Most people will be aware of the tragic story of Thalidomide, a drug that was produced in order to prevent morning sickness in pregnant women. However, though this drug may have been effective initially, due to it’s chirality, the other isomer present in the drug (Thalidomide B) resulted in many birth defects when women later gave birth.
This was a horrendous event that of course, drug companies are seeking to avoid, therefore vigorous testing and research is necessary to avoid this occurring in the future.
So what is chirality? Chirality is in simple terms, the fact that certain molecules have the ability to exist in mirror images of each other, so like our hands, they look alike but cannot be superimposed.
Chirality then is directly correlated to the research being conducted in the School of Chemistry. Dr Niek Buurma and his team, in conjunction with AstraZeneca, and Dr Andrew Leach of Liverpool John Moore’s University, selected a range of compounds from literature, to analyse which of them could racemize, and how quickly this process would occur.
“The project actually started 10 years ago” Dr Buurma explained, “I was talking with one of my friends who worked for AstraZeneca at the time, and we wanted to know something about compounds that racemized, and we started to look at whether there was a lot of information available, and we found absolutely nothing!”
This was the commencement of the journey, as Dr Buurma and team set out to find data points that would help them put pieces of the puzzle together so that some concrete conclusions could be made.
Though the project started with very little ground to work on, this soon took off, as with the use of circular dichroism spectroscopy and 1H NMR and problem solving, the team were able to detect whether compounds would racemize and how quickly this would happen – which was their aim from the beginning. This means that pharmaceutical companies can save time and money, as there will no longer be a need to spend time developing a drug which in the long run, will racemize, no longer be effective and lead to the harm of consumers.
In the abstract of the publication, we find a general scheme of the work that was done: “We show that rate constants for racemization (measured by ourselves and others) correlate well with deprotonation energies from quantum mechanical (QM) and group contribution calculations. Such calculations thus provide predictions of the second-order rate constants for general-base-catalyzed racemization that are usefully accurate. When applied to recent publications describing the stereoselective synthesis of compounds of purported biological value, the calculations reveal that racemization would be sufficiently fast to render these expensive syntheses pointless.” *
So Bryony, how did you get involved with the project?
Bryony: “I was actually working at AstraZeneca last year, and I spoke to Niek about getting involved with the project, because I did analytical chemistry last year and I wanted to do an ‘analytical’ based project. And since it was in collaboration with AstraZeneca, it seemed like the perfect project!” *laughs*
What advice would you give to a student who is looking to get into research, perhaps even with their own idea?
Bryony: “I think if they know what sort of area it’s in, the first thing to do would be to talk to people in that specific area, and if they have their own idea talk it through with them.”
Niek: “I would say that what Bryony did was exactly the right thing because research projects can be really tough, but they become easier when you are interested in what you are doing, and I could see that with Bryony when she told me the work she had done with AstraZeneca, I could see that she was really interested in it.
What would you say was the most rewarding part of being involved in such a project?
Bryony: “In working for a pharmaceutical company, you know how important it is to get stuff like this right and essentially it’s going to affect people’s lives in the long run, so that’s why I really like doing it, because I know it’s going to help someone”
Niek: “For me (I think) I absolutely love puzzles, chemical puzzles and it’s amazing to see how through fundamental research, you can really solve problems or make discovery more efficient which is going to be useful for absolutely everyone. As Bryony was saying it’s the fact that you can do something that you like which is actually useful for everyone!”
*Ballard, A.et al. 2017. A quantitative approach to predicting rate constants for aqueous racemization allows pointless stereoselective syntheses to be avoided. Angewandte Chemie – International Edition (10.1002/anie.201709163)