|Professor in the Department of Chemistry||CG116K||+44 (0) 191 33 42592|
|Member of the Centre for Sustainable Chemical Processes|
AnnMarie O'Donoghue was born in Dublin (Ireland) and obtained her undergraduate BSc degree in chemistry from University College Dublin. She remained at the same institution for her PhD studies in physical organic chemistry under the supervision of Professor Rory More O’Ferrall on the formation and reactions of reactive carbocation intermediates. She was awarded a Fulbright Fellowship to pursue postdoctoral studies in the University at Buffalo, the State University of New York (USA). There she worked on the dynamics of the proton transfer reactions of triosephosphate isomerase. She returned to University College Dublin for a brief period in 2002 as a short-term Lecturer in Organic Chemistry. In 2003, she was awarded a Marie Curie Fellowship for postdoctoral studies on the directed evolution of proteins in the Department of Biochemistry, University of Cambridge (UK). In 2005 she moved to a Lectureship in Organic Chemistry in the Department of Chemistry, Durham University (UK). Apart from a career break in 2008-2009 due to the birth of twins, she has since remained in Durham University as an independent researcher and was promoted to Senior Lecturer in 2012, Reader in 2016 and Full Professor in 2020. Her research focuses on mechanistic studies of organic and biological transformations. She is the 2014 Winner of the Josef Loschmidt Award for Physical Organic Chemistry.
Our research focuses on organic and biological reaction mechanisms with an emphasis on catalysis. Through understanding the strategies underpinning catalysis, we aim to inform the design of improved (enzymic and non-enzymic) catalyst systems. Our research aligns with both the 'Physical Organic Chemistry' and ‘Bioactive Chemistry and Synthesis' Research Groupings in the department and also overlaps with key themes associated with the ‘Biophysical Sciences Institute’. We use a physical organic chemistry (POC) approach towards deciphering reaction mechanisms based on organic synthesis, reaction kinetics, pKa determination and structure-activity studies. We are well-equipped for a range of kinetic methods. Our laboratory houses CARY50 and CARY100 UV-visible spectrophotometers, both equipped with cell changers, that may be thermostatted to temperatures in the 0-100 °C range, and an Applied Photophysics stopped flow spectrophotometer with UV-visible, diode array and fluorescence detection. Our kinetic methods normally rely on the analysis of the incorporation of 2H/13C and other isotopic labels for which we use our state-of-the-art NMR and mass spectral facilities in the department.
Mechanistic Studies of Organocatalysis
Prior to 2000, developments in catalysis had largely focused on metal-based systems. More recently there has been a huge increase in interest in the design and application of non-metal containing organocatalysts. Although the potential for organocatalysis had been recognized some time ago, only recently has attention focused on exploiting this form of catalysis. Organocatalysts are often cheaper, less toxic and less moisture sensitive than many metal-containing analogues. Despite the large increase in the application of small molecule organocatalysts there have been few detailed studies of catalytic mechanism. Catalytic efficiency is still typically inferior to metal-containing catalyst systems and chemoselectivity remains a challenge. In order to fully realize the potential of recent synthetic developments, a molecular-level understanding is required to inform the design of more efficient and selective organocatalysts. Recently, there has been a move towards organocatalysis in more sutainable solvent media including aqueous solution. An improved mechanistic understanding of organocatalytic reactions is needed for the design of better catalysts.
Our group is generally interested in enzyme catalysis of reactions that proceed via unstable carbanion, carbocation, or radical intermediates. Our interests in enzyme catalysis particularly focus on understanding how enzymes achieve such remarkable product specificities. Significant attention has been devoted to the origin of the extraordinary rate accelerations achieved by enzymes, however, much less focus has been dedicated to the key question of how enzymes suppress competing side reactions and achieve product chemoselectivities.
