A 700 MHz broadband cryoprobe and NMR spectrometer at UCL Chemistry

Lead Research Organisation: University College London
Department Name: Chemistry

Abstract

There are different types of scientific equipment in each university. But one type which is most widely used by hundreds, from undergraduate students to emeritus staff, is nuclear magnetic resonance (NMR) spectroscopy. The advantage of NMR relies on its versatility and applicability to nearly any kind of material. The NMR of a liquid, mainly a solution of a material in a solvent, is particularly widespread due to the ease of use and the rich information content provided by well-resolved signals. The major problem in NMR, however, is sensitivity: we usually need milligrams of a sample to collect an NMR signal. Sensitivity is measured as a signal-to-noise ratio on a standard sample. One way to improve it is to increase the magnetic field strength. After about 25 years of magnet developments, a saturated state was approached. A breakthrough came in 1999 when the temperature of the probe coil and other parts was dropped drastically giving a >4-fold increase in sensitivity. This translates into a >16-fold reduction in time. The introduction of cryoprobes in NMR can be compared to the implementation of fast processors in computers. The increase in sensitivity means that we can now measure not only 1H or 31P with nearly 100% natural abundance but also 13C or 15N of small amounts of sample.

The main objective of this proposal is to introduce the first broadband cryoprobe at the highest 1H frequency of 700 MHz into a daily research of a diverse range of materials and drugs in Physical and Life sciences. To give a few examples, the new equipment will be used in such studies as the origin of life, drug discovery, cancer research, metabonomics, batteries, polymers and catalysis. The equipment will be installed in UCL, which has a £385M total EPSRC support. It will become part of the existing NMR facility in UCL Chemistry, with 4 solution and 1 solid-state NMRs. The 700 MHz instrument will be the highest field instrument at UCL Chemistry and will underpin both chemical biologyand materials research.

In recent years, several new appointments have been made, many of which actively use NMR, including Prof Battaglia - the chemistry of biological polymers, Dr Powner - origins of life via chemical pathways leading to biological form and function, multicomponent reactions, sulphur and phosphorus chemistry, Dr Chudasama (named by Forbes magazine as one of the world's top scientists under the age of 30) - novel biotechnology drugs for selective delivery of chemotherapy to tumour cells via combinations with antibodies, Dr Bronstein - conjugated fused aromatic small molecules and polymers for use in optoelectronics. Within a short time, Dr Powner has become our leading NMR user, running >35% of the total number of NMR spectra. His research will gain considerably from the multinuclear and improved signal dispersion capabilities of the new instrument.

In addition to addressing the increased demand within UCL Chemistry, the new equipment will be used by >15 other UCL departments, which have joint EPSRC supported research projects with Chemistry, including Biochemical Engineering, Chemical Engineering, Eastman Dental Institute, School of Pharmacy, Wolfson Institute and others.

As this is a unique facility with the first helium-cooled broadband cryoprobe in the UK, the use of the new equipment will be extended to include other UK universities and research institutions in order to address their need in NMR of less studied nuclei. The operation of the facility will be fully automated to provide high throughput. Remote access will also be enabled for users from outside UCL Chemistry.

It is expected that the new facility will provide more comprehensive structural information by expanding NMR to nearly all atoms present in a molecule, not just 1H and 13C. This will enable drawing detailed structure-property relationships, which in turn will enhance our ability to design new advanced materials and drugs with desired properties and functions.

Planned Impact

Development of new materials and drugs with desired properties relies on our knowledge of their structure and dynamics. The most versatile technique in this regard is NMR spectroscopy. Applied separately on each type of nucleus present in a material NMR provides much-needed selectivity for structure and dynamics studies, which in turn advances our ability to design new materials and drugs.

The major problem of NMR, however, is its sensitivity, requiring larger quantities of samples than other methods. The objective of this proposal is to establish a 700 MHz NMR facility with a helium-cooled broadband cryoprobe. The proposed facility will be unique in the sense that it will combine multiple cutting-edge NMR technologies into a single all-in-one instrument dedicated to comprehensive studies of materials at the atomistic level. It will provide record levels of sensitivity for NMR measurements enabling experiments considered as unfeasible until recently, such as 19F NMR detections at micromolar concentrations or natural abundance NMR of 15N in the absence of nearby protons.

To our knowledge, there is no such facility in the world, making this instrument unique as multinuclear NMR equipment at the internationally leading level. Therefore, the requested equipment meets national needs by establishing a unique world-leading research activity. As such, it will be available to students and staff from UK academia and industry.

The immediate beneficiaries will include the EPSRC funded projects. Researchers from London and other UK universities will be provided with the full walk-up access to the new facility. In UCL Chemistry alone, the facility will have a direct impact on the research of >20 groups. The highest sensitivity of multinuclear NMR facility combined with fully automated and remote operation will satisfy requests from hundreds of users promptly, expediting wide impact of the facility.

The impact of the proposed facility on fundamental and applied sciences spans Chemistry, Materials Science, Biology, Physics, Medicine, Healthcare, Engineering, Geology and others. The research enabled by the new equipment is relevant to the strategic EPSRC themes:

1. Energy (EP/K014714 £3.7M, EP/N009533 £1.3M, EP/L017091 £840K)
2. Healthcare Technologies (EP/K031953 £11M, EP/M01732X £564K)
3. Manufacturing the Future (EP/L017709 £2.3M, EP/K014897 £1.9M, EP/N01572X £778K)
4. Physical Sciences (EP/K004980 £970K, EP/M02220X £345K)
5. Research Infrastructure (CRUK&EPSRC Cancer Imaging Centre at KCL&UCL)

The new equipment will benefit research falling within the four Grand Challenges of Chemical Sciences and Engineering:

(i) Dial-a-Molecule - 100% efficient synthesis
(ii) Directed Assembly of Extended Structures with Targeted Properties
(iii) Systems Chemistry: Exploring the Chemical Roots of Biological Organisation
(iv) Utilising CO2 in Synthesis and Transforming the Chemicals Industry

The research benefiting from the new facility is also relevant to 2 out of 4 Grand Challenges in Physics:

(i) Nanoscale Design of Functional Materials and
(ii) Understanding the Physics of Life,

as well as in Healthcare Technologies:

(i) Developing Future Therapies and
(ii) Optimising Treatment.

Thus, the new equipment will contribute towards addressing long-term public expectations and industrial needs identified by EPSRC. For example, the amidation reaction by Dr Sheppard will be crucial for direct amide synthesis, the most commonly used reaction in the pharmaceutical industry, which is a sector of huge importance to the UK economy.

The principal and substantial impacts will come from the work done by many groups using the new facility, which will affect lives of broader social groups through developments of, e.g., new batteries, solar panels, drugs and healthcare products. The new facility will also impact research into diagnostics and therapy of such diseases as cancer, liver cirrhosis and multiple sclerosis.

Publications

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Description Many research groups from UCL and other UK academic and industrial organisations have already made use of the multinuclear 700 MHz NMR facility at UCL/Chemistry. It is likely that the research carried out by these groups will lead to significant developments supported by patents. As an example, verification of the identity of compounds on the 700 MHz NMR was carried out on a confidential basis for a commercial company. This is expected to support a patent application process, provided that any of compounds that have been analysed at UCL demonstrate a useful level of biological activity as a starting point in the herbicide/fungicide/insecticide sphere. We have also run over 330 NMR spectra for Abcam Plc (Cambridge) between November 2017 and March 2020. The 19F NMR capability of the facility was used by researchers from Key Organics, as well as from UCL School of Pharmacy. Since July 2017, the facility has been used by users from the UCL Dementia Research Centre on a regular basis, which focuses on clinical research into various forms of dementia.

The new facility was also used for training new users. In particular, 118 and 116 new users were trained in 2017/18 and in 2018/19. Over the last 10 months in 2019/20, we have trained 124 new users.

There are many key findings by the users of the multinuclear 700 MHz NMR facility at UCL/Chemistry. Below we list some of them received in response to our request to contribute to this report (last updated in March 2020):

Dr Gareth Williams and Karolina Dziemidowicz, PhD Candidate (School of Pharmacy, UCL): The 700MHz NMR facility, including its 19F NMR capability, was used in our project titled "Perfluorophenyl azide functionalisation of biodegradable polymers". This project focuses on the surface modification of electrospun polycaprolactone fibres to enable therapeutic protein delivery.

