Research Guides

My role in the CRL is as the Director of NMR Spectroscopy for Organic Chemistry & Chemical Biology which means I am responsible for managing the core NMR facilities, services and support staff.  I am also professor of magnetic resonance and my research interests revolve around the application of solution-state NMR techniques to address questions of structure, function and dynamics of "small" molecules in organic chemistry and chemical biology. Many of the projects in which I become involved arise through collaborations with groups across the department and the university more widely.

Protein-ligand binding studies by NMR Spectroscopy

The interaction of small molecules with protein targets is an area in which NMR spectroscopy can play a key role, providing information on the behavior of the small molecule and on structural changes in the protein itself. A wide range of techniques are available to probe such interactions (such as saturation transfer difference and WaterLOGSY) and we are interested in further developing and applying such methods to a variety biological systems. We also employ protein-observe methods when isotopically labelled macromolecules are available. We apply these methods to 2-oxoglutarate dependent Fe(II) enzymes, in collaboration with Prof. Chris Schofield.   

NMR methods for studying small molecules

Despite their relatively small size, many molecules encountered in the laboratory of synthetic and medicinal chemists have structures that can prove surprisingly difficult to define reliably, especially in relation to stereochemistry. We are interested in exploring the application of novel methods and developing these further to help better elucidate small molecule structures. Methods that are currently of interest are those based on pure shift methodology (broadband proton decoupled proton spectroscopy), methods for fluorinated molecules, and the use of residual dipolar couplings (RDCs) as alternatives to traditional scalar couplings and NOEs.

High-Resolution NMR Techniques in Organic Chemistry. 3rd Edition
T. D. W. Claridge, Elsevier Science, 2016.

TOCSY
T. D. W. Claridge, in Multidimensional NMR Methods for the Solution State, (Eds. G. A. Morris and J. W. Emsley), John Wiley & Sons Ltd, Chichester, 2010.

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Stereoselective Production of Dimethyl-Substituted Carbapenams via Engineered Carbapenem Biosynthesis Enzymes.
Refaat B. Hamed, Luc Henry, Timothy D. W. Claridge, and Christopher J. Schofield, ACS Catalysis, 2017, 7, 1279−1285. [DOI: 10.1021/acscatal.6b02509]

Aromatic and antiaromatic ring currents in a molecular nanoring.
Martin D. Peeks, Timothy D. W. Claridge, Harry L. Anderson, Nature, 2017, 541, 200-203. [DOI: 10.1038/nature20798]

Post-translational mutagenesis: A chemical synthetic strategy for exploration of protein side-chain diversity.
Tom H. Wright, Ben J. Bower, Justin M. Chalker, Gonçalo J. L. Bernardes, Rafal Wiewiora, Wai-Lung Ng, Ritu Raj, Sarah Faulkner, M. Robert J. Vallée, Anuchit Phanumartwiwath, Oliver D. Coleman, Marie-Laëtitia Thézénas, Maola Khan, Sébastien R. G. Galan, Lukas Lercher, Matthew W. Schombs, Stefanie Gerstberger, Maria E. Palm-Espling, Andrew J. Baldwin, Benedikt M. Kessler, Timothy D. W. Claridge, Shabaz Mohammed, Benjamin G. Davis, Science, [DOI: 10.1126/science.aag1465]

Nanorings with Copper(II) and Zinc(II) Centers: Forcing Copper Porphyrins to Bind Axial Ligands in Heterometallated Oligomers.
Jonathan Cremers, Sabine Richert, Dmitry V. Kondratuk, Tim D. W. Claridge, Christiane R. Timmel, and Harry L. Anderson,
Chemical Science, 2016, 7, 6961-6968. [DOI: 10.1039/C6SC01809B]

Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases.
Rasheduzzaman Chowdhury, Ivanhoe K. H. Leung, Ya-Min Tian, Martine I. Abboud, Wei Ge, Carmen Domene, François-Xavier Cantrelle, Isabelle Landrieu, Adam P. Hardy, Christopher W. Pugh, Peter J. Ratcliffe, Timothy D. W. Claridge & Christopher J. Schofield, Nat. Commun. 2016, 7:12673, [DOI: 10.1038/ncomms12673].

Scalar cross-relaxation detected in the NOESY spectra of Oxazolidines and Thiazolidines.
Tharindi D. Panduwawala, Laia Josa-Culleré, Ilya Kuprov, Barbara Odell, Mark G. Moloney, and Timothy D. W. Claridge.
J. Org. Chem. 2016, 81, 4142-4148 [DOI: 10.1021/acs.joc.6b00458]

Harnessing NMR relaxation interference effects to characterise supramolecular assemblies.
Gogulan Karunanithy, Arjen Cnossen, Henrik Müller, Martin D. Peeks, Nicholas H. Rees, Timothy D. W. Claridge, Harry L. Anderson and Andrew J. Baldwin.
Chem. Comm. 2016, 52, 7450-7453 [DOI: 10.1039/C6CC02544G]

