This essay was written by lower-sixth former Jack Doyle, and shortlisted for the 2020 Fifth Form Transitional Research Project. The following provides a short abstract to the full essay, which can be found at the bottom.
Estimated read time of abstract: 3 minutes Estimated read time of essay: 15 minutes
In 2019 the University of Liverpool published their findings, in the British medical journal, on the unusual and unprecedented rise in infant mortalities within the UK. [1]This conclusion made goes entirely against the tide of lowering infant mortality rates in high income countries. In contraray to common belief, we are not yet at the stage where every child born will be healthy or even survive, and this is amplified across lower income countries around the world. There are many causes to new-born death and disability, with one of them being the lack of blood flow to brain leading to brain tissue being damaged, this is called neonatal hypoxic encephalopathy (HIE’s) [2]. There are numerous research groups worldwide that are looking into ways of treating and preventing this condition, minimising its impact on babies globally. One of the exciting and promising treatments that has shown potential in early trials is Xenon, an inert gas found in our atmosphere.
Xenon is easy to administer which means can be used in pre-existing and low cost delivery settings, with the onset of effects on the baby being rapid and controllable [3]. Xenon has a high tendency to combine with lipids, meaning that it can cross across the placenta to the baby. This tendency to combine with lipids also leads it to it being able to bypass some of the hurdles the brain puts up to prevent substances getting into it [4]. Side effects to the mother, due to delivery occurring through the mother by inhalation, seem to be minimal with the effects on the baby also being similarly minute [5]. The gas itself is expensive, caused by the arduous extraction of this gas, however multiple systems are being developed that could recycle this gas from patients. This would make Xenon treatment much more feasible and economically viable, even for use in lower income countries [6]. More work has to be done to rule out harmful interactions with other treatments, however current understanding suggests there aren’t significant interactions known.
Most importantly there have been numerous studies shown that suggest that it has beneficial effects on the outcomes of new-borns in treatment pre and post delivery. Furthermore, it has been shown that not only does it halt the progression of damage but it also potentially reverses tissue damage to a certain degree, however the way in which it does this nor the reliability of these findings are known. [7] [8] [9]
Currently the treatments for this HIE’s in newborns are very limited with the only widespread treatment is cooling. This has been shown to have an effect on limiting damage, but does not have that high of a success rate nor the ability to reverse damage. Therefore new treatments need to be developed, and the use of treatments alongside cooling could be an effective method of treatment. Studies showing Xenon in conjunction with cooling have also shown a potential benefit above Xenon solely. [10]
Despite all this there have also been a number of studies that show it does not have a noteworthy beneficial effect, therefore the evidence for it working is conflicting. Theoretically and on paper it should work effectively with a number of academics and researchers that I have talked to suggesting that it could have some benefit. More research would need to be done on this and its effects before Xenon could be used in confidence, but it is a promising drug for a fatal condition that desperately needs effective treatments.
With thanks to Dr Richard Daneman (Department of Neurosciences and Pharmacology at University of California, San Diego) and to Dr Robert Dickinson (Department of Surgery and Cancer at Imperial College, London)
To view Jack’s full article, follow this link below.
H. S. M. S. Y. N. F. I. S. M. T Goto 1, “Xenon provides faster emergence from anesthesia than does nitrous oxide-sevoflurane or nitrous oxide-isoflurane,” June 1997. [Online]. Available: https://pubmed.ncbi.nlm.nih.gov/9197295/. [Accessed 28 October 2020].
F. John Dingley, F. George P. Findlay, F. Bernard A. Foëx, P. John Mecklenburgh, F. Mohammed Esmail and P. F. Roderick A. Little, “A Closed Xenon Anesthesia Delivery System,” Anesthesiology , January 2001. [Online]. Available: https://anesthesiology.pubs.asahq.org/article.aspx?articleid=1945203. [Accessed 28 October 2020].
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*. T. L. J. X. H. T. Y. W. H. Z. M. H. P. H. M. a. M. M. Daqing Ma, “Xenon Preconditioning Protects against Renal Ischemic-Reperfusion Injury via HIF-1α Activation,” April 2009. [Online]. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663824/. [Accessed 28 October 2020].
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M. P. a. D. M. F. M. Sandra E. Juul, “Pharmacological neuroprotective strategies in neonatal brain injury,” 1 March 2015. [Online]. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929237/. [Accessed 28 October 2020].
Winner of the University of Gloucestershire Biosciences Essay Competition 2020 with a £1000 cash prize, this short read article was written by sixth-former Matt Gray.
Estimated read time: 5 minutes
Imagine a world where meat is environmentally friendly, where plastic is green and microbes suck all those pesky greenhouse gases out of the sky. I concede that it is a ridiculously far-fetched scenario. Or is it? The relatively new field of synthetic biology has outlandishly claimed that all of this is not just possible, but probable.
The lines between synthetic biology and other closely related fields such as genetic engineering are truly blurred which means defining synthetic biology is challenging. However, for the purposes of this essay I will use a definition drafted by a consensus of European experts which states that “Synthetic biology is the engineering of biology: the synthesis of complex, biologically based (or inspired) systems, which display functions that do not exist in nature” (1). Effectively, synthetic biology seeks to design new systems and life processes that provide a valuable function to humans.
One of the biggest problems facing the world today is food security. By 2050 the UN predicts food production will need to increase 70% from 2013 levels to feed the growing population (2). But with 90% of fish stocks having been used up (3), land degradation and the unsustainable demand for meat (4) how is this possible without devastating ecological impact? Synthetic biology may hold the answer. Fish feed is the biggest cost of the $232 billion dollar fish farming industry and one of the biggest causes of overfishing for small fish such as anchovies which are ground up to make the feed (5). What if you could engineer microbes that would make the fish feed from greenhouse gases rather than fish. Novonutrients, a Californian company, has used synthetic biology to do exactly that. They have successfully engineered microbes to absorb carbon dioxide and create protein as their product (6). Does synthetic biology also hold the answer to the unsustainable demand for meat (7)? Synthetic biology allowed the now ubiquitous impossible burger to achieve its “meaty” taste by taking the DNA from soy plants and inserting it into modified yeast cells (8). These yeast cells then serve as mini factories producing heme, the magic molecule responsible for the taste. With lab grown eggs (9) and foie-gras (10) already in production synthetic biology is a genuine way to keep “meat” as part of our diets long into the future.
