Chemistry World blog (RSC)
‘As for monkshood and wolfsbane, they are the same plant, which also goes by the name of aconite.’ – Severus Snape, Harry Potter and the Philosophers Stone by J. K. Rowling
In Harry Potter’s very first potions lesson he learnt about the magical properties of aconite. Muggle chemists, it seems, are only one step behind the magical world.
Aconitine – spelt slightly differently by scientists – has a highly complex structure that has never before been synthesised in the lab. But now, Duncan Gill from the University of Huddersfield, UK, has been awarded a £133,481 grant to develop a synthetic route to obtain this illusive molecule.
Attempts to make aconitine began after Czech chemist Karel Wiesner revealed its chemical structure in 1959. Weisner went on to publish several papers on the synthesis of alkaloids and terpenoids, an important initial step towards making the molecule. However, it wasn’t until last year that a major milestone was reached, when a team of researchers from the Memorial Sloan Kettering Cancer Institute, New York, announced the total synthesis of the related compound, neofinaconitine. Building on the work of his predecessors, Gill will have to develop new chemical methods to reach his target molecule.
If successful, Gill, who has previously worked as a process chemist at AstraZeneca, will need to be particularly careful when handling this compound. Aconitine is a potent neurotoxin and has been dubbed the ‘Queen of poisons’. One of the most notable references to aconitine comes from William Shakespeare’s Romeo and Juliet: it is the main ingredient in the toxic potion drunk by Romeo with fatal consequences.
The grant has been provided by the Leverhulme Trust and will be enough to employ a full-time post-doctoral advisor. Only time will tell if they can bring this fictional favourite to life in a laboratory setting.
Guest post by Heather Cassell
Sometimes it happens when I’m reading a research paper, sometimes when I’m doing an experiment, analysing data or learning a new technique; or more often when I’m reading Twitter. It’s that moment when you discover something new and interesting, or re-discover a fact that you used to know, and it makes you pause and think ‘ooh, that’s interesting’. For me the discovery usually leads to a massive detour into reading things other than those I was meant to be reading or working on, but I always learn something from it and sometimes it’s actually relevant to my work. Whether it directly affects research or not, the ‘ooh, that’s interesting’ moment is at the heart of scientific investigation.
It can be great when it happens during an experiment, but it can also be deeply frustrating. An unexpected result forces you to seriously consider what is happening and to plan more experiments to further examine the anomaly. This encourages you to combine techniques, make use of all of the resources at your disposal or even seek out new collaborators. If the anomalous result is reliably proved correct and reproducible, then you will need to do more research to explain it. At its best, this is a very exciting time as you will get to learn new skills, create new knowledge and develop partnerships. At its worst, it can shatter your previous assumptions or even show that your idea or product is not as good as you think.
Personally, I really enjoy the flurry of activity associated with learning something new, especially a new experimental technique. I was recently involved with some experiments using atomic force microscopy (AFM) – I had a vague idea of what it was but I had never used this technique before. The analysis produced some amazing pictures but I had no idea what they meant, so I spent an enjoyable afternoon learning all about how AFM works and comparing the results we produced with results already published. The next time we used the machine I could analyse the images as they were formed, which was really helpful for determining if it was showing what we wanted or not. The ‘ooh, that’s interesting’ moment had provided the push I needed to learn a new skill.
Outside the lab, I really love spending time on Twitter. With so many scientists (and non-scientists) from different fields providing links to articles and blogs, there’s always more than enough to read. Just 10 minutes reading tweets can leave me with countless browser tabs open and new favourites to read. It’s now easier than ever to share your ‘ooh, that’s interesting’ moments with the world, meaning a tweet from a researcher half way across the globe can inspire new ways to think about my own research.
It is this process of discovery and continuous learning that is one of the main things I love about science. Now, back to Twitter…
Guest post by Rowena Fletcher-Wood
Scurvy plagued early sailors, and although many treatments were tried and promoted, a simple cure was masked for centuries behind a series of mistakes and misunderstandings.
This story begins at sea, long into a voyage after the fresh food stock had long run out and the sailors were left with only grains, hardtack and cured meats to eat. The sailors would become desperate as scurvy began to set in. Sailors were lost to scurvy in vast numbers, with estimates as high as two million lives lost between 1500–1800 AD.
Scurvy is an unpleasant disease in every way. Although symptoms take weeks or months to develop, they get very nasty. First you become lethargic, anaemic and pale, and all of your joints and muscles ache. You lose your appetite and begin to develop spots on your thighs and legs. Soon you become feverish, sick, and weak; gums soften and bleed, legs swell, old wounds reopen. Depression sets in. Eventually, scurvy takes hold completely: your teeth fall out and gums turn blue, you bleed beneath your skin and from the follicles of hairs. You suffer cardiac arrest and die.
