Efficient iridium N-heterocyclic carbene catalysts for signal amplification by reversible exchange in dimethyl sulfoxide

Hyperpolarization by signal amplification by reversible exchange (SABRE) is a promising route toward fast, low-cost, and repeatable sensitivity enhancement for nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI). Because dimethyl sulfoxide (DMSO) is biocompatible and dissolves a broad range of organic and biological substrates, performing SABRE directly in DMSO could substantially widen the scope of parahydrogen-based hyperpolarization toward biomedical applications. To date, however, DMSO has been regarded as an inefficient SABRE medium for the conventional [Ir(IMes)(COD)Cl] catalyst, which provides only modest enhancements relative to methanol. Here we report two new iridium N-heterocyclic carbene (NHC) catalysts—the [Ir(COD)Cl] complexes of 1,3-dibenzylimidazol-2-ylidene (Ir-Imid) and 1,3-dibenzylbenzimidazol-2-ylidene (Ir-Benzimid)—that deliver the highest 1 H SABRE enhancements reported in DMSO to date. Across five representative substrates, the new catalyst improves the enhancement factor for protons at the same position by about 1.23 to 3.24 times compared to Ir-IMes. Density functional theory (DFT) calculations of the catalyst–substrate–parahydrogen complexes relate these trends to the average axial and equatorial Ir–ligand bond lengths and provide rational design guidance for further development of SABRE catalysts that operate efficiently in DMSO.