Prof David Selwood (Wolfson Institute for Biomedical Research, UCL): Cancers hide (cloak) themselves from immune system attack by several means. The new chemicals described by us block one of these cloaking mechanisms and reveal the tumour to the immune system. This establishes a new way to treat tumours. The key finding is that the immune response of regulatory T-cells can be affected by a small molecule antagonist of the neuropilin-1 protein. The discovery of this antagonist (EG01377) is described in our paper titled "Small Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor Activity with Immune Modulation through Reduction of Transforming Growth Factor Beta (TGFß) Production in Regulatory T-Cells".

Prof Matthew Powner (Department of Chemistry, UCL, co-applicant in the EPSRC application for the multinuclear 700 MHz NMR facility):
1. We have demonstrated diamidophosphate can be harnessed to achieve Strecker amino acid synthesis. The high yield of N-phosphoro-aminonitriles and their selective transformations provides new insights into prebiotic amino acid synthesis and activation.
2. We have developed a new method to achieve a divergent synthesis of purine and pyrimidine nucleotide with the natural sugar stereochemistry.
3. We have developed a new prebiotic strategy to access nucleotide 5'-phopshates in water. The new strategy opens new pathways to explore nucleotide syntheses and activations, which are closely aligned with the biochemical strategies exploited by extant life. We have now developed this work further to realise acetylation controlled nucleotide photoanomerisation.
4. We have discovered chemoselective peptide ligation in water (see Canavelli et al. published in Nature, 2019).
5. We have demonstrated that N-phospho amino nitriles can not only be highly efficiently synthesised in neutral water but the neutral phosphorostrecker reaction provide excellent selectivity for proteinogenic amino acid over non-natural a,a-disubstituted amino nitrile (see Ashe et al in Nature - Communications Chemistry, 2019).
6. We have developed new chiral aldehydes for analysis and as standards to use for investigating the chemical composition of meteorite samples in collaboration with scientists at the Solar System Exploration Division, NASA Goddard Space Flight Center, USA (see Aponte et al in ACS Earth Space and Chemistry, 2019).

Dr Hien Nguyen (City University): We have developed a range of novel low cost, portable and selective fibre optic chemical sensors for the detection of drugs and heavy metals. The use of the NMR facility at UCL is essential in the organic synthesis stage where various novel fluorescent receptors have been developed and used as the sensing materials for the sensors. Two papers have been published in 2019/20, titled "Novel coumarin-based pH-sensitive fluorescent probes for the highly alkaline pH region" and "A Turn-On Fluorescence-Based Fibre Optic Sensor for the Detection of Mercury".

Dr Vijay Chudasama (Department of Chemistry, UCL): The use of the UCL 700MHz NMR facility was paramount in helping us elucidate the structure of two different tautomers of a medicinally important heterocycle - indazole. This was the key finding during the development of synthesis for both indazole tautomers through use of a single branch point intermediate. We were able to develop the efficient formation of 1H- and 2H- indazoles from a single branch point intermediate. The UCL 700MHz NMR facility was also used to characterise the structure of all the analogues formed through this method.

Drs Hannah Woodward, Dr Ben Atkinson and David Steadman (Alzheimer's Research UK UCL Drug Discovery Institute): We regularly use the 700 MHz and other NMR instruments at UCL Chemistry to obtain high-resolution NMR spectra. This allows us to fully characterise all of the small molecules that we synthesise in our research projects, which are aimed at finding modulators of targets implicated in the progression of Alzheimer's or other neurodegenerative diseases. As an example, a new efficient chiral synthesis of enantiopure arimoclomol was reported recently. This arimoclomol has progressed to human clinical studies for evaluation as a potential treatment for SOD1 (superoxide dismutase 1 gene) positive familial amyotrophic lateral sclerosis (ALS). Off-target pharmacology was evaluated against a representative set of drug targets and showed modest binding to a few kinases. Pharmacokinetic data was generated in vivo in mouse and showed a low brain : plasma ratio. The reported pharmacology and pharmacokinetic studies will be helpful in gaining a better understanding of the pharmacokinetic-pharmacodynamic relationship of arimoclomol in disease models. Overall, our research projects are aimed at finding small molecule modulators of targets implicated in the progression of Alzheimer's or other neurodegenerative diseases. We have submitted a patent application which has compounds that were characterised on the 700 as well as a research paper which is currently under review with Med. Chem. Comm. journal of the Royal Society of Chemistry. Tool compounds for use in neurodegenerative research and compounds for use as inhibitors of key targets for the treatment of neurodegenerative diseases were discovered recently.

Dr Salvador Tomas (Department of Biological Sciences, Birkbeck College): By allowing the careful characterization of the relevant molecular tools and the analysis of self-assembly, data gathered using UCL NMR facility has enabled us to (i) develop a mathematical model of cooperative assembly in supramolecular polymers; (ii) carry out the detailed study of chemical reactivity in lipid vesicles, and (iii) develop a mathematical model of membrane adhesion. The UCL NMR facility helped us to characterise the cooperativity in self-assembly described in our publication.

Prof Erik Arstad, Dr Thibault Gendon and Dr Michael Porter (Institute of Nuclear Medicine, UCL and Department of Chemistry, UCL): The 700 MHz NMR facility together with other NMRs at UCL Chemistry is used in our research on a daily basis as part of our research on aromatic radiofluorination. In addition to routine analysis, the NMR spectrometers were used to elucidate reaction mechanisms and predict the outcome of the radiofluorination reactions. In particular, the 700 MHz NMR was used to confirm the structure of complex molecules, otherwise difficult to analyse with the other instruments. We have shown that the efficiency of aromatic radiofluorination using dibenzothiophene sulfonium salts is correlated with the 19F NMR chemical shift of the non-radioactive fluorinated reference. Recently, we have reported a novel intramolecular ring-closing reaction of biaryl thioethers that give access to highly functionalized dibenzothiophene sulfonium salts under mild conditions. The resulting precursors react regioselectively with [18F]fluoride to give [18F]fluoroarenes in predictable radiochemical yields. The strategy expands the available radiochemical space and provides superior labelling efficiency for clinically relevant Positron Emission Tomography (PET) tracers.

Dr Michael Porter (Department of Chemistry, UCL): We have developed novel organic transformation. The 700 MHz NMR has been valuable in identifying and quantifying the products from (i) a novel electrochemical trifluoromethylation and (ii) a novel oxidative cyclisation of homopropargylic sulfonamides.

Prof Claire Carmalt and Dr Caroline Knapp (Department of Chemistry, UCL): Our NMR studies, including variable-temperature measurements, have focused on gallium alkoxides (please see our recently published paper titled "Structural and Dynamic Properties of Gallium Alkoxides", DOI: 10.1021/acs.inorgchem.9b01496). These are useful as precursors to gallium oxide, which in turn is used in the formation of amorphous oxide semiconductors employed in thin film photovoltaic devices, as well as in the development of processes towards sustainable high quality transparent conducting oxide (TCO) films and gas sensing materials. The NMR spectra of chloro gallium bis(alkoxides) were found to vary with the nature of the ligand and the temperature and allowed to establish the dynamics of the molecules studied.

