Core Capability for Chemistry Research - Leeds

Lead Research Organisation: University of Leeds
Department Name: Sch of Chemistry

Abstract

In Part A of our Bid, the School of Chemistry, University of Leeds requests funds to purchase a 600 MHz NMR Spectrometer, a Single Crystal XRD Spectrometer and a Variable Pressure SEM.

The 600 MHz NMR Spectrometer will replace the main service instrument in the School, which is used by 75% of the academic staff. The new instrument will have low and high (variable) temperature and multinuclear capability (including 11B) and is employed for more complex analyses, including selective excitation experiments, more 'exotic' nuclei detection, dynamics studies, and for (very) sample limited data collections. It will also provide increased resolution as compared with the existing instrument and a shielded (high cryogen hold time) magnet and new probes will provide greatly improved signal-to-noise characteristics for all nuclei. The spectrometer will primarily be used to provide the School service, but its superior performance as compared with our old instrument means that the facility can also be opened up to less experienced users for specialist applications.

The new single crystal diffractometer system will replace a failing 10 year old instrument and will support the work of approximately 50% of the academic staff in the department, providing vital access to structural determination. The instrument will have a microfocus X-ray source that has dual wavelength (Mo and Cu) capacity, along with peripheral equipment such as a cryogenic crystal cooling unit and server for raw data storage and backup. The new system will have enhanced and expanded capabilities in comparison with our current set-up through improved power and sensitivity, and the ability to determine absolute configuration of light-atom samples which we cannot currently do.

A variable pressure FEG-SEM with integral EDX (energy-dispersive X-ray spectroscopy) will provide new capability and will enable high resolution imaging and elemental analysis of solid samples at the nanometer level. The instrument will be equipped with a temperature-control stage, and we will also purchase software enabling automated analysis of multiple samples. In addition, it will have multiple ports which will permit interfacing with further analytical tools (such as atomic force microscopy (AFM)). That the instrument can be operated from high to low vacuum provides maximum flexibility, allowing analysis of both conducting and non-conducting samples. We also need to purchase a metal coating unit to coat larger, non-conducting samples which can be prone to charging. The request of a variable pressure FEG-SEM reflects the changing landscape of chemistry research in the UK. While chemistry departments have not traditionally housed electron microscopes, as research areas such as materials chemistry continue to grow in importance, and the specification of microscopes continues to improve, it is essential that researchers have ready access to high specification instruments.

Part B of the proposal makes the case for establishment of a centre for "High Resolution Analytical Transmission Electron Microscopy (TEM) of Beam Sensitive Materials" with purchase of a state-of-the-art Titan Krios cryo-electron TEM which combines high resolution 2D imaging with electron tomography and advanced analytical techniques (electron energy loss spectroscopy (EELS) and electron diffraction). This instrument makes it possible for the first time to look at dose-sensitive structures with such high resolution that atomic imaging of soft matter becomes a reality.

In Part B we also request new capability with the purchase of a liquid cell holder for a TEM, and an AFM to integrate with the SEM purchased in Part A. A powder XRD will also bring new capability to the school. Finally, we request a LC-MS(MS) mass spectrometer to replace our workhorse, user-operated instrument and a 600 MHz instrument, equipped with a cold probe which will replace an existing instrument and bring new resolution capabilities.

Planned Impact

The N8 Research Partnership has an excellent record of bringing business interests and academic research together to drive economic and scientific success. For example, in five years, the N8 Research Partnership has worked with over 200 businesses, ranging from large national and multi-national organisations to SMEs, generated over £41m in additional income and created more than 60 jobs, has been responsible for the creation of projects such as Regener8 and METRC (centres of specialist expertise to bring academia and business needs together), and has instigated the N8 Industrial Innovation Forum to promote and maximise links between leading private sector R&D and the UK research base.

