Stopped-Flow NMR Spectroscopy for the Physical and Life Sciences
Lead Research Organisation:
University of Leicester
Department Name: Chemistry
Abstract
Nuclear Magnetic Resonance (NMR) spectroscopy is one of the most powerful analytical techniques available to scientists. It is information-rich and provides details on a molecule's structure, shape and interactions. As such, NMR spectroscopy is an essential tool for research across the physical and life sciences.
In traditional NMR spectroscopy, there is an unavoidable and significant delay between the preparation of a sample and the recording of data. Therefore, when measuring chemical changes by NMR spectroscopy, critical information is missed.
This proposal will fund a unique and transformative NMR spectroscopy package that includes a stopped-flow module. This module, which is the first commercially available device of its type, allows samples to be prepared inside the spectrometer. Therefore, data collection can start immediately after a sample is prepared, which means the full story of a molecule's journey in a reaction or its interactions with other species can be monitored in real time.
The requested instrument also includes a sensitive NMR spectrometer, where key electronic parts of the instrument are cryogenically cooled to increase sensitivity. This is essential, as it will allow faster data collection and the ability to record information for molecules that are present in low quantities.
The equipment will transform the abilities of scientists who use NMR spectroscopy. For example, synthetic chemists will be able to new gain knowledge of reaction mechanisms, the steps by which one molecule is converted into another. This will allow them to design and discover new processes that are more efficient and selective. For example, medicines maybe sustainably manufactured by optimising the structure and performance of a catalysts. Biological chemists will be able to use this equipment for the direct, quantitative and non-intrusive investigation of the chemical processes of disease. This new knowledge will allow them to identify the chemistry underpinning such biology and will lead to the development of new treatments. Materials chemists will be able to study the solution state structure of electrolytes and novel liquids, which will lead to the development of improved batteries.
In traditional NMR spectroscopy, there is an unavoidable and significant delay between the preparation of a sample and the recording of data. Therefore, when measuring chemical changes by NMR spectroscopy, critical information is missed.
This proposal will fund a unique and transformative NMR spectroscopy package that includes a stopped-flow module. This module, which is the first commercially available device of its type, allows samples to be prepared inside the spectrometer. Therefore, data collection can start immediately after a sample is prepared, which means the full story of a molecule's journey in a reaction or its interactions with other species can be monitored in real time.
The requested instrument also includes a sensitive NMR spectrometer, where key electronic parts of the instrument are cryogenically cooled to increase sensitivity. This is essential, as it will allow faster data collection and the ability to record information for molecules that are present in low quantities.
The equipment will transform the abilities of scientists who use NMR spectroscopy. For example, synthetic chemists will be able to new gain knowledge of reaction mechanisms, the steps by which one molecule is converted into another. This will allow them to design and discover new processes that are more efficient and selective. For example, medicines maybe sustainably manufactured by optimising the structure and performance of a catalysts. Biological chemists will be able to use this equipment for the direct, quantitative and non-intrusive investigation of the chemical processes of disease. This new knowledge will allow them to identify the chemistry underpinning such biology and will lead to the development of new treatments. Materials chemists will be able to study the solution state structure of electrolytes and novel liquids, which will lead to the development of improved batteries.
Organisations
Publications
Chothia SY
(2023)
Quantitative detection of formaldehyde using solid phase microextraction gas chromatography-mass spectrometry coupled to cysteamine scavenging.
in Scientific reports
Pulis A
(2023)
Recent Advances in Catalysis Using Organoborane-Mediated Hydride Abstraction
in Synlett
Emms VL
(2023)
N-Acyloxymethyl-phthalimides deliver genotoxic formaldehyde to human cells.
in Chemical science
Bowles A
(2023)
A Blueprint for the Stabilization of Sub-Valent Alkaline Earth Complexes**
in Chemistry - A European Journal
Bowles AWJ
(2024)
Heavy Alkaline Earth Cyclic (Alkyl)(Amino)Carbene Complexes Supported by Aryl-Silyl Amides.
in Inorganic chemistry
Bowles AWJ
(2024)
Mechanochemical Synthesis, Characterization and Reactivity of a Room Temperature Stable Calcium Electride.
