Professor Mark Searle
Structural role of p62 in the regulation of signal transduction and autophagy
Funding: BBSRC (£379K)
Background: Joint-funding with Dr. Robert Layfield (School of Biomedical Sciences) has been secured to research the molecular basis for how mutations in key signalling proteins like p62 compromise biological function, with consequences for human diseases. The research program will investigate, using high-resolution NMR methods, details of the oligomeric structure of p62 and its mode of recognition of polyubiquitin chains involved in NF-kB signalling and autophagy. Post-translational modification by ubiquitin is a universal signalling mechanism which underpins a large amount of cell physiology.
Dr Ross Denton
Sustainable Phosphorus Chemistry: Catalytic SN2 Reactions
Funding: EPSRC (£430K)
Background: Phosphorus-based nucleophilic substitution reactions currently generate one molecule of phosphorus waste per molecule of product produced. This impacts very heavily on the environmental footprint of the chemistry. This research programme will deliver a new range of substitution reactions that are catalytic with respect to the phosphorus component. This will be achieved by converting phosphine oxides – the nuisance by-products from the conventional stoichiometric reactions into catalysts using consumable oxalate reagents resulting in highly atom efficient nucleophilic substitution reactions.
Professor Jonathan Hirst
DichroCalc: DNA Dichroism Calculations
Funding: BBSRC (£125K)
Background: In this research, we seek to provide a computational tool for relating the structure of DNA in SOLUTION to biophysical experiments that measure the interaction of DNA with polarized light. Such experiments can complement other approaches, using NMR or infrared spectroscopy. Expertise developed at Nottingham over the past decade makes us almost uniquely well-placed to advance the theory necessary to calculate the optical spectroscopy of DNA accurately. This will involve quantum chemical calculations on Nottingham’s 12-teraflop high performance computer (HPC). In addition, our web-server, DichroCalc, is the only one world-wide, where scientists can upload biological macromolecular structures and get back a calculated circular dichroism spectrum.
Dr Ross Denton
The Development of catalytic Mitsunobu reactions
Funding: EPSRC (£125K)
Background: The Mitsunobu reaction is used in chemical laboratories around the world on a daily basis. However, at present, this reaction generates two molecules of waste for every molecule of product formed. Aim: To develop new catalytic versions of the Mitsunobu reaction for the creation of carbon-heteroatom bonds. Outcomes: Given that the new catalytic reactions will generate water as the sole by-product they will be of direct benefit to scientists involved in the synthesis of fine chemicals e.g. pharmaceuticals and will be used widely.
Dr Richard Wheatley
A theoretical and experimental study of nitric oxide complexes
Funding: EPSRC (£784K)
Background: Nitric oxide (NO) is involved in biochemistry, the formation of smog and acid rain, and the depletion of ozone in the atmosphere. However, our ability to predict the activity of NO is severely limited. The aim is to use theory and experimental methods to obtain information about NO-X complexes, where X includes a number of diatomic molecules, rare gas atoms, and methane. The outcome is to learn more about the intricate, potentially far-reaching implications of exactly how all the different quantum mechanical and relativity related aspects of the bonding combine.
Dr Steve Liddle
UNCLE: Uranium in Non-Conventional Ligand Environments
Funding: European Research Council (€1M)
Background: The award, which is the first ERC Starting Independent Researchers Grant to be won by the University of Nottingham, will support new projects and ideas for fundamental molecular uranium chemistry by developing new compounds containing uranium-metal bonds, assessing their intrinsic reactivity patterns, defining structure-bonding relationships, and developing a better understanding of actinide chemical bonding from an integrated experimental and theoretical approach.
Professor Barry Lygo
Developing Small Organic Molecule Catalysts for Large-Scale Processes
Funding: (£200K)
Background: The aim is of this collaborative project is to investigate strategies for the rapid optimization of organic molecule catalysts for large-scale applications. This study will focus on small organic molecule catalysts and their use in key C-C and C-O bond forming processes. A feature of this study will be a close collaboration with AZ Process R and D which will allow us to combine their expertise in scale-up chemistry with our expertise in new catalyst development.
Dr Elena Bichoutskaia
New Carbon Nanotube Based Devices for Force/Mass Measurements and Data Storage
Funding: EPSRC Career Acceleration Fellowship (£750K)
Background: This Fellowship focuses on the study of novel properties of advanced functional materials at the nanoscale, and the development of new carbon nanotube based devices in the areas of electromechanics and data storage.