What about pollution? In 2016 researchers discovered two enzymes that allowed bacteria to feed on PET plastic (11) – most commonly used for plastic water bottles – and since then researchers have been feverishly working to improve their effectiveness. In 2020 researchers at a synthetic biology lab at the University of Plymouth identified that when two separate enzymes PEThase and METhase were combined they could degrade PET 6 times faster than before (12). Currently PET is recycled by heating it to a whopping 270C which – aside from being expensive – releases volatile organic compounds which exacerbate air pollution. Although enzymes like these are not yet commercially viable in the near future they could provide a cleaner, safer and less energy intensive solution to recycling plastic. But why stop there? Currently plastics are manufactured from crude oil – a substance so environmentally notorious it needs no introduction – but what if we could create them from a different material. Newlight Technologies has created an enzyme which combines methane – the 2nd most abundant greenhouse gas (13) – and air to form a plastic-like biomaterial (14). With plastics made from greenhouse gases and recycled by supercharged enzymes a whole new industry of green materials could form.
That’s how I believe synthetic biology could save the world by repurposing greenhouse gases, creating green materials and ensuring food security, but how might it destroy it?
In 2002 researchers created the first ever synthetic virus, based on polio (15) and in 2017 Canadian researchers published a study about how they had used mail order genetic components to synthesise horsepox, one of smallpox’s closest cousins (16). The potential for smallpox to be synthesised and unleashed upon the unvaccinated modern world is horrifyingly real and although organizations have taken action to minimise the risk of bioterrorism, for example the CDC in America retains copies of smallpox vaccines, its potential in the hands of a rogue state is frightening. Synthetic biology’s ethical quandaries don’t end with bioterrorism. Fears of scientists playing god, designer babies and the potential for too much power to fall into far too few hands also loom over the field.
Yet it is irrefutable that the age of synthetic biology is here and it will affect all of our lives. I therefore believe there has never been a more important time to be a biologist to ensure that the opportunities presented by synthetic biology are used for prosperity and progress rather than pandemics and predatory politics.
References
1. Synthetic biology: promises and challenges. Serrano, Luis. 1, s.l. : Molecular Systems Biology, 2007, Vol. 3.
11. A bacterium that degrades and assimilates poly(ethylene terephthalate). Yoshida, Shosuke, et al. 6278, s.l. : Science, 2016, Vol. 351.
12. Characterization and engineering of a two-enzyme system for plastics depolymerization. s.l. : Proceedings of the National Academy of Sciences of the United States of America, 2020.
This essay was written by upper-sixth former Alex Thow, and a finalist for the 2020 Independent Learning Assignment. The following provides a short abstract to the full essay, which can be found at the bottom.
Estimated read time of abstract: 5 minutes Estimated read time of essay: 45 minutes
Quantum mechanics is difficult. It is confusing. It is illogical. Albert Einstein himself hated the concept, stating, “If it is correct, it signifies the end of physics as a science”. Erwin Schrödinger, one of the great names in early quantum mechanics, said, “I do not like it, and I am sorry I ever had anything to do with it”. Even Richard Feynman, one of the greatest teachers physics has ever seen, went so far as to say, “I think I can safely say nobody understands quantum mechanics.” Despite all this, it manages to answer some of the most interesting questions out there in a beautiful way. In my ILA I explored the answer to the question of how it is certain molecules have colour.
To begin we must mention molecular orbitals (MOs). Some of the mathematics behind these MOs is discussed in the main text, but unfortunately it is too complicated to go into here, so the results will have to speak for themselves. Electrons in molecules are never in one place – we have quantum mechanics to thank for that. They are spread out unevenly around the molecule and the regions that they occupy are the MOs. There are many MOs in each molecule to accommodate all the electrons, as only two electrons can occupy any given orbital due to an effect called the Pauli exclusion principle. The different distribution of electron density within each MO leads to the MOs having different energies. The highest energy MO with an electron in it is called the HOMO (highest energy occupied molecular orbital) and the lowest energy MO that does not contain an electron is called the LUMO (lowest energy unoccupied molecular orbital). These orbitals are key in so many areas of chemistry, including the chemistry of colour, as it turns out that an electron in the HOMO can absorb the energy in a photon and jump up the LUMO. The energy of a photon of light is directly proportional to the frequency of the light, and so the energy gap between the HOMO and the LUMO determines the colour of light that is absorbed. The colour we see is simply the complementary colour to what is absorbed, as the rest of the spectrum is reflected.
Now, my ILA would have been a lot shorter if it were simple for the HOMO-LUMO energy gap to be in the right range for visible light to be absorbed, but unfortunately this is not the case for most molecules as they generally absorb UV light. The main structural feature that coloured molecules require is something called a conjugated system, which is a chain of alternating double and single bonds (these are generally bonds between carbon atoms as the molecules we are interested in are organic). A clear example of this is in beta-carotene, the molecule that gives carrots their orange colour.
A structure like this results in an important phenomenon called delocalisation, which spreads out the MOs over the chain, allowing the electrons to move freely across it. It is actually possible to come up with an expression relating the length of the chain to the absorbed wavelength, which was done in my ILA. The result is that a molecule needs a conjugated system with at least five or six double bonds before it can absorb visible light, and hence we see why most molecules are in fact colourless.
The synthesis of dyes requires an understanding of their structure. We already know that they must contain a conjugated system, and this part of the dye is called the chromophore. Any additional groups attached slightly alter the colour of the dye and are called auxochromes. The variety of structures this vary broad description allows is immense. A number of the chromophores explored in my ILA are shown below to show just how varied the dyes can be.
It is all well and good being able to create dyes, but they are useless if we have no way of attaching them to materials. Material structure is very diverse, but often the materials we dye have polymer structures. For example, plant fibres are composed of cellulose, a polymer of glucose. Animal fibres are made of proteins which are chains of amino acids. Even synthetic materials such as nylon are polymers. These polymers can stack together and align, creating a fibrous structure with pores running through it. The dye molecules are able to travel through these pores and attach themselves to the material through different kinds of bonding.
Direct dyes are the simplest to apply as these form strong enough interactions, often ionic or strong dispersion forces, to hold the dye in place without any other input. Another type of dyes called reactive dyes can quite literally react with the material, forming strong covalent bonds to it. An example of this is shown below.
