Supramolecular Chemistry
The broad area of research in the group is supramolecular chemistry and bioorganic chemistry. We are interested in understanding how molecules interact, how they recognise each other, how they fold and how they can assemble into larger, multi-component systems. Supramolecular chemistry focuses on the intermolecular interactions between molecules, such as hydrogen bonding, the hydrophobic effect, metal-ligand coordination, interactions and electrostatic effects. The goal of our research is to understand the role of non-covalent interaction in biological and chemical systems, to utilise supramolecular interactions to manipulate biological systems, and to take inspiration from biology to build new and complex chemical architectures, host-gest systems and adaptive materials.
Current areas of research include.
• Enzyme-mediated Dynamic Combinatorial Chemistry
• Stimuli-Responsive Supramolecular Materials
• Systems Chemistry
Enzyme-mediated Dynamic Combinatorial Chemistry
Dynamic Combinatorial Chemistry (DCC) is a selection-based methodology for the synthesis of oligomers that relies upon self-assembly under thermodynamic control to direct the synthesis of complex architectures. Small molecule building blocks are reacted together via reversible reactions to give a dynamic equilibrium mixture of oligomers called a Dynamic Combinatorial Library (DCL). In the absence of any external influences, the system will naturally favour the formation of the species with the greatest intrinsic stability. By adding a guest molecular (a template), one can manipulate the system and stabilise alternative products.
In our group we are developing the concept of Enzyme-Mediated Dynamic Combinatorial Chemistry, by merging enzymology with supramolecular chemistry. We employ enzymes that catalysed reversible reactions to generate dynamic mixtures of interconverting bio-oligomers, and we exploit artificial (synthetic) molecular templates that bind to, stabilise and thus amplify the synthesis of chosen products. Current projects utilise this approach for the templated enzymatic synthesis of oligosaccharides.
We have shown that the selective enzymatic synthesis of different cyclodextrins can be achieved by adding different templates to CGTase-mediated dynamic cyclodextrin mixtures. We can even template the synthesis of unusual large-ring cyclodextrins formed from 9 and 10 glucose units.
D. Larson, S. R. Beeren, 2019, ‘Enzyme-mediated dynamic combinatorial chemistry allows out-of-equilibrium template-directed synthesis of macrocyclic oligosaccharides’, Chem. Sci., 43, 9981-9987.
D. Larson, S. R. Beeren, 2020, ‘Tuning the outcome of enzyme-mediated dynamic cyclodextrin libraries to enhance template effects’, Chem. Eur. J., Accepted Articles
Stimuli-Responsive Supramolecular Materials
A stimuli-responsive material is one that adapts to its environment – the application of an external stimuli causes a change in the molecular or supramolecular structure of the material resulting in altered physical or chemical properties and function. External stimuli range from physical stimuli (e.g. temperature, light) to chemical stimuli (e.g. signalling molecules, ligands, receptors, pH) and biological stimuli (e.g. enzymes). Such ‘smart’ materials have huge potential in the area of nanomedicine, for transport and controlled delivery of active compounds, such as drugs and contrasts agents, and for responsive surfaces in biosensing. Projects in this area are aimed at the development of stimuli-responsive delivery systems, supramolecular probes for biomacromolecules, sensors and self-healing polymers.
D. Larsen, P. M. Bjerre, S. R. Beeren, 2019 ‘Light-controlled out-of-equilibrium assembly of cyclodextrins in an enzyme-mediated dynamic system’, Chem. Commun., 55, 15037-15040.
S. R. Beeren and O. Hindsgaul, 2013, ‘Nature’s dendrimer: characterizing amylopectin as a multivalent host’, Angew. Chem., Int. Ed., 52, 11265-11268.
S. R. Beeren and O. Hindsgaul, 2014, ‘A fluorescence assay that detects long branches in the starch polysaccharide amylopectin’ Chem. Commun., 50, 1530-1532.
Systems Chemistry
Molecules and molecular interactions in nature exist not in isolation, but within complex chemical networks. Nevertheless, chemists and biochemist typically investigate binding interactions on individual isolated compounds. Systems chemistry, which is the study of complex mixtures of interacting synthetic molecules is a new but increasingly important field. Advances in this field require the availability of analytical tools to resolve and distinguish individual components in a mixture and the availability of simple methods to simultaneously quantify multiple competing binding interactions in mixtures. Projects in this area are looking at ways to use supramolecular chemistry together with NMR spectroscopy to study mixtures of interacting molecules.
S. Meier and S. R. Beeren, 2014, ‘Simultaneous determination of binding constants for multiple carbohydrate hosts in complex mixtures’, J. Am. Chem. Soc., 136, 11284-11287
S. R. Beeren and S. Meier, 2015, Supramolecular chemical shift reagents inducing conformational transitions: NMR analysis of carbohydrate homooligomer mixtures’, Chem. Commun., 51, 3073-3076.