From genome mining and green synthesis, to tackling tuberculosis and computational methods to help cure malaria, the chemists of tomorrow have been busy showcasing their talents as part of the Society of Chemical Industry Young Chemists Panel’s National Undergraduate Online Poster Competition 2021.
A snapshot of these students’ talents is bottled below in their own words. So, which one of these 15 entries do you think contains the most potential?
Emmanuelle Acs et al., University of Glasgow
Natural products have always had a privileged place in drug development programmes, but their discovery is long and tedious. Genome mining arises as a solution allowing the finding of compounds never seen before. Using an array of bioinformatic softwares, the myxobacterial genome was explored for new Ribosomally and Post-Translationally modified Peptides (RIPPs). Myxobacteria are soil-dwelling bacteria known for the number of secondary metabolites they produce, and they have proven to hide many more within their genome. Indeed, our analyses have led to the potential discovery of nine new myxobacterial natural products. The nature and class of these products is to be confirmed by biosynthesis in the laboratory.
Olivia Baldwin et al., University of Birmingham
Lanthanides were thought to be biologically irrelevant until the discovery of bacteria containing the lanthanide-dependent methanol dehydrogenase (Ln-MDH) enzyme. There has been interest in exploiting the attractive properties of the lanthanides by the de novo design of artificial proteins, aiming to explore protein structures and functions not observed in biology. Here, a lanthanide-binding peptide, CS1-0, has been designed de novo and shown to bind to europium and pyrroloquinoline-quinone (PQQ), a key component of the Ln-MDH active site. This partial recreation of a biologically relevant lanthanide binding site is a step towards the ultimate goal of de novo design, to create functional artificial metalloproteins with simplified structures.
Janko Hergenhahn et al., University of Oxford
Template-directed synthesis provides a route to achieve porphyrin nanorings by favouring ring-closure reaction over oligomerisation. A structurally new template with 12 binding sites has been proposed for the synthesis of novel porphyrin rings; however, initial unsuccessful reactions have raised questions about the binding efficiency of this template to the linear substrate. We have employed classical and quantum modelling together with experimental techniques to explore template-substrate binding in solution and shed light on this process. Titration experiments and modelling have enabled us to study the occupancy of different binding sites and quantify the influence of strain on binding, further guiding novel designs.
Kieran Benn et al., University of Edinburgh
Hydrocyanation offers an orthogonal route to synthetically ubiquitous amines. Current hydrocyanation methodologies are dominated by the use of acutely toxic hydrogen cyanide gas and transition metal catalysts. Here the application of main-group catalysis and transborylation is reported for the formal hydrocyanation of functionalised alkenes. The catalytic protocol was optimised and applied to a broad range of substrates (20 examples), including examples where chemoselectivity was demonstrated in the presence of reducible functionalities and Lewis basic groups. Mechanistic studies support a proposed catalytic cycle in which B–N/B–H transborylation was a key to catalyst turnover.
Students at the University of Glasgow have used computational analysis to help tackle malaria.
Xiyue Leng et al., University of Birmingham
Antimicrobial peptides are increasingly employed as new-generation antibiotics, with their amphiphilic nature (contain both hydrophobic and cationic components) mimicked by polymers to enable a more cost-effective approach. However, there is a lack of a quantitative pre-experiment indicator to provide a prospect on their potency. The overall hydrophobicity represented by LogP/SA was proposed to rapidly identify candidates in future designing to reduce synthetic efforts. We show a comparison study between two computational tools used to calculate LogP/SA: ChemBio3D and Materials Studio, in terms of the predictive power and sensitivity, followed by the synthesis of copolymers with a different cationic side chain based on the calculation results.
Mirjam-Kim Rääbis et al., University of Glasgow
Traditional small molecule therapeutics in medicinal chemistry often require high doses to inhibit the target protein, leading to issues with safety and drug resistance. Proteolysis targeting chimeras (PROTACs) are a new class of molecule that combat these issues, as they can use the body’s own protein degradation systems to degrade targets even at low drug doses. Virus-targeting chimeras (VIRTACs) can use a similar mechanism to target viral proteins. This project uses molecular docking studies to explore potential VIRTAC warheads that target the papain-like protease of SARS-CoV-2, in an attempt to find a potential treatment to COVID-19 that would, among other benefits, offer a lower risk of antiviral resistance.
