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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Aponte J C (2019) Analyses of Aliphatic Aldehydes and Ketones in Carbonaceous Chondrites in ACS Earth and Space Chemistry

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Fernández-García C (2018) Selective aqueous acetylation controls the photoanomerization of a-cytidine-5'-phosphate. in Chemical communications (Cambridge, England)

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Gibson SM (2018) Dihalohydration of Alkynols: A Versatile Approach to Diverse Halogenated Molecules. in European journal of organic chemistry

 
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 200 NMR spectra for Abcam Plc (Cambridge) between November 2017 and March 2019. Since July 2017, the facility has been used by users from the UCL Dementia Research Centre, which focuses on clinical research into various forms of dementia.

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:

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".

Dr 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.

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.

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 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.

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.

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.[9] 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.

Prof Claire Carmalt and Dr Caroline Knapp (Department of Chemistry, UCL): Our NMR studies, including variable-temperature measurements, have focused on gallium alkoxides. 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 and Prof Tom Sheppard (Department of Chemistry, UCL):
1. 1. For the publication submitted on "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 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. New fragments with suitable physico-chemical properties were formed from carbohydrate biomass-derived compounds for medicinal chemistry applications.
2. For the publication submitted on '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. 3. For the publication soon to be submitted on '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.

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 a 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. Monomeric composition of PHAs are 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 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.

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.

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.

Dr Bob Scroeder and Lewis Cowen, PhD Candidate (Department of Chemistry, UCL): Polymeric and molecular semiconductors based on benzodifurandionebased oligo(pphenylene vinylene (BDOPV) have recently 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.

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.

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 ? 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)

In addition to those listed above, the 700 MHz NMR instrument has been used by:
Prof Jim Anderson (Department of Chemistry, UCL)
Dr Jamie Baker (Department of Chemistry, UCL)
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 Chris Blackman (Department of Chemistry, UCL)
Dr Hugo Bronstein (Department of Chemistry, UCL)
Dr Kreso Bucar (Department of Chemistry, UCL)
Dr Gemma Louise-Davis (Department of Chemistry, UCL)
Prof Xiao Guo (Department of Chemistry, UCL)
Dr Stefan Howorka (Department of Chemistry, UCL)
Dr Tung Chun Lee (Department of Chemistry, UCL)
Dr Derek MacMillan (Department of Chemistry, UCL)
Dr Justin Warne (Div of Infection & Immunity, UCL)
Dr Robert Palgrave (Department of Chemistry, UCL)
Prof William Motherwell (Department of Chemistry, UCL)
Prof Gopinathan Sankar (Department of Chemistry, UCL)
Dr Rose King (Institute of Sustainable Heritage, UCL)
Prof Kishor Gulabivala (Eastman Dental Institute, UCL)
Dr Philip Lowden (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)
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)
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)
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 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.
Dr 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.
Dr Hien Nguyen (City University): Through publications and commercialisation.
Dr Vijay Chudasama (Department of Chemistry, UCL): Our work described above 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.
Drs Hannah Woodward 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.
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. Further refinement of these mathematical models.
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.
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 and Prof Tom Sheppard (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.
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 nanoarchitectures 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 Scroeder 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.
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.
Sectors Aerospace, Defence and Marine,Agriculture, Food and Drink,Chemicals,Education,Electronics,Energy,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL https://www.nature.com/articles/s42004-019-0124-5004-019-0124-5
 
Description There are various 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. Dr Salvador Tomas (Department of Biological Sciences, Birkbeck College): Our findings are relevant in abiogenesis. They, therefore, are contributing to a better understanding of life's origin, a scientific question at heart, but with strong philosophical and religious undertones that impact outside academy. My 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 reduce (and at the fullest of their development, eliminate) the scourge of cancer and infectious diseases. Finally, by developing mathematical tools that describe (and allow to predict the behaviour) of smart nano-vesicles my 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. Prof Helen Hailes and Prof Tom Sheppard (Department of Chemistry, UCL): The findings are likely to have non-academic impacts in the longer term. Two manuscripts have been submitted, one other is under preparation. Prof Tom Sheppard (Department of Chemistry, UCL): Two papers have been published which are likely to have non-academic impacts in future. Prof Alethea Tabor (Department of Chemistry, UCL): The findings 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 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. 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 for knowledge exchange between university and museum institutions.
First Year Of Impact 2019
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 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 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 2015
 
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
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