Hybrid Open Porous Frameworks as Artificial MetalloEnzymes – HOPFAME

These ambitious objectives will be achieved by developing four original tools and methods:
- In silico screening of functional chiral PCPs by computational modelling,
- Synthesis of tailored made porous cavities by post-synthesis of chiral functions on PCPs, including amino acids, peptides and biological grafts and combining them with organometallic catalytic grafted centres.
- Short range characterisation of PCPs using cutting edge characterization spectroscopic techniques,
- In-depth understanding molecular recognition at molecular level in chiral MOFs by modelling guest-host interactions

The development of original functional chiral PCPs will be based on rational design approaches. It will consist in a tight integration of Computational chemistry and experimental investigations at three levels:
- Creation of a (combinatorial-virtual) library of functional chiral PCPs (made from different host PCPs, chiral grafts, loading,...) the computational pre-screening strategy will identify potentially interesting candidates based on synthesis feasibility,
- Synthesis such promising candidates and study host-guest interactions of the so-obtained reduced sub-set of functional PCPs through Monte Carlo docking simulations as applied in enzymes; models will be validated by adsorption/separation measurements on chiral substrates,
- Experimental investigation of dynamic kinetic resolution on targeted chiral PCPs and in depth study of chiral host-guest systems through first principle DFT calculations.

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HOPFAME will contribute to the overall goal of improving France intellectual property portfolio related to future chemical industry. Patent applications will be filed on each invention that meets the patentability criteria and has sufficient commercial potential. Key elements in the HOPFAME plan for management of the results are:
• Transparency of ownership of results is ensured by reporting detailed minutes of each meeting and information exchanges by of all means.
• Easy IP management and decision making since CNRS is the management body for the 2 partners (no consortium agreement required)
• Early identification of areas in which potential results are expected (deliverables);

We can envisage the feasibility of functional solids developed in the frame of HOPFAME at industrial scale thanks first to the possible kilogram scale synthesis of starting PCPs. At IRC we are involved in the FP7 project NanoMOF in which Johnson Matthey is in charge of the up-scaling of MOF synthesis. Six MOFs are also already industrially produced by BASF. Moreover during the ANR ACACIA31 project, IFPEN developed the kilogram scale synthesis of a MOF discovered at IRC, the SIM-1.
Concerning the post-synthetic functionalization of PCPs with amino acids, oligopeptides are already prepared by solid phase peptide synthesis on resins, the technology transfer from resin to MOF can be envisaged in line with the results (reaction conditions and yields) obtained during HOPFAME.

Publication:
Enantiopure Peptide-Functionalized Metal-Organic Frameworks
J. Bonnefoy, A. Legrand, E.A. Quadrelli, J. Canivet, D. Farrusseng, Journal of the American Chemical Society, 2015, DOI: 10.1021/jacs.5b05327.

Patent:
Méthode de greffage d'oligopeptides dans des matériaux hybrides poreux.
Canivet, Jerome; Bonnefoy, Jonathan; Quadrelli, Elsje Alessandra; Farrusseng, David (2014) FR1454772

HOPFAME vision: We believe that functional porous coordination polymers (PCP) can be used as model materials for mimicking enzymes. The well organized structure of PCP and softness shall enable the modeling/understanding of molecular recognition properties. The successful use of chiral PCPs for stereoselective enrichment will be a crucial step towards the design of ideal asymmetric heterogeneous catalysts.

The objective of HOPFAME is to demonstrate that the functionalisation of well-selected PCPs by grafting flexible chiral moieties such as amino acids or short peptide sequences will provide an environment which mimics enzymes. Hence, they shall enable chiral molecular recognition, tending to the blue-sky objective of 100% enantioselectivity.

These ambitious objectives will be achieved by developing four original tools and methods:
- In silico screening of functional chiral PCPs by computational modelling,
- synthesis of tailored made porous cavities by post-synthesis of chiral functions on PCPs, including amino acids, peptides and biological grafts and combining them with organometallic catalytic grafted centres.
- short range characterisation of PCPs using cutting edge characterization spectroscopic techniques,
- In-depth understanding molecular recognition at molecular level in chiral MOFs by modelling guest-host interactions

The development of original functional chiral PCPs will be based on rational design approaches. It will consist in a tight integration of Computational chemistry and experimental investigations at three levels:
- Creation a (combinatorial-virtual) library of functional chiral PCPs (made from different host PCPs, chiral grafts, loading,...) the computational pre-screening strategy will identify potentially interesting candidates based on synthesis feasibility,
- Synthesis such promising candidates and study host-guest interactions of the so-obtained reduced sub-set of functional PCPs through Monte Carlo docking simulations as applied in enzymes; models will be validated by adsorption/separation measurements on chiral substrates,
- Experimental investigation of dynamic kinetic resolution on targeted chiral PCPs and in depth study of chiral host-guest systems through first principle DFT calculations.