Miriam Turner et al., Newcastle University
Tuberculosis remains one of the top 10 causes of death worldwide, therefore there exists an unmet clinical need for new and improved therapeutics that tackle increasing bacterial resistance and affordability issues. Previous studies indicate N-substituted amino acid hydrazides exhibit good activity against several strains of Mtb. Ongoing structure-activity relationship studies utilising isoniazid, a variety of amino acids, and the active imidazo[1,2-a]pyridine-3-carboxy moiety of clinical candidate Q203 have also demonstrated excellent activities. Herein we report the results of our continued evaluation of this architecture, using a scaffold hopping approach to explore the potential of this pharmacophore as a new anti-tubercular drug.
Skye Brettell et al., University of Glasgow
Malaria continues to pose a significant challenge to humanity. Resistance to several frontline antimalarials represents a considerable threat, marking the need for new drugs with novel mechanisms of action. Kinase inhibitors represent a potential new class of antimalarials. TCMDC-135051 is a hit compound with activity against malarial kinase PfCLK3 as well as potency in liver, blood and sexual stage parasites. During this project, sequential analysis of the PfCLK3 catalytic domain identified key structural differences between the target and its human orthologs. Molecular docking studies of TCMDC-135051 analogues using GOLD then yielded potential lead compounds with predicted high affinity for the target kinase.
Matteo Albino et al., University of York
The strain-induced contortion of non-planar, chiroptically-active helicenes caused by fjord steric repulsive interactions is well known. Fjord-mediated planarisation, on the other hand, is far less common and has typically only been achieved via inherently strong covalent bond formation. Herein, I present the properties and density functional theory (DFT) analysis of electroactive azahelicenes exhibiting unexpected through-space π-electronic stabilisation in the reduced states as a result of non-covalent fjord bonding effects. Computational modelling of optical spectra and aromatic-induced current densities reveal that lone pair-repulsive nitrogens in the fjord promote favourable ring currents and reversible helicene planarisation.
Sam Andrew Young et al., Northumbria University
The synthesis of metal chelating molecules, specifically hydroxypyridones (HOPOs), have been identified as potential therapeutic agents for treating Parkinson’s Disease (PD) as bidentate ligands at the two oxygen donor atoms. These ligands are selective for ferric iron in the body, which is expected to stop the reduction of this iron accumulated in the brains of PD sufferers, hindering the Haber-Weiss mechanism from taking place in the mitochondria of the cell and preventing the associated degeneration of the cells. The lipophilicity of these HOPOs is vital to the process, allowing the molecule to transverse the blood-brain barrier, the addition of a triphenylphosphonium group on the HOPO is thought to increase therapeutic effect.
At Heriot Watt University, students have investigated the skin irritation potential of nanoclays using an IATA
Adelaide Lunga et al., Loughborough University
The aim of this project is to develop a short synthesis of N-acetylcolchinol using a greener and step-economical pathway. First, aldol condensation of 3-hydroxyacetophenone and 3,4,5-trimethoxybenzaldehye using ethanolic NaOH produced the respective chalcone. The product was reduced electrochemically in DMSO:MeOH (4:1) employing carbon electrodes and NEt4Cl to the saturated benzylic alcohol, which was converted to an acetamide via Ritter reaction using H2SO4 in MeCN. In the final step, the conditions were optimised to enable electrochemical oxidative coupling of the aromatic groups to give the desired N-acetylcolchinol. This novel four-steps reaction sequence avoids use of transition metal catalysts or toxic reagents.
Yi Xiao et al., University of Oxford
Human endosulfatases (SULFs) are enzymes on the cell surface and in the extracellular matrix that hydrolyse 6-O-sulfate on glucosamine units within heparan sulfate proteoglycans. SULFs are involved in growth and development, muscle regeneration and tumour growth via various signaling pathways, with untapped therapeutic and diagnostic potentials. However, profiling SULFs remains a challenge. Antibodies detect their presence, but do not indicate their activity state. The current activity assay is a global sulfatase assay and is not selective in a biological sample. We propose a novel small-molecule probe to profile SULF activity by exploiting the formation of 1,6-anhydrosugar, which can be potentially used in isolated proteins and in vitro.
Alexander Pine et al., University of Greenwich
Solubility parameters are important for pharmaceutical formulations, paint formulations and new material development. There is a need to improve the accuracy of solubility calculations, and to be able to make rapid predictions of the solubility of new molecular structures. In this project, a range of Python plugins, and open-source codes have been used to develop a Lasso linear regression machine learning model to predict the Hansen solubility parameters (HSP) - δd, δp and δh, which represents dispersion forces, dipole-permanent dipole forces and hydrogen bonding respectively with the intention of making faster and more accurate prediction in solubility.