There is a strong driving force for enzymes to follow the same mechanism observed for the corresponding non-enzymatic reaction in solution. Thus an understanding of non-enzymatic solution chemistry is a prerequisite to the study of enzyme mechanisms, and is also a key principle of our research. This encompasses the study of classical reaction intermediates such as carbocations, carbanions and carbenes. More recently, we have a significant additional focus on the formation, reactions and applications of stable organic radicals.
Vacancies and further information
For PhD positions or summer scholarships please contact Dr AnnMarie O’Donoghue via email (email@example.com)
- Physical Organic Chemistry
- Organic Reaction Mechanism
- Enzyme Mechanisms
Chapter in book
- Maguire, O., & O'Donoghue, A. (2015). Homogeneous Acid Catalysis in Nonasymmetric Synthesis. In M. North (Ed.), Sustainable catalysis : without metals or other endangered elements. Part 1 (38-64). Royal Society of Chemistry. https://doi.org/10.1039/9781782622093-00038
- Massey, R., & O'Donoghue, A. (2013). Acid-Base Chemistry of Carbenes. In R. Moss, & M. Doyle (Eds.), Contemporary carbene chemistry (75-106). (1). Wiley. https://doi.org/10.1002/9781118730379.ch3
- Murray, J., Hodgson, D. R., & O’Donoghue, A. C. (2023). Going Full Circle with Organocatalysis and Biocatalysis: The Latent Potential of Cofactor Mimics in Asymmetric Synthesis. Journal of Organic Chemistry, https://doi.org/10.1021/acs.joc.2c02747
- Duan, Z., Young, C. M., Zhu, J., Slawin, A. M., O'Donoghue, A. C., & Smith, A. D. (2023). Rate and equilibrium constants for the addition of triazolium salt derived N-heterocyclic carbenes to heteroaromatic aldehydes. Chemical Science, 14(1), 162-170. https://doi.org/10.1039/d2sc05704b
- Zhu, J., Moreno, I., Quinn, P., Yufit, D. S., Song, L., Young, C. M., …O’Donoghue, A. C. (2022). The Role of the Fused Ring in Bicyclic Triazolium Organocatalysts: Kinetic, X-ray, and DFT Insights. Journal of Organic Chemistry, 87(6), 4241-4253. https://doi.org/10.1021/acs.joc.1c03073
- Collett, C. J., Young, C. M., Massey, R. S., O'Donoghue, A. C., & Smith, A. D. (2021). Kinetic and Structure–Activity Studies of the Triazolium Ion– catalyzed Intramolecular Stetter Reaction. European Journal of Organic Chemistry, 2021(26), 3670-3675. https://doi.org/10.1002/ejoc.202100384
- Quinn, P., Smith, M. S., Zhu, J., Hodgson, D. R., & O’Donoghue, A. C. (2021). Triazolium Salt Organocatalysis: Mechanistic Evaluation of Unusual Ortho-Substituent Effects on Deprotonation. Catalysts, 11(9), Article 1055. https://doi.org/10.3390/catal11091055
- Massey, R. S., Murray, J., Collett, C. J., Zhu, J., Smith, A. D., & O'Donoghue, A. C. (2021). Kinetic and structure–activity studies of the triazolium ion-catalysed benzoin condensation. Organic and Biomolecular Chemistry, 19(2), 387-393. https://doi.org/10.1039/d0ob02207a
- Maguire, O. R., Taylor, B., Higgins, E. M., Rees, M., Cobb, S. L., Simpkins, N. S., …O'Donoghue, A. C. (2020). Unusually high α-proton acidity of prolyl residues in cyclic peptides. Chemical Science, 11(29), 7722-7729. https://doi.org/10.1039/d0sc02508a
- Maguire, O. R., Zhu, J., Brittain, W. D., Hudson, A. S., Cobb, S. L., & O’Donoghue, A. C. (2020). N-Terminal speciation for native chemical ligation. Chemical Communications, 56(45), 6114-6117. https://doi.org/10.1039/d0cc01604g