There are, however, situations when the dye cannot hold itself onto the material well enough, and a mordant must be used. Mordants are inorganic metal salts that help fix a dye to a material. The metal ion in the mordant forms something called a chelation with both the dye molecule and the material, acting as a bridge between them, holding them together. The structure of one of these chelations is shown here.
Dyes are not just useful in the chemical world; they occur all the time in nature too. Two interesting examples I covered in my ILA were retinal and chlorophyll. Retinal is able to harness its ability to absorb visible light to help us see colour by altering its structure when it absorbs light. Chlorophyll is able to use the energy it absorbs from visible light to help plants photosynthesise. So, it really is impossible to go anywhere without seeing, wearing, or using dyes in some shape or form and it is impossible to deny their importance in our world.
To view Alex’s full article, follow this link below.
This essay was written by lower-sixth former Ishan Nathan, and shortlisted for the 2020 Fifth Form Transitional Research Project. The following provides a short abstract to the full essay, which can be found at the bottom.
Estimated read time of abstract: 2 minutes Estimated read time of essay: 15 minutes
The academic study of prime numbers has been of mathematical interest for centuries and over time remarkable progress has been made in understanding the unique properties and patterns of these numbers. Over the last fifty years, the discovery of mathematical models has aided the progression of computer science. Whilst encryption, previously used for communication in the wars, has now been adopted into quotidian life. Mathematicians have discovered new methods for the secure transmission of information and have augmented them by introducing new messaging platforms using encryption algorithms based on prime numbers.
It is widely accepted that Prime numbers are important in the field of number theory as they act as the “atoms of arithmetic”. They are defined as natural numbers greater than one, that are only divisible by exactly two numbers, one and itself. Mathematicians first studied primes explicitly in 300BC in Ancient Greek Mathematics, where Euclid proved that there was an infinitude of primes. Since then the understanding of primes has developed and the characteristics of primes enable it to have profound applications in security codes, blockchain analysis, cicada’s cycles, and Cryptography. Nevertheless, mathematicians do not understand the primes fully, due to their enigmatic behaviour whereby they appear to act randomly despite having some aspects of their behaviour which are predictable.
Prime numbers and their application to modern-day life is not always apparent, as is their properties and patterns. Yet prime numbers play a fundamental part in our lives and act as a cornerstone for both: day to day messaging on encrypted platforms such as WhatsApp, and for consumers’ online e-commerce activities. The emergence of the internet has led to an increase in the number of online transactions taking place all over the internet on sites like eBay and Amazon, and modern-day cryptographic methods establish a mechanism for a secure form of communication.
The RSA algorithm relies upon the quick speed for performing operations to determine large primes, and the computer-intensive reverse process in factorising large integers, in turn assuring the security of public-key cryptography. It is this high level of encryption that ensures the world of e-commerce to function protecting our sensitive information such as credit cards from the global market place. Yet what if there was a way to overcome this?
The Riemann Hypothesis is widely accepted as one of the biggest mathematical unproven conjectures of our millennium. It is argued that the Riemann Hypothesis predicts the distribution of the primes and their unpredictable behaviour better than any other theorem. An abstract proof of the Riemann Hypothesis will undoubtedly enhance our understanding of primes and thus could lead to vulnerabilities within asymmetric cryptography. However, primes are special and they are like no other group of numbers. Despite mathematicians limited understanding of these numbers, a secure online communication network across the world has been created; just imagine the possibilities that could unravel when understanding the true enigmatic behaviour of prime numbers.
To view Ishan’s full article, follow this link below.
This essay was written by lower-sixth former Moog Clyde, and shortlisted for the 2020 Fifth Form Transitional Research Project. The following provides a short abstract to the full essay, which can be found at the bottom.
Estimated read time of abstract: 1 minute Estimated read time of essay: 11 minutes
In 1654, the Chevalier de Mere, a French nobleman, posed the notorious ‘Problem of the Points’ to Blaise Pascal, an esteemed mathematician. The Problem of the Points concerned a game of chance containing two players with equal chances of winning any given round, and posed the question of how to split the stakes if one gambler has to leave the game prematurely. Despite several attempts, finding a definitive solution stumped even the greatest minds of the previous two hundred years, most notably Luca Pacioli (the ‘Father of Accounting’ ) in 1494 and Niccolò Tartaglia (solver of cubic equations and the first to apply maths to the paths of cannonballs, otherwise known as ballistics) in 1556. Even the great Galileo failed to discover a reasonable solution to the problem. Pascal was determined to find a logical and fair solution, and thus reached out to Pierre de Fermat, a brilliant mathematician himself. In their resulting correspondence, the pair developed the first explicit reasoning about what today is known as ‘expected value’ and laid the groundwork of probability, earning them both joint title of ‘the Fathers of Probability.’
Although it is easy to underplay the significance of this breakthrough as merely a clever, tidy solution, to appease opposing gamblers, in reality, it was truly revolutionary. It is difficult to understate how vast and significant the cognitive shift across Europe that occurred following this solution was. The notion that you can hang numbers into the future was alien to mathematicians merely years before this solution was proposed. Soon, others began to see the possibilities that this concept generated.
Within three years Christiaan Huygens adapted Fermat’s theory into a coherent pamphlet entitled ‘De Ratiociniis in ludo aleae,’ which was used as the standard text on probability for the next 50 years. Huygens attributed his developments to “some of the best mathematicians of France” (i.e. Pascal and Fermat). This text spread like wildfire among the academic community as it was evident that the new science of probability had the potential to transform the world. In the next few years, Huygens’ text was ripped out of the context of gambling and thrust into several aspects of life, including law and maths. In particular it was applied to a very different, brand new data set: mortality tables. Almost immediately, by using specific intricate data, insurance shifted from a form of blind gambling, based on hunches and guessing, to a remarkably accurate science.
It now is clear that this rapid chain reaction of discovery underpins all notions of mathematical ‘expected value’ and insurance came not from savvy merchants but from avid gamblers, eager to improve their craft.
To view Moog’s full article, follow this link below.
This essay was written by upper-sixth former Ben Watkins, and a finalist for the 2020 Independent Learning Assignment. The following provides a short abstract to the full essay, which can be found at the bottom.
Estimated read time of abstract: 1 minute Estimated read time of essay: 15 minutes
Is it possible that there are always two places on earth with the same temperature and pressure? How does the game show Blockbusters have any implications on algebraic topology? Can a general equilibrium ever be reached in an economy? Perhaps most crucially of all, can you ever truly mix a cup of tea?