Professor Mike George
Carbon Dioxide and Alkanes as Electron-sink and Source in a Solar Nanocell: towards Tandem Photosynthesis of Carbon Monoxide and Methanol.
Funding: EPSRC (£1.6M)
Background: A major solar energy challenge is the goal of artificial synthesis in which sunlight is used to generate fuels or high energy chemicals. We aim to create a solar device which will drive the coupled photo-conversion of methane and carbon dioxide into methanol and carbon monoxide respectively.
Dr Deborah Kays
The Stabilisation of Novel Bonding Modes in Group 2 Complexes
Funding: EPSRC (£305K)
Background: This project seeks to isolate as yet unknown Be22+ and Ca22+ species, complexes featuring covalent bonds between Be and Ca and the transition metals, and new metal-rich group 2 cluster compounds. The analysis of the structure/bonding and reactivity patterns of these compounds will provide benchmarks for the development of descriptions of bonding in organometallic species, expanding the knowledge of Group 2 chemistry.
Dr Steve Liddle
Lanthanide Heteroatom-Stabilised Alkylidenes: A New Approach to Multiply Bonded Lanthanide Chemistry
Funding: EPSRC (£300K)
Background: Transition metal alkylidenes play a central role in synthesis and polymer chemistry and are extensively studied. In contrast, lanthanide alkylidenes are yet to be developed despite the proclivity of the lanthanides for highly novel reactions. Using a new approach this project aims to rapidly expand the area and investigate new reactivity patterns.
Dr Pete Licence
Ionic Liquids in-vacuo; marrying Surface Science with Solution Chemistry
Funding: EPSRC (£878K)
Background: Ionic liquids are, in general, organic based salts with melting points that are below room temperature. Because they are composed entirely of ions, they have an almost zero vapour pressure; they do not evaporate even under vacuum. This means that ionic liquids are difficult to ignite, unlike most of the solvents that are conventionally used for chemical synthesis. We have recognised that this lack of volatility allows ionic liquids to be used in a whole range of analytical instruments that require ultra high vacuum (UHV) for their operation. We are using a range of UHV techniques ranging from XPS, SIMS and TPD to explore both the fundamental physical properties of ionic liquids and subtle interactions between ionic liquid solvents and catalytically active metals in solution.
Dr John E Moses
Developing Click Chemistry for Chemical Arrays: In Situ Formation & Diverse Transformations of Organic Azides
Funding: EPSRC Array Chemistry Call (£350K)
Background: Click Chemistry: Click chemistry is a modular synthetic approach towards the assembly of new molecular entities. This powerful strategy relies mainly upon the construction of carbon�heteroatom bonds using spring-loaded reactants. Click chemistry serves as a powerful strategy in the quest for function, and can be summarised in one sentence: "all searches must be restricted to molecules that are easy to make".
Dr. Neil Oldham
Mapping Polyubiquitin Topology
Funding: BBRSC (£425K)
Background: Ubiquitin, a small highly conserved protein, is responsible for the regulation of almost all cellular processes. It often exists in the form of polymer chains connected through different linkages - giving rise to distinct topologies. Little is known about the function and relative importance of polyubiquitin chain lengths and linkages in the cell. We are developing and using mass spectrometry techniques to address these important questions.
Dr. Neil Oldham
Inhibitors of the Eukaryotic translation initiation factor 4E (eIF4E)
Funding: Cancer Research UK (£360K)
Background: eIF4E is a component of the complex responsible for delivering mRNA to the ribosome during protein translation. 4E is overexpressed in tumour cells and its availability is usually the limiting step in the translation of malignancy-related proteins - making it an attractive target for cancer therapy. As part of a collaborative project we are screening for potential 4E inhibitors using mass spectrometry to detect protein-ligand non-covalent complexes.
Professor Panos Soultanas
Single Molecule Investigations of Bacterial DNA RemodellingProteins
Funding: BBRSC (£419K)
Background: DnaD and DnaB are proteins from Bacillus subtilis, originally thought to be involved in the primosomal protein cascade which sets the stage for the initiation of DNA replication. Recent collaborative studies with Prof. Panos Soultanas (Chemistry) and Stephanie Allen (Pharmacy) have discovered that these proteins have novel DNA remodelling activities which were equivalent to those of nucleoid-associated proteins (NAPs) found in E.coli (such as H-NS, HU and IHF). The work aims to obtain new fundamental insights into the mechanisms by which these proteins remodel DNA.
