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Durham University

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Staff Profile

Dr David R.W. Hodgson

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Associate Professor in the Department of Chemistry
Telephone: +44 (0) 191 33 42123

(email at

Research Overview

My research group employs the mechanistic tools of physical organic chemistry to approach biological and synthetic chemistry problems. Key themes are the use of kinetics and the understanding and exploitation of physicochemical properties to enable more effective synthetic chemistry and bioconjugation procedures.

We use these ideas to deliver new methods for the preparation of nucleosides and nucleotides. Our ability to understand reactivity, especially in aqueous solutions, has enabled us to develop convenient bioconjugation procedures for nucleic acids. Our mechanistic approach is also applied to enzymes and understanding polysaccharide biopolymer systems. Our research group is affiliated to the Durham-York Research Consortium.

Nucleosides and Nucleotides

We use aqueous and non-aqueous approaches to prepare nucleosides, nucleotides and phosphate ester mimics. Nucleosides are challenging substrates for synthetic chemists because of their solubility characteristics. They are often barely soluble in both organic solvents and water as a result of intermolecular interactions between nucleoside molecules. This problem is particularly acute for guanosine systems that form gels through hydrogen bonding interactions between guanine base units. We have overcome this problem through using basic conditions that remove a key hydrogen bond donor owing to its relatively low pKa value (~9.5). Once the proton has been removed, substrates are soluble in aqueous media, however, this mandates the use of other tactics to allow functional group transformations to take place and subsequent purification of crude materials to be undertaken.

When organic solvents are employed, there is a requirement to use organic-solvent-soluble phosphate anions to prepare nucleoside di- and triphosphate species. Traditionally, alkylammonium salts have been used in this role, however, they are extremely hygroscopic and the water that they introduce can often have hugely deleterious effects on methods that are used to form phosphoanhydride bonds. We have prepared an alternative organic cation-pyrophosphate salt that does not take up moisture and is a convenient replacement for alkylammoniums.

Understanding Reactivity through Kinetics

We use kinetics to understand how molecules react with each other and how we can improve selectivity through understaning the relative rates of competing hydrolysis processes. Phosphorus (V) chlorides are often considered to be incompatioble with water, however, through understaning the relative rates of hydrolysis vs aminolysis processes we have developed 'click' processes that use POCl3, PSCl3 and their hydrolysis products, which are also effective phosphorylating agents.

We have found that phosphodichloridate anion and its thio analogue, which are both water soluble, are highly selective N-phosphoryaltion agents. Their selectivity derives from the fact that they are anionic AND electrophilic, thus they discriminate against hydroxide anion as a competing nucleophile, but not against neutral amines. Their half-lives are in the order of minutes making them convenient to use without needing rapid mixing systems.


We have developed suites of bioconjugation protocols for nucleic acid and polysaccharide biopolymer systems. Our nucleic acid studies build on our synthetic protocols that give ready access to guanosine derivatives that are initiators for T7 RNA polymerase. The 'handles' that are incorporated can be readily modified with affinity tags or fluorphores for immobilisation and detection purposes.

Polysaccharide biopolymers are the most abundant resources offered by nature and we can capitalise upon them through the development of new conjugation techniques that provide modified systems with new materials properties and bioactivities.

Research Groups

Department of Chemistry

  • Bioactive Chemistry and Synthesis
  • Physical Organic and Assembly

Research Interests

  • Enzymes
  • Nucleotides
  • Physical Organic Chemistry
  • Aqueous Reactivity
  • Nucleic Acids
  • Bioconjugation

Selected Publications

Chapter in book

  • Hodgson, David R.W. (2017). Physicochemical Aspects of Aqueous and Nonaqueous Approaches to the Preparation of Nucleosides, Nucleotides and Phosphate Ester Mimics. In Advances in Physical Organic Chemistry. Williams, N.H. & Williams, I.H. Elsevier. 50.

Journal Article

  • Rozatian, Neshat, Beeby, Andrew, Ashworth, Ian W., Sandford, Graham & Hodgson, David R. W. (2019). Enolization rates control mono- versus di-fluorination of 1,3-dicarbonyl derivatives. Chemical Science
  • Rozatian, Neshat, Ashworth, Ian W., Sandford, Graham & Hodgson, David R. W. (2018). A Quantitative Reactivity Scale for Electrophilic Fluorinating Reagents. Chemical Science 9(46): 8692-8702.
  • Linthwaite, V.L., Janus, J.M., Brown, A.P., Wong-Pascua, D., O’Donoghue, A.C., Porter, A., Treumann, A., Hodgson, D.R.W. & Cann, M.J. (2018). The identification of carbon dioxide mediated protein post-translational modifications. Nature Communications 9: 3092.
  • Eguaogie, Olga, Cooke, Leonie A., Martin, Patricia M. L., Ravalico, Francesco, Conway, Louis P., Hodgson, David R. W., Law, Christopher J. & Vyle, Joseph S. (2016). Synthesis of novel pyrophosphorothiolate-linked dinucleoside cap analogues in a ball mill. Organic and Biomolecular Chemistry 14(4): 1201-1205.
  • Conway, L. P., Mikkola, S., O’Donoghue, A. C. & Hodgson, D. R. W. (2016). The Synthesis, Conformation and Hydrolytic Stability of an N,S-bridging Thiophosphoramidate Analogue of Thymidylyl-3ʹ,5ʹ-Thymidine. Organic & Biomolecular Chemistry 14(30): 7361-7367.
  • Korhonen, H. J., Bolt, H. L. & Hodgson, D. R. W. (2015). A procedure for the preparation and isolation of nucleoside-5’-diphosphates. Beilstein Journal of Organic Chemistry 11: 469-472.
  • Joubert, Fanny, Musa, Osama, Hodgson, David R. W. & Cameron, Neil R. (2015). Graft copolymers of hydroxyethyl cellulose by a ‘grafting to’ method: 15N labelling as a powerful characterisation tool in ‘click’ polymer chemistry. Polymer Chemistry 6(9): 1567-1575.
  • Korhonen, Heidi J., Bolt, Hannah L., Vicente-Gines, Leyre, Perks, Daniel C. & Hodgson, David R. W. (2015). PPN pyrophosphate: A New Reagent for the Preparation of Nucleoside Triphosphates. Phosphorus, Sulfur, and Silicon and the Related Elements 190(5-6): 758-762.
  • Carvalho, A., O’Donoghue, A. C., Hodgson, D. R. W. & Kamerlin, S. C. L. (2015). Understanding Thio-Effects in Simple Phosphoryl Systems: Role of Solvent Effects and Nucleophile Charge. Organic and Biomolecular Chemistry 13(19): 5391-5398.
  • Skipsey, M., Hack, G., Hooper, T. A., Shankey, M. C., Conway, L. P., Schröder, M. & Hodgson, D. R. W. (2013). 5’-Deoxy-5’-hydrazinylguanosine as an initiator of T7 RNA polymerase-catalyzed transcriptions for the preparation of labeling-ready RNAs. Nucleosides, Nucleotides, and Nucleic Acids 32(12): 670-681.
  • Delley, R.J., O'Donoghue, A.C. & Hodgson, D.R.W. (2012). Hydrolysis studies of phosphodichloridate and thiophosphodichloridate ions. The Journal of Organic Chemistry 77(13): 5829–5831.

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