Professor Ann O'Donoghue

Professor

Affiliations
Affiliation	Telephone
Professor in the Department of Chemistry	+44 (0) 191 33 42592

Biography

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.

Research Interests

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, pK_a 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.

Enzyme Mechanism

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.