Development and applications of an efficient NMR ligand-based binding assay for γ-butyrobetaine hydroxylase (BBOX).
Amjad Khan, Robert K. Lesniak, Anna M. Rydzik, Hwanho Choi, Ivanhoe K. H. Leung, Jürgen Brem, Michael A. McDonough, Christopher J. Schofield, and Timothy D. W. Claridge.
MedChemComm, 2016, 7, 873-880. [DOI: 10.1039/C6MD00004E]

Glycosyldiselenides as lectin ligands detectable by NMR in biofluids.
Ignacio Pérez-Victoria, Omar Boutureira, Tim D. W. Claridge and Benjamin G. Davis, Chem. Comm, 2015, 51, 12208-12211

Anomalous Nuclear Overhauser Effects in Carbon-Substituted Aziridines: Scalar Cross-Relaxation of the First Kind.
Ilya Kuprov, David M. Hodgson, Johannes Kloesges, Christopher I. Pearson, Barbara Odell, and Timothy D. W. Claridge, Angew. Chem. Int. Ed. 2015, 54, 3697-3701.

Caterpillar Track Complexes in Template-Directed Synthesis and Correlated Molecular Motion.
Shiqi Liu, Dmitry V. Kondratuk, Sophie A. L. Rousseaux, Guzmµn Gil-Ramírez, Melanie C. O’Sullivan, Jonathan Cremers, Tim D. W. Claridge, and Harry L. Anderson. Angew. Chem. Int. Ed. 2015, 54, 5355–5359

Monitoring conformational changes in the NDM-1 Metallo-β-lactamase by ¹⁹F NMR
Anna M. Rydzik, Jürgen Brem, Sander S. van Berkel, Inga Pfeffer, Anne Makena, Timothy D. W. Claridge, Christopher J. Schofield, Angew. Chem. Int. Ed. Engl., 2014, 53, 3129-3133

Fluoromethylated derivatives of carnitine biosynthesis intermediates – synthesis and applications.
Anna M. Rydzik, Ivanhoe K. H. Leung, Armin Thalhammer, Grazyna T. Kochan, Timothy D. W. Claridge  and Christopher J. Schofield, Chem. Commun., 2014, 50, 1175-1177 ​

A Discrete Three-Layer Stack Aggregate of a Linear Porphyrin Tetramer: Solution-Phase Structure Elucidation by NMR and X-Ray Scattering.
Marie Hutin, Johannes K. Sprafke, Barbara Odell, Harry L. Anderson and Tim D. W. Claridge, J. Am. Chem. Soc., 2013, 135, 12798−12807.

Reporter ligand NMR screening method for 2-oxoglutarate oxygenase inhibitors
Ivanhoe K. H. Leung, Marina Demetriades, Adam P. Hardy, Clarisse Lejeune, Tristan J. Smart, Andrea Szöllössi, Akane Kawamura, Christopher J. Schofield, Timothy D. W. Claridge, J. Med. Chem., 2013, 56, 547-555. ​

Conformational analysis of fluorinated pyrrolidines using ¹⁹F-¹H scalar couplings and heteronuclear nOes
​Lorraine E. Combettes, Philip Clausen-Thue, Mike King, Barbara Odell, Amber L. Thompson, Véronique Gouverneur, and Tim D. W. Claridge, Chem. Eur. J, 2012, 18, 13133-13141​

An approach to enzyme inhibition employing reversible boronate ester formation
Ivanhoe K. H. Leung, Tom Brown Jr, Christopher J. Schofield, Timothy D. W. Claridge., Med. Chem. Comm., 2011,  2, 390-395. ​

Using NMR Solvent Relaxation to Investigate Metalloenzyme-Ligand Binding Interactions
Ivanhoe K. H. Leung, Emily Flashman, Kar Kheng Yeoh, Christopher J. Schofield and Timothy D. W. Claridge, J. Med. Chem., 2010, 53, 867-875.

Group epitope mapping considering relaxation of the ligand (GEM-CRL): Including longitudinal relaxation rates in the analysis of saturation transfer difference (STD) experiments
Sebastian Kemper, Mitul K. Patel, James C. Errey, Benjamin G. Davis, Jonathan A. Jones, Timothy D. W. Claridge, J. Magn. Reson., 2010, 203, 1-10.

Monitoring the Activity of 2-Oxoglutarate Dependent Histone Demethylases by NMR Spectroscopy: Direct Observation of Formaldehyde
Richard J. Hopkinson, Refaat B. Hamed, Nathan R. Rose, Timothy D. W. Claridge, and Christopher J. Schofield, ChemBioChem, 2010, 11, 506-510.

Studies on the reaction of glutathione and formaldehyde using NMR
Richard J. Hopkinson, Philippa S. Barlow, Christopher J. Schofield and Timothy D. W. Claridge, Org. Biomol. Chem., 2010, 8, 4915-4920.

Saturation Transfer Difference NMR reveals functionally essential kinetic differences for a sugar binding repressor protein
Ignacio Pérez-Victoria, Sebastian Kemper, Mitul K. Patel, John Edwards, James C. Errey, Lucia F. Primavesi, Matthew J. Paul, Timothy D. W. Claridge, and Benjamin G. Davis, Chem. Comm., 2009, 5862-5864