In addition to the N8 Research Partnership, individual departments have been highly successful in forging links with industry. Examples include one of the first Centres for Industrial Collaboration (Leeds), the Michael Barber Centre for Mass Spectrometry (Manchester), the Centre for Chemical Instrumental Analysis and Services (Sheffield), the JEOL Nanocentre (York), the Strategic Partnership with P&G at Durham and the Centre for Materials Discovery (Liverpool). Additional investment to provide state of the art instrumentation and equipment would only strengthen these collaborative partnerships.

The N8 Universities also actively participate in an "Industrial Innovation Forum" which was initiated by the N8 Research Partnership, HEFCE and TSB to connect leading businesses such as Unilever, AstraZeneca, BAE, Dyson and P&G with research intensive universities and other key organisations and networks involved in innovation. The Forum aims to provide a catalyst for open innovation by matching industrial requirements with scientific solutions and insight, creating ideas and understanding by linking talent and expertise, and enabling cross-sector knowledge exchange. Through the Forum, companies have already expressed an interest in reciprocal sharing and usage of equipment. In addition to N8 programmes such as this, all the partner Universities have strong local links to business via their dedicated Business Engagement teams, providing dedicated support to establish direct links and to protect IP. The research supported by the proposed equipment will be developed, shared, and ultimately provide benefit for the UK economy through individual departments own business engagement activities with SMEs and Knowledge Transfer Partnerships, and through links established within N8 programmes. Each Department involved in this bid has an extensive set of interactions with SMEs, who will benefit from the proposed equipment investment through a combination of joint research programmes, direct hosting of SME researchers in our Departments and by the provision of enhanced analytical services.

Publications

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Avery CA (2015) (±) cis-Bisamido epoxides: A novel series of potent FXIII-A inhibitors. in European journal of medicinal chemistry

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Barnard A (2015) Selective and potent proteomimetic inhibitors of intracellular protein-protein interactions. in Angewandte Chemie (International ed. in English)

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Bawazer LA (2015) Genetic algorithm-guided discovery of additive combinations that direct quantum dot assembly. in Advanced materials (Deerfield Beach, Fla.)

 
Description Under this grant, the School of Chemistry purchased a 600 MHz NMR instrument, an Agilent (now Rigaku) dual Cu/Mo source single crystal X-ray diffractometer with an Oxford Cryosystems 700 Series Cryostream, and an FEI nova-NanoSEM with EDX (energy-dispersive X-ray spectroscopy) system.

The X-ray diffractometer allows routine data collections from between 100K and 400K. Additionally, the system has been modified to function with our existing Oxford Cryosystems Helix system, allowing data collections down to around 30K. The new instrument has led to a significant increase in the number of datasets collected compared to our previous system, significantly expanded our user base and, particularly due to the use of the Cu X-ray source, allowed us to investigate a wider range of sample types than was previously possible. We are now able to routinely investigate samples which previously required a synchrotron, which has had a significant impact on our research into complex supramolecular architectures, which tend to crystallise with large unit cells and are very weakly diffracting due to significant disorder. The ability to routinely investigate small organic crystals and determine absolute stereochemistry of a sample has led to an increase in usage from organic colleagues within the department and inclusion of the crystal data in their research publications. We have also worked from colleagues outside the School, particularly in the School of Chemical and Process Engineering, investigating pharmaceutically relevant materials, which has led to joint publication. Additionally, the instrument continues to have an impact in our research in coordination and organometallic chemistry, switchable materials, catalysis and process development chemistry and has supported high level publications including in Journal of the American Chemical Society, Nature Chemistry and Chemical Science.