Prof Helen Hailes (Department of Chemistry, UCL):
1. For the publication "Functionalised tetrahydrofuran fragments from carbohydrates or sugar beet pulp biomass", the facility was invaluable in characterizing the products generated from biomass-derived starting materials. Selective dehydration of pentose sugars was achieved under basic or acidic conditions, and the equipment allowed NMR reaction monitoring and the ability to distinguish between the isomeric products formed. Fragments for medicinal chemistry applications containing primary alcohol, ketone, carboxylic acid or amine functional groups were generated, suitable for incorporation into fragment/lead libraries. Funding EPSRC (EP/K503745/1) and building upon outputs from EP/K014897.
2. For the publication 'A Biomimetic Phosphate Catalyzed Pictet-Spengler Reaction for the Synthesis of 1,1'-Disubstituted and Spiro-Tetrahydroisoquinoline Alkaloids', the facility was invaluable for reaction monitoring as the products are readily oxidized, hygroscopic and difficult to purify. In this work, a range of novel 1,1'-disubstituted and spiro-tetrahydroisoquinoline alkaloids were readily prepared in one-step and good yields, via this atom-efficient, sustainable synthetic route. Funding BBRSC (BB/N01877X/1).
3. For the publication 'Ene-reductases from a drain metagenome for the selective bioreduction of bicyclic enones', the facility was essential to determine the stereochemistry of ene-reductase enzyme products. In this work, a sequence-based functional metagenomics strategy was used to identify novel ene-reductase enzymes from a drain metagenome. Several new ene-reductases were discovered and effectively applied in the stereoselective bioreduction of bicyclic Wieland-Miescher and Hajos-Parish ketones. Notably, this is the first time such bulky substrates have been successfully transformed with wild-type ene-reductases and the enzymes also showed remarkable organic solvent robustness which is ideal for industrial applications. Funding BBRSC BB/N01877X/1 & BB/L007444/1.
4. For the publication 'Acceptance and Kinetic Resolution of Alpha-Methyl-Substituted Aldehydes by Norcoclaurine Synthases', we have reported the unusual acceptance of alpha-substituted aldehydes, by wild-type Thalictrum flavum Norcoclaurine Synthases to give tetrahydroisoquinoline products. Moreover, the kinetic resolution of several alpha-substituted aldehydes to give tetrahydroisoquinolines with two defined chiral centres in a single step with high conversions was achieved. Active site-mutants of Thalictrum flavum Norcoclaurine Synthases were then used which demonstrated the potential to enhance the stereoselectivities in the reaction and improve yields. Funding BBRSC (BB/N01877X/1).
5. A manuscript titled 'Identification and applications of new epoxide hydrolases from the genomic data of soil bacteria' was recently submitted (funding Wellcome Trust), which focuses on new epoxide hydrolases for use in synthesis.


Prof Tom Sheppard (Department of Chemistry, UCL):
1. The study of boron-mediated reactions in organic synthesis and reactions of organoboron compounds is greatly facilitated by the use of 11B NMR. However, the identification and characterization of reaction intermediates in often complex systems is far from trivial, as 11B NMR does not provide any detailed structural information. We have shown that greater insight into the structures present in such systems can be obtained by using DFT chemical shift calculations to support or exclude proposed reaction intermediates. We have reported a rapid and accessible approach to the calculation of 11B NMR shifts that is applicable to a wide range of organoboron compounds.
2. We have shown how dihalohydration reactions of propargylic alcohols can be used to access a wide variety of useful halogenated building blocks. A novel procedure for dibromohydration of alkynes has been developed, and a selection of dichloro and dibromo diols and cyclic ethers were synthesized. The dihalohydration of homo-propargylic alcohols provides a useful route to 3-halofurans, which were shown to readily undergo cycloaddition reactions under mild conditions. A novel ring expansion of propargylic alcohols containing a cyclopropylalkyne is shown to provide access to halogenated alkenyl-cyclobutanes.

Prof Alethea Tabor (Department of Chemistry, UCL): has used the 700 MHz NMR machine to continue her studies on the folding and biological activity of the tarantula toxin ProTx-II. This is an inhibitory cystine knot (ICK) peptide which shows highly selective and potent binding to the Nav1.7 ion channel and hence is an important lead for the treatment of chronic pain. In recent work her group have developed methods for preparing analogues of ProTx-II that can be derivatised with biotin or fluorophores, or with photoactivatible groups, to probe the binding of ProTx-II to Nav1.7, and they have used 700 MHz NMR to demonstrate whether the resulting peptides are correctly folded.

Dr Mukhlesur Rahman (School of Health, Sports and Bioscience, University of East London; Currently in Liverpool John Moores University): Have discovered terpenes with potential antibacterial activity against a series of clinical isolates of multi-drug resistant and methicillin resistant staphylococcus aureus. The structures of compounds were established using the analysis of one-dimensional and two-dimensional NMR data and mass spectra.

Prof Ipsita Roy and Dr Pooja Bassnet (Department of Life Science, University of Westminster): We have used the 700MHz NMR facility for the research project involving the production of a family of biodegradable polymers such as polyhydroxyalkanoates (PHAs). PHAs are produced by a range of bacterial species using fermentation technology. We use NMR to identify the structure of the PHAs produced. The monomeric composition of PHAs is affected by the type of carbon substrate and the media composition. PHAs are used for a range of medical applications such as medical device development (coronary artery stents, nerve conduits, wound healing patches), as tissue engineering scaffolds in Regenerative Medicine and in controlled drug delivery.

Fane F. K. Mensah, PhD Candidate, and Prof Geraldine Cambridge (Division of Medicine, Centre of Rheumatology Research, UCL): CD24 expression on pro-B cells plays a role in B cell selection and development in the bone marrow. We previously detected higher CD24 expression and frequency within IgD+ naïve and memory B cells in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) compared with age-matched healthy controls (HC). In reference [13], we have reported the results of our investigations of the relationship between CD24 expression and B cell maturation. The relationship between CD24 expression to cycles of proliferation and metabolism in purified B cells from HC was investigated using the 700MHz NMR facility at UCL Chemistry. Currently, there is a manuscript under preparation in which we describe changes in an additional 26 metabolites using the spectral data obtained on the 700MHz NMR facility at UCL Chemistry. In both studies, we used the 700 MHz NMR to study the metabolic processes that occur during B cell maturation upon in vitro stimulation by measuring the relative levels of different metabolites present in the culture medium. For the first time, we have been able to follow changes in metabolite concentrations as well as changes in B cell phenotypes throughout in vitro B cell culture. This has not been done before and the developed assay can be used to test interventions during culture to follow changes in metabolite consumption and secretion, specific for B cells.

Prof Junwang Tang and Dr Christopher Windle (Department of Chemical Engineering, UCL): We have discovered a new catalyst for the selective oxidation of methane. Two manuscripts have been submitted to Journal of American Chemical Society (Covalent grafting of molecular catalysts on C3NxHy as robust, efficient and well-defined photocatalysts for solar fuel synthesis ) and Advanced Materials (Rational Design of High-Concentration Ti3+ in Porous Carbon-Rich TiOx Nanosheets for Highly-Efficiency Photocatalytic Ammonia Synthesis).

Prof Ivan Parkin and Cláudio Lourenco, PhD Candidate (Department of Chemistry, UCL): The aim of our project is to investigate active components of peroxide- and ROS-based antimicrobial systems which promote cleaning and antimicrobial effects (ROS = Reactive Oxygen Species). NMR studies are crucial for the determination of the stoichiometry of chemical reactions under different atmospheric conditions and concentrations. We also aim at developing new analytical methods for investigating the way in which different reactant chemicals interact with components of biofilms and biofouling. Improved, novel chemistries would have widespread application in a range of disinfectant applications. On a different project, we have already used the 700MHz facility to determine the authenticity of different glue samples.

Prof Ivan Parkin and Georgia Fleet, PhD Candidate (Department of Chemistry, UCL): A new method is being developed for analysing biofilm residues in collaboration with the Eastman dental hospital and GSK that uses the 700MHz NMR instrument.

Prof Chris Blackman (Department of Chemistry, UCL): A novel nickel dialkylaminoalkoxide precursor has been developed for chemical vapour deposition (CVD) of nickel oxide. A manuscript based on this work was recently submitted to Physica Status Solidi A.

Prof Gopinathan Sankar and Junwen Gu, PhD Candidate (Department of Chemistry, UCL): We investigate the mesoporous structure formation from commercial zeolite while maintaining the microporous character within the same crystal. Here the effect of pH (between 9 and 11) induced by the use of mild organic ammonium hydroxides and cetyltrimethylammonium bromide (CTAB) on the formation of mesostructures is of particular interest. The investigation also involves the determination of the effect of Si/Al ratio of the starting zeolite Y on the mesostructure formation within the same pH range. The work also will investigate the creation of macroporous silicalite material resulting in macropores within silicalite crystals.

