficult control of a mono-copper center in both I and II oxidation states by a simple tripodal ligand. Very few biomimetic complexes have combined a metal ion and a hydrophobic cavity. In order to evaluate such cavity effects, the design of the model system must associate a cavity to a biomimetic coordination core in such a way that once coordinated, the labile metal site will be either embedded in or oriented toward the cavity. Thanks to the smaller size of the models, investigations of the redox properties become possible but still require detailed analyses by transient electrochemical methods and in some cases, the development of specific techniques.
Our focus: cavity-controlled mono-copper sites, modeling mono-copper enzyme active sites
The past three years, four groups have unified their effort to explore the supramolecular aspects of the redox and reactivity properties of biomimetic mono-copper complexes within the framework of the ANR “calix-zymes” (2005-2008). One of the keys for success was the association of synthetic chemistry, coordination chemistry, supramolecular chemistry and electrochemists. An important synergy resulted from this multidisciplinary association: most results would not have been obtained without a strong interaction between the four groups. The objectives of this first ANR project were vast and ambitious. Crucial results have been obtained, among which validation of the concept of cavity-control for a redox metal ion: much groundwork related to various synthetic and methodological fields have been done and new research fields have been opened.
This new project lies in the continuity of our efforts taking advantage of our progress the past few years for a better control of the syntheses of the sophisticated systems and of the methodologies allowing the exploration of their properties. Whereas the effect of confinement of a redox metal on the coupling between the electron transfer and host/guest properties has began to be unraveled, an important challenge is the understanding of the reactivity of the "insulated" metals towards O2 and PROS, as well as the protonation reaction. As well electrode modification by supramolecular biomimetic systems is an important goal in matter of nanodevices for analysis and catalysis. As this project focuses on the cavity effect on redox metal centers, it also proposes the exploration of a new system that is completely different from the calix[6]arene-based ones, although still cavity-based, thus extending the advantages of the concept. Instead of a funnel-like, it presents a bowl shape (resorcinarene-based) and two coordination sites (instead of one for the calix) available for exogenous binding in cis position. This will widen the field of investigation of the concept.

Project coordination

Olivia REINAUD (UNIVERSITE DE PARIS V - RENE DESCARTES) – olivia.reinaud@parisdescartes.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

SCR CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE BRETAGNE ET PAYS- DE-LA-LOIRE
CEMCA CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE BRETAGNE ET PAYS- DE-LA-LOIRE
LCBPT-UPD UNIVERSITE DE PARIS V - RENE DESCARTES

Help of the ANR 639,999 euros
Beginning and duration of the scientific project: - 48 Months

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