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

Peter Spannring,Martin C Feiters,Philipp P M Schleker,Marco Tessari,Bram J A Van Weerdenburg,Meike Emondts,Paul Tinnemans,Niels K J Hermkens,Nick G J Van Der Zwaluw,Bernhard Blümich,Floris P J T Rutjes,Indrek Reile

doi:10.1002/chem.201601211

Peter Spannring, Martin C Feiters + Show 10 more

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https://doi.org/10.1002/chem.201601211

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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 Earth's 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.

Highlights

Hyperpolarization (HP) methods enhance nuclear magnetic resonance (NMR) signals, overcoming the fundamental problem of low sensitivity.[1]
Design and synthesis of the water-soluble signal amplification by reversible exchange (SABRE) catalyst We surmise that the apolar nature of the catalysts involved, rather than the low solubility of H2 in D2O, has hitherto prevented successful SABRE
Based on a new Ir-N-heterocyclic carbenes (NHCs) catalyst, [Ir(Cl)(IDEG)(COD)], we report here the first SABRE system to operate exclusively in D2O, that www.chemeurj.org

Summary

Introduction

Hyperpolarization (HP) methods enhance nuclear magnetic resonance (NMR) signals, overcoming the fundamental problem of low sensitivity.[1]. It is desired to use HP methods in magnetic resonance imaging (MRI) for medical diagnosis.[1,11,12] For such clinical applications, the methods should meet the following conditions: a) polarization of a wide range of substrates without chemical alteration; b) fast and continuous polarization without contamination; c) heteronuclei with long relaxation times should be [b] M.

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