Parahydrogen Hyperpolarization Allows Direct NMR Detection of α‐Amino Acids in Complex (Bio)mixtures

Abstract

The scope of non-hydrogenative parahydrogen hyperpolarization (nhPHIP) techniques has been expanding over the last years,w ith the continuous addition of important classes of substrates.F or example,p yruvate can nowb e hyperpolarized using the Signal Amplification By Reversible Exchange (SABRE) technique,o ffering af ast, efficient and low-cost PHIP alternative to Dynamic Nuclear Polarization for metabolic imaging studies.S till, important biomolecules such as amino acids have so far resisted PHIP,unless properly functionalized. Here,wereport on an approach to nhPHIP for unmodified a-amino acids that allows their detection and quantification in complex mixtures at sub-micromolar concentrations.This method was tested on human urine,inwhich natural a-amino acids could be measured after dilution with methanol without any additional sample treatment.

Advancing homogeneous catalysis for parahydrogen-derived hyperpolarisation and its NMR applications

“…18b ) in complex bio-mixtures. 49 The applications of these catalysts in NMR mixture analysis and biofluid analysis has been clearly demonstrated and further examples are expected in the years ahead.…”

“…29,35,48 This is particularly useful in mechanistic studies involving iridium dihydride complexes 38 and the detection of low concentrations of metal complexes for which enhanced hydride resonances may be diagnostic of particular ligands in complex mixtures. 38,[49][50][51] Reactivity of this type is exploited in SABRE as enhanced hydride polarisation can be transferred to other sites in the catalyst (this is discussed in more detail in Section 7). 29 Other catalysts utilise photochemistry to promote ligand loss pathways and produce enhanced hydride NMR signals.…”

“…50,51 In these examples, peak overlap, even within the hydride region of 1 H NMR spectra, can often become a problem due to the large number of SABRE-amenable analytes in the mixture. It is therefore often advantageous to use 2D NMR methods such as COSY, 188,189 DOSY 190,191 or others 49,51 to provide increased chemical resolution between analytes.…”

Missing Pieces in Structure Puzzles: How Hyperpolarized NMR Spectroscopy Can Complement Structural Biology and Biochemistry

“…Unfortunately, SABRE requires nonaqueous solvents, painfully reducing its application portfolio. [140][141][142][143][144] In the context of biomolecular NMR, small metabolites have been reported, such as glycine, histidine, phenylalanine, [145,146] pyruvate, [147] adenine, [148] adenosine, [148] nicotic acid, [149] and nicotinamide. [150][151][152][153][154][155][156][157][158] Concerning proteins, the required organic solvent is problematic.…”