Analysis of chemical exchange in iridium N-heterocyclic carbene complexes using heteronuclear parahydrogen-enhanced NMR

Abstract

The signal amplification by reversible exchange process (SABRE) enhances NMR signals by unlocking hidden polarization in parahydrogen through interactions with to-be-hyperpolarized substrate molecules when both are transiently bound to an Ir-based organometallic catalyst. Recent efforts focus on optimizing polarization transfer from parahydrogen-derived hydride ligands to the substrate in SABRE. However, this requires quantitative information on ligand exchange rates, which common NMR techniques struggle to provide. Here, we introduce an experimental spin order transfer sequence, with readout occurring at 15N nuclei directly interacting with the catalyst. Enhanced 15N NMR signals overcome sensitivity challenges, encoding substrate dissociation rates. This methodology enables robust data fitting to ligand exchange models, yielding substrate dissociation rate constants with higher precision than classical 1D and 2D 1H NMR approaches. This refinement improves the accuracy of key activation enthalpy ΔH‡ and entropy ΔS‡ estimates. Furthermore, the higher chemical shift dispersion provided by enhanced 15N NMR reveals the kinetics of substrate dissociation for acetonitrile and metronidazole, previously inaccessible via 1H NMR due to small chemical shift differences between free and Ir-bound substrates. The presented approach can be successfully applied not only to isotopically enriched substrates but also to compounds with natural abundance of the to-be-hyperpolarized heteronuclei. Current efforts to enhance NMR signals using the signal amplification by reversible exchange (SABRE) focus on optimizing polarization transfer from parahydrogen-derived hydride ligands to the substrate, but this requires quantitative information on ligand exchange rates, which common NMR techniques struggle to provide. Here, the authors introduce an experimental spin order transfer sequence with readout occurring at hyperpolarization-enhanced 15N nuclei that are directly interacting with the SABRE catalyst, enabling robust evaluation of ligand chemical exchange.