in Journal of the American Chemical Society
Pavan AR
(2024)
Cereblon-recruiting proteolysis targeting chimeras (PROTACs) can determine the selective degradation of HDAC1 over HDAC3.
in Chemical communications (Cambridge, England)
Chothia S
(2024)
Formaldehyde quantification using gas chromatography-mass spectrometry reveals high background environmental formaldehyde levels
in Scientific Reports
Fang J
(2024)
Cobalt(III)-Macrocyclic Scaffolds with Anti-Cancer Stem Cell Activity.
in Molecules (Basel, Switzerland)
Fang J
(2024)
Anti-Cancer Stem Cell Cobalt(III)-Polypyridyl Complexes Containing Salicylic Acid
in Inorganics
Dearman SMG
(2024)
Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides.
in Beilstein journal of organic chemistry
Stevens M
(2024)
Synthesis and characterization of alkali metal iminophosphoranomethanide complexes
in Polyhedron
Winfrey L
(2024)
H2 O · B(C6 F5 )3 -Catalyzed para-Alkylation of Anilines with Alkenes Applied to Late-Stage Functionalization of Non-Steroidal Anti-Inflammatory Drugs.
in Chemistry (Weinheim an der Bergstrasse, Germany)
Allen J
(2024)
Helical dinuclear 3d metal complexes with bis(bidentate) [S,N] ligands: synthesis, structural and computational studies.
in Dalton transactions (Cambridge, England : 2003)
Smalley JP
(2024)
MDM2 Antagonist Idasanutlin Reduces HDAC1/2 Abundance and Corepressor Partners but Not HDAC3.
in ACS medicinal chemistry letters
Elsherbeni SA
(2024)
Accessing Highly Substituted Indoles via B(C6F5)3-Catalyzed Secondary Alkyl Group Transfer.
in The Journal of organic chemistry
Alvarez-Montoya A
(2024)
B(C6F5)3-Catalyzed Dehydrogenation of Pyrrolidines to Form Pyrroles.
in ACS catalysis
Singh K
(2025)
The Anti-Cancer Stem Cell Properties of Copper(II)-Terpyridine Complexes with Attached Salicylaldehyde Moieties.
in Chembiochem : a European journal of chemical biology
Allen J
(2025)
Organozinc ß-Thioketiminate Complexes and Their Application in Ketone Hydroboration Catalysis
in Organometallics
| Description | We are still very early in the lifetime of the instrument (<12 months post installation) and as such the equipment's potential has not yet been reached, and the data that has obtained has not fully been exploited. However, we have made important achievements. Preliminary data has lead to publications that describe new methodology that has allowed the synthesis of novel compounds with improved anti-inflammatory properties and this knowledge is being used to develop potential anti-cancer stems cell agents. It has also helped generate new knowledge around HDAC enzymes, targets for oncology and neuro-degenerative and cardiovascular diseases. In addition, the data gained has added to the fundamental knowledge base in synthetic inorganic chemistry and will allow researchers to explore the properties of molecules that have never been isolated before. In terms of the use of the instrumentation, we have learnt to use some of the unique features that have never been used in combination (dual receive and stopped-flow), and this will greatly improve throughput. In addition to this, >20 users have been trained to use the basic functions of the equipment, and 6 users have been trained for the more advanced usage, and the RTP is now an expert user. This training has developed skills within the university, including cross-College. Also noteworthy, is that we have had requests for usage of the equipment as part of funding applications (inc. UKRI), and are starting external national and international collaborations for use of the equipment. |
| Exploitation Route | The funding was for equipment, and the expected outcomes of its use are covered in more detail in the grant. In short, the equipment will allow academic and industrial researchers to monitor chemical processes that are relatively fast via NMR spectroscopy, which is one of the most information rich spectroscopic techniques. We anticipate the equipment will lead to more efficient and sustainable chemical processes, a better understating of biological processes, and a new way to study materials use, for example, in batteries. |
| Sectors | Chemicals Creative Economy Education Energy Environment Healthcare Manufacturing including Industrial Biotechology |
| Description | Developing PROTACs for the target validation of individual Histone Deacetylase corepressor complexes |
| Amount | £945,026 (GBP) |