The NMR instrument purchased is the main service instrument in the School and is used by 75% of the academic staff. It is used for specialist research applications on a limited user-base or service-provided basis, has low and high (variable) temperature and multinuclear capability,and is employed for more complex analyses, including selective excitation experiments, more 'exotic' nuclei detection, dynamics studies, and for (very) sample limited data collections. The instrument also provides sufficient resolution for small molecule work. As a highlight, unified synthetic approaches have been developed that yield large numbers of diverse molecular scaffolds with controlled molecular properties suitable for discovery applications (D. J. Foley, A. Nelson and S. P, Marsden, Angew. Chem. Int. Ed. 2016, 55, 13650). Many of these synthetic approaches have been translated into small molecules libraries within the European Lead Factory (ELF); in total, around 15 000 screening compounds prepared using approaches developed in Leeds have been added to the distinctive public compound collection of the ELF (Drug Discovery Today 2015, 20, 1310). In addition, a range of scaffolds with properties for central nervous system (CNS) drug discovery applications has been developed (Drug Discovery Today 2017, DOI:10.1016/j.drudis.2017.01.008).

The FEG-SEM (scanning electron microscope with field emission gun) purchased is a new capability within the School of Chemistry, and supports research in a wide range of areas including materials chemistry, biomineralisation and bio-inspired crystallisation, nanoscience and crystal engineering. As an important capability, the SEM has a CBS detector which makes it possible to image non-conductive samples without surface coating. It also has software which facilitates automated screening of a large number of samples. The instrument is supported by a technician who assists users to run samples, and provides training for regular users. It has been used by users from outside the School of Chemistry, and from other universities. A large number of research papers have been published based on data acquired using this instrument in journals such as Nature Materials, Nature Chemistry, Nature Communications, Advanced Materials and Advanced Functional Materials. Examples of work supported includes the analysis of crystals with composite structures, where these were synthesised using bio-inspired routes. By occluding additives ranging from small molecules to organic and inorganic nanoparticles and sub-micron particles within a range of host single crystals it has been possible to generate materials with novel properties and to better understand the mechanisms by which additives control crystal growth. As an example of the use of the automated screening capability, this was used in high-throughput analysis of calcium carbonate Precipitation in the presence of amino acids (Crystal Growth Design, doi: 10.1021/acs.cgd.6b00741).

Many projects have also used more than one of these instruments. A particularly exciting example was the discovery of a hitherto unknown and unclassified example of mechanical entanglement of chemical species. In the solid state a [Cu6L6] metallacyclic complexes forms what we have dubbed a Borromean chain-mail arrangement. A Borromean ring is where three cyclic entities are entangled and inseparable but do not have any chain-links between them. Chemical Borromean rings and networks have been reported before but this example is unique in that an infinite arrangement Borromean arrangement of rings is formed in 2D whereby each ring is part of six different Borromean ring association. The material was characterised by crystallography and SEM as the crystals grew in an unusual hollow straw morphology. This work was published in Nature Chemistry and gained significant social media attention being in the top 5% of all research outputs scored by Altmetrics. A further example is the development of novel iridium-based catalysts for redox-neutral 'borrowing hydrogen' alkylation of amines by alcohols. These catalysts show vastly improved activity and - more importantly - solvent and substrate tolerance than previous catalysts. The family of catalysts is being patented and their commercialisation under development. The use of NMR and (particularly) X-ray crystallography was essential for the characterisation of these complexes and the understanding of their catalytic prowess.
Exploitation Route The research and training delivered by the School of Chemistry covers a wide spectrum of fundamental and applied research which supports the health, prosperity and sustainability of the UK. This is demonstrated by the production of patents and the foundation of operating spin-out companies. Taking into account its size, this makes Leeds School of Chemistry one of the most successful chemistry departments in bringing its research through to industrial exploitation.
Sectors Agriculture

Food and Drink

Chemicals

Energy

Environment

Healthcare

Manufacturing

including Industrial Biotechology

URL http://www.chem.leeds.ac.uk/
 
Description These instruments have made a significant impact on research across the School of Chemistry. To provide some examples, SEM data is a fundamental part of industrially-funded projects in the field of inorganic materials manufacture and graphene-based functional materials.
First Year Of Impact 2017
Sector Chemicals,Energy,Manufacturing, including Industrial Biotechology
Impact Types Societal

