Norcott, Philip orcid.org/0000-0003-4082-2079, Rayner, Peter J. orcid.org/0000-0002-6577-4117, Green, Gary G.R. orcid.org/0000-0003-1977-7509 et al. (1 more author) (2017) Achieving High 1H Nuclear Hyperpolarization Levels with Long Lifetimes in a Range of Tuberculosis Drug Scaffolds. Chemistry : A European Journal. pp. 16990-16997. ISSN 1521-3765
Abstract
Despite the successful use of isoniazid, rifampicin, pyrazinamide and ethambutol in the treatment of tuberculosis (TB), it is a disease of growing global concern. We illustrate here a series of methods that will dramatically improve the magnetic resonance imaging (MRI) detectability of nineteen TB-relevant agents. We note that the future probing of their uptake and distribution in vivo would be expected to significantly enhance their efficacy in disease treatment. This improvement in detectability is achieved by use of the parahydrogen based SABRE protocol in conjunction with the 2H-labelling of key sites within their molecular structures and the 2H-labelling of the magnetization transfer catalyst. The T1 relaxation times and polarization levels of these agents are quantified under test conditions to produce a protocol to identify structurally optimized motifs for future detection. For example, deuteration of the 6-position of a pyrazinamide analogue leads to a structural form that exhibits T1 values of 144.5 s for 5-H with up to 20 % polarization. This represents a >7-fold extension in relaxation time and almost 10-fold improvement in polarization level when compared to its unoptimized structure.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details |
Keywords: | catalysis,hyperpolarization,isotopes,SABRE,tuberculosis |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York The University of York > Faculty of Sciences (York) > Chemistry (York) The University of York > Faculty of Sciences (York) > Psychology (York) |
Funding Information: | Funder Grant number WELLCOME TRUST 098335/Z/12/Z |
Depositing User: | Pure (York) |
Date Deposited: | 09 Nov 2017 14:10 |
Last Modified: | 26 Jan 2025 00:11 |
Published Version: | https://doi.org/10.1002/chem.201703278 |
Status: | Published online |
Refereed: | Yes |
Identification Number: | 10.1002/chem.201703278 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:123750 |