Scurvy is caused by a deficiency in vitamin C (ascorbic acid), which is present in many foods – including tomatoes, sweet peppers, strawberries and spinach – but in particular citrus fruits. Several pathways in the body rely on vitamin C; it is vital for building collagen in tissues. We also use it for lipid metabolism, neurotransmission and strengthening bone and blood vessels. Although many species are capable of synthesising their own vitamin C, humans and a few other animals cannot – it is an essential nutrient that must come from our diet. But until 1927, we didn’t even know it existed.
The ancient Greek physician Hippocrates knew that fresh fruit, especially citrus, had an antiscorbutic effect – it could prevented and cure scurvy. In 1747, James Lind systematically proved that the addition of citrus fruit to the diet both treated and prevented the disease, in a candidate for the first ever clinical trial. But the medical establishment were not convinced, and continued to promote other approaches, including good hygiene, exercise, avoiding tinned meat and improving morale. Some of these approaches were successful, including prescribing the peppery herb scurvy-grass, which is related to horseradish. Unknown at the time, scurvy-grass leaves are rich in vitamin C.
A common belief was that the acidic principle treated scurvy: doctors believed any acid would do and that citric acid in fresh fruits was merely the best. Accidental destruction of ascorbic acid in treatments that would otherwise have been effective was common. Although vitamin C is present in milk, this was destroyed by the new process of pasteurisation, leaving bottle-fed babies susceptible to scurvy. James Lind himself was guilty too, bottling and selling lime juice that promptly oxidised and became useless.
When the 1867 Merchant Shipping Act insisted that all ships carry citrus fruits, fresh lemons were substituted for cheap, abundant West Indian limes which were more acidic but had only a quarter of lemons’ ascorbic acid content. These fruits were juiced, stored in air and piped through copper tubing, oxidising the vitamin C. Later tests in 1918 showed the juice to be almost useless, but at the time this was masked by simultaneous advances in diet and marine travel that reduced the prevalence of scurvy.
We owe the discovery of vitamin C to guinea pigs. Two Norwegian physicians, Axel Holst and Theodor Frølich, decided in 1907 to induce in guinea pigs a disease called beriberi, now known to be cause by a deficiency of vitamin B1. They used the same dietary restrictions they had used to induce the disease in pigeons, but the guinea pigs developed scurvy instead. Pigeons produce their own vitamin C, but like us, guinea pigs cannot. This was an exciting moment in medical history: the diseased guinea pigs were the first examples of non-human scurvy sufferers.
In 1932, the Hungarian biochemist Albert Szent-Györgyi posted a sample of hexuronic acid – which he had isolated in 1927 – to the University of Pittsburgh, asking them to test it on guinea pigs with scurvy. The results would gain him the Nobel prize for medicine five years later, and hexuronic acid was renamed ascorbic acid to celebrate its antiscorbutic effect.
Decades of nutritional experiments and almost–correct hypotheses had seen scurvy become increasingly rare, but it took almost 200 years – from Lind’s nutritional trials to Szent-Györgyi’s experiments – to identify the secret in citrus fruits.
Guest post from Tom Branson
A bright new reaction scheme has found its way to the cover of Inorganic Chemistry. Not content with old standard representations, this journal has been given the professional touch.
Framing metal complexes
The image puts a well needed shine on the conventional reaction scheme and perhaps suggests that we should now be teaching undergrads to paint as well as honing their ChemDraw skills. Two states of a porphyrin derivative complexed with zinc are shown here framed in audacious, golden swirls. And why not? If you’re proud of your work then go ahead and put a huge golden frame around it.
Let’s take a look at that zinc phthalocyanine complex, expertly drawn binding to HS–. Then give it a proton, follow the two giant arrows and you reach liberated hydrogen sulfide and the original zinc phthalocyanine. In case you hadn’t got it yet, the artwork explains for us that this process is all about protonation. The background is also a nice touch. A fantastic network of neurons is on show, blasting off new thoughts of possible bioinorganic applications. Hydrogen sulfide is known to play a role in neurotransmission and its reactivity with metal complexes may find practical applications in that field.
This journal cover art was created by artist Shanna Zentner. She was recommended to the authors of the article by colleagues at the University of Oregon, after she had previously produced artwork for other faculty members.
Zentner’s foray into the scientific literature started when her husband needed a cover for a chemistry journal. They thought a painting of the research would do nicely and so Zentner’s chemistry art career took off. Since then her painting skills have been commissioned for a number of other journal covers, with the artist and scientists often meeting to discuss the work and how to develop the imagery. Zentner champions science communication and believes that this type of work is ‘invaluable to the advancement of scientific literacy in the general public.’
