Iridium N-Heterocyclic Carbene Complexes as Efficient Catalysts for Magnetization Transfer from para-Hydrogen

Abstract

While the characterization of materials by NMR is hugely important in the physical and biological sciences, it also plays a vital role in medical imaging. This success is all the more impressive because of the inherently low sensitivity of the method. We establish here that [Ir(H)2(IMes)(py)3]Cl undergoes both pyridine (py) loss as well as the reductive elimination of H2. These reversible processes bring para-H2 and py into contact in a magnetically coupled environment, delivering an 8100-fold increase in 1H NMR signal strength relative to non-hyperpolarized py at 3 T. An apparatus that facilitates signal averaging has been built to demonstrate that the efficiency of this process is controlled by the strength of the magnetic field experienced by the complex during the magnetization transfer step. Thermodynamic and kinetic data combined with DFT calculations reveal the involvement of [Ir(H)2(η2-H2)(IMes)(py)2]+, an unlikely yet key intermediate in the reaction. Deuterium labeling yields an additional 60% improvement in signal, an observation that offers insight into strategies for optimizing this approach.

Harnessing polarisation transfer to indazole and imidazole through signal amplification by reversible exchange to improve their NMR detectability

“…This is achieved by creating a SABRE catalyst that acts as a scaffold to bind both p ‐H 2 and the substrate such that it allows polarisation transfer through the resulting scalar coupling network. The process of SABRE is also affected by the magnetic field that is experienced by the catalyst during this process that is often called the polarisation transfer field (PTF) 6. An active SABRE catalyst can break the symmetry of these two protons in one of two ways detailed in Scheme 1 for indazole, where the co‐ligand is acetonitrile and the precatalyst is [IrCl(COD)(IMes)] 1a 7.…”

“…As the original substrate molecule is reformed after ligand dissociation, there is no change in its chemical identity during this process, but it has now become a hyperpolarised (HP) species. SABRE catalysts based on N ‐heterocyclic carbene (NHC) iridium complexes that contain 1,3‐bis(2,4,6‐trimethylphenyl)imidazol‐2‐ylidene (IMes) or 1,3‐bis(2,4,6‐trimethylphenyl)‐4,5‐dihydroimidazol‐2‐ylidene (SIMes) ligands are used in this study,8, 9 although studies on other templates and a range of substrates have been described in the literature 6, 9, 10. A number of theoretical approaches have been used to model the SABRE effect, of which the level‐anti‐crossing approach provides a readily understandable solution 11.…”

“…Another is the use of high‐sensitivity methods in analytical chemistry. [ 10 , 13 ] Other routes to hyperpolarisation include dynamic nuclear polarisation,2 parahydrogen‐induced polarisation[ 6 , 14 ] with substrate functionalisation and spin‐exchange optical pumping. [ 10 , 15 ]…”

“…using the first generation of phosphine‐based SABRE catalysts4 were observed to produce a 2‐fold NMR signal enhancement [6a] . A study on imidazole by Moreno et al [10d] .…”

“…A study on imidazole by Moreno et al [10d] . using the second generation of carbene‐based SABRE catalysts [6b] produced an improved response. Chekmenev et al has also reported on the 15 N hyperpolarisation of imidazole, with the supplementary information suggesting that a 100‐fold 1 H signal enhancement is produced in H‐2 and 50‐fold gain in H‐4 and H‐5.…”