Single-Chain Fluorinated Catalysts for Efficient SABRE Pyruvate Hyperpolarization and <100 ppb Iridium in Aqueous Solutions

Data linked to the work in the title: Federico Floreani,[a] Ahmed Faramawy,[a] Federico De Biasi,[a] Denis Badocco,[a] Salvatore Mamone,[b] Callum A. Gater,[c] Simon B. Duckett,[c] Cristina Tubaro*[a] and Gabriele Stevanato*[a] [a] F. Floreani, Dr. A. Faramawy, Dr. F. De Biasi, Prof. D. Badocco, Prof. C. Tubaro, Prof. G. StevanatoDepartment of Chemical SciencesUniversità di PadovaVia Marzolo 1, 35131, Padova (Italy)E-mail: [e-mail] [e-mail] [b] Prof. S. MamoneDept. MESVA (Life, Health & Environmental Sciences)Università dell’AquilaVia Vetoio SNC, Località Coppito, 67100, L’Aquila (Italy) [c] Dr. C. A. Gater, Prof. S. B. DuckettCentre for Hyperpolarisation in Magnetic ResonanceUniversity of York (UK)Heslington, York YO10 5NY Abstract Signal Amplification by Reversible Exchange (SABRE) delivers rapid and inexpensive NMR signal enhancement using parahydrogen-derived spin order, but biomedical translation requires catalysts that simultaneously deliver high polarization efficiency together with minimal residual metal contamination. Here we introduce a class of single-chain fluorinated Ir–NHC catalysts for SABRE hyperpolarization of [1-13C]pyruvate that resolves this longstanding trade-off. Retention of carbene backbone unsaturation preserves SABRE efficiency, enabling ~4% 13C polarization with 50% parahydrogen, comparable to the benchmark Ir–IMes catalyst and approximately threefold higher than the previously reported perfluorinated Ir–SIMesF2 system under identical conditions. Combined with redissolution SABRE, aqueous extraction, and fluorinated silica filtration, one of these catalysts, Ir-IMesF1, yields aqueous hyperpolarized solutions containing <100 ppb residual iridium, which is the lowest value reported to date. The resulting aqueous formulations simultaneously deliver efficient SABRE hyperpolarization and ultra-low residual iridium contamination, enabling real-time monitoring of in vitro pyruvate-to-lactate conversion under partial parahydrogen enrichment. Acknowledgements This research has been funded/co-funded by the European Union (ERC StG, HYPMET, 101117082). Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible for them. SBD and CAG thank the UK Research and Innovation (UKRI) under the UK government’s Horizon Europe funding guarantee [grant number EP/X023672/1] and Norman Turner (N0013902). The Bruker D8 Venture diffractometer at the Department of Chemical Sciences of the University of Padova was funded by the MUR-Dipartimenti di Eccellenza-grantC2. We thank Prof. Marco Ruzzi and Prof. Lorenzo Franco for insightful discussions.