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Our Research

Research in the Butler Group is focussed on the design and synthesis of luminescent host molecules (or probes) for the selective recognition of biologically important substrates. These molecules are being developed into new tools for imaging, diagnostics and bioassay technologies.


A fundamental goal of our research is to create supramolecular tools with real-world applications in biological and medical research. Research projects in the Butler group are therefore multidisciplinary in nature; students receive training in a range of techniques in organic and peptide synthesis, molecular recognition, advanced optical spectroscopy, bioassay development and cellular imaging.


We are actively pursuing commercial exploitation of our molecular probes in biomedical sensing applications. We are currently working with Mast Group Ltd. (UK-based manufacturers of diagnostic technologies) to translate our anion-selective probes into new clinical diagnostic assays and products in their portfolio. This project exploits our patented hydrogel-based sensing technology (Euro. Pat. App. 3 844 241, 2021) developed in collaboration with Dr Helen Willcock (Materials).

Supramolecular Enzyme Reaction Monitoring

We are developing luminescent anion receptors, based on designed lanthanide complexes, capable of binding and sensing nucleoside polyphosphate anions (e.g. ATP, ADP, GTP) in vitro and in living cells. Our synthetic receptors are able to monitor real-time changes in the concentrations of specific anions as they occur in enzymatic reactions, which could facilitate drug discovery research.

For example, we are developing molecules that can report on the phosphorylation of proteins, a process catalysed by kinase enzymes. Abnormal phosphorylation of proteins is the primary cause of many types of cancer. Synthetic receptors that can monitor protein phosphorylation are very well suited to screen for potential inhibitors or activators of kinase activity, and thus will facilitate the development of new therapeutic agents for the treatment of diseases such as cancer.

Macromolecular MRI Contrast Agents

We are developing new synthetic approaches to polymeric MRI contrast agents. MRI is an invaluable tool for imaging tumours and diagnosing disease. Commercial contrast agents have been used in the clinic since the 1980s, and are based on discrete Gd(III) complexes, which enhance the image contrast by increasing relaxation of local water molecules. However, these contrast agents are far from optimal, and the image contrast is nowhere near the theoretical maximum. We have designed monomeric Gd complexes bearing two polymerisable arms, which can be readily polymerised in a single step to form macromolecules with different architectures (e.g., hyperbranched polymers). By limiting the local motion of the Gd(III) complex through crosslinking of the monomer, we will deliver contrast agents with at least 7-fold higher relaxivities compared to commercial agents. This could enable lower, safer doses of the contrast agent to be used for MR imaging.

Key Words

Molecular Probes for Visualising Protein-Protein Interactions

A new conjugation strategy for site-selective labelling of proteins with stable lanthanide tags is being developed, to enable improved analysis of protein-protein interactions (PPIs). We have developed a emissive and paramagnetic molecules which react selectively with cysteine residues on proteins via a nucleophilic substitution reaction. This creates a stable and rigid linker to the protein, which is being exploited to develop: (1) paramagnetic lanthanide tags to facilitate protein NMR analysis; (2) FRET-based imaging probes, which can be used to visualise protein-protein and protein-ligand interactions in living cells.

  • Organic Synthesis

  • Supramolecular Chemistry

  • Fluorescent Probes

  • Host-Guest Recognition

  • Cellular Imaging

Key Publications 

Tuning the anion binding properties of lanthanide receptors to discriminate nucleoside phosphates in a sensing array

S. H. Hewitt, G. Macey, R. Mailhot, M. R. J. Elsegood, F. Duarte, A. M. Kenwright and S. J. Butler. Chem. Sci., 2020, 11, 3619-3628.

Featured in the 'Mechanics of Supramolecular Chemistry Collection' and the '2020 Chemical Science HOT Article Collection'.

A simple, robust, universal assay for real-time enzyme monitoring by signalling changes in nucleoside phosphate anion concentration using a europium(III)-based anion receptor

S. H. Hewitt,  R.Ali, R. Mailhot, C. R. Antonen, C. A. Dodson and S. J. Butler, Chem. Sci., 2019, 10, 5373-5381.

DOI: 10.1039/C9SC01552C

Edge Article.

Application of Lanthanide Luminescence in Probing Enzyme Activity

S. H. Hewitt and S. J. Butler, Chem. Commun. 2018, 54, 6635 – 6647.

DOI: 10.1039/C8CC02824A548

2018 Emerging Investigators Special Issue

Cationic Europium Complexes for Visualizing Fluctuations in Mitochondrial ATP Levels in Living Cells

R. Mailhot, T. Traviss-Pollard, R. Pal and S. J. Butler, Chem. Eur. J., 2018, 24,10745–10755. DOI: 10.1002/chem.201801008

A Continuous Luminescence Assay for Monitoring Kinase Activity: Signalling the ADP/ATP Ratio using a Discrete Europium Complex

S. H. Hewitt, J. Parris, R. Mailhot and S. J. Butler*, Chem. Commun., 2017, 53, 12626-12629.

DOI: 10.1039/c7cc05887j

Featured on Front (Inside) Cover

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