- Linthwaite, V., Janus, J., Brown, A., Wong-Pascua, D., O’Donoghue, A., Porter, A., …Cann, M. (2018). The identification of carbon dioxide mediated protein post-translational modifications. Nature Communications, 9, Article 3092. https://doi.org/10.1038/s41467-018-05475-z
- Grant, J. A., Lu, Z., Tucker, D. E., Hockin, B. M., Yufit, D. S., Fox, M. A., …O'Donoghue, A. C. (2017). New Blatter-type radicals from a bench-stable carbene. Nature Communications, 8, Article 15088. https://doi.org/10.1038/ncomms15088
- Conway, L., Mikkola, S., O’Donoghue, A., & Hodgson, D. (2016). The Synthesis, Conformation and Hydrolytic Stability of an N,S-bridging Thiophosphoramidate Analogue of Thymidylyl-3ʹ,5ʹ-Thymidine. Organic and Biomolecular Chemistry, 14(30), 7361-7367. https://doi.org/10.1039/c6ob01270a
- Collett, C., Massey, R., Taylor, J., Maguire, O., O'Donoghue, A., & Smith, A. (2015). Rate and Equilibrium Constants for the Addition of N-Heterocyclic Carbenes into Benzaldehydes: A Remarkable 2-Substituent Effect. Angewandte Chemie International Edition, 54(23), 6887-6892. https://doi.org/10.1002/anie.201501840
- Carvalho, A., O’Donoghue, A., Hodgson, D., & Kamerlin, S. (2015). Understanding Thio-Effects in Simple Phosphoryl Systems: Role of Solvent Effects and Nucleophile Charge. Organic and Biomolecular Chemistry, 13(19), 5391-5398. https://doi.org/10.1039/c5ob00309a
- O'Donoghue, A., & Kamerlin, S. (2014). Editorial overview: Mechanisms: Chemical and computational probes of biological mechanism. Current Opinion in Chemical Biology, 21, viii-x. https://doi.org/10.1016/j.cbpa.2014.07.025
- Zanda, M., & O'Donoghue, A. (2013). Young Career Focus: Dr. AnnMarie O'Donoghue (Durham University, UK). Synthesis: Journal of Synthetic Organic Chemistry, 45(13), A89-A90. https://doi.org/10.1055/s-0033-1338881
- Collett, C., Massey, R., Maguire, O., Batsanov, A., O'Donoghue, A., & Smith, A. (2013). Mechanistic insights into the triazolylidene-catalysed Stetter and benzoin reactions: role of the N-aryl substituent. Chemical Science, 4(4), 1514-1522. https://doi.org/10.1039/c2sc22137c
- Massey, R., Collett, C., Lindsay, A., Smith, A., & O'Donoghue, A. (2012). Proton Transfer Reactions of Triazol-3-ylidenes: Kinetic Acidities and Carbon Acid pKa Values for Twenty Triazolium Salts in Aqueous Solution. Journal of the American Chemical Society, 134(50), 20421-20432. https://doi.org/10.1021/ja308420c
- Delley, R., Bandyopadhyay, S., Fox, M., Schliehe, C., Hodgson, D., Hollfelder, F., …O'Donoghue, A. (2012). peri-Dimethylamino substituent effects on proton transfer at carbon in α-naphthylacetate esters: a model for mandelate racemase. Organic and Biomolecular Chemistry, 10(3), 590-596. https://doi.org/10.1039/c1ob06525d
- Delley, R., O'Donoghue, A., & Hodgson, D. (2012). Hydrolysis studies of phosphodichloridate and thiophosphodichloridate ions. Journal of Organic Chemistry, 77(13), 5829-5831. https://doi.org/10.1021/jo300808m
- Higgins, E., Sherwood, J., Lindsay, A., Armstrong, J., Massey, R., Alder, R., & O'Donoghue, A. (2011). pKas of the conjugate acids of N-heterocyclic carbenes in water. Chemical Communications, 47(5), 1559-1561. https://doi.org/10.1039/c0cc03367g