My ILA provides insight into Brouwer’s fixed point theorem, a theorem found in the field of algebraic topology. It uncovers how a remarkable and seemingly counterintuitive result in what is often considered to be an abstract field of mathematics can have such broad and pertinent results in the real world. However, this isn’t to say that this ILA doesn’t uncover the result of this theorem for the sake of the beauty of it as much as uncovering it for the sake of its applications. Indeed, Luitzen Egbertus Jan Brouwer himself (the discoverer of this theorem as well as often being called ‘the Father of Topology’) was very much an upholder of this mentality: that maths has great importance for the sake of maths itself. Philosophically, Brouwer was a neo-intuitionist, which means that he thought of mathematics as purely a mental phenomenon, the result of constructive mental activity rather than uncovering any principles of an objective reality. He is often quoted in saying that “The construction itself is an art, its application to the world an evil parasite.”
To view Ben’s full article, follow this link below.
This essay was written by upper-sixth former Salvatore Nigrelli, and was the winner of the STEM category for the 2020 Independent Learning Assignment. The following provides a short abstract to the full essay, which can be found at the bottom.
Estimated read time of abstract: 4 minutes Estimated read time of essay: 1 hour 15 minutes
Supramolecular chemistry is all about making functional molecular assemblies without chemically bonding the component molecules together. Take the reaction scheme below:
Figure 1 The Formation of a Tennis Ball Capsule
In this scheme, two molecules are held together only using hydrogen bonds, to form a tennis ball shaped capsule. So it is the art of the supramolecular chemist to try and find innovative ways of making complex assemblies, with only a handful of intermolecular forces at their disposal. This is particularly shown in a type of structure called supramolecular cages.
Cages are ubiquitous throughout the world of chemistry. The Buckyball (Figure 2, is a simple type of molecular cage, consisting of 60 carbon atoms in a spherical shell arrangement.
Figure 2 The Structure of a Buckyball
Supramolecular cages take this idea one step further and ask the question: Can we design assemblies that allow us to put a small molecule ‘prisoner’ inside the cage?
Take the Buckyball again. Using a type of complex reaction sequence called a molecular surgery reaction, it is possible to open the Buckyball up and place a water molecule inside, held in by the London forces it can form with the cage walls, transforming the Buckyball into an exciting supramolecular cage (Figure 3).
Figure 3 A Buckyball with an Encapsulated Water Molecule Inside
But you may ask, is there actually any point in making these tiny molecular prisons, or is it purely to indulge a few curious supramolecular chemists? The answer is that, although the field is relatively new, it is becoming paramount that the applications of supramolecular cages are innumerable, from security to chemical analysis, and even cancer therapy.
Cyclobutadiene is a pesky, annoying molecule – mainly because it reacts with itself extremely quickly in a dimerisation/isomerisation reaction to produce cyclooctatetraene:
Figure 4 The Dimerisation/Isomerisation Reaction of Cyclobutadiene
This self-reacting property of cyclobutadiene makes it extremely difficult to probe its chemical structure. Until only a few years ago, the only way that it had been achieved was by holding the molecules in an argon matrix close to absolute zero. However, with the advent of supramolecular cages, all of this changed. If you make a single cyclobutadiene molecule inside a type of supramolecular cage called a carcerand (Figure 5), no other molecules can get to it, so it stays in its original, undimerised form, and can be analysed using NMR spectroscopy. This is a classic example of how supramolecular cages are already revolutionising the field of chemistry.
Figure 5 An Example of a Carcerand
However, not all of the uses of supramolecular cages lie in a lab. The cage below is one such cage with extremely promising applications. In the presence of picric acid molecules, the cage can encapsulate one of them. Once the picric acid is inside the cage, it is close enough for a type of photochemical process called a Förster Resonance Energy Transfer to take place, which causes the cage to completely change colour. This is incredibly useful because picric acid is one of the most common explosives, so cages like these could be used in the next generation of fast, accurate explosives detectors and save countless lives.
Figure 6 A Supramolecular Cage to be Used in Explosives Detection
Looking into the monumental applications of supramolecular cages got me thinking – could I use the skills in supramolecular chemistry that I picked up over the course of my ILA and design a novel type of supramolecular cage to solve a real world problem? I decided to try and solve the problem of fluorouracil as a chemotherapy drug. The essence of the issue is that fluorouracil is an extremely promising cancer drug, but it also readily attacks brain tissue, and so its use is limited to very extreme cases. This appealed to me as a problem to solve because of the great positive impact that it would have, and the fact that fluorouracil (Figure 7) has a number of structural features that make it very attractive to supramolecular chemists.
Figure 7 The Structure of Fluorouracil
Fluorouracil can form three strong interactions with its fluorine and two nitrogen atoms that would allow it to be readily encapsulated. So if a cage with three parallel bars could be designed, it would strongly bind the fluorouracil molecule. However, finding a chemical arrangement that allows this to take place proved to be difficult, as it is a rare occurrence in chemistry. In the end, I managed to work out that if the cage used molybdenum centres with thiophene ligands, a trigonal prismatic arrangement around the molybdenum atom would be obtained (Figure 8) , making the three parallel bars possible.
Figure 8 A Molybdenum-Thiophene Complex Showing a Trigonal Prismatic Geometry
The key principle behind the cage is that the fluorouracil molecule stays inside the cage, so it cannot react with anything, until it enters the cancer cells, where the cages are opened, thereby allowing the fluorouracil to kill only the intended cancer cells. This targeted opening is a rather unusual feature of molecules, and so in the end I used the fact that, if nitrophenyl ether groups (Figure 9) were placed on each bar, in the presence of a targeted beam of UV light, the cage could be successfully opened once inside the intended cancer cells.
Figure 9 A Nitrophenyl Ether Group
My final cage design is shown below:
Figure 10 My Final Cage Design
To summarise how my design works: Outside of the body, fluorouracil is encapsulated inside the cage, then a solution containing the encapsulated fluorouracil is injected into the patient’s bloodstream. Whilst inside the cage, no other molecules can get to the fluorouracil so it cannot react with anything and cause its bad side effects. Once the cage reaches the cancerous cells, using UV light, the cages in the cancer cells are opened, releasing the fluorouracil and killing only the intended cells. Therefore, this scheme allows for fluorouracil to be used to treat cancer patients, without causing any negative side effects.