Dr Gemma Louise-Davis (Department of Chemistry, UCL). The 700 MHz NMR has been used in following projects:
1. Preparation of metallasilsesquioxanes as novel precursors for MRI contrast agents. This project involves the development of new precursors in the development of high signal contrast agents for MRI. Utilising traditional inorganic synthetic chemistry techniques, complexes composed of Gd-chelates can be prepared as used in the development of nanostructured contrast agents with significantly higher signal than traditional molecular agents, whilst reducing the risk of metal leakage and dangers associated with this.
2. Development of hybrid organic-inorganic composites for diagnostic MRI contrast agents. Medical imaging agents capable of changing their signal profile in situ in the body could be exploited for non-invasive disease diagnostics, of value to clinical medicine. In this project, thermoresponsive polymer species are being developed which can respond to specific environmental markers. In combination with well-established high signal nanocomposite MRI contrast agents, these can hence provide a new route to contrast agents whose signal can be turned 'on' or 'off' in the presence of disease.
3. Targeted imaging agents using glycan chemistry. Bowel cancer is a highly prevalent disease which is often diagnosed at late stages the due lack of symptoms in the earlier, more treatable stages. As such, a route to early diagnosis of this disease is key to increasing survival rates. Current screening through colonoscopies uses diagnostic technician skills to observe and identify cancerous polyps, which are often difficult to distinguish from healthy polyps present in the bowel. This project aims to use sugar chemistry to develop a tool to assist with colonoscopic evaluations of polyps. Targeting of sugars released by cancerous polyps will be exploited to 'tag' these polyps with a high signal imaging agent which will aid easy diagnosis during colonoscopic examinations.

Dr Simoni Da Ros (Bartlett School Env, Energy & Resources, Faculty of the Built Environment, UCL): In the project dealing with historic plastics of cultural heritage significance, it has been discovered that hydrolysis plays an important role on the degradation of cellulose acetate and cellulose nitrate materials, as observed by the reduction in the degree of substitution of reference materials which have been aged thermally. In this same project, it has also been verified that plasticiser loss and cellulose acetate deacetylation are not independent processes and may impact each other. Such discoveries were only feasible due to the high sensitivity of the 700MHz instrument, which allowed for the development of accurate methods to determine plasticiser content and degree of substitution. In summary, analysis involving the UCL 700MHz NMR facility has supported the hypothesis that deacetylation plays an important role in the degradation processes of cellulose acetate historic plastics. Experiments have been carried out to determine the relationship between environmental variables such as storage temperature and relative humidity and the rate of deacetylation. Experiments have also evaluated the kinetics of plasticiser loss in different environments and data acquired using the NMR facility have supported the hypothesis that the loss of diethyl phthalate from cellulose acetate may be diffusion controlled.

Dr Bob Schroeder and Lewis Cowen, PhD Candidate (Department of Chemistry, UCL):
1. Mechanism of Fluoride Doping of BDOPV Organic Semiconductor. Polymeric and molecular semiconductors based on benzodifurandionebased oligo(pphenylene vinylene (BDOPV) have been shown to have high electron mobilities. Fluoride anions can be used as n-dopants, i.e. a means of introducing negative charge carriers on to BDOPV molecular semiconductors. The mechanisms by which these charges are introduced and the structure of the doped semiconductor are poorly understood. We use NMR experiments in conjunction with other spectroscopic techniques to probe the structural changes in BDOPV organic semiconductors induced by the introduction of n-doping fluoride anions. Both 1H and 19F NMR titrations of a fluoride anion source with organic semiconductor have given insight into the mechanism of doping in two different solvents. It was discovered that fluoride anions act as a base to deprotonate water in non-protic solvents, it is then the resultant hydroxyl anions which go on to form a complex with the semiconductor. 700 MHz NMR was used to identify strongly hydrogen bonding phenol type protons in the 1H NMR. When carried out in the protic solvent chloroform, fluoride anions deprotonate the solvent and doping is quenched.
2. Quaternary Ammonium Moieties as n-Dopants for Organic Semiconductors. The 700 MHz NMR was used as part of a full spectroscopic characterisation of self-doping organic semiconductors. A combination of 1H, 13C and 2D NMR studies has allowed us to begin a structural characterisation of the doped species which has never been attempted before. We have now developed an understanding of what intramolecular reactions may be taking place. The structural data from the 700 MHz NMR combined with device performance data is helping us understand the optimum conditions for and the activation energy of doping.

Dr Jon Wilden (Department of Chemistry, UCL): The work in the Wilden group is focused around two main themes (i) new radical methodology including development and mechanistic aspects of transition metal-free reactions, and (ii) the development of novel peptidomimetics and biologically active molecules. The 700 MHz NMR was used for structure determinations and characterisations in the following research projects: 1) Kate Peck: Enamine Sulfonamide-Alkyne Cycloaddition Reactions; 2) Mark Radigois: Fundamental Studies on Electron Transfer Reactions (EPSRC PDRA EP/M02220X/1); 3) Theodore Hayes: A Novel Enediyne Synthesis from Alkynyl Sulfonamides via Non- Classical Carbenoids; 4) Yi Luo: Towards Understanding the Synthesis and Reactivity of Alkynyl Sulfonamides; 5) Ana-Miruna Androniciu: Synthesis of alpha-aminosulfonamide peptidomimetics. Recently, the 700MHz NMR was also used in the project titled "Electrochemical Reduction of Aerial O2 for Clean, Green, Allylic and Propargylic C-H Activation Reactions".

Prof Jim Anderson (Department of Chemistry, UCL): A divergent total synthesis of some complex natural products has been developed. The 700MHz NMR facility was instrumental in deciphering complex stereochemistry in small quantities of advanced intermediates when we were working out our synthetic route.

Dr Jamie Baker (Department of Chemistry, UCL): Albumin-drug conjugates and cysteine-to-lysine transfer antibody fragments were studied. Amongst other things, we have used the 700MHz NMR facility to probe the rates associated with new bioconjugation reactions. We have used these findings to develop reagents for the construction of next-generation protein conjugates, which allow the selective delivery of drugs (or detectable moieties for diagnostics) to target cells.

Dr Cally Haynes (Department of Chemistry, UCL): The 700 MHz NMR was used to obtain a full spectral characterisation of newly synthesised metal-organic amphiphiles. The title of the relevant project is 'Anion controlled assembly of metal-organic amphiphiles'. The expected long-term findings of this project will be of interest to diverse chemical research fields including supramolecular chemistry, inorganic materials, soft materials, drug delivery and catalysis.

Dr Stefan Howorka (Department of Chemistry, UCL): Insight into the structure and function of photosensitive chemical probes has been achieved via collaborations within UCL Chemistry (Tracey Clarke, Jon Wilden, Guiseppe Battaglia), within UCL (Stephan Beck, UCL Cancer), Cambridge (Hugo Bronstein, Shankar Balasubramanian). We have uncovered the relationship between BODIPY structure and spectroscopic properties to design fluorophores for bioimaging. We have also gained insight into the solvent-dependent photophysics of a red-shifted, biocompatible coumarin photocage. In addition, we have developed a photo-responsive small-molecule approach for the opto-epigenetic modulation of DNA methylation.

Dr Alistair Miller (Darr House): The analysis carried out on the 700MHz NMR allowed to develop collaboration with University of Exeter, leading to a PhD project titled "Authentication of compounds for screening for insecticidal activity."

Dr Abil Aliev (Department of Chemistry, UCL, principal investigator in the EPSRC application for the multinuclear 700 MHz NMR facility):
1. The structure of a new compound, Cp(IPr)Ru(H)2SiH(Ph)Cl (IPr = 1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene) has been established using 1H, 13C and 29Si NMR chemical shifts and J couplings, as well as the X-ray structural analysis and DFT calculations. (in collaboration with Dr J. Saßmannshausen, The Francis Crick Institute).
2. We have used 300 MHz and 700 MHz NMR instruments to measure 119Sn chemical shift anisotropy (CSA) and have shown that a static powder pattern must be analysed in order to improve the accuracy of the CSA asymmetry measurements. (in collaboration with Dr A. Bartok, Rutherford Appleton Laboratory, and Prof J Yates, Department of Materials, University of Oxford).
3. Through detailed NMR measurements and their analysis, we have compared noncovalent interaction of sulfur and oxygen. It was found that compared to oxygen, the sulfur atom is able to interact with the almost equal facility over the entire range of pi systems studied. The results are important for understanding noncovalent interactions present in proteins (in collaboration with Prof Motherwell, Department of Chemistry, UCL, and Prof Coles. School of Chemistry, University of Southampton). An invited review was also published in 2019 in Chemistry - A European Journal of Chemistry.

