In agrochemical research, the ability to access agrochemical building blocks with a range of functionalities is important in the lead optimisation stages. However, traditional synthetic routes are not appropriate for this purpose, as all functionalities are usually introduced at the start of the multistep synthesis, and the whole synthetic sequence must be repeated for each new compound. Developing methods that make it possible to introduce a functionality to the already-synthesised molecule (so-called late-stage functionalisation) has thus recently become an important topic. Free radicals are usually very short-lived and many people assume that radical reactions have poor selectivity and are not very useful synthetically. However, this is not the case. Radical reactions are often quite selective, tolerant to a range of functional groups and proceed under mild conditions. Therefore, radical reactions are well suited for late-stage functionalisation, and there are many recent examples of their successful use for this purpose. The big disadvantage of radical reactions, however, is that they need initiators which are either highly toxic (e.g., transition metal ions) or dangerous (e.g., peroxides). The aim of this project is to develop an electrochemical method for generating organic radicals which will then be used for late-stage functionalisation of heteroarenes and saturated heterocycles, which are common motifs in agrochemicals. Electrochemistry is a very clean method for initiation of radical reactions which does not involve any other reagents. For instance, carboxylate anions can be reduced at the anode to form carboxyl radicals which promptly lose CO2 to yield alkyl radicals (Kolbe reaction). In this project, the alkyl radicals thus formed will be used to functionalise a range of heteroarenes and saturated heterocycles molecules. The reactions will be monitored by spectroelectrochemical techniques; the mechanistic information obtained will help us optimise reaction conditions and investigate the scope of the new reactions. In the later stages of the project, a series of different reactions will be explored, and the new approach will be applied to agrochemical targets.
In Nature the production of hydrogen and methane fuel molecules from readily available starting materials such as water and carbon dioxide is achieved selectively, efficiently and rapidly by electrocatalytic redox-metalloenzymes containing non-precious transition metal active sites. The outstanding recent scientific advances made in molecular biology have made the development of biofuel technologies based on these enzymes a reality, but such applications require a complementary toolkit of physical chemistry methods that can dissect how DNA sequence and protein structure relates to function. Classic bio-electrochemistry methods developed in the 1980s have been a powerful way to probe the active site reactivity of such enzymes, but they have been unable to map the electron transfer processes which underpin the catalysis. Therefore, we have been limited to a narrowly active-site focussed view of enzyme mechanism. This project will transform the state of the art in bio-electrochemistry to deliver a powerful new technique that can "see" the electron-transfer processes of the highly evolved and essential electron-transfer reaction centres in redox-enzymes, and deconvolute their role in electrocatalysis. This will be achieved by deploying advanced computational methods to integrate intelligent experimental design into electrochemistry to develop a methodology that lets us separate and accurately model the electron transfer processes of an enzyme bound to substrate, and chemical biology methods to develop linker molecules for light-activated electrografting of proteins and enzymes onto electrodes. We will showcase the power of this new electrochemical enzymology toolkit by conducting previously impossible hypothesis-led investigations and enzyme-discovery projects into i) cellulose-degrading LPMOs that play a crucial role in biorefinery enzyme cocktails and ii) hydrogenases, Ni+Fe or Fe-only metalloenzymes that are as rapid and efficient at hydrogen-catalysis as platinum.
Biopharmaceuticals, also known as biologic medical products (biologics for short) are medicinal products manufactured in or extracted from biological systems and are distinct from synthesized pharmaceutical products. Examples include vaccines against diseases such as polio and therapeutics used to treat numerous diseases, such as cancer and arthritis. These therapeutics are often molecules called monoclonal antibodies that are made by the immune system, our inbuilt anti-disease defense mechanism. Perhaps one the best known examples of this is Trastuzumab (trade name; Herceptin), a monoclonal antibody that is used to treat certain breast cancers. Production of these biologics is expensive and this translates into a high financial cost to health care providers. This project aims to alter the cells that make monoclonal antibodies for therapeutic use, so that they make larger amounts with reduced production costs. This should increase the availability of these powerful therapeutics.
The atmosphere is composed to millions of chemical compounds. Each of these compounds can have distinct properties chemical and physical but also biological and medical. Our ability to understand these compounds is dependent upon the instrumentation available to us. New advances in instrumentation (high resolution GC-TOF systems) allow us to investigate the composition of the atmosphere in unprecedented detail. However, these new instruments provide a deluge of data that needs to be stored and process. By storing all of the data, rather than throwing away the data that is not yet understood we will create a virtual air archive which can be exploited into the future as our ability to understand the complex instrumentation and chemistry involved becomes more refined. BACCUS provides hardware to deal with this data deluge, provide software and computers to support to analyse and visualise the data and provides some computation to initially interpret the results.
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.