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Computationally-Guided Development of a Chelated NHC-P Iridium(I) Complex for the Directed Hydrogen Isotope Exchange of Aryl Sulfones

[Image: see text] Herein, we report the rational, computationally-guided design of an iridium(I) catalyst system capable of enabling directed hydrogen isotope exchange (HIE) with the challenging sulfone directing group. Substrate binding energy was used as a parameter to guide rational ligand design...

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Autores principales: Kerr, William J., Knox, Gary J., Reid, Marc, Tuttle, Tell, Bergare, Jonas, Bragg, Ryan A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587147/
https://www.ncbi.nlm.nih.gov/pubmed/33123410
http://dx.doi.org/10.1021/acscatal.0c03031
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author Kerr, William J.
Knox, Gary J.
Reid, Marc
Tuttle, Tell
Bergare, Jonas
Bragg, Ryan A.
author_facet Kerr, William J.
Knox, Gary J.
Reid, Marc
Tuttle, Tell
Bergare, Jonas
Bragg, Ryan A.
author_sort Kerr, William J.
collection PubMed
description [Image: see text] Herein, we report the rational, computationally-guided design of an iridium(I) catalyst system capable of enabling directed hydrogen isotope exchange (HIE) with the challenging sulfone directing group. Substrate binding energy was used as a parameter to guide rational ligand design via an in silico catalyst screen, resulting in a lead series of chelated iridium(I) NHC-phosphine complexes. Subsequent preparative studies show that the optimal catalyst system displays high levels of activity in HIE, and we demonstrate the labeling of a broad scope of substituted aryl sulfones. We also show that the activity of the catalyst is maintained at low pressures of deuterium gas and apply these conditions to tritium radiolabeling, including the expedient synthesis of a tritium-labeled drug molecule.
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spelling pubmed-75871472020-10-27 Computationally-Guided Development of a Chelated NHC-P Iridium(I) Complex for the Directed Hydrogen Isotope Exchange of Aryl Sulfones Kerr, William J. Knox, Gary J. Reid, Marc Tuttle, Tell Bergare, Jonas Bragg, Ryan A. ACS Catal [Image: see text] Herein, we report the rational, computationally-guided design of an iridium(I) catalyst system capable of enabling directed hydrogen isotope exchange (HIE) with the challenging sulfone directing group. Substrate binding energy was used as a parameter to guide rational ligand design via an in silico catalyst screen, resulting in a lead series of chelated iridium(I) NHC-phosphine complexes. Subsequent preparative studies show that the optimal catalyst system displays high levels of activity in HIE, and we demonstrate the labeling of a broad scope of substituted aryl sulfones. We also show that the activity of the catalyst is maintained at low pressures of deuterium gas and apply these conditions to tritium radiolabeling, including the expedient synthesis of a tritium-labeled drug molecule. American Chemical Society 2020-09-01 2020-10-02 /pmc/articles/PMC7587147/ /pubmed/33123410 http://dx.doi.org/10.1021/acscatal.0c03031 Text en This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Kerr, William J.
Knox, Gary J.
Reid, Marc
Tuttle, Tell
Bergare, Jonas
Bragg, Ryan A.
Computationally-Guided Development of a Chelated NHC-P Iridium(I) Complex for the Directed Hydrogen Isotope Exchange of Aryl Sulfones
title Computationally-Guided Development of a Chelated NHC-P Iridium(I) Complex for the Directed Hydrogen Isotope Exchange of Aryl Sulfones
title_full Computationally-Guided Development of a Chelated NHC-P Iridium(I) Complex for the Directed Hydrogen Isotope Exchange of Aryl Sulfones
title_fullStr Computationally-Guided Development of a Chelated NHC-P Iridium(I) Complex for the Directed Hydrogen Isotope Exchange of Aryl Sulfones
title_full_unstemmed Computationally-Guided Development of a Chelated NHC-P Iridium(I) Complex for the Directed Hydrogen Isotope Exchange of Aryl Sulfones
title_short Computationally-Guided Development of a Chelated NHC-P Iridium(I) Complex for the Directed Hydrogen Isotope Exchange of Aryl Sulfones
title_sort computationally-guided development of a chelated nhc-p iridium(i) complex for the directed hydrogen isotope exchange of aryl sulfones
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587147/
https://www.ncbi.nlm.nih.gov/pubmed/33123410
http://dx.doi.org/10.1021/acscatal.0c03031
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