Hydrogen sulfide reactivity
The actual research probes more deeply into the mechanism of H2S binding to both zinc and cobalt phthalocyanine complexes. The team, led by Michael Pluth, show that whilst the zinc variety reversibly binds HS–, the cobalt complex is instead reduced by HS– and can be oxidised back when exposed to air. This redox activity results in a colour change that could be used in colorimetric HS– detection.
Head over to Inorganic Chemistry for the full article and more bright results with metal phthalocyanine complexes.
Guest post by JessTheChemist
‘The noblest exercise of the mind within doors, and most befitting a person of quality, is study’ – Ramsay
A few years ago I had the pleasure of meeting Jack Dunitz at the Swiss Federal Institute of Technology (ETH) in Zurich. Little did I know that he was the academic great-great-grandson of the UK’s first chemistry Nobel Laureate, Sir William Ramsay. After discovering this connection, I decided to delve deeper to see which other chemistry legends Ramsay is connected to.
Ramsay began his career as an organic chemist, but his prominent discoveries were in the field of inorganic chemistry. At the meeting of the British Association in August 1894, Ramsay and Lord Rayleigh both announced the discovery of argon, after independent research. Ramsay then discovered helium in 1895 and systematically researched the missing links in this new group of elements to find neon, krypton, and xenon1. These findings led to Ramsay winning his Nobel prize in 1904 in ‘recognition of his services in the discovery of the inert gaseous elements in air, and his determination of their place in the periodic system’.
Ramsay worked with a wide range of chemists before winning his Nobel prize. At the start of his career Ramsay worked with Rudolf Fittig in Tübingen, Germany. Fittig, a successful organic chemist, is particularly known for discovering the pinacol coupling reaction. Ramsay’s noteworthy academic brothers via Fittig are Ira Remsen and Theodor Zincke. Remsen is recognised for contributing to the discovery of the first artificial sweetener: his co-worker, Constantin Fahlberg, accidentally discovered Saccharin by failing lab etiquette 101 – not washing his hands after a day working in the laboratory.2 On the other hand, Zincke is most famous for supervising the father of nuclear chemistry, Otto Hahn, who claimed the Nobel prize in chemistry (1944) ‘for his discovery of the fission of heavy nuclei’.3 This makes Ramsay the academic uncle of Hahn.
As well as academic brothers and nephews, Ramsay’s direct academic descendants have also achieved greatness. Frederick Soddy, Ramsay’s academic son, carried out research into radioactivity and proved the existence of isotopes, for which he won the 1921 Nobel Prize in chemistry.4 Unfortunately for the chemistry community, Soddy’s interests diverted to economics and politics, so he has no prominent academic offspring to speak of. Interestingly, he also has a lunar crater named after him! Other chemistry Nobel prize-winning descendants of Ramsay include the two-time winner, Frederick Sanger (1958, 1980), and Barry Sharpless (2001), who are both his academic great-great-grandsons. Ramsay also has more diverse Nobel prize winners in his family tree, with two winners for physiology or medicine: Har Gobind Khorana (1968) and Konrad Bloch (1964).
This summary of Ramsay’s academic family is by no means the complete list, but this does demonstrate that one great chemist can have an enormous effect on the generations of chemists to come. As you can see, Nobel prize winners seem to have excellent academic dynasties, but perhaps it isn’t the fact that their mentor won a Nobel prize that inspired them to greatness but their work ethic and abstract way of thinking.
In future posts we will look at other Nobel prize winners and the effect that they may have had on their academic offspring. If there is a particular winner that you would like to see featured, you can contact me on Twitter (@Jessthechemist).
1: Sir William Ramsay – Biographical. Nobelprize.org. Nobel Media AB 2013. Web. 6 Jan 2014.
2: Chemical Heritage Magazine ‘the persuit of sweet:a history of saccharin’
3: Otto Hahn – Biographical. Nobelprize.org. Nobel Media AB 2013. Web. 6 Jan 2014.
4: Frederick Soddy – Biographical. Nobelprize.org. Nobel Media AB 2013. Web. 7 Jan 2014.
I am a postdoctoral fellow at the Institute of Process Research and Development (iPRD) at the University of Leeds. My research is on the synthesis of chiral amines relevant to the pharmaceutical industry but I have a general interest in organic chemistry, catalysis and sustainable methodologies. When I am not in the lab, I blog at The Organic Solution on a range of topics including chemical research, postdoc life and outreach experiences. Recently, I have become interested in the connection between chemists across the globe which has led me to create an academic twitter tree.
To continue this academic tree theme, this blog will explore certain strands of the chemistry Nobel Laureate family tree using the Royal Society of Chemistry’s Chemical Connections. The blog will delve into the life and heritage of different chemistry Nobel Laureates and, amongst other things, we shall find out if having a Nobel winner in your lineage could have an effect on your career, for example, does having a Nobel winner in your ancestry mean you are more likely to achieve academic greatness? If there is a Nobel winner that you would like to see featured, please get in touch.