Specialized iNANO Lecture by Assoc. Prof. Sophie R. Beeren, DTU

Associate Professor Sophie R. Beeren, Department of Chemistry, Technical University of Denmark

Enzyme-mediated dynamic combinatorial chemistry with cyclodextrins

Dynamic combinatorial chemistry (DCC) is a well-established methodology for the templated synthesis of complex molecular architectures, wherein molecular building blocks are linked together using reversible reactions to give dynamic mixtures of oligomers under thermodynamic control [1]. While a range of reversible covalent reactions have been examined for DCC, enzyme-catalysed reactions have been little explored in this context. In this talk I will present Enzyme-Mediated Dynamic Combinatorial Chemistry, wherein an enzyme is employed to take seemingly stable (bio)molecules and turn them into a dynamic mixture of interconverting (bio)-oligomers.

Cyclodextrins (CDs) are macrocycles formed from a-1,4-linked glucopyranose units. Cyclodextrins with 6, 7, and 8 glucose units (α- β- and γ-CD) are important hosts for the encapsulation of hydrophobic
molecules and are widely utilised in the food, pharmaceutical and cosmetics industries. I will discuss how dynamic mixtures of interconverting cyclodextrins can be generated by the action of cyclodextrin
glucanotransferase (CGTase) [2]. Templates can then be used to direct the selective synthesis of specific cyclodextrins, including modified cyclodextrins and large-ring cyclodextrins with more than 8 glucose units [3]. By using stimuli-responsive templates, we can control the outcome of this enzymatic reaction by means of light [4], pH change [5] and redox chemistry.

Figure 1. Cyclodextrin glucanotransferase (CGTase) converts cyclodextrins from static molecules into a dynamic mixture of interconverting cyclic and linear oligosaccharides. Templates (guest molecules) can be added to control which cyclodextrin products are formed.

References
[1] Corbett, P. T.; Leclaire, J.; Vial, L.; West, K. R.; Wietor, J.-L.; Sanders, J. K. M.; Otto, S., Chem. Rev., 2006, 106, 3652-3711.
[2] Larsen, D.; Beeren, S. R., Chem. Sci., 2019, 10, 9981-9987.
[3] Larsen, D.; Ferreira, M.; Tilloy, S.; Monflier, E.; Beeren, S. R., Chem. Commun., 2022, 58, 2287-2290.
[4] Yang, S.; Larsen, D.; Pellegrini, M.; Meier, S.; Mierke, D. F.; Beeren, S. R.; Aprahamian, I., Chem., 2021, 7, 2190-2200.
[5] Samuelsen, L.; Larsen, D.; Schönbeck, C.; Beeren, S. R., Chem. Commun., 2022, 58, 5152-5155.