Alexander David Robertson et al., The University of Glasgow
This research considers computational modelling of a SPAAC reaction involving cyclononyne. DFT calculations were performed on the strain promoted reaction between cyclononyne and mesyl azide. Three low energy conformers of cyclononyne with Cs, C2 and C1 symmetry were found with similar energy. The transition structures for the corresponding cycloaddition with mesyl azide were found and the C2 conformer was the lowest in energy. Product structures were found leading to the identification of the thermodynamic product of the reaction. Distortion/interaction analysis showed that the cycloalkyne was already significantly pre-constrained to its reacting geometry.
Holly King et al., Heriot Watt university
Clays are natural nanomaterials consisting of mineral silicate layers. They have several functional uses in everyday life. An example of nanoclays that carry out a wide range of roles is smectites which include montmorillonite (MMT), bentonite and hectorite. These nanoclays can be used in cosmetics, altering their appearance and in pharmaceuticals as drug carriers and wound dressings. Integrated approach to testing and assessment (IATA) aim to collect all relevant data into one easy to understand format that can be used to group materials. Using an IATA dedicated to skin irritation/corrosion it was found that MMT was safe for use. However, hectorite was found to be toxic at high doses indicating that it is a possible irritant to the skin.
If you’d like to see these students’ full posters, go to: https://istry.co.uk/postercompetition/5/?date_example=2021-06-28
Tracking pollen can help scientists better understand pollinator behaviour.
Pollination and pollination services are key for productive farming. In fact, many farms actively manage pollination, bringing in bees or planting effective field margins.
Fluorescent quantum dots on a bee show the distribution of the marked pollen. Image: Corneile Minnaar
Despite the importance of pollination, for many years research has been limited as there is no efficient way to study pollen distribution or track individual pollen grains.
Scientists at the university have developed an innovative method to track pollen using quantum dots.
Tracking pollen with quantum dots. Source: Stellenbosch University
Quantum dots are nanocrystals that emit bright fluorescent light when exposed to UV light. The quantum dots were equipped with lipophilic (fat-loving) ligands to allow them to stick to the fatty outer layer of pollen grains. The fluorescent colour of the quantum dots can then be used to track any pollen they have adhered to.
University students from across the UK came to SCI HQ in London on Friday 7 December 2018 for a day of face-to-face business and innovation and entrepreneurship training, which was exclusively available to entrants to the Bright SCIdea Challenge 2019.
The students heard from experts in their fields on topics such as ‘Managing the Money’, ‘Defining the Market’, Intellectual Property (IP) and ‘How to Pitch’.
Sharon Todd, SCI’s Executive Director, introduces the students to SCI and the Bright SCIdea Challenge.
David Prest, from our corporate supporter Drochaid Research Services, talks to delegates about defining the market and taking their product from lab to the market.
Our Bright SCIdea applicants learnt about IP from Charlotte Crowhurst, a patent lawyer and partner from Potter Clarkson.
Martin Curry from our sponsor STEM Healthcare teaches the audience about managing the money of a business.
Libby Linfied – one-third of our 2018 UCL winners Team Glucoguard – spoke about her experience and journey to last year’s final.
Victor Christou, CEO of Cambridge Innovation Capital and 2018 Head Judge, ran an interactive session on how to pitch.
Groups were given everyday objects to pitch to Victor.
The students made compelling arguments for a plug adapter, hi-vis vest, ‘phone pillow’ and lunchbox.
Delegates and trainers mingled at a wine reception in the evening.
The Bright SCIdea Challenge 2019 final will take place on Tuesday 19 March 2019 at SCI HQ in London. Teams will compete for a chance to win £5,000!
Tweaking the chemical structure of the antibiotic vancomycin may offer a new route to tackle the burgeoning problem of antibiotic-resistant bacteria, researchers in Australia have discovered.
Vancomycin has been used since the late 1950s to treat life-threatening infections caused by Gram-positive bacteria, including methicillin-resistant S. aureus (MRSA). The antibiotic works by binding to a precursor of the cell wall component, peptidoglycan, Lipid II, thus inhibiting bacterial growth.
Lipid II is present in both Gram-positive and Gram-negative bacteria. However, in Gram-negative bacteria it is protected by an outer membrane. In Gram-positive bacteria, Lipid II is embedded in the cell membrane but part of the molecule – a pentapeptide component – sticks out, which is what vancomycin binds to.
