CATAMERS

Catalytic Foldamers: Engineering a Second Coordination Sphere Around a Hydrogenase Mimic

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 Obiettivo del progetto (Objective)

'The protein environment that surrounds metalloenzyme active sites imparts a wide range of effects that facilitate catalysis. Supramolecular supports for homogenous catalysis may model a number of these effects. However, the use of dendrimers or polymers to provide directed second coordination sphere effects is limited by their unpredictable/unstable structures. Foldamers, based on aromatic amide units, have structures that are both highly stable and predictable in a wide range of solvents. These qualities and the modular approach to their synthesis allows for engineering of cavities of defined size with an organized array of functional groups. This project plans to explore the application of foldamers as supramolecular supports for small molecule mimics of metalloenzyme active sites, specifically [FeFe]-hydrogenase, and in doing so develop a new generation of hydrogenase models with a well defined and tunable second coordination sphere. The research involves the in silico design, and chemical synthesis of foldamers that incorporate small molecule models of [FeFe]-hydrogenase. Through electrochemical and variable temperature NMR studies, the effect of the support on the fluxional and electrocatalytic properties of the model complex will be studied. The applicant has experience in the synthesis and characterization of biomimetics of [FeFe]-hydrogenase and the use of supramolecular supports (cyclodextrins) for their encapsulation. Through joining a host lab in France that specializes in the synthesis and structural characterization of aromatic amide foldamers, this expertise in bioinspired catalysts will be transferred via the proposed cooperative work. Additionally the applicant would act as an envoy between the host lab and a group in Germany, with whom the host lab has an established collaboration, for the spectroelectrochemical study of the foldamer complex systems, thus expanding the transfer of knowledge.'

Introduzione (Teaser)

Scientists developed novel supramolecular hosts for small molecular guests that mimic industrially relevant enzymes. The host structure appears to alter the properties of the guest in a tuneable way, promising exciting control over catalytic activity.

Descrizione progetto (Article)

Catalysis, the process by which the rate and thus yield over time of a reaction is increased by chemical matchmakers (catalysts), is highly important for industry. Enzymes are nature's catalysts and hydrogenases are an important class of these compounds.

Hydrogenases are metalloenzymes, enzymatic proteins with tightly bound metal ions essential to their functions. The protein surrounding the metal (active) site can affect catalytic function in direct and indirect ways. Direct effects are due to covalent binding to the metal itself, forming the first coordination sphere. Indirect effects are due to non-covalent (e.g. hydrogen) bonding to the molecules (ligands) around the metal forming the second coordination sphere.

Supramolecular supports may reproduce a number of second coordination sphere effects. Scientists developed supramolecular supports for molecular models of [FeFe]-hydrogenase with EU funding of the project 'Catalytic foldamers: Engineering a second coordination sphere around a hydrogenase mimic' (CATAMERS). Foldamers, molecular chains or oligomers with highly stable and predictable structures, were used as hosts for [FeFe]-hydrogenase mimics containing a diiron complex to achieve a well defined and tuneable second coordination sphere.

Extensive development was required to synthesise the two new monomer units from which the foldamers were produced, one to attach the diiron complex and one to house the catalyst. This work not only led to realisation of the oligomers but also enabled the introduction of a wide variety of functional groups, paving the way for greater diversification of foldamers in the future. Interestingly, there was no evidence of hydrogen bonding between the diiron complex and the foldamers scaffold. The complex was free to turn, rotating fast enough to equilibrate each iron site with no significant distortions in the symmetry of the complex.

Despite what appears to be minimal control of the foldamer scaffold, the design affects the electrochemical properties of the diiron complex as the second coordination sphere is built around it. Such activity promises great potential for fine-tuning of the reactivity of metal complexes. Dehydrogenases are used in important industrial reactions related to energy applications such as hydrogen production and methane oxidation, and CATAMERS has opened the door to development of synthetic mimics with greater efficacy at lower cost.