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.与标题所述研究相关的数据集： 费德里科·弗洛雷亚尼（Federico Floreani）[a]、艾哈迈德·法拉马维（Ahmed Faramawy）[a]、费德里科·德·比亚西（Federico De Biasi）[a]、丹尼斯·巴多科（Denis Badocco）[a]、萨尔瓦多·马莫内（Salvatore Mamone）[b]、卡勒姆·A·盖特（Callum A. Gater）[c]、西蒙·B·达基特（Simon B. Duckett）[c]、克里斯蒂娜·图巴罗*[a] 与加布里埃莱·斯特瓦纳托*[a] [a] F. 弗洛雷亚尼、A. 法拉马维博士、F. 德·比亚西博士、D. 巴多科教授、C. 图巴罗教授、G. 斯特瓦纳托教授 帕多瓦大学化学科学系，意大利帕多瓦，马尔佐洛路1号，35131 电子邮箱：[e-mail]；[e-mail] [b] S. 马莫内教授 拉奎拉大学生命、健康与环境科学系（MESVA），意大利拉奎拉，韦托伊奥大街SNC，科皮托园区，67100 [c] C. A. 盖特博士、S. B. 达基特教授 英国约克大学磁共振超极化中心，赫斯林顿，约克 YO10 5NY 摘要 可逆交换信号放大（Signal Amplification by Reversible Exchange, SABRE）技术利用仲氢衍生的自旋有序性，可实现快速且低成本的核磁共振（Nuclear Magnetic Resonance, NMR）信号增强，但面向生物医学的转化应用需要催化剂同时具备高极化效率与极低的金属残留污染。本研究报道了一类用于[1-13C]丙酮酸SABRE超极化的单链氟化铱-氮杂环卡宾（Ir–NHC）催化剂，解决了这一长期存在的权衡难题。保留卡宾骨架的不饱和性可维持SABRE的极化效率，在50%仲氢条件下可实现约4%的13C极化，与基准催化剂Ir–IMes相当，且约为相同条件下此前报道的全氟化Ir–SIMesF2体系的3倍。结合重溶SABRE、水相萃取与氟化硅胶过滤工艺，其中一款催化剂Ir-IMesF1可制备出残留铱含量低于100 ppb的水相超极化溶液，这是目前已报道的最低值。所得水相制剂兼具高效的SABRE超极化能力与极低的铱残留污染，可在部分仲氢富集条件下实现体外丙酮酸向乳酸转化的实时监测。 致谢 本研究由欧盟（European Union）资助/共同资助（欧洲研究委员会启动基金，ERC StG, HYPMET, 101117082）。本文所表达的观点仅代表作者本人，未必反映欧盟或欧洲研究委员会（European Research Council, ERC）的立场。欧盟及资助机构不对本文内容承担任何责任。SBD与CAG感谢英国研究与创新署（UK Research and Innovation, UKRI）在英国政府地平线欧洲（Horizon Europe）资助保障框架下的资助（项目编号：EP/X023672/1），以及诺曼·特纳（Norman Turner, N0013902）的支持。帕多瓦大学化学科学系的布鲁克D8 Venture衍射仪由意大利大学与研究部卓越院系项目（MUR-Dipartimenti di Eccellenza）资助，项目编号C2。我们感谢马可·鲁齐（Marco Ruzzi）教授与洛伦佐·佛朗哥（Lorenzo Franco）教授提供的富有启发性的讨论。