Meike Emondts

A New Ir-NHC Catalyst for Signal Amplification by Reversible Exchange in D2O

Abstract NMR signal amplification by reversible exchange (SABRE) has been observed for pyridine, methyl nicotinate, N‐methylnicotinamide, and nicotinamide in D2O with the new catalyst [Ir(Cl)(IDEG)(COD)] (IDEG=1,3‐bis(3,4,5‐tris(diethyleneglycol)benzyl)imidazole‐2‐ylidene). During the activation and hyperpolarization steps, exclusively D2O was used, resulting in the first fully biocompatible SABRE system. Hyperpolarized 1H substrate signals were observed at 42.5 MHz upon pressurizing the solution with parahydrogen at close to the Earths magnetic field, at concentrations yielding barely detectable thermal signals. Moreover, 42‐, 26‐, 22‐, and 9‐fold enhancements were observed for nicotinamide, pyridine, methyl nicotinate, and N‐methylnicotinamide, respectively, in conventional 300 MHz studies. This research opens up new opportunities in a field in which SABRE has hitherto primarily been conducted in CD3OD. This system uses simple hardware, leaves the substrate unaltered, and shows that SABRE is potentially suitable for clinical purposes.

Direct Hyperpolarization of Nitrogen-15 in Aqueous Media with Parahydrogen in Reversible Exchange

Signal amplification by reversible exchange (SABRE) is an inexpensive, fast, and even continuous hyperpolarization technique that uses para-hydrogen as hyperpolarization source. However, current SABRE faces a number of stumbling blocks for translation to biochemical and clinical settings. Difficulties include inefficient polarization in water, relatively short-lived 1H-polarization, and relatively limited substrate scope. Here we use a water-soluble polarization transfer catalyst to hyperpolarize nitrogen-15 in a variety of molecules with SABRE-SHEATH (SABRE in shield enables alignment transfer to heteronuclei). This strategy works in pure H2O or D2O solutions, on substrates that could not be hyperpolarized in traditional 1H-SABRE experiments, and we record 15N T1 relaxation times of up to 2 min.

Hyperpolarizing Water with Parahydrogen

Studies of water-based systems are of fundamental interest for nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) as water is the most abundant and important medium for global living. Hence, increasing the polarization of water and dissolved compounds is particularly attractive for biomedical applications such as investigations of intermolecular interactions and metabolite structures as well as for imaging purposes. In this work, we show a new approach based on para enriched hydrogen (p-H2 ) that enables the hyperpolarization of bulk water if a suitable catalytic system is employed. The results indicate that the polarization is transferred by a new exchange mechanism.

Non-Pairwise Interactions in Parahydrogen Experiments: Nuclear Exchange of Single Protons Enables Bulk Water Hyperpolarization

Hyperpolarization with parahydrogen (p-H2 ) is a fast developing field in NMR, which enables overcoming the inherent low sensitivity of this important technique. The hyperpolarization of solvents, particularly of water, offers a wide range of applications for structural investigations of macromolecules and biomedical imaging. Until lately, only organic solvents could be polarized by means of parahydrogen via coherent redistribution of polarization (SABRE mechanism). In this study, we investigate in detail the mechanism of the recently reported bulk water hyperpolarization with a combination of theoretical and experimental methods, finally showing a chemical exchange pathway of single protons as basis for the enhancement. The prerequisites for preserving hyperpolarization upon separation of the two hydrogen atoms of p-H2 are demonstrated by theoretical examinations of the boundary conditions for the hyperpolarization experiments in accordance with the OneH-PHIP theory. These findings yielded the proposal of the novel NEPTUN mechanism (Nuclear Exchange Polarization by Transposing Unattached Nuclei) as the non-hydrogenative equivalent to the established OneH-PHIP and thus the missing link in parahydrogen hyperpolarization theory.