To view Salv’s full article, follow this link below.
This article was written by fifth-former Janek Czarnek, and provides a shortened abstract of his original essay titled: “The Use of Pesticides: Beneficial or Detrimental”. To view his complete article, click the link at the end.
Estimated read time: 4 minutes
The Uses and Consequences of Pesticides and the Viability of Alternatives
It is clear that pest protection is key to agricultural sustainability globally, which is now more important than ever, as with a rapidly growing human population the demand for food is only becoming greater. It is estimated that between 26% and 40% of the world’s crop yield is lost each year due to pests, and this could rise up to 52% to 80% without the use of crop protection (1). Pesticides are chemical compounds used to kill pests, which can include any destructive organism that is a vector of disease or attacks crops or livestock. Not only are pesticides effective, at least in some circumstances, at directly eliminating the threat of pests, but they can also have secondary benefits such as preserving soil quality (1). However, although pesticides may be effective in some circumstances, their true long-term effectiveness and the consequences that they impose on non-target plants and animals pose an important question about their suitability for continued usage. Pesticides can have devastating consequences on non-target organisms and biodiversity, especially on fish where upon entering water sources can kill many fish through acute poisoning or oxygen depletion (2). Considering these effects on biodiversity, alongside increasing resistance to pesticides due to their great usage, are pesticides an effective long-term solution? Are they beneficial or detrimental to us, humans, and non-target plants and animals?
Although there are many consequences to pesticide usage, one cannot forget the crucial role they play in crop protection that serves benefits both for food and biofuel production, as well as in disease control and infrastructure maintenance. A full evaluation of how pesticide usage should change in the coming years must consider how their impacts can be mitigated and whether there are viable alternatives that can effectively protect crops on the scale needed.
Firstly, it is important to note that in some cases the consequences of pesticide usage can largely be mitigated through more careful, and even more regulated, application of these chemicals in a way that is less impactful on the surrounding ecosystems and organisms in addition to those who apply them. Mitigations of the consequences of pesticide use can include simply reading and following labels more closely (3), or using pesticides that do not leach and using more direct application rather than spray application to reduce pesticide drift and subsequently reducing the effects on surrounding ecosystems (3). Farmers can also be advised to leave a ‘buffer zone’ of crops around the edges of fields and agricultural land where pesticides have been used in order to reduce the chance of non-target plants and animals coming into contact with the pesticides (3). Responsible pesticide application can also include taking into consideration the surrounding geography as well as the weather; pesticides should be applied in dry conditions where rainfall is not forecasted because this prevents leaching and surface-run off water carrying the pesticide chemicals away and potentially affecting non target organisms (4). Similarly, pesticides should be avoided where the temperatures are high and when plants are suffering drought as this will increase the rate of transpiration where pesticides can dissolve into water and be dispersed (4). Many other precautions can also be taken; however, it is important to realise that many of the damaging consequences of pesticides can be reduced by taking actions considerate of the surroundings and using them responsibly.
On the other hand, safer alternatives that can still effectively protect crops are always preferable. Many of these alternatives come under the branch of organic integrated pest management, which includes several methods to control pests in an environmentally sustainable manner (5). An important part of this is effectively preventing pest populations growing in large numbers through methods such as companion planting, where plants that repel certain insects are planted, and biological control, where natural predators are introduced to organically control pest populations (6). An example of introducing natural predators is that of utilising ladybird larvae which are effective at managing aphid populations (6) or other symbiotic relationships such as that of fish in rice fields where fish will eat the pests attracted to the rice (7). In Bangladesh it was observed that pest infestation in rice fields containing only rice were 40-167% higher than those that also contained fish (7). Preventive measures can also be combined with increased monitoring of pests and mechanical pest control through means such as fences and nets to reduce access of pests to crops. Alternative chemical means to protect crops have been developed through genetic modification; for example, the genomes of maize and cotton have been altered to include genes that make the plant toxic to pests and hence protect themselves and the surrounding crops (8). All these methods can greatly reduce the impact that pesticides have on biodiversity, the recent Global Biodiversity Outlook 5 indicated that none of the 20 Aichi Biodiversity targets had been reached in the last decade (9) and the Living Planet Report 2020 has said that between 1970 and 2016 there has been a 68% decrease globally in populations of mammals, amphibians, birds and reptiles on average (10); this is up from 60% in 2018 when looking at the period 1970 to 2014 (11). Considering these many alternatives to protect crops from damage from pests, and the need now more than ever to do everything we can to stop reducing global biodiversity, it seems clear that action should be taken to increase the usage of these alternatives that greatly reduce the impact on non-target organisms.
Therefore, in conclusion, pesticides used for agricultural crop protection and other uses with exposure to the surrounding environment are detrimental and have far reaching consequences throughout ecosystems, on both plants and animals, as well as for ourselves. Although pesticides also have important benefits, these will become less effective in the future and can be replaced by alternatives that pose significantly less danger to us and non-target organisms. Moving forward we must ensure that the transition to these safer alternatives is carefully managed, so that they do not affect the availability of food and ensure that they can be provided on the necessary scale. Although this transition may take time, it is clear that pesticides do not have a place in our long-term solution for crop protection from pests and are overall more detrimental than beneficial.
To view Janek’s full article, follow this link below.
2. Fishel, Frederick M. Pesticide Effects on Nontarget Organisms. EDIS University of Florida IFAS Extension. [Online] [Cited: 7 October 2019.] https://edis.ifas.ufl.edu/pi122.
7. Halwart, M. and M.V., Gupta (eds.).Culture of Rice in Fish Fields. s.l. : FAO and The WorldFish Center, 2004. [Cited: 9 July 2020.] http://www.fao.org/3/a-a0823e.pdf.
This long-read article was written by sixth-former Salvatore Nigrelli.
Estimated read time: 9 minutes
Few molecules can be said to have completely transformed our understanding of science. Zeise’s salt (potassium trichloro(ethylene)platinate(II)), however, is one of these few.
Yellow crystals of Zeise’s salt were first isolated in 1827 by William Christopher Zeise, a Danish pharmacologist working at the University of Copenhagen. Upon stoichiometric analysis, Zeise concluded that the salt consisted of platinum and ethene, making it the first organometallic compound ever to be discovered. But, unbeknownst to Zeise, these pretty little crystals were about to revolutionise chemistry.