| Funding ID | MR/Z506059/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2025 |
| End | 12/2027 |
| Description | Electrocatalytic Cross-Coupling Reactions with Heterogeneous Single Atom Catalysts |
| Amount | £153,499 (GBP) |
| Funding ID | EP/Y002628/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2024 |
| End | 04/2025 |
| Description | Multimetallic CO2 Reduction Catalysts as Artificial Cofactors |
| Amount | £165,322 (GBP) |
| Funding ID | EP/Y002695/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2024 |
| End | 02/2026 |
| Description | Organoborane-catalysed approaches to biologically active amines |
| Amount | £455,776 (GBP) |
| Funding ID | EP/Y00146X/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2024 |
| End | 12/2026 |
| Title | CCDC 2296869: Experimental Crystal Structure Determination |
| Description | Related Article: Ana Alvarez-Montoya, Joseph P. Gillions, Laura Winfrey, Rebecca R. Hawker, Kuldip Singh, Fabrizio Ortu, Yukang Fu, Yang Li, Alexander P. Pulis|2024|ACS Catalysis|14|4856|doi:10.1021/acscatal.3c05444 |
| Type Of Material | Database/Collection of data |
| Year Produced | 2024 |
| Provided To Others? | Yes |
| URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc2h32k8&sid=DataCite |
| Title | CCDC 2305442: Experimental Crystal Structure Determination |
| Description | Related Article: Ana Alvarez-Montoya, Joseph P. Gillions, Laura Winfrey, Rebecca R. Hawker, Kuldip Singh, Fabrizio Ortu, Yukang Fu, Yang Li, Alexander P. Pulis|2024|ACS Catalysis|14|4856|doi:10.1021/acscatal.3c05444 |
| Type Of Material | Database/Collection of data |
| Year Produced | 2024 |
| Provided To Others? | Yes |
| URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc2hd031&sid=DataCite |
| Title | CCDC 2365605: Experimental Crystal Structure Determination |
| Description | Related Article: Alex W. J. Bowles, Yu Liu, Matthew P. Stevens, Fabrizio Ortu|2024|Inorg.Chem.|||doi:10.1021/acs.inorgchem.4c03494 |
| Type Of Material | Database/Collection of data |
| Year Produced | 2024 |
| Provided To Others? | Yes |
| URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc2kdlvf&sid=DataCite |
| Title | Helical dinuclear 3d metal complexes with bis(bidentate) [S,N] ligands: synthesis, structural and computational studies |
| Description | Raw data for the publication entitled: Helical dinuclear 3d metal complexes with bis(bidentate)[S,N] ligands: synthesis, structural and computationalstudies Dalton Transactions, 2024, DOI: 10.1039/D4DT02395A Authors:Jamie Allen, Jörg Saßmannshausen, Kuldip Singh, Alexander F. R. Kilpatrick* These folders contain the raw data which were used to prepare the above publication. Information regarding the raw files of the DFT calculations. The zip-files in this section containing the raw-data of the DFT calculations leading to the Zn, Co and Fe calculated structures. As filenames are notoriously bad in handling special characters, the names of the folder appear different from what is being used in the final publication. We try to provide as much information as possible to facilitate the usage of these results. Thus: Abbreviation publication Abbreviation folder Abbreviation filename [Zn(3)2] Zn3-2 SNdipp2Zn [Co(3) 2] Co3-2 SNdipp2Co [Fe(3) 2] Fe3-2 SNdipp2Fe [Zn2(µ-2)2] Zn2-2 zn2 [Co2(µ-2)2] Co2-2 co2 [Fe2(µ-2)2] Fe2-2 fe2 Some test calculations were performed as well utilizing Gaussian-09. They can be found in a folders with the suffix -G09 or -g09. The closed shell compound [Zn2(µ-2)2] was investigated further. In order to look into the influence of the used Grimme dispersion correction, we re-calculated the final result without that correction. These files are in the Zn2-2-pbe0 folder. Furthermore, we used [Zn2(µ-2)2] and removed one of the Zn atoms and replaced the dangling bonds with H. We then fully optimized that structure. The results are in the Zn2-2-cut folder. Information regarding the raw characterisation data The raw characterisation data files for all nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, cyclic voltammetry (CV), single crystal X-ray diffraction (XRD) and solution magnetometry studies are enclosed in separate .zip files. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2024 |
| Provided To Others? | Yes |
| URL | https://zenodo.org/doi/10.5281/zenodo.13858221 |
