“Quinine: The bite is in the bark!” received first place at ChemiSTEAM 2021.
Quinine. To me, there is scarcely found a chemical compound that bears a larger significance to the art – and meaning – of synthetic chemistry than quinine. From its humble beginnings as a medicinal tree bark to its contemporary uses as a bitterant in tonic water, the story of quinine is one which blends history and chemistry along the path of its discovery, isolation and eventual synthesis.
Our story begins in the dense Andean jungles of western South America. For centuries, Indigenous tribes regarded the bark of the cinchona tree – native to these jungles and very rich in quinine content – as an effective treatment for various illnesses. Elders and apothecaries alike told legends of fever-ridden individuals, disoriented and lost within the deep jungles of the Andes, who would drink from stagnant pools of cinchona-contaminated water to find their wits miraculously restored. In the late 16th century, fate would carry cinchona bark – and its associated medicinal qualities – on a trans-Atlantic journey into Europe in the hands of Spanish Jesuit missionaries.
In the centuries preceding, malaria – a tremor-inducing disease accompanied by high fevers and tremendous discomfort – would claim the lives of thousands in Europe, wreaking havoc on common citizens and nobility alike. As the presence of cinchona bark – aptly referred to as Jesuit’s bark – spread across the European continent, fate would find its niche use as an anti-malarial agent. As a result, it soon became one of the most sought-after commodities brought across the Atlantic on ships from the dense Andean jungles of the New World to the Old. Still, however, citizens and apothecaries alike were blind to the reason as to why cinchona bark was such an effective treatment – still, they were restricted by their lack of insight as to the chief medicinal ingredient in the bark – quinine. As a result, the use of this bark as a medicinal treatment remained hampered into the 19th century by problems with dosage and availability.
In 1820, however, we see our historical diatribe amalgamate with synthetic chemistry as famed French chemists Pelletier and Caventou perform the very first isolation of quinine out of cinchona bark. The isolation of this natural product and ensuing availability of purified quinine would pave the way for its large-scale, international use. In a near-instant, society was able to spread into malaria-ridden regions of the world previously deemed untraversable, paving the way for the globalized world that exists into modernity. Millions of pounds of cinchona bark were exported for use as its chief source changed from the dense Andean jungles of South America into the Dutch-governed plantations on the islands of Java (present day Indonesia) – by 1913, 97% of the global supply of cinchona bark would be produced on these Dutch plantations in South-East Asia. With effective strategies in place for the isolation of quinine out of cinchona bark, alongside effective methods for the cultivation of the bark itself, it appeared that the story of quinine could be laid to rest. However, a final chapter in the quinine story was yet to be written – that of its synthesis.
The synthesis of quinine had levied the eyes of chemists since its isolation. In fact, it was during an attempted synthesis of quinine over the Easter weekend of 1856 that 18-year-old William Henry Perkin would make his famed discovery of mauvine dye – a discovery that would launch the birth of the modern chemical industry. In the years that followed, while a synthetic route to manufacture quinine was deemed as intriguing, it carried with it little urgency as a result of the abundant availability of the compound via natural product isolation. This tide would change, however, during World War II as the western world would have its trade links to the Dutch-plantations of Java – their principal source of cinchona bark – severed. Enter R.B Woodward – a legendary figure to many synthetic chemists and a man who needs no introduction. In 1944, while working as an assistant professor at Harvard University alongside postdoctoral researcher William von Eggers Doering, Woodward achieved the first (formal) total synthesis of quinine. These two researchers – both under the age of 30 – were hailed as war heroes for their efforts as their faces were plastered across news stations and magazines around the world. While their synthesis would find itself too contrived to be of actual industrial value, it represents a valiant ending to a synthetic journey that had been pursued by chemists for centuries.
About the artwork:
This painting depicts the structure of quinine, coloured to match the approximate electronic topography of each atom. Overlayed is a rough depiction of the FID and 1H-NMR spectrum of the compound.
In modernity, if faced with the question of “what is quinine” it becomes remarkably simple to arrive at more answers than one could ever make use of. Dozens of reviews exist detailing every single aspect pertaining to quinine, all of which are available to us in the 21st century in a split-second after a quick Google search. As a chemist – and as a citizen in the modern era – it is important to appreciate the four-hundred years of advancement that led us to this point. From its discovery in the dense Andean jungles, through to its medicinal use across Europe in its non-isolated form as ground-up tree bark, quinine aided society before society even had a hint of insight into why it behaved as it did. To me, quinine represents the ultimate goal of synthetic chemistry – to discover a compound out of nature that helps humanity, isolate it such that it can be used globally and devise a method for its synthesis.
About the artist:
Adam is a third-year PhD student working in the lab of Prof. Stephen Newman at the University of Ottawa. His research concerns itself largely with developing new strategies for the nickel-catalyzed activation of strong carbon-oxygen bonds. Knowing how difficult it is to find adequate ways to bridge the gap between art and science, he is thankful for the opportunity to present his work in this edition of CIC NEWS. For more on Adam’s contributions to science and art, visit his website at www.thechempire.com.
Adam also took part in ChemiSTEAM 2020. Take a look back at Adam’s entry from 2020 in this past issue of CIC News.