A week in the life of a Radical Chemist
G’day! Welcome to the inaugural #RealTimeChemInFocus post, where I aim to give you a bit of an insight into the world of a radical chemist. Radical in the sense that I work with free radicals (molecules or atoms with an unpaired electron), not my political/social leanings. Read on for an introduction to our work on respiratory disease and atmospheric pollutants as I walk you through a typical week in the life of an organic chemistry PhD student.
The WHO estimates that roughly 7 million deaths per year are caused by exposure to air pollution. It is now well known that living in highly polluted areas makes you more susceptible to maladies such as respiratory disease, allergy, asthma and even death. My PhD aims to work out the underlying chemical processes, or chemical entities, responsible for these biological effects. Using a bottom-up approach, we expose simple biomolecules to pollutant gases and see what kind of havoc they wreak.
The week begins with an outline of the research tasks ahead and, like most, this is one dominated by organic synthesis. For us, this is purely a means to an end. Each peptide we wish to study is carefully designed with respect to amino acid sequence and composition. As we work on gram scale, it is typically more cost effective to synthesise these peptides in-house. That means grunt work and grunt work means coffee, lots and lots of coffee.1
Synthesising each peptide involves protection of the amino acids, a coupling reaction, followed by extraction/washing and purification. Building up larger peptides, such as tri- or tetra-peptides, also involves deprotection and another coupling/work-up. To work efficiently, I often do two or three reactions simultaneously. Each reaction uses the same solvent, reagents and work-up procedure so this saves a lot of time.
The end of the week brings a busy day. Friday means more coffee (#FilterFriday!), our department’s organic chemistry seminar and, today, our group meeting and a couple of radical reactions. These experiments are the true focus of my PhD – new, original research, delving into the effects atmospheric pollutants may have on our body. That means its time to take those peptides prepared earlier in the week and treat them with some ‘pollution’, today it will be nitrogen dioxide (NO2•).
Every time you drive your car you are emitting not only carbon dioxide but also nitrogen oxides (collectively referred to as NOx gases) such as NO2•. This is one of the most abundant radicals in our atmosphere and has been implicated in respiratory disease, being toxic by inhalation. Once upon a time we obtained gas cylinders of pure nitrogen dioxide. As Australia does not produce it locally, they were shipped from overseas but sadly the freight costs are exorbitant and it can be surprisingly difficult to convince a ship captain to receive a cylinder of toxic NO2• gas. Tyranny of distance strikes again. We now produce our own nitrogen dioxide in the lab.
While chemistry is famous for beautiful colours, the field of organic chemistry is typically characterised by white solids, colourless oils and clear solutions. Peptide chemistry doubly so. My favourite chemical reaction, for reasons now obvious, is the classic reaction between copper and concentrated nitric acid. Nitric acid is slowly dripped over solid copper metal (such as the copper penny above), producing a brown noxious gas – our pollutant, nitrogen dioxide. The copper is converted from Cu0 to Cu2+, forming a gorgeous, bright blue solution of copper nitrate. Meanwhile, the nitrogen dioxide passes through a drying tube and is condensed as a liquid which allows us to react a known quantity with our peptides.
Once we have treated our peptides with this simulated pollution, we go through a painstaking process of identifying each product that is formed. This involves repeated HPLC purifications and characterisation with analytical techniques including HRMS, MS/MS, multi-dimensional NMR and, when I’m lucky, X-ray crystallography. Our results so far show that nitrogen dioxide and ozone are a destructive force, modifying residues or cleaving peptide chains. For a nice article on our latest research check out “Nitrogen dioxide and ozone: a sinister synergy” via Chemistry World or the accompanying paper published in Organic and Biomolecular Chemistry.
Over the last few years I have taken great pleasure in becoming a part of the online chemistry community. In particular, the burgeoning #RealTimeChem community is extremely welcoming, friendly and engaging. Whether it’s talking about the latest Nature paper, whingeing about that guy who just lined up 6 hours worth of samples on the NMR queue or asking for tips about how to get that postdoc you’ve always wanted – there’s something for chemists of all kinds. A PhD can sometimes be quite a solitary experience and I love having the opportunity to engage with passionate, creative and ambitious people from all around the globe. Get on there, #RealTimeChem and tweet me some time.
1 Thankfully, I live in Melbourne, Australia’s coffee mecca (sorry Sydney), surrounded by multiple coffee roasters.
Luke Gamon is in the final year of his PhD in chemistry at The University of Melbourne, Australia. Under the supervision of A/Prof Uta Wille, he is currently investigating the effects of pollution on biological molecules. Passions include coffee, baking sourdough, photography, sci-comm and board games.
Blogs at A Radical Approach lukegamon.wordpress.com