 
Description EPSRC programme grant
Amount £2,700,000 (GBP)
Funding ID EP/N013573/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 02/2016 
End 01/2021
 
Description EPSRC responsive mode
Amount £570,000 (GBP)
Funding ID EP/P016618/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 03/2017 
End 03/2020
 
Description Platform Grant
Amount £1,408,821 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 12/2015 
End 11/2020
 
Description Responsive mode
Amount £574,490 (GBP)
Funding ID EP/P016618/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 04/2017 
End 05/2020
 
Description Responsive mode
Amount £402,890 (GBP)
Funding ID EP/R023492/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 04/2018 
End 04/2021
 
Title Data for CEJ Ir-cages 2017 
Description Data depository for publication "Homochiral self-sorted and emissive Ir(III) metallo-cryptophanes", V. E. Pritchard, D. Rota Martir, S. Oldknow, S. Kai, S. Hiraoka, N. J. Cookson, E. Zysman-Colman, M. J. Hardie, Chem. Eur. J. 2017, 23, 6290-6294 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact NA 
URL http://archive.researchdata.leeds.ac.uk/136/
 
Title Data for CEJ Ir-complex 2017 
Description Data depository for publication "Multimetallic and mixed environment iridium(III) complexes: A modular approach to luminescence tuning using a host platform", V. E. Pritchard, D. Rota Martir, E. Zysman-Colman, M. J. Hardie, Chem. Eur. J., 2017, 23, 8839-8849. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact NA 
 
Title Data for Organomet 2016 
Description Data depository for publication "Tris-rhenium fac-tricarbonyl polypyridine-functionalised cyclotriguaiacylene ligands with rich and varied emission", F. L. Thorp-Greenwood, V. E. Pritchard, M. P. Coogan, M. J. Hardie, Organometallics, 2016, 35, 1632-1642 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact NA 
URL http://archive.researchdata.leeds.ac.uk/48/
 
Title Data for Supramol Chem 2017 
Description Data depository for publication "Tris-N-alkylpyridinium-functionalised cyclotriguaiacylene hosts as axles in branched [4]pseudorotaxane formation", F. L. Thorp-Greenwood, A. D. Brennan, S. Oldknow, J. J. Henkelis, K. J. Simmons, C. W. G. Fishwick, M. J. Hardie, Supramol. Chem. 2017, 29, 430-440 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact NA 
URL http://archive.researchdata.leeds.ac.uk/95/
 
Title Data for Supramol Chem 2018 
Description Data depository for "Metallo-cryptophane cages from cis-linked and trans-linked strategies", N. J. Cookson, J. M. Fowler, D. P. Martin, J. Fisher, J. J. Henkelis, T. K. Ronson, F. L. Thorp-Greenwood, C. E. Willans, M. J. Hardie, Supramol. Chem., 2018, 30, 255-266 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact NA 
URL http://archive.researchdata.leeds.ac.uk
 
Title Data to support study "2D networks of metallo-capsules and other coordination polymers from a hexapodal ligand" 
Description Data to support study of coordination polymers of hexakis(isonicotinoyl)cyclotricatechylene (L) including those of [M3L2] composition with M = Re, Co, Cu or Ni 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Title Data to support study 'Fully collapsed "imploded" cryptophanes in solution and the solid state' 
Description Spectroscopic data and diffraction data for study of new cryptophanes with imploded structures. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
 
Title data for CEJ MOF 2019 
Description Data repository for publication "Complex phase behaviour and structural transformations of metal-organic frameworks with mixed rigid and flexible bridging ligands", H. D. J. Arkawazi, R. Clowes, A. I. Cooper, T. Konno, N. Kuwamura, C. M. Pask, M. J. Hardie, Chem. Eur. J. 2019, 25, 1353-1362 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact NA 
URL http://archive.researchdata.leeds.ac.uk/468/
 