In addition to those listed above, the 700 MHz NMR instrument has been used by:
Prof Andrea Sella (Department of Chemistry, UCL, in collaboration with researchers from Department of Physics, UCL)
Prof Charles Marson (Department of Chemistry, UCL)
Prof Giuseppe Battaglia (Department of Chemistry, UCL)
Dr Hugo Bronstein (Department of Chemistry, UCL)
Dr Kreso Bucar (Department of Chemistry, UCL)
Prof Xiao Guo (Department of Chemistry, UCL)
Dr Derek MacMillan (Department of Chemistry, UCL)
Dr Robert Palgrave (Department of Chemistry, UCL)
Prof William Motherwell (Department of Chemistry, UCL)
Dr Tung Chun Lee (Institute for Materials Discovery, UCL)
Prof Jonathan Knowles (Eastman Dental Institute, UCL)
Prof Kishor Gulabivala (Eastman Dental Institute, UCL)
Dr Elaine Allan (Eastman Dental Institute, UCL)
Dr Justin Warne (Division of Infection & Immunity, UCL)
Dr Kerstin Sander (Centre for Radiopharmaceutical Chemistry, UCL)
Dr Rose King (Institute of Sustainable Heritage, UCL)
Dr Stephen Hilton (School of Pharmacy, UCL)
Dr Matthew Todd (School of Pharmacy, UCL)
Dr Philip Lowden (Birkbeck College)
PDRA Dr Islam Saidul (Department of Chemistry, UCL)
PDRA Dr Daniel Whitaker (Department of Chemistry, UCL)
PDRA Dr Christian Fernández-García (Department of Chemistry, UCL)
PDRA Dr Laure Benhamou (Department of Chemistry, UCL)
PDRA Dr Thibault Gendron (Department of Chemistry, UCL)
PDRA Dr Dana Chan (Department of Chemistry, UCL)
PDRA Dr Fabien Thoreau (Department of Chemistry, UCL)
PDRA Dr Fatih Sirindil (Department of Chemistry, UCL)
PDRA Dr Yangwei Deng (Department of Chemistry, UCL)
PDRA Dr Robert James Smith (Wolfson Institute, UCL)
PDRA Dr Ben Graham (Wolfson Institute, UCL)
PDRA Dr Suresh Moorthy (Institute for Materials Discovery, UCL)
PDRA Dr Fahima Idiris (School of Pharmacy, UCL)
PDRA Dr Ben Woods (Birkbeck College)
PhD Candidate Cristina Perez Rivero (University of Westminster)
PhD Candidate Yakub Naheem (Royal Free Hospital, UCL)
PhD Candidates Ankan Biswas and Sara Malferrari (Royal Free Hospital, UCL)
PhD Candidate Zalike Keskin Erdogan (Eastman Dental Institute, UCL)
PhD Candidate Mohammad Aljaber (Eastman Dental Institute, UCL)
PhD Candidate Benjamin Bowles (School of Pharmacy, UCL)
Dr Rachel Platel (Lancaster University)
Dr Andrew Atkinson (Kings College)
Prof Eduardo Humeres (Federal University of Santa Catarina, Brazil)
Dr. Fabiola Sciscione (Royal Free Hospital, UCL)
Prof Craig Butts and PhD Candidate Catherine McIntyre (Bristol University)
PhD Candidate Nazanin Owji (Eastman Dental Institute, UCL)
PhD Candidate Sarene Saw (Eastman Dental Institute, UCL)
Drs Louise-Anne Pilcher and John Wong (Abcam)
Dr Will Travis (Gurit UK)
Drs Daniel Dumas and Mrs Lorna Bankole (Key Organics Ltd)
PhD Candidate Prachi Dubey (University of Westminster)
PhD Candidate Lorena Lizarraga (University of Westminster)
PhD Candidate Chivu Alexandru (Royal Free Hospital, UCL)
PhD Candidate Huang He (Chemical Engineering, UCL)
PhD Candidate Holly Siddique (School of Health, Sports and Bioscience, University of East London)
Dr Obeng Melody (Royal Free Hospital, UCL)
Dr James Sipthorp (Alzheimer's Research UK UCL Drug Discovery Institute)
Dr Elliott Bayle (Alzheimer's Research UK UCL Drug Discovery Institute)

