Synthesis, Biological and Supramolecular Chemistry

Research in this unit is focused on answering fundamental questions relating to molecular structure, chemical reactivity and physical properties. Our programmes concerning the discovery and development of efficient enabling methods and the design of bespoke functional molecules provide novel chemical entities and processes to tackle major societal challenges, spanning sustainability (energy, chemical feedstock, agriculture), next generation therapeutics and diagnostics. Our research is supported by the Centre for Chemical and Materials Analysis, which offers high quality spectroscopic analysis, including NMR, Mass Spectrometry, X-ray Diffraction and HPLC.

Areas of expertise

Asymmetric synthesis; carbohydrate chemistry; cascade reactions; catalysis discovery; catalysis design; functional molecules; lipids; scaffold design and molecular diversity; natural products; organic reaction mechanisms; organocatalysis; organometallic chemistry; peptides; reactive intermediates; reaction design; sustainable chemistry; synthetic organic chemistry; transition metal-mediated reactions.

Research unit leader

Areas of interest

Polymerisation and depolymerisation catalysis, sustainable polymer chemistry, degradable polymers, 3D printing, biomedical materials, organic catalysis, stereochemistry in polymeric materials.

Representative publication: Independent Control of Elastomer Properties through Stereocontrolled Synthesis.

Angew. Chem. Int. Ed. (2016) 55, 13076 – 13080

Independent Control of Elastomer Properties through Stereocontrolled Synthesis

Elastomers are typically tri- or multi-block copolymers that owe their properties to phase separation of the polymer blocks to form hard and soft domains that infer the strength and flexibility respectively. Conversely, natural rubber and gutta percha display different mechanical properties as a result of the different stereochemistry of the double bonds in the polymer backbone. Using stereospecific, organocatalyzed click chemistry the materials properties can be controlled which allows the decoupling of mechanical properties, physical properties and materials’ degradation to  provides a new design space for elastomers.

Research unit members

Areas of interest

Catalysis, organic methodology and synthesis, molecular design, organometallics, reaction mechanisms

Representative publication: Divergent C-H Insertion-Cyclization Cascades of N-Allyl Ynamides

Holly V. Adcock, Elli Chatzopoulou and Paul W. Davies. Angew. Chem. Int. Ed. 54 (2015) 15525-15529.

Divergent C-H Insertion-Cyclization Cascades of N-Allyl YnamidesThis paper introduces  new reactivity in which competing and divergent pathways are controlled by choice of catalyst. New reactivity modes and sequences, including the unprecedented formation of gold carbenes by alkyne insertion into a CH bond, allow the selective and efficient preparation of different products from the same starting materials.

Areas of interest

Bioinorganic chemistry – peptide design – lanthanides – coiled coils – artificial metalloproteins

Representative publication: De Novo Design of Ln(III) Coiled Coils for Imaging Applications

Berwick, M. R.; Lewis, D. J.; Jones, A. W.; Parslow, R. A.; Dafforn, T. R.; Cooper, H. J.; Wilkie, J.; Pikramenou, Z.; Britton, M. M.; Peacock, A. F. A.* (2014), De Novo Design of Ln(III) Coiled Coils for Imaging ApplicationsJ. Am. Chem. Soc., 136, 1166-1169.

De Novo Design of Ln(III) Coiled Coils for Imaging Applications

Areas of interest

Chemical Biology and Bioconjugation Strategies · Diversity-Oriented Synthesis · Medicinal Chemistry · Molecular Synthesis and Catalysis

Representative publication: Photoactivable Glycolipid Antigens Generate Stable Conjugates with CD1d for Invariant Natural Killer T Cell Activation

Veerapen, N., Kharkwal, S. S., Jervis, P., Bhowruth, V., Besra, A. K., North, S. J., Haslam, S. M., Dell, A., Hobrath, J., Quaid, P. J., Moynihan, P. J., Cox, L. R., Kharkwal, H., Zauderer, M., Besra, G. S., Porcelli, S. A. (2018). Bioconjugate Chem. 29(9), 3161–3173.

Photoactivable Glycolipid Antigens Generate Stable Conjugates with CD1d for Invariant Natural Killer T Cell ActivationA wide range of glycolipids bind to the protein CD1d.  Through judicious choice of glycolipid, the resulting complex is capable of activating iNKT cells to elicit an immune response.  Whilst careful optimisation of the glycolipid structure has delivered some potent iNKT-cell activators, dissociation of the glycolipid ligand from the CD1d molecule remains a problem for their potential therapeutic application in immunotherapies.  In this paper, we describe the first functional CD1d–glycolipid conjugate in which ligand dissociation is now no longer an issue.  This bioconjugation technology provides novel tool compounds for studying the mechanism of iNKT-cell biology and opens up a new immunotherapy strategy for future clinical application.

