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Steric and electronic effects on the (1)H hyperpolarisation of substituted pyridazines by signal amplification by reversible exchange

Utility of the pyridazine motif is growing in popularity as pharmaceutical and agrochemical agents. The detection and structural characterisation of such materials is therefore imperative for the successful development of new products. Signal amplification by reversible exchange (SABRE) offers a rou...

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Autores principales: Rayner, Peter J., Burns, Michael J., Fear, Elizabeth J., Duckett, Simon B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650576/
https://www.ncbi.nlm.nih.gov/pubmed/33729592
http://dx.doi.org/10.1002/mrc.5152
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author Rayner, Peter J.
Burns, Michael J.
Fear, Elizabeth J.
Duckett, Simon B.
author_facet Rayner, Peter J.
Burns, Michael J.
Fear, Elizabeth J.
Duckett, Simon B.
author_sort Rayner, Peter J.
collection PubMed
description Utility of the pyridazine motif is growing in popularity as pharmaceutical and agrochemical agents. The detection and structural characterisation of such materials is therefore imperative for the successful development of new products. Signal amplification by reversible exchange (SABRE) offers a route to dramatically improve the sensitivity of magnetic resonance methods, and we apply it here to the rapid and cost‐effective hyperpolarisation of substituted pyridazines. The 33 substrates investigated cover a range of steric and electronic properties and their capacity to perform highly effective SABRE is assessed. We find the method to be tolerant to a broad range of electron donating and withdrawing groups; however, good sensitivity is evident when steric bulk is added to the 3‐ and 6‐positions of the pyridazine ring. We optimise the method by reference to a disubstituted ester that yields signal gains of >9000‐fold at 9.4 T (>28% spin polarisation).
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spelling pubmed-86505762021-12-20 Steric and electronic effects on the (1)H hyperpolarisation of substituted pyridazines by signal amplification by reversible exchange Rayner, Peter J. Burns, Michael J. Fear, Elizabeth J. Duckett, Simon B. Magn Reson Chem Special Issue Research Articles Utility of the pyridazine motif is growing in popularity as pharmaceutical and agrochemical agents. The detection and structural characterisation of such materials is therefore imperative for the successful development of new products. Signal amplification by reversible exchange (SABRE) offers a route to dramatically improve the sensitivity of magnetic resonance methods, and we apply it here to the rapid and cost‐effective hyperpolarisation of substituted pyridazines. The 33 substrates investigated cover a range of steric and electronic properties and their capacity to perform highly effective SABRE is assessed. We find the method to be tolerant to a broad range of electron donating and withdrawing groups; however, good sensitivity is evident when steric bulk is added to the 3‐ and 6‐positions of the pyridazine ring. We optimise the method by reference to a disubstituted ester that yields signal gains of >9000‐fold at 9.4 T (>28% spin polarisation). John Wiley and Sons Inc. 2021-04-05 2021-12 /pmc/articles/PMC8650576/ /pubmed/33729592 http://dx.doi.org/10.1002/mrc.5152 Text en © 2021 The Authors. Magnetic Resonance in Chemistry published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Special Issue Research Articles
Rayner, Peter J.
Burns, Michael J.
Fear, Elizabeth J.
Duckett, Simon B.
Steric and electronic effects on the (1)H hyperpolarisation of substituted pyridazines by signal amplification by reversible exchange
title Steric and electronic effects on the (1)H hyperpolarisation of substituted pyridazines by signal amplification by reversible exchange
title_full Steric and electronic effects on the (1)H hyperpolarisation of substituted pyridazines by signal amplification by reversible exchange
title_fullStr Steric and electronic effects on the (1)H hyperpolarisation of substituted pyridazines by signal amplification by reversible exchange
title_full_unstemmed Steric and electronic effects on the (1)H hyperpolarisation of substituted pyridazines by signal amplification by reversible exchange
title_short Steric and electronic effects on the (1)H hyperpolarisation of substituted pyridazines by signal amplification by reversible exchange
title_sort steric and electronic effects on the (1)h hyperpolarisation of substituted pyridazines by signal amplification by reversible exchange
topic Special Issue Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650576/
https://www.ncbi.nlm.nih.gov/pubmed/33729592
http://dx.doi.org/10.1002/mrc.5152
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