and many others.
Exploitation Route Prof David Selwood (Wolfson Institute for Biomedical Research, UCL): Our findings described above could be developed into a new modality of anti-tumour treatment.
Prof Matthew Powner (Department of Chemistry, UCL, co-applicant in the EPSRC application for the multinuclear 700 MHz NMR facility): Our findings are of interest to those involved in researching chemical origins of life, as well pharmaceuticals and fine chemicals. Selective peptide ligations can be used more generally and more specifically for developing a model for the origins of life on Earth and the context of prebiotic chemistry on exo-planets.
Dr Hien Nguyen (City University): Through publications and commercialisation.
Dr Vijay Chudasama (Department of Chemistry, UCL): Our work has the potential to be used by medical groups who wish to synthesise analogues of heterocyclic-based bioactive compounds for testing. As the two tautomers are observed to have differing bioactive effects, the synthesis, therefore, gives easy access to a much larger range of potentially useful indazole analogues. We have developed several methodologies for the synthesis of pharmaceutically-relevant indazoles, benzodiazepines and small molecule drug conjugate scaffolds. We envisage our findings would be particularly useful to those developing more efficient synthesis for pharmaceutically relevant molecules and therapeutics.
Drs Hannah Woodward, Dr Ben Atkinson and David Steadman (Alzheimer's Research UK UCL Drug Discovery Institute): The reported studies described above will contribute towards a better understanding of pharmacokinetic and pharmacodynamic properties of an experimental drug. Tool compounds discovered could be used for further study and research to understand neurodegenerative diseases and disorders.
Dr Salvador Tomas (Department of Biological Sciences, Birkbeck College): The use the mathematical tools developed to build up smart lipid vesicles with a range of applications. Our research results can be used by those involved in the development of responsive nanomaterials and nanoreactors for sensing and drug delivery.
Prof Erik Arstad, Dr Thibault Gendon and Dr Michael Porter (Institute of Nuclear Medicine, UCL and Department of Chemistry, UCL): The radiochemistry we developed is likely to have a significant impact on radiopharmaceutical research and lead to the development of the next generation diagnostic tracers. We are already planning for translation of one such tracer for first in human studies. The method we published allows radiochemists to acquire the 19F NMR spectrum of the molecule they wish to radiolabel and quickly determine whether our new radiolabelling methodology is suitable to their target or not. We have developed a new type of leaving groups (dibenzothiophene sulfonium salts) for nucleophilic aromatic substitution, and have developed this as a platform for manufacturing of diagnostic positron emission tomography (PET) tracers.
Dr Michael Porter (Department of Chemistry, UCL): The reactions we have developed may have more widespread use for the synthesis of biologically active compounds in the pharmaceutical and agrochemical sectors. Our research is relevant to developments of pharmaceuticals and agrochemicals.
Prof Claire Carmalt and Dr Caroline Knapp (Department of Chemistry, UCL): Understanding the dynamics of gallium alkoxide precursors will be useful to others involved in the development of new oxide semiconductors, transparent conducting oxide (TCOs) films and gas sensing materials.
Prof Helen Hailes (Department of Chemistry, UCL):
1. Both Astra Zeneca and GSK have samples of the fragments prepared for use in fragment libraries and will provide feedback on an annual basis.
2. We have 2 collaborators, one academic group and a company who are screening the products.
3. The grant is co-funded by ALMAC group and the company have the enzymes for industrial applications.
4 & 5. New enzyme applications.
Prof Tom Sheppard (Department of Chemistry, UCL): The findings described above could be used by others for 11B NMR characterisations of reaction intermediates and products. The methodology developed by us can be employed for the preparation of various classes of organic compounds, including those which are of interest to the pharmaceutical industry.
Prof Alethea Tabor (Department of Chemistry, UCL): The methods developed for the studies of folding and aggregation of peptide toxins and peptide surfactants can be employed by other researchers working in the area of biomedicine and peptide chemistry.
Dr Mukhlesur Rahman (School of Health, Sports and Bioscience, University of East London; Currently in Liverpool John Moores University): Bioassay-guided phytochemical investigation on members of Zingiberacae family can be further explored for the identification of lead anti-Staphylococcal compounds.
Prof Ipsita Roy and Dr Pooja Bassnet (Department of Life Science, University of Westminster): We use NMR to identify the structure of biodegradable polymers, which are useful for a range of medical applications such as medical device development (coronary artery stents, nerve conduits, wound healing patches), as tissue engineering scaffolds in Regenerative Medicine and in controlled drug delivery.
Fane F. K. Mensah, PhD Candidate, and Prof Geraldine Cambridge (Division of Medicine, Centre of Rheumatology Research, UCL): Experiments reported by us have not been done before. The developed assay can be used to test interventions during the cell culturing in order to follow changes in metabolite consumption and secretion specific for B cells.
Prof Junwang Tang and Dr Christopher Windle (Department of Chemical Engineering, UCL): Our findings provide significant information for the development of new more efficient methane oxidation catalysts.
Dr Stefan Goulding (Department of Chemical Engineering, UCL): We study material formation on the nanoscale by molecular self-assembly and build functional nano-architectures for a variety of fields ranging from chemical sensing and biomedical diagnostics to photovoltaics and optical coatings.
Prof Ivan Parkin and Cláudio Lourenco, PhD Candidate (Department of Chemistry, UCL): The work is relevant for disinfectant applications.
Dr Simoni Da Ros (Bartlett School Env, Energy & Resources, Faculty of the Built Environment, UCL): The findings are expected to impact on the conservation strategies in museums and archives or any institution concerned about the preservation of historic plastics. Moreover, by understanding the mechanism of degradation, and its main causes, the research may contribute to the development of recycling technologies, which is very important for the management of global solid plastic waste.
Dr Bob Schroeder and Lewis Cowen, PhD Candidate (Department of Chemistry, UCL): Our research is of interest to those involved in the design and synthesis of functional materials for organic electronic applications. An insight into the relatively unknown mechanisms of n-type doping in organic semiconductors allows others to achieve efficient doping in new materials. The development of stable self-doping organic semiconductors will make device processing using doped materials much easier. Lightweight processable energy harvesting materials specifically in organic thermoelectrics and organic photovoltaics.
Prof Jim Anderson (Department of Chemistry, UCL): The divergent synthetic route developed by us will be used for the synthesis of similar alkaloid targets for the investigation of their biological activity.
Dr Jamie Baker (Department of Chemistry, UCL): Reagents and methods for the construction of protein conjugates, such as the ones we have developed, are widely sought. For example, antibody-drug conjugates represent a rapidly class of targeted therapeutics, with 3 approved in the last year. However the reactions to attach the drugs to antibodies are known to be suboptimal - we anticipate our reactions could have a major contribution to the next generation of such conjugates.
Dr Cally Haynes (Department of Chemistry, UCL): The expected long-term findings of the project using the 700MHz facility will be of interest to diverse chemical research fields including supramolecular chemistry, inorganic materials, soft materials, drug delivery and catalysis.
Dr Stefan Howorka (Department of Chemistry, UCL): Develop new photosensitive chemical tools to advance chemical biology, molecular biology, and biomedicine.
Dr Abil Aliev (Department of Chemistry, UCL, principal investigator in the EPSRC application for the multinuclear 700 MHz NMR facility): 1. The work on Ru-H ··· Si interaction will be of interest to those working in the area of organometallic chemistry, as well in studies of a noncovalent interaction in general; 2. Others working in the area of solid-state NMR spectroscopy, as well as structural characterisations of solid materials, will benefit from the results published by us using tin NMR; 3. The interest in noncovalent interactions has been grown fast over the last two decades and our publication titled "Noncovalent Interactions of pi Systems with Sulfur - The Atomic Chameleon of Molecular Recognition" will benefit those interested in noncovalent interactions of sulfur and oxygen atoms. Dr Abil Aliev was invited to write a review article following this publication (DOI doi.org/10.1002/chem.201900854).
Sectors Aerospace, Defence and Marine,Agriculture, Food and Drink,Chemicals,Education,Electronics,Energy,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Culture, Heritage, Museums and Collections,Pharmaceuticals and Medical Biotechnology

URL https://www.ucl.ac.uk/bartlett/heritage/research/projects/current-projects/complex
 
Description There are various wide-ranging impacts associated with the research work of the users of the multinuclear 700 MHz NMR facility at UCL/Chemistry. Below we list some of them received in response to our request to contribute to this report: Prof David Selwood "Small Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor Activity with Immune Modulation through Reduction of Transforming Growth Factor Beta (TGFß) Production in Regulatory T-Cells": Translational funding has been secured for this project going forward. Dr Hien Nguyen (City University): We are working with several companies to commercialize what we have developed with the aim to provide a fast screening solution to yield new information on what is an important aspect of improving the environment. Dr Vijay Chudasama (Department of Chemistry, UCL) "A facile route to 1H- and 2H-indazoles from readily accessible acyl hydrazides by exploiting a novel aryne-based molecular rearrangement.": Potentially could contribute to the research in the area of new drug discovery. Several methodologies were developed for the synthesis of pharmaceutically-relevant indazoles, benzodiazepines and small molecule drug conjugate scaffolds. We envisage our findings would be particularly useful to those developing more efficient synthesis for pharmaceutically relevant molecules and therapeutics. Dr Salvador Tomas (Department of Biological Sciences, Birkbeck College): Our findings are relevant in abiogenesis. They, therefore, contribute to a better understanding of life's origin. Our research will boost the development of programmable drug delivery vehicles. The potential societal impact of such devices is difficult to overstate: they will decisively contribute to drastically reducing (and at the fullest of their development, eliminating) the scourge of cancer and infectious diseases. Finally, by developing mathematical tools that describe and allow to predict the behaviour of smart nano-vesicles our research is contributing to the development of artificial protocells, the building blocks of soft-matter based robots inspired by the architecture of living organisms. The development of this new field of robotics is a medium-long term prospect but has the potential to revolutionise the manufacturing industry in a not too distant future. Our research is also of interest to those involved in the development of responsive nanomaterials and nanoreactors for sensing and drug delivery. Prof Helen Hailes: The findings are likely to have non-academic impacts in the longer term. Five papers have been published and one manuscript has been submitted. Prof Tom Sheppard (Department of Chemistry, UCL): Ten papers have already been published which are likely to have non-academic impacts in future. Prof Alethea Tabor (Department of Chemistry, UCL): The findings of our research are likely to have non-academic impacts once the results have been published. Dr Mukhlesur Rahman (School of Health, Sports and Bioscience, University of East London; Currently in Liverpool John Moores University): The research described in our publication titled "Terpenes from Zingiber montanum and Their Screening against Multi-Drug Resistant and Methicillin Resistant Staphylococcus aureus" will contribute towards the identification of lead anti-Staphylococcal compounds. Fane F. K. Mensah, PhD Candidate, and Prof Geraldine Cambridge (Division of Medicine, Centre of Rheumatology Research, UCL): The condition Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been poorly studied. Nevertheless, various publications have pointed abnormalities in the immune system as well as in the metabolism of the patients. Our paper titled "CD24 Expression and B Cell Maturation Shows a Novel Link With Energy Metabolism: Potential Implications for Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome" contributed to both of these findings and has been very well received by both the scientific and patient community. Funding for biomedical research in ME/CFS has been very limited in both the UK and outside of the UK. Scientific research and publications, such as our paper, contribute towards the better understanding of ME/CFS and other diseases. Prof Junwang Tang and Dr Christopher Windle (Department of Chemical Engineering, UCL): In the long term the catalyst developed by us may find use in industrial methane reforming. We have already discovered the structure of the reaction products using the 700MHz facility, e.g., isotopic ammonia and molecular catalysts. It is very important to identify the final isotopic products in order to avoid misunderstanding of the underlying chemical processes. Dr Simoni Da Ros (Bartlett School Env, Energy & Resources, Faculty of the Built Environment, UCL): For the project dealing with historic plastics of cultural heritage significance, the findings are contributing to the knowledge exchange between universities and museums. Drs Hannah Woodward, Dr Ben Atkinson and David Steadman (Alzheimer's Research UK UCL Drug Discovery Institute): Tool compounds discovered could be used for further study and research to understand neurodegenerative diseases and disorders. Dr Stefan Howorka (Department of Chemistry, UCL): The research results are of potential interest to bioimaging and small-molecule probe development in chemical/biotech industry. Dr Abil Aliev and Prof William Motherwell (Department of Chemistry, UCL): The work on noncovalent interactions promotes our understanding and controlling of three-dimensional molecular recognition in chemical reactions and biological processes, as well as in supramolecular chemistry, pharmaceutical sciences, host-guest complexation and crystal engineering. Prof Matthew Powner (Department of Chemistry, UCL): The published research results in such a high-impact journal as Nature have advanced our understanding origins of life. They are also relevant to pharmaceutical and fine chemical industries. Prof Ivan Parkin (Department of Chemistry, UCL): The research undertaken is expected to be of interest to healthcare professionals. Prof Erik Arstad, Dr Thibault Gendon and Dr Michael Porter (Institute of Nuclear Medicine, UCL and Department of Chemistry, UCL): We have developed a new type of leaving groups (dibenzothiophene sulfonium salts) for nucleophilic aromatic substitution, and have developed this as a platform for manufacturing of diagnostic positron emission tomography (PET) tracers. The chemistry is particularly relevant for PET chemistry, but we expect it will also find widespread use in synthetic chemistry as the leaving group we developed has been shown (by others) to be exceptionally well suited for Pd-couplings, i.e. allows coupling with 90% yield in the presence of aryl iodides Our findings have led to a £1.2 million grant from the MRC (subject to contract) for testing of a novel diagnostic tracer in humans for the first time. Please note that there are also impacts and research results of the confidential nature, details of which cannot be revealed here at this time.
Sector Chemicals,Education,Electronics,Energy,Healthcare,Culture, Heritage, Museums and Collections,Pharmaceuticals and Medical Biotechnology
Impact Types Cultural,Societal,Economic,Policy & public services