Professor Mark Searle
Specificity in protein-ligand recognition: characterisation of a novel conformational switch in the UBA domain of the p62 protein.
Funding: BBSRC (£340K)
Background: p62 is a multi-functional scaffold protein involved in signalling pathways linked to regulation of bone metabolism. Mutations in p62 lead to human skeletal disorders and are a common cause of Paget's disease of bone. We are using NMR structural methods to probe the molecular basis for the physiological role of p62 to understand the effects of mutations on disease.
Dr Rob Stockman
New Multi-Component Reactions for Array Synthesis
Funding: EPSRC/GSK (£350K)
Background: The project will extend our previous work on the four-component synthesis of chiral non-racemic sulfinimines to five and six-component couplings, and adapt these methods to automation, delivering a versatile synthesis of chiral amine derivatives suitable for array chemistry.
Dr Rob Stockman
Complexity From Symmetry
Funding: EPSRC (£758,402)
Background: This programme of work will set out to develop a new strategy for synthesising complex molecules in very short synthetic sequences. This new strategy will combine two techniques that can reduce the number of operations required to synthesise complex molecules: bi-directional synthesis (where a molecule is built up from the middle in two directions at once), and tandem reactions (where a series of reactions are carried out in a cascade, and thus require just one operation). The operation-reducing power of combining these two techniques was shown by us in a recent synthesis of histrionicotoxin, a potent frog toxin that is a useful biological probe for the mechanisms of action of the nervous system. Bi-directional synthesis intrinsically forms symmetrical products. In the case of the synthesis of many compounds of biological or material interest, asymmetric products are required for the correct properties to predominate. Thus we propose to develop a method of desymmetrisation, which we will "build-in" to the bidirectional synthesis strategy. We will design tandem reactions that react with one end of the symmetrical molecule in one way, and will react in a different manner at the other end of the molecule, thus intrinsically desymmetrising the substrate. Bi-directional synthesis will be used to synthesise a range of symmetrical chain-like molecules with functionality in the middle and functionality at either end. A variety of different tandem reactions will be used to "fold" these chains in on themselves, creating new, much more complicated molecular scaffolds. This "complexity generation" will give us new and exciting molecules which can be used to make complex natural products (like the anti-cancer compound lepidiformine, for example), or for use as starting points for the synthesis of un-natural compounds for testing against a range of different biological activities.
Dr Jeremy Titman
Solid-State NMR at 850 MHz: A World-leading UK facility to deliver advances in Materials Science, Chemistry, Biology, Earth Science and Physics
Funding: EPSRC (£3.7M)
Background: The consortium has recently placed an order worth over £3M for a dedicated solid-state NMR instrument operating at the highest currently available magnetic field (to be located in Warwick). Only three similar instruments exist worldwide.
Dr Simon Woodward
Defining a new functional group: New approaches and uses for enanime N-oxides
Funding: EPSRC (£213K)
Background: The chemistry of enamine N-oxides has only ever been investigated twice since the dawn of modern organic synthesis. We are using these rare species to explore unusual rearrangements and reversal the polarity of the intermediate in a classical1,4-addition reactions.
Professor Sandy Blake
High Pressure Coordination Chemistry
Funding: EPSRC (£169K)
Background: We discovered that applying high pressure to a crystal of a simple palladium metal complex containing three sulfur atoms caused it to polymerise into a chain. The crystal also changed colour from orange to really deep black. This happened at a pressure of around 44,000 atmospheres and we are probing the reasons for the colour change by carrying out theoretical calculations. We have also found that another complex, containing palladium and six sulfur atoms, shows multiple colour changes as the applied pressure in changed. We are looking at other simple palladium complexes, and some with other metals such as platinum or gold, to see what happens to them under pressure, and we have found some surprising effects.
We are also using pressure to look at what happens to organic molecules inside the channels of porous metal-organic frameworks. These are promising candidates for the efficient storage of gases like hydrogen, which can be used as clean fuel sources for cars. We need to find out where the molecules interact with the inner surfaces of the pores, because that will help us to understand what makes the most efficient containers.
This work is mostly carried out in a dedicated high pressure X-ray crystallography laboratory in the School of Chemistry, but also at Diamond Light Source, the UK's newest and biggest scientific facility.