Investigation on the isotopic exchange radiofluorination of the pentafluorosulfanyl group
The pentafluorosulfanyl group (-SF<sub>5</sub>) is one of the most promising fluorinated functional groups, recently developed as an alternative to the trifluoromethyl group (-CF<sub>3</sub>) in drug design. Fluorine-18 allows researchers to investigate <i>in vivo</i> activity and biodistribution of novel fluorinated drugs; however, currently no methods are reported to radiolabel -SF<sub>5</sub> moieties. In this work we report the first successful radiolabelling of such a group by isotopic exchange, and we show peculiar reaction trends. We studied this reaction using model compounds and functionalized amino acids, also adopting an unbiased approach to reaction optimization to minimize cognition bias. The results have been analyzed by standard statistical methods and Artificial Intelligence (AI) tools. Finally, we serendipitously discovered the production of two radioactive products from one precursor, that we hypothesize being positional radioisotopologues that interact differently with the chromatographic stationary phase; if further proven, this finding hints, for the first time, at a case of chemical differences between molecules containing <sup>19</sup>F and <sup>18</sup>F.
Authors
- Martina Lessio (ORCID: https://orcid.org/0000-0002-5143-9924)
- Hugh G. Hiscocks (ORCID: https://orcid.org/0000-0002-5587-8289)
- Luke Hunter (ORCID: https://orcid.org/0000-0002-8678-3602)
- James O. Hill (ORCID: https://orcid.org/0000-0003-4690-2264)
- Peter J. H. Scott (ORCID: https://orcid.org/0000-0002-6505-0450)
- Giancarlo Pascali (ORCID: https://orcid.org/0000-0001-7919-8416)
- Alison T. Ung (ORCID: https://orcid.org/0000-0002-5665-0702)
- Patrick B. Ryan (ORCID: https://orcid.org/0000-0002-9727-2138)
- A. F. Brooks (ORCID: https://orcid.org/0000-0003-4295-792X)
- Rhys Johnston
- Wei Huang (ORCID: https://orcid.org/0009-0005-3493-4228)
- Gabrielle Weerasinghe
Institutions
- University of Technology Sydney (AU)
- The University of Sydney (AU)
- Australian Nuclear Science and Technology Organisation (AU)
- The University of Queensland (AU)
- University of Michigan (US)
- UNSW Sydney (AU)
- Cooperative Trials Group for Neuro-Oncology (AU)
Publication Details
- Journal
- Organic & Biomolecular Chemistry
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1039/d5ob01419k
- Citations
- 1
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.79
Funders
- University of Michigan
- Australian Nuclear Science and Technology Organisation
- National Imaging Facility
- Australian Institute of Nuclear Science and Engineering
- Fulbright Australia
- University of New South Wales
- National Institutes of Health