 
Description NMR Metabonomics for the Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome by Researchers from UCL Centre of Rheumatology and New Zealand
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Title Research Tools & Methods of Confidential Nature 
Description Research tools and methods of confidential nature are developed using the 700 MHz facility in collaboration with researchers from academic institutions and commercial companies. 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? No  
Impact Due to the confidential nature, no details can be revealed at this stage. 
 
Title NMR Chemical shift anisotropy measurements 
Description Using 300 MHz and 700 MHz NMR instruments, it has been shown that static lineshape measurements are better suited for accurate measurements of the chemical shift anisotropy than those based on magic-angle spinning. 
Type Of Material Data analysis technique 
Year Produced 2017 
Provided To Others? Yes  
Impact Accurate measurements of chemical shift anisotropy is important for materials, chemistry and biological sciences. 
URL https://www.sciencedirect.com/science/article/pii/S0926204017301303?via%3Dihub
 
Description COMPLEX: The Degradation of Complex Modern Polymeric Objects in Heritage Collections: A System Dynamics Approach. 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Dr Simoni Ros collaborates with the UCL Institute for Sustainable Heritage in a research project named as COMPLEX: The Degradation of Complex Modern Polymeric Objects in Heritage Collections: A System Dynamics Approach. This project is led by Professor Associate Dr Katherine Curran, principal investigator and responsible for acquiring the starting grant from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 716390).
Collaborator Contribution From the collaboration named above, a new MSc project has been started in the UCL MSc Applied Analytical Chemistry, in which the student Luka Nunar will explore NMR spectroscopy to develop new methodologies for the quantification of plasticiser contents and the degradation extent in historic plasticised artifacts based on solution and solid-state 1H and 13C NMR techniques. The UCL 700 MHz NMR facility has also contributed to two MRes dissertation projects from the UCL Institute for Sustainable Heritage, involving the students Isabella del Gaudio (title: Study of water sorption and diffusion in cellulose acetate) and Rose King (title: Plasticiser loss from cellulose acetate), which have investigated degradation processes of cellulose acetate, involving the investigation of deacetylation and plasticiser loss. The research has evolved in PhD projects involving the same students and both projects currently benefit from their use of the UCL 700 MHz NMR facility.
Impact [1] In preparation for submission in the Polymer Degradation and Stability journal: "Quantifying the degradation state of plasticised cellulose acetate-based historic artefacts by NMR spectroscopy", by Simoní Da Ros, Abil E. Aliev, Isabella del Gaudio, Rose King, Anna Pokorska, Mark Kearney, Katherine Curran. [2] Argyro Gili, Rose King, Luca Mazzei, Josep Grau-Bové, Robert Koestler, Michael Petr, Odile Madden, Simoní Da Ros, Katherine Curran. Modelling and Measuring the Diethyl Phthalate Plasticiser loss from Cellulose Acetate in different ventilation scenarios. Presented at "The Plastics Heritage Congress 2019", Lisbon, 2019. (Oral presentation) [3] Del Gaudio I, Hunter-Sellars E, Da Ros S, Parkin I, Duncan J, Moore A, Williams D, Curran K. Stability of cellulose acetate films in museum collections. Presented at "The Polymer Degradation Discussion Group Conference", Malta, 2019. (Poster presentation) [4] Argyro Gili, Rose King, Luca Mazzei, Simoní Da Ros, Josep Grau-Bové, Robert Koestler, Michael Petr, Odile Madden, Katherine Curran. A Predictive Model and Measurements for the Impact of Ventilation on Diethyl Phthalate Plasticiser Loss from Cellulose Acetate. Presented at the "Plastics and Peril Conference", Cambridge, 2020. (Poster presentation) [5] Argyro Gili, Rose King, Luca Mazzei, Simoní Da Ros, Josep Grau-Bové, Robert, Koestler, Michael Petr, Odile Madden, Katherine Curran. Decision making in conservation based on modelling and measuring diethyl phthalate plasticiser loss from cellulose acetate in varied ventilation conditions. Presented at the "Plastics and Peril Conference", Cambridge, 2020. (Oral presentation)
Start Year 2019
 
Description Drugs for treatment of neurodegenerative diseases 
Organisation Dementia Discovery Fund
Country United Kingdom 
Sector Private 
PI Contribution Compounds are sought for use as inhibitors of key targets for treatment of neurodegenerative diseases such as neurodegeneration, Alzheimer's disease and dementia. The 700MHz NMR facility is used for structural characterisation of newly synthesised compounds.
Collaborator Contribution Dementia Discovery Fund is a spin out company.
Impact The following publications are relevant: Beilstein J. Org. Chem. 2019, 15, 2790-2797. doi:10.3762/bjoc.15.271 Med. Chem. Commun. 2019, 10, 1361 DOI: 10.1039/c9md00096h
Start Year 2019
 
Description Metagenomic ene-reductases for the bioreduction of sterically challenging enones 
Organisation Almac Group
Country United Kingdom 
Sector Private 
PI Contribution Prof H. Hailes (Department of Chemistry, UCL), Dr J. Ward (Biochemical Engineering, UCL), Dr C. Orengo (Structural and Molecular Biology, UCL) and Dr Tom Moody (Almac) are involved in this collaboration. The 700MHz facility was essential to determine the stereochemistry of ene-reductase enzyme products. In this work, a sequence-based functional metagenomics strategy was used to identify novel ene-reductase enzymes from a drain metagenome. Several new ene-reductases were discovered and effectively applied in the stereoselective bioreduction of bicyclic Wieland-Miescher and Hajos-Parish ketones. Notably, this is the first time such bulky substrates have been successfully transformed with wild-type ene-reductases and the enzymes also showed remarkable organic solvent robustness which is ideal for industrial applications. Funding BBRSC BB/N01877X/1 & BB/L007444/1
Collaborator Contribution The enzymes prepared by Prof H. Hailes (Department of Chemistry, UCL), Dr J. Ward (Biochemical Engineering, UCL) and Dr C. Orengo (Structural and Molecular Biology, UCL) are used in the company. For detailed description, see D. Dobrijevic, L. Benhamou, A. E. Aliev, N. Dawson, D. Baud, D. Méndez Sánchez, N. Tappertzhofen, T. S. Moody, C. A. Orengo, H. C. Hailes, J. M. Ward, 'Ene-reductases from a drain metagenome for the selective bioreduction of bicyclic enones', RSC Adv., 2019, 9, 36608-36614. A new iCASE studentship was also funded starting in Sept 2020 on a new enzyme type. Another grant application has been submitted by Prof H Hailes (UCL) together with Almac. There are contracts that were signed (with Biochemical Engineering, UCL) with MTAs included and materials (enzymes) were transferred that are being used in commercial applications. Almac contributed £132k and an industrial perspective/time at attendance for meetings, etc.
Impact Publication in RSC Advances in 2019: D. Dobrijevic, L. Benhamou, A. E. Aliev, N. Dawson, D. Baud, D. Méndez Sánchez, N. Tappertzhofen, T. S. Moody, C. A. Orengo, H. C. Hailes, J. M. Ward, 'Ene-reductases from a drain metagenome for the selective bioreduction of bicyclic enones', RSC Adv., 2019, 9, 36608-36614.
Start Year 2017
 