Title data for CEJ cryptophanes 2019 
Description Data repository for publication "Fully collapsed "imploded" cryptophanes in solution and the solid state", F. L. Thorp-Greenwood, M. J. Howard, L. T. Kuhn, M. J. Hardie, Chem. Eur. J. 2019, 25, 3536 -3540. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact NA 
URL http://archive.researchdata.leeds.ac.uk/481/
 
Title data for Chem Sci 2018 
Description Data repository for publication "Structure-switching M3L2 Ir(III) coordination cages with photo-isomerising azo-aromatic groups", S. Oldknow, D. Rota Martir, V. E. Pritchard, M. A. Blitz, C. W. G. Fishwick, E. Zysman-Colman, M. J. Hardie, Chem. Sci. 2018, 9, 8150-8159. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact NA 
URL http://archive.researchdata.leeds.ac.uk/413/
 
Title data for CrystEngComm 2018 
Description Data depository for publication "2D networks of metallo-capsules and other coordination polymers from a hexapodal ligand", F. L. Thorp-Greenwood, G. T. Berry, S. S. Boyadjieva, S. Oldknow, M. J. Hardie, CrystEngComm, 2018, 20, 3960 - 3970. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact NA 
URL http://archive.researchdata.leeds.ac.uk/378/
 
Title data for Dalton Trans 2019 
Description Data repository for publication "Cyclotriveratrylene-tethered trinuclear palladium(II)-NHC complexes; reversal of site selectivity in Suzuki-Miyaura reactions", J. M. Fowler, E. Britton, C. M. Pask, C. E. Willans, M. J., Hardie, Dalton Transactions, 2019, 48, 14687-14695. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact NA 
URL http://archive.researchdata.leeds.ac.uk/577/
 
Description ADS 
Organisation AstraZeneca
Department Research and Development AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution We have used the assets from partners in activity-directed synthesis
Collaborator Contribution THe partners have provided assets (protein, assay) and helped align the project with end-user need
Impact None to date
Start Year 2016
 
Description ADS 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution We have used the assets from partners in activity-directed synthesis
Collaborator Contribution THe partners have provided assets (protein, assay) and helped align the project with end-user need
Impact None to date
Start Year 2016
 
Description ADS 
Organisation Max Planck Society
Country Germany 
Sector Charity/Non Profit 
PI Contribution We have used the assets from partners in activity-directed synthesis
Collaborator Contribution THe partners have provided assets (protein, assay) and helped align the project with end-user need
Impact None to date
Start Year 2016
 
Description AZ screening 
Organisation AstraZeneca
Department Research and Development AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution Screening compounds
Collaborator Contribution HT screening
Impact None yet
Start Year 2014
 
Description Astra Zeneca Case award 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution Standard Case collaboration agreement.
Collaborator Contribution Academic input, hosting of 3-month research placement.
Impact None yet
Start Year 2014
 
Description Eli Zysman-Colman 
Organisation University of St Andrews
Department School of Chemistry St Andrews
Country United Kingdom 
Sector Academic/University 
PI Contribution Synthesis of a series of iridium-complexes and iridium-based supramolecular cages
Collaborator Contribution Measurement of photophysical properties of the cages
Impact Publications: "Homochiral self-sorted and emissive Ir(III) metallo-cryptophanes", V. E. Pritchard, D. Rota Martir, S. Oldknow, S. Kai, S. Hiraoka, N. J. Cookson, E. Zysman-Colman, M. J. Hardie, Chem. Eur. J. 2017 DOI:10.1002/chem.201701348 "Multimetallic and mixed environment iridium(III) complexes: A modular approach to luminescence tuning using a host platform", V. E. Pritchard, D. Rota Martir, E. Zysman-Colman, M. J. Hardie, Chem. Eur. J., accepted. 2017 DOI:10.1002/chem.201700237 "Structure-switching M3L2 Ir(III) coordination cages with photo-isomerising azo-aromatic groups", S. Oldknow, D. Rota Martir, V. E. Pritchard, M. A. Blitz, C. W. G. Fishwick, E. Zysman-Colman, M. J. Hardie, Chem. Sci. 2018, 9, 8150-8159. DOI:10.1039/c8sc03499k Unsuccessful funding application to EPSRC
Start Year 2015
 