Areas of interest

Synthetic organic chemistry; Free radicals; Photochemistry; Natural product synthesis; Organosulfur and organoselenium chemistry; Peri-interactions; Medicinal chemistry

Representative publication: Carbamoyl radical-mediated synthesis and semipinacol rearrangement of β-lactam diols

Marie Betou, Louise Male, Jonathan W. Steed and Richard S. Grainger. Chemistry – A European Journal 2014, 20, 6505-6517 DOI: 10.1002/chem.201304982

Carbamoyl radical-mediated synthesis and semipinacol rearrangement of β-lactam diolsThis paper reports a conceptually novel entry into bridged bicyclic lactams through ring expansion of fused beta-lactam diols. The core structures that can be prepared through this methodology are represented in a range of biologically important natural and non-natural products, and are ripe for further functionalization as rigid three-dimensional scaffolds for medicinal chemistry applications. The work builds on our group’s free-radical cyclisation methodology to access functionalized, cis-fused bicyclic lactams. The use of cyclic phosphoranes to rearrange diols has little precedent and through this work is shown to be potentially a more general alternative to the rearrangement of epoxides.

Areas of interest

Supramolecular chemistry, DNA sensing, modified nucleic acids, bioorganometallic chemistry, drug discovery, electrochemistry, fluorescence spectroscopy

Representative publication: Macrocyclic Metal Complex−DNA Conjugates for Electrochemical Sensing of Single Nucleobase Changes in DNA

Jean-Louis H. A. Duprey, James Carr-Smith, Sarah L. Horswell, Jarosław Kowalski and James H. R. Tucker  J. Am. Chem. Soc. 2016, 138, 746−749.

Macrocyclic Metal Complex−DNA Conjugates for Electrochemical Sensing of Single Nucleobase Changes in DNAThe direct incorporation of macrocyclic cyclidene complexes into DNA via automated synthesis results in a new family of metal-functionalized DNA derivatives that readily demonstrate their utility through the ability of one redox-active copper(II)-containing strand to distinguish electrochemically between all four canonical DNA nucleobases at a single site within a target sequence of DNA.

Areas of interest

Luminescent probes, metal complex design, lanthanide chemistry and photophysics, nanoparticles for detection and monitoring, nanoprobes for drug delivery, disease targeting, photophysics, sensors

Representative publication: Iridium Nanoparticles for Multichannel Luminescence Lifetime Imaging, Mapping Localization in Live Cancer Cells

King, S. M., Claire, S.  Teixeira, R.I   Dosumu, A.N.,  Carrod, A.J.,  Dehghani, H., Hannon,  Ward, A.D.,  Bicknell, R.,  Botchway, S.W,  Hodges, N.J,  and Pikramenou, Z  J. Am. Chem. Soc. 2018, 140, 10242-10249. Iridium nanoparticles for imaging in cancer cells based on luminescence lifetime

We have developed gold nanoparticles detected by for two photon lifetime imaging using a short-lived (picosecond) and a long-lived (microsecond) lifetime signal, introducing two-channel imaging of nanoparticles leading to dual monitoring and imaging of the two signals independently.

The studies not only show dual monitoring and imaging of two lifetime signals but also reveal unprecedented long lifetimes of the iridium nanoparticles in cells.

Research Collaborations

MSC team leaders are actively engaged with both industrial and academic partners within the UK and overseas as well as in collaborative projects across the University (School of Biosciences, School of Chemical Engineering and the College of Medical and Dental Sciences). This includes cross-disciplinary areas of research activity covered by the School of Chemistry's research themes, in particular Chemical Biology and Drug Discovery  and Chemistry for Healthcare Technologies.

Wider engagement

Molecular synthesis can catalysis plays a crucial role in maintaining and improving our standard of life. Members of the Unit work closely with the Royal Society of Chemistry, the Society of Chemical Industry and the Royal Society as committee members, panel officers and Industry Fellows, to enable effective knowledge transfer across academia and industry and to enhance public awareness of this central area of Chemistry.

Contact

Enquiries about specific aspects of their research areas should be addressed to individual research group leaders. For more general enquiries about working with the SBS Unit, please contact Professor Andrew Dove (SBS Unit Lead). Information on various postgraduate (PhD and Masters) degree opportunities can be found on our postgraduate opportunities page.