Quantitative Trace Analysis of Complex Mixtures Using SABRE Hyperpolarization

Abstract

Signal amplification by reversible exchange (SABRE) is an emerging nuclear spin hyperpolarization technique that strongly enhances NMR signals of small molecules in solution. However, such signal enhancements have never been exploited for concentration determination, as the efficiency of SABRE can strongly vary between different substrates or even between nuclear spins in the same molecule. The first application of SABRE for the quantitative analysis of a complex mixture is now reported. Despite the inherent complexity of the system under investigation, which involves thousands of competing binding equilibria, analytes at concentrations in the low micromolar range could be quantified from single-scan SABRE spectra using a standard-addition approach.

Quantitative NMR Studies of Multiple Compound Mixtures

“…Atkinson et al [61] proposed a new hyperpolarization technique, named as signal amplification by reversible exchange (SABRE) to address low sensitivity problem. This technique has been successfully applied in quantitative trace analysis of complex mixtures [62]. In the past decade, the use of NMR for complex mixture analysis gained great attention due to its unbiased and robust nature, as well as its employment in high-throughput mode, particularly in metabolomics area [63].…”

NMR Hyperpolarization Techniques of Gases

“…Although the vast majority of SEOP experiments have employed the spin I=1/2 noble gas isotopes 129 Xe and 3 He, the quadrupolar species 21 Ne (I=3/2), [36] 83 Kr (I=9/2), [37] and 131 Xe [38] (I=3/2) can also be polarized via this method. For the alkali metal vapor, Rb is most-commonly employed for practical reasons-including its low melting point [39] (facilitating vaporization) and the availability of high-powered lasers resonant with its D1 transition [40] ; however, K and Cs are also utilized (particularly for 3 He [41] and 129 Xe, [42] respectively).…”

“…images can be acquired during a single breath hold; sufficient signal can be attained despite low density of gas compared to liquid. While liquid HP contrast agents are injected in vivo to probe metabolism [19] (extensively discussed in many recent reviews) [20] or used otherwise, [21] they typically cannot be used to probe gas-phase processes in vitro or in vivo. This mini-review focuses on the techniques allowing the production of HP gases with particular application to their use in biomedical applications, and explores some examples from materials science.…”

Computational (DFT) and Experimental (EXAFS) Study of the Interaction of [Ir(IMes)(H)2(L)3] with Substrates and Co‐substrates Relevant for SABRE in Dilute Systems

“…[3] We also observed alinear dependence of the signal intensityo npyridine concentration and recently exploited this feature for quantitative NMR analysisw ith SABRE of ac omplexm ixture with al arge number of substrates. [16] Addition of substrate (Py) and co-substrate (mTz) leads theoretically to the formation of ar ange of complexes, 1 + + , 2a + + , 2b + + , 3a + , 3b + + ,a nd 4 + + .T he relative abundance of these complexes depends on the concentrations of the substrate, co-substrate, and metal complex,a sd epicted in Figure 1. Althought his method is successful, some of these complexes do not contribute to the observed hyperpolarization of Py (3b + + , 4 + + , 5 + + ), and others have not been detected on aN MR timescale (1 + + , 2b + + ).…”