Description Fragments 
Organisation Astex Pharmaceuticals
Department Astex Therapeutics Ltd
Country United Kingdom 
Sector Private 
PI Contribution New synthetic methods for fragment-based ligand discovery
Collaborator Contribution Steering of project
Impact No
Start Year 2017
 
Description MPI 
Organisation Max Planck Society
Department Max Planck Institute for Molecular Physiology
Country Germany 
Sector Academic/University 
PI Contribution Screening compounds
Collaborator Contribution HT screening and follow-up biology
Impact None to date
Start Year 2014
 
Description PPIs 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution Leeds is leading an EPSRC programme grant on protein-protein interactions that involves AstraZeneca, Domainex and Northern Institute for Cancer Research
Collaborator Contribution Expertise, assays, other assets, collaboration, secondments
Impact N/A- only just started
Start Year 2016
 
Description PPIs 
Organisation Domainex
Country United Kingdom 
Sector Private 
PI Contribution Leeds is leading an EPSRC programme grant on protein-protein interactions that involves AstraZeneca, Domainex and Northern Institute for Cancer Research
Collaborator Contribution Expertise, assays, other assets, collaboration, secondments
Impact N/A- only just started
Start Year 2016
 
Description PPIs 
Organisation Newcastle University
Country United Kingdom 
Sector Academic/University 
PI Contribution Leeds is leading an EPSRC programme grant on protein-protein interactions that involves AstraZeneca, Domainex and Northern Institute for Cancer Research
Collaborator Contribution Expertise, assays, other assets, collaboration, secondments
Impact N/A- only just started
Start Year 2016
 
Description Scaffolds for CNS drug discovery 
Organisation Takeda Pharmaceutical Company
Department Takeda Global Research & Development Centre (Europe)
Country United Kingdom 
Sector Private 
PI Contribution Developed approaches for assessing, designing and preparing scaffolds for CNS drug discovery
Collaborator Contribution Ensuring alignment with end-user need
Impact A computational tool for assessing CNS scaffolds, and syntheses of prioritised scaffolds (described in Drug Discovery Today paper aimed at end-users)
Start Year 2014
 
Description Takeda 
Organisation Takeda Cambridge Ltd
Country United Kingdom 
Sector Private 
PI Contribution Development of CNS scaffolds
Collaborator Contribution Supervision. Input to project
Impact None to date
Start Year 2014
 
Description Top down approach to molecular scaffolds 
Organisation AstraZeneca
Department Research and Development AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution Development of routes to diverse molecular scaffolds
Collaborator Contribution Alignment with end-user need
Impact None to date
Start Year 2016
 
Description X-ray crystallographic fragment screening 
Organisation Diamond Light Source
Country United Kingdom 
Sector Private 
PI Contribution Access to high-throughput XCHEM facility
Collaborator Contribution We provided fragments which were screened against targets at Diamond
Impact Fragment hits against epigenetic protein targets (output currently underreview)
Start Year 2015
 
Title Syntheses of lead-like scaffolds 
Description Development of practical syntheses of a range of lead-like molecular scaffolds that aligned with the needs of high-throughput screening collections for the pharmaceutical industry 
IP Reference  
Protection Protection not required
Year Protection Granted
Licensed Commercial In Confidence
Impact None
 
Company Name Redbrick Molecular Limited 
Description  
Year Established 2017 
Impact None yet
Website http://www.redbrickmolecular.com
 
Company Name Redbrick Molecular Limited 
Description  
Year Established 2017 
Impact The company has only been established for ca. 12 months but is already generating sales revenue.
Website http://www.redbrickmolecular.com