As news spread through the scientific community about Zeise’s discovery of the first organometallic compound, scientists from across the world rushed to try and synthesise more. In the years that followed, a plethora of weird and wonderful organometallic molecules were discovered, from cisplatin in 1845 to diethyl zinc in 1848. A new field of chemistry had been born. Since then, organometallic compounds have revolutionised a whole variety of different fields from polymers and plastics to medicine. In fact, it is now believed that Zeise’s salt could be the next big breakthrough in the battle against cancer.
The more that it was analysed, the more the question of the bonding in Zeise’s salt baffled chemists. No one could come up with an explanation of its bonding that agreed with its molecular formula. The answer finally came in the 1950s, more than 120 years after Zeise’s salt was first discovered, and it required the invention of a completely new theory of bonding that shook the world of theoretical chemistry and transformed the way that we think about molecules. Not bad for a few yellow crystals produced in a pharmacologist’s lab in Copenhagen.
Synthesis
Zeise’s original 1830 paper was entitled:
‘De chloride platinae et alcohole vini sese invicem permutabilis nec non de novis substantiis inde oviundis’
(The reaction between platinous chloride and wine alcohol and on the new substances arising therefrom)
In this paper, he laid out a method for producing Zeise’s salt by reacting platinum (IV) chloride with ethanol. Although the precise reaction was unknown at the time, it is now known to be:
When the potassium salt of [PtCl6]2- is used, upon evaporation of excess ethanol, yellow crystals of KPtCl3(C2H4) form. It is these crystals that are called Zeise’s salt.
This reaction is an example of a redox reaction; the platinum (IV) in [PtCl6]2- is reduced to platinum (II) in [PtCl3(C2H4)]– and ethanol (the reducing agent) is oxidised to form an aldehyde – ethanal in this case.
However, surprisingly, almost immediately after the publication of his first paper, Zeise published a second paper outlining a much more effective synthesis of his newly discovered salt that gave a much higher yield.
The reaction involved reacting platinum (II) chloride with ethanol:
[PtCl4]2- + C2H5OH [PtCl3(C2H4)]– + Cl– + H2O
Unlike the original reaction, this is not a redox reaction – the platinum atom is in the same oxidation state in [PtCl4]2- and [PtCl3(C2H4)]– – which suggests that there is a much more complicated mechanism underpinning this reaction.
There is no literature on the mechanism for this reaction, so the following mechanism is one that I have devised which I think is the most appropriate way of representing the actual reaction that is occurring:
The first stage of this reaction is the dehydration of ethanol into ethene. Such a step is possible due to a combination of energy input (the reaction is carried out at 170°C) and the action of the filled dyz orbital in the platinum atom of [PtCl4]2-.
The filled dyz orbital of the platinum atom provides an area of high electron density and so exerts an attractive force on one of the hydrogen atoms in ethanol, thereby weakening the C-H bond. The high temperature means that the ethanol molecules have high kinetic energies, so when they collide, enough energy is transferred to break this weakened C-H bond heterolytically, forming a H+ ion and a carbanion [scheme 1].
Scheme 1 The mechanism for the breaking one of ethanol’s C-H bonds to produce a carbanion.
Then, a H+ ion produced in scheme 1 bonds with one of the lone pairs on the oxygen atom, forming a H2O group (which is a good leaving group). The lone pair on the carbanion then forms a bond between the two carbon atoms, creating a double bond; however, carbon atoms cannot have more than four bonds, so the C-O bond breaks and the H2O leaving group is released, forming ethene and water [scheme 2].
Scheme 2 The mechanism for the formation of ethene and water from the carbanion.
The second stage of this reaction is the substitution of one of the chloride ions in [PtCl4]2- for ethene. This is possible because the two Cl– ions in [PtCl4]2- are ligands, i.e. bonded to Pt by a coordination complex, which makes them easy to remove in ligand substitution reactions.
[PtCl4]2- consists of two chlorine atoms and two Cl– ligands bonded to a platinum atom. Due to the large difference in electronegativity between chlorine and platinum, the Pt-Cl bond is very polar, giving the platinum atom a δ+ charge. The double bond in ethene is an area of very high electron density and therefore acts as a nucleophile and is attracted to the δ+ charge on the platinum atom. The double bond in ethene then forms a coordination complex with the platinum atom forcing one of the Pt-Cl– coordination complexes to break, yielding [PtCl3(C2H4)]– and Cl– [scheme 3].
Scheme 3 The mechanism for the formation of [PtCl3(C2H4)]–.
There is a large yield of metallic platinum from this method of synthesising Zeise’s salt. This is due to a redox reaction that also occurs in which ethanol reduces [PtCl4]2- to platinum metal and is itself oxidised to ethanal:
[PtCl4]2-+ C2H5OH Pt + CH3COH + 4H+ + 4Cl–
This secondary reaction provides evidence for the mechanism that I have suggested because it shows that [PtCl4]2- plays a minimal role in the dehydration of ethanol to ethene because otherwise it would react in a redox reaction with ethanol rather than dehydrating it.
Infrared Spectral Analysis
Before considering the bonding in Zeise’s salt, we must first show that the platinum-ethene interaction in the molecule is in fact a bond and not simply a strong intermolecular force. The way that I will prove this is using the infrared (IR) spectra of Zeise’s salt and the reactants used to synthesise it. My logic behind this method is as follows: IR spectra show the different bonds present within substances – intermolecular forces of attraction do not show up on IR spectra
– therefore, if there is a peak present in the IR spectrum of Zeise’s salt that is not present in any of the spectra of the reactants, such a peak must be due to a bond that is not present in any of the reactants but is present in Zeise’s salt. The only bond in Zeise’s salt not present in any of its reactants is the platinum-ethene interaction. Therefore if such an inexplicable peak shows up on the IR spectrum, it shows that the platinum-ethene interaction is in fact a bond and not any other type of interaction.
The IR spectrum for Zeise’s salt in its crystalline hydrate form, which also contains waters of crystallisation, is:
(AIST spectral database)
Through the process of peak labelling by comparing this spectrum with the IR spectra of ethene, K2PtCl4, and waters of crystallisation (obtained from the IR spectrum for gypsum), it is now possible to determine if there are any unexplained peaks:
Peak A is due to the O-H bonds in the waters of crystallisation stretching.