The researchers at the University of Queensland’s Institute for Molecular Biology (IMB), led by director of superbug solutions Matt Cooper, reasoned that if they could increase the ability of vancomycin to bind to the bacterial membrane, this would make it more difficult for bacteria to develop resistance to it.
‘Our strategy was to add components to vancomycin so that the new derivatives – which we call “vancapticins” – could target more widely the membrane surface,’ explains Mark Blaskovich, senior research chemist at IMB. ‘By providing two binding sites – the membrane surface and the membrane-embedded Lipid II - this allows binding to resistant strains in which the Lipid II has mutated to reduce interactions with vancomycin.’
In addition, the researchers say that the vancapticins have been designed to take advantage of compositional differences between mammalian and bacteria cell membranes – ie bacterial cells have a greater negative charge. The vancapticins have greater selectivity for bacterial cells over mammalian cells, potentially reducing off-target effects and giving a better safety profile. A series of structure–activity studies showed that some of the vancapticins were more than 100 times more active than vancomycin.
Hospital-Associated Methicillin-resistant Staphylococcus aureus (MRSA) Bacteria. Image: NIAID
This membrane-targeting strategy, the researchers say, has the potential to ‘revitalise’ antibiotics that have lost their effectiveness against recalcitrant bacteria as well as enhance the activity of other intravenous-administered drugs that target membrane associated receptors.
John Mann, emeritus professor of chemistry at Queen’s University Belfast, UK, comments: ‘Bacteria have developed numerous strategies to modify the binding, uptake and expulsion of antibiotics, and thus develop resistance. So, it is especially exciting to see the development of these new vancomycin derivatives that enhance the membrane binding properties of the antibiotic, thus enhancing its efficacy and beating the bacteria at their own game.’
Energy storage is absolutely crucial in today’s world. More than just the batteries in our remote controls, more even than our mobile phones and laptops; advancements in energy storage could solve the issues with renewable power, preserving energy generated at times of low demand.
Advances in lithium-ion batteries have dominated the headlines in this area of late, but a variety of developments across the field of electrode materials could become game changers.
1. In the beginning, there were metals
The Daniell cell, an early battery from 1836 using a zinc electrode. Image: Daderot
Early batteries used metallic electrodes, such as zinc, iron, platinum, and lead. The Daniell cell, invented by British chemist John Frederic Daniell and the historical basis for the volt measurement, used a zinc electrode just like the early batteries produced by scientists such as Alessandro Volta and William Cruickshank.
Alterations elsewhere in the Daniell cell substantially improved its performance compared with existing battery technology and it became the industry standard.
2. From acid to alkaline
Waldemar Jungner: the Swedish scientist who developed the first Nickel-Cadmium battery. Image: Svenska dagbladets årsbok 1924
Another major development in electrode materials came with the first alkaline battery, developed by Waldemar Jungner using nickel (Ni) and cadmium (Cd). Jungner had experimented with iron instead of cadmium but found it considerably less successful.
The Ni–Cd battery had far greater energy density than the other rechargeable batteries at the time, although it was also considerably more expensive.
3. Smaller, lighter, better, faster
Organic materials for microbattery electrodes are tested on coin cells. Image: Mikko Raskinen
Want your electronic devices to be even smaller and lighter? Researchers from Aalto University, Finland, are working on improving the efficiency of microbatteries by fabricating electrochemically active organic lithium electrode thin films.
The team use lithium terephthalate, a recently found anode material for a lithium-ion battery, and prepare it with a combined atomic/molecular layer deposition technique.
4. There’s more to life than lithium
50-70% of the world’s known lithium reserves are in Salar de Uyuni, Bolivia. Image: Anouchka Unel
Lithium-ion batteries have dominated the rechargeable market since their emergence in the 1990′s. However, the rarity of material means that, increasingly, research and development is focused elsewhere.
Researchers at Stanford University, USA, believe they have created a sodium ion battery with the same storage capacity as lithium but at 80% less cost. The battery uses sodium salt for the cathode and phosphorous for the anode.
5. Back to the start
Advances are also being made in the electrode materials used in artificial photosynthesis. Video: TEDx Talks
Hematite and other cheap, plentiful metals are being used to create photocatalytic electrode materials by a team of scientists from Tianjin University, China. The approach, that combines nanotechnology with chemical doping, can produce a photocurrent more than five times higher than current approaches to artificial photosynthesis.
You can read an interview with the recipient of SCI’s 2017 Castner Medal, who delivered the lecture Developments in Electrodes and Electrochemical Cell Design, here.