| Title | Helical dinuclear 3d metal complexes with bis(bidentate) [S,N] ligands: synthesis, structural and computational studies |
| Description | Raw data for the publication entitled: Helical dinuclear 3d metal complexes with bis(bidentate)[S,N] ligands: synthesis, structural and computationalstudies Dalton Transactions, 2024, DOI: 10.1039/D4DT02395A Authors:Jamie Allen, Jörg Saßmannshausen, Kuldip Singh, Alexander F. R. Kilpatrick* These folders contain the raw data which were used to prepare the above publication. Information regarding the raw files of the DFT calculations. The zip-files in this section containing the raw-data of the DFT calculations leading to the Zn, Co and Fe calculated structures. As filenames are notoriously bad in handling special characters, the names of the folder appear different from what is being used in the final publication. We try to provide as much information as possible to facilitate the usage of these results. Thus: Abbreviation publication Abbreviation folder Abbreviation filename [Zn(3)2] Zn3-2 SNdipp2Zn [Co(3) 2] Co3-2 SNdipp2Co [Fe(3) 2] Fe3-2 SNdipp2Fe [Zn2(µ-2)2] Zn2-2 zn2 [Co2(µ-2)2] Co2-2 co2 [Fe2(µ-2)2] Fe2-2 fe2 Some test calculations were performed as well utilizing Gaussian-09. They can be found in a folders with the suffix -G09 or -g09. The closed shell compound [Zn2(µ-2)2] was investigated further. In order to look into the influence of the used Grimme dispersion correction, we re-calculated the final result without that correction. These files are in the Zn2-2-pbe0 folder. Furthermore, we used [Zn2(µ-2)2] and removed one of the Zn atoms and replaced the dangling bonds with H. We then fully optimized that structure. The results are in the Zn2-2-cut folder. Information regarding the raw characterisation data The raw characterisation data files for all nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, cyclic voltammetry (CV), single crystal X-ray diffraction (XRD) and solution magnetometry studies are enclosed in separate .zip files. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2024 |
| Provided To Others? | Yes |
| URL | https://zenodo.org/doi/10.5281/zenodo.13858220 |
| Title | Mechanochemical synthesis, characterization and reactivity of a room temperature stable calcium electride |
| Description | This deposition contains all supporting data for a submission to a peer reviewed journal. The work covers the synthesis and characterisation of a new electride material, containing spectroscopic/magnetic measurements (NMR, UV-vis, IR, EPR, SQUID), X-ray diffraction data (single crystal XRD, powder XRD), and computational analysis (DFT, AIRSS). |
| Type Of Material | Database/Collection of data |
| Year Produced | 2024 |
| Provided To Others? | Yes |
| URL | https://figshare.le.ac.uk/articles/dataset/Mechanochemical_synthesis_characterization_and_reactivity... |
| Title | Mechanochemical synthesis, characterization and reactivity of a room temperature stable calcium electride |
| Description | This deposition contains all supporting data for a submission to a peer reviewed journal. The work covers the synthesis and characterisation of a new electride material, containing spectroscopic/magnetic measurements (NMR, UV-vis, IR, EPR, SQUID), X-ray diffraction data (single crystal XRD, powder XRD), and computational analysis (DFT, AIRSS). |
| Type Of Material | Database/Collection of data |
| Year Produced | 2024 |
| Provided To Others? | Yes |
| URL | https://figshare.le.ac.uk/articles/dataset/Mechanochemical_synthesis_characterization_and_reactivity... |
| Title | Synthesis, characterization and reactivity of a series of alkaline earth and rare earth iminophosphoranomethanide complexes |
| Description | This dataset contains epxerimental data and theoretical calculations outputs in support of an imminent paper submission. The supporting data contains NMR spectroscopic analysis (multinuclear NMR, Evans method characretisations), UV-vis spectroscopic data and Infra-re spectroscopic data. Additionally, the folder contain crystallographic data in the form of .cif file (Crystallography Information File), which contain essential metric parameters characteristic for each molecular structure. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2024 |
| Provided To Others? | Yes |
| URL | https://figshare.le.ac.uk/articles/dataset/Synthesis_characterization_and_reactivity_of_a_series_of_... |