Peak B is due to the merging of the peaks due to the Pt-Cl bonds stretching and the C-H bonds stretching.
Peak C is a weak signal that is due to the C-H bonds bending.
Peak D is due to the O-H bonds in the waters of crystallisation bending.
Peak E is due to the C=C double bond stretching (this is shifted right by around 150 cm-1 from the corresponding peak in the IR spectrum of ethene because of the interaction between the platinum atom and the double bond).
Peak F is due to the Pt-Cl– bond stretching.
Peak G is due to the C=C double bond bending.
Peak H is a weak signal due to the Pt-Cl bonds bending.
Peak I is a weak signal due to the Pt-Cl– bond bending.
Peak J is an unexplained peak.
Since there is an unexplained peak on the spectrum, this shows that the platinum-ethene interaction is in fact a bond rather than an intermolecular force. In fact, 406 cm-1 (the wavenumber of the unexplained peak) corresponds exactly with the universally accepted wavenumber for the platinum-ethene bond (Grogan & Nakamoto, 1966).
Bonding
The bonding in Zeise’s salt is a problem that puzzled chemists for over a hundred years after it was first discovered. In many representations, the platinum atom appears (incorrectly) to be bonded directly to the C=C double bond rather than to any particular atom.
To solve this problem, three chemists: Michael Dewar, Joseph Chatt, and L.A. Duncanson created a revolutionary new theory of bonding for transition metals, which is now known as the Dewar-Chatt-Duncanson (DCD) theory of bonding in their honour.
At the crux of the DCD theory of bonding is the action of both filled and empty d orbitals in the outer shells of transition metal atoms, which interact with bonding and antibonding orbitals of other atoms.
This is exactly what occurs in Zeise’s salt in a process called η2 bonding. The vacant dx2-y2 orbital receives electron density from the σ bonding orbital component of the C=C double bond in a process called σ donation. This creates a σ bonding orbital between the platinum atom and the two carbon atoms [scheme 4].
Scheme 4 σ donation between the σ component of the C=C double bond and the vacant dx2– y2 orbital of the platinum atom (black and white represent opposite phases of the orbitals).
The filled dyz orbital then donates electron density to the vacant π* antibonding orbital component of the C=C double bond in a process called π acceptance [scheme 5]. This creates a π backbond between the platinum atom and the two carbon atoms. Since an antibonding orbital is being filled, this weakens the C=C double bond, causing it to lengthen and its vibrational energy to lower – which is why the peak corresponding to the C=C double bond stretching is shifted to a lower wavenumber on the IR spectrum of Zeise’s salt compared with that of ethene.
Scheme 5 π acceptance between the filled dyz orbital of the platinum atom and the vacant π* orbital component of the C=C double bond.
This weakening of the C=C double bond due to the filling of the π* antibonding orbital also causes the molecular orbital to rehybridise from sp2 to sp3, which changes the molecular geometries around the carbon atoms from trigonal planar to tetrahedral. This causes the hydrogen atoms to move and face away from the incoming PtCl3 group (as shown in scheme 5).
The bonding in Zeise’s salt is further complicated by a phenomenon known as the trans effect, which is that for molecules with square planar geometries, like Zeise’s salt, certain groups will remove electron density from, and thereby weaken the bonding of, the group trans (opposite) to them. This occurs in Zeise’s salt because the very electronegative Cl– group opposite the ethene group removes electron density from the platinum-ethene bond causing it to weaken and lengthen – the platinum-ethene bond length in Zeise’s salt is 2.340 Å, while the Pt-Cl bond length is 2.303 Å.
Once all of these bonding complications are considered, the final molecular geometry of
Zeise’s salt is:
Figure 1 The molecular geometry of Zeise’s salt (University of Boston, Massachusetts).
Importance of Zeise’s Salt
In 2015, it was discovered by researchers at the universities of Berlin and Innsbruck that Zeise’s salt can bind strongly to DNA. Although no full mechanism has been published, shown below is the mechanism that I think best describes the interactions that are occurring based on the reactions of similar compounds (such as cisplatin) and analysis of the proposed interactions involved:
Upon entry into the cell, Zeise’s salt undergoes a ligand substitution reaction. Cl– – as it is a good leaving group – is substituted for a water molecule to produce the dichloroaqua(ethylene)platinate(II) ([PtCl2(H2O)(C2H4)]).
Scheme 6 The mechanism for the ligand substitution stage of the reaction.
Now that there is a H2O ligand bonded to the platinum atom, [PtCl2(H2O)(C2H4)] can form hydrogen bonds with the four nucleobases [scheme 7] once the DNA double helix has been unravelled by DNA helicase at the start of the replication process.
Scheme 7 Hydrogen bonding between [PtCl2(H2O)(C2H4)] and (clockwise from top left) cytosine,adenine, guanine and thymine.
If the bases are hydrogen bonded to [PtCl2(H2O)(C2H4)]–, they cannot hydrogen bond to their complementary base. This means that the DNA double helix cannot reform and so no new DNA can be produced, which kills the cell. When Zeise’s salt is administered to cancerous tissue, by the above mechanism, the cancerous cells are unable to replicate their mutated DNA, which stops the cancer from spreading, and kills the cancerous cells. Although healthy cells suffer the same effects, since cancer cells replicate their DNA at a much higher rate than healthy body cells, the rate of death of cancerous cells is far higher than that of healthy cells.
Conclusion
William Christopher Zeise is one of chemistry’s forgotten heroes. It is amazing how some yellow crystals, made in a dingy laboratory in Copenhagen, have not only forged an entirely new branch of chemistry, but have also revolutionised the theory of chemical bonding. It seems like every time Zeise’s salt is looked at by scientists, it yields something new and important, and with the discovery of its possible use as an anti-cancer drug, it seems likely that Zeise’s salt has a bright future and will play an extremely important role in our society in years to come.
Bibliography
Balacco, G., & Natile, G. (1990). Formation of Platinum-Enamine Complexes by Reaction of Zeise’s salt with Secondary Amines. Journal of the Chemical Society, DaltonTransactions.
Bond, G. (1964). Platinum Metal Salts and Complexes as Homogenous Catalysts. PlatinumMetals Review, 92-98.
Grogan, M., & Nakamoto, K. (1966). Infrared Spectra and Normal Coordinate Analysis of Metal-Olefin Complexes. I. Zeise’s Salt Potassium Trichloro(ethylene)platinate(II) Monohydrate. Journal of the American Chemical Society , 5454-5460.