Description Noncovalent Interactions of p Systems with Sulfur 
Organisation University of Southampton
Department Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution The relative strength of noncovalent interactions between a thioether sulfur atom and various p systems in designed top pan molecular balances was determined by NMR spectroscopy. Compared to its oxygen counterpart, the sulfur atom displays a remarkable ability to interact with almost equal facility over the entire range of p systems studied, with the simple alkene emerging as the most powerful partner. With the exception of the O···heteroarene interaction, all noncovalent interactions of sulfur with p systems are favoured over oxygen.
Collaborator Contribution Experimental structure determinations in the solid state were carried by our partners Dr. G.J.Tizzard and Prof. S. J. Coles from School of Chemistry, University of Southampton.
Impact Publication at http://onlinelibrary.wiley.com/wol1/doi/10.1002/anie.201708485/abstract
Start Year 2017
 
Description Peptide ligation in water 
Organisation Simons Foundation
Country United States 
Sector Charity/Non Profit 
PI Contribution Amide bond formation is one of the most important reactions in both chemistry and biology. In 2007, the ACS Green Chemistry Institute voted 'amide formation avoiding poor atom economy reagents' as the top challenge for organic chemistry; this remains an unmet challenge. The universal genetic code establishes that the biological role of peptides predates Life's last universal common ancestor and that peptides played an essential role in the origins of life on Earth. Prof. M Powner (Chemistry, UCL) and his group have demonstrated the facile, selective and iterative coupling to a-aminonitriles in water to make peptide bonds. The unique reactivity of a-aminonitriles provides a direct link between the canonical peptide structures of biology and prebiotic synthesis. Traceless sulfide-mediated peptide ligation has been applied to the coupling reactions of all amino acid residues, with remarkably selective coupling in all cases. It was shown that the unique reactivity a-aminonitriles makes them singularly well-suited to (protecting-group-free) ligation at neutral pH.
Collaborator Contribution Simons Foundation has contributed £120k towards the 700MHz NMR facility used by Prof. M Powner (Chemistry, UCL) and his group in their research.
Impact Publication in Nature: Canavelli, P., Islam, S., Powner, M.W. Peptide ligation by chemoselective aminonitrile coupling in water. Nature, 571, 546-549 (2019). doi:10.1038/s41586-019-1371-4.
Start Year 2017
 
Description Precursor design to develop new compounds for use in thin film growth 
Organisation Pilkington Glass
Country United Kingdom 
Sector Private 
PI Contribution Prof Claire Carmalt and Prof Ivan Parkin (Chemistry, UCL) are involved in investigating precursor design to develop new compounds for use in thin-film growth (Impact Acceleration Account award to UCL 201720, EP/R511638/1 and for grant EP/L017709)
Collaborator Contribution The partners provide research placements for our students and analysis of the thin films which we deposit. They are also involved in technical meetings with us and the students and provide advice on scale up. They are currently funding 4 EngD or PhD studentships and each studentship has a confidentiality agreement
Impact The UCL 700MHz NMR facility allowed for a detailed characterisation of a ZnO precursor and information of the structure of the compound formed.
Start Year 2017
 
Description Tetrahydrofuran fragments from carbohydrates or sugar beet pulp biomass 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution Professor Helen Hailes (Department of Chemistry, UCL), Professor Tom Sheppard (Department of Chemistry, UCL), Dr Gary Lye (Biochemical Engineering, UCL) and Dr Christopher J. Tame (GSK) are involved in this collaboration. For details, see the following publication: L. Benhamou, R. W. Foster, D. P. Ward, K. Wheelhouse, L. Sloan, C. J. Tame, D.-K. Bucar, G. J. Lye, H. C. Hailes, T. D. Sheppard, 'Functionalised tetrahydrofuran fragments from carbohydrates or sugar beet pulp biomass', Green Chem., 2019, 21, 2035-2042. For this publication, the facility was invaluable in characterizing the products generated from biomass-derived starting materials. Selective dehydrations of pentose sugars were achieved under basic or acidic conditions, and the equipment allowed NMR reaction monitoring and the ability to distinguish between the isomeric products formed. Fragments for medicinal chemistry applications containing primary alcohol, ketone, carboxylic acid or amine functional groups were generated, suitable for incorporation into fragment/lead libraries. Funding EPSRC (EP/K503745/1) and building upon outputs from EP/K014897.
Collaborator Contribution GSK and AstraZeneca have added the samples of the chiral fragments prepared by Professor Helen Hailes (Department of Chemistry, UCL), Professor Tom Sheppard (Department of Chemistry, UCL) and Dr Gary Lye (Biochemical Engineering, UCL) for use in their fragment libraries. For further details, see the following publication: L. Benhamou, R. W. Foster, D. P. Ward, K. Wheelhouse, L. Sloan, C. J. Tame, D.-K. Bucar, G. J. Lye, H. C. Hailes, T. D. Sheppard, 'Functionalised tetrahydrofuran fragments from carbohydrates or sugar beet pulp biomass', Green Chem., 2019, 21, 2035-2042.
Impact Joint publication in Green Chemistry: L. Benhamou, R. W. Foster, D. P. Ward, K. Wheelhouse, L. Sloan, C. J. Tame, D.-K. Bucar, G. J. Lye, H. C. Hailes, T. D. Sheppard, 'Functionalised tetrahydrofuran fragments from carbohydrates or sugar beet pulp biomass', Green Chem., 2019, 21, 2035-2042.
Start Year 2017
 
Description Tin chemical shift anisotropy in tin dioxide 
Organisation Rutherford Appleton Laboratory
Department Scientific Computing Department
Country United Kingdom 
Sector Public 
PI Contribution Experimental NMR measurements of 119Sn and 31P NMR powder lineshapes using 300 MHz and 700 MHz NMR facilities.
Collaborator Contribution Computational predictions of NMR chemical shift anisotropy
Impact Publication at https://www.sciencedirect.com/science/article/pii/S0926204017301303?via%3Dihub#!
Start Year 2017
 
Description Tin chemical shift anisotropy in tin dioxide 
Organisation University of Oxford
Department Department of Materials
Country United Kingdom 
Sector Academic/University 
PI Contribution Experimental NMR measurements of 119Sn and 31P NMR powder lineshapes using 300 MHz and 700 MHz NMR facilities.
Collaborator Contribution Computational predictions of NMR chemical shift anisotropy
Impact Publication at https://www.sciencedirect.com/science/article/pii/S0926204017301303?via%3Dihub#!
Start Year 2017
 
Description A visit and spectra for The King Fahad Academy Bromyard Avenue London 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact A visit took place on 31 October 2017, during which the NMR equipment including the new 700 MHz NMR was demonstrated. This was followed by measurements of NMR spectra for the student projects (Extended Essay in Chemistry).
Year(s) Of Engagement Activity 2017
 
Description NMR visits for schools 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact The new equipment was demonstrated to school pupils visiting UCL Chemistry on the Spectroscopy Day in September 2017 and in April 2018.
Year(s) Of Engagement Activity 2017,2018,2019
URL https://www.ucl.ac.uk/chemistry/schools/schools-programme
 
Description Provision of NMR service to users from Industry and Academia 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Users from other UCL departments and other UK universities visited the facility. Spectra were recorded on the new facility for users from other universities, as well as from industrial companies.
Year(s) Of Engagement Activity 2017,2018,2019,2020