Research Guides

My role in the CRL is as the Director of NMR Spectroscopy for Organic Chemistry which means I am responsible for managing the core NMR facilities, services and support staff.  I am also a University Research Lecturer 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, with examples summarised below.

Protein-ligand binding studies by NMR Spectroscopy

The interaction of small molecules with protein targets is an area in which NMR spectrsocopy 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 have been investigating the use of water relaxation methods as a means of detecting ligand binding with paramagnetic proteins and are applying this it 2-oxoglutarate dependent Fe(II) enzymes involved in oxygen sensing, in collaboration with Prof. Chris Schofield.   

NMR diffusion studies of molecular size, shape and interactions

The study of molecular mobility in solution is now amenable to study by NMR spectroscopy on suitably equipped modern NMR instruments through new pulsed field gradient techniques. There are many areas in small molecule NMR where the characterisation of molecular associations has notable significance, including peptide aggregation, organometallic complexation, small-molecule encapsulation (host-guest chemistry), supramolecular systems and so on. We are employing NMR-based diffusion studies in collaborations with a number of groups in the department to look at the solution-state properties of oligomeric porphyrins, organic dendrimers and ion-pairing complexes.

High-Resolution NMR Techniques in Organic Chemistry. 2nd Edition
T. D. W. Claridge, Elsevier Science, Oxford, 2009.

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.

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

A C-linked Glycomimetic in the Gas Phase and in Solution: Synthesis and Conformation of the Disaccharide Manα(1,6)-C-ManαOPh
Ludovic Drouin, E. Cristina Stanca-Kaposta, Priptal Saundh, Antony J. Fairbanks, Sebastian Kemper, Timothy D. W. Claridge, and John P. Simons, Chem. Eur. J., 2009, 15, 4057-4069.