Hunt, L. (1984). The First Organometallic Compounds. Platinum Metals Review, 76-83.
La Salle University. (n.d.). Introduction to Organometallic Chemistry 3. Philadelphia.
Meieranz, S., Stefanopoulou, M., Rubner, G., Bensdorf, K., Kubutat, D., Sheldrick, W. S., & Gust, R. (2015). The Biological Activity of Zeise’s Salt and its Derivatives. AngewandteChemie, 1-5.
Merck KGaA. (2020). IR Spectrum Table and Chart. Retrieved from Sigma Aldrich Web Site:
This article was written by sixth-former James Miller.
Estimated read time: 4 minutes
I know that there are many articles on the internet discussing the implications of COVID-19 on the planet, and our time-limited efforts to save it, almost all written by people more specialised and knowledgeable than myself. Instead, what I hope to put to you today a less detailed but more overarching outlook on the situation and how we, as environmentalists, can make the best of it.
Direct Impacts:
With many countries shutting down borders to international travel and millions under lockdown, scientists at the Global Carbon Project predict a reduction in world carbon emissions by potentially more than 5% this year, a significant decrease considering that emissions have been steadily rising by 1.8% on average annually.
Further, air pollution, that kills an estimated 8.8 million people every year, is freefalling. Satellite imagery from NASA shows NO2 concentrations dropping dramatically over urban areas in China. In fact, it was thought that the measures implemented to contain Coronavirus might save more lives through reductions in air pollution than through actually preventing transmission, according to the Hugo Observatory (although I’m not sure whether that prediction still stands in light of how the pandemic has developed).
Viral videos have circulated social media showing wildlife returning to empty towns, starting to fill the spaces left by humans. While many, such as the Dolphins filmed returning to Venetian Canals, were false (and in fact were filmed hundreds of miles away) there have been plenty of reliable recorded cases. In Venice itself, where motorised transport has been hugely reduced, the water is crystal clear – silt is no longer being churned up from the bed. With the clearer water have arrived small shoals of fish, and Cormorants that feed on them. In Sardinia Wild Boar have been roaming the streets, in Wales Mountain Goats have been terrorising towns, and in Vancouver Orca have been returning closer to shore than witnessed in the last 50 years. With humans sealed safely inside our pods, our deserted urban landscape is turning into a modern Chernobyl.
But I’m afraid those looking for a silver lining from this pandemic will find the virus is by no means all good news for the environment. The projected reduction in emissions, if it does occur, is a temporary blip in an ever-increasing trend. A single year of reduced emissions is of little relevance in global warming – what matters is our cumulative anthropogenic emissions over time, our ‘carbon budget’ that we’re quickly using up. In fact, by virtue of having reduced particulates in the air, temperatures could temporarily increase, as those particles normally reflect some of the incoming radiation into Earth’s atmosphere. What’s more, overall, COVID-19 may well increase emissions long term through the rebound effect – where, in an effort to reboot their economies, countries relax environmental legislation. This is already happening in China and the US, the greatest polluters in the world.
Especially applicable to those of us in the conservation movement, political lobbying has largely come to a standstill, as we respect governments’ need to focus on the pressing global health crisis. Conservation charities are also going to go through a very difficult period, and will need all the help they can get.
The most worrying concern that I have, however, is what individuals and authorities are trying to get away with while international attention is diverted. I have heard accounts of Bolsonaro, Brazil’s President (a rather nefarious individual at the best of times) taking the opportunity to forcefully evict indigenous people from shanty towns, before bulldozing their homes to the ground. There are fears that poaching may increase as wildlife parks around the world close to the public. In our very own country, HS2 is powering on with its deforestation program, felling beloved ancient woodland and sending bat roosts and bird nests tumbling to the ground.
A poor year for conservation?
Perhaps the issue of the greatest relevance to campaigners and activists is the postponement of all the major environmental UN Summits scheduled for this year. We were due landmark meetings on oceans, biodiversity, sustainable development and climate change. It was meant to be an ‘environmental super year’ that activists had been gearing up to for months. The delay again has a variety of implications and has been met with mixed reactions. On one hand, we face such urgent timescales that a delay of even a few months is a crushing blow. However, there are some potential advantages. The US presidential election is due on Nov 3rd, so there is a chance that a Democrat might be in power, in which case the USA would likely rejoin the Paris Agreement and pursue more ambitious reductions. This could lead political leaders in other countries to adopt stronger plans as well. It will also give campaigners time to adjust to the situation and better prepare to influence decisions.
A Green Recovery
A particular opportunity presented by the pandemic is the chance to redesign our economy as it is rejuvenated: to put it through, as Caroline Lucas puts it, a ‘green recovery’. There will soon come some big decisions to be made by the Chancellor as to where money shall be invested, and those decisions will determine whether we run down the same tracks as the after 2008 depression (seeing emissions accelerate), or whether we take this unprecedented opportunity to radically change our economy and start to steer the ship away from the looming iceberg. We must, above all else, ensure we don’t solve one crisis by piling fuel on another. Depending on how the situation develops, the summits next year may be timed well to influence that recovery for many countries around the world.But I hope also that lockdown will make a lasting impression on society: that we will not go back to business as before, because we can’t afford to. Governments now can no longer deny the ability to make drastic changes of the type that the climate crisis demands. Companies may have seen potential to reduce unnecessary travel in their operations. People, now savouring their rationed outdoor time, might reconnect with nature and value it more than they otherwise would have done.
A Time for Reflection
Finally, bearing all of the above in mind, what does this mean for campaigners? We now all find ourselves with the prospect of being housebound for several months, unable to penetrate the media or influence our preoccupied politicians. I see this as an unfortunate opportunity. A chance to reflect on lobbying strategies and how to be more effective. A chance to develop our understanding of the science behind and politics surrounding everything we’re fighting for. And foremost, a chance to build wider international communities and stronger local communities. Political involvement of any sort keeps you very busy, trying to keep track of any developments and changes. This might be the most time we get given to prepare for anything, ever again. And it so happens to occur just before what may be the most important year in our lifetime for environmental politics.
I wish everyone the best over the coming months. Keep safe.
[PtCl3(C2H4)]– + 3Cl– + H2O + CH3COH + 2H+
The Unchained Library 