Toward Nanomolar Detection by NMR Through SABRE Hyperpolarization

Abstract

SABRE is a nuclear spin hyperpolarization technique based on the reversible association of a substrate molecule and para-hydrogen (p-H2) to a metal complex. During the lifetime of such a complex, generally fractions of a second, the spin order of p-H2 is transferred to the nuclear spins of the substrate molecule via a transient scalar coupling network, resulting in strongly enhanced NMR signals. This technique is generally applied at relatively high concentrations (mM), in large excess of substrate with respect to metal complex. Dilution of substrate ligands below stoichiometry results in progressive decrease of signal enhancement, which precludes the direct application of SABRE to the NMR analysis of low concentration (μM) solutions. Here, we show that the efficiency of SABRE at low substrate concentrations can be restored by addition of a suitable coordinating ligand to the solution. The proposed method allowed NMR detection below 1 μM in a single scan.

Delivering strong 1 H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange

“…The hyperpolarized agent can then be detected in a second step by NMR or MRI methods. Protio-nicotinamide (1) was one of the first substrates to be polarized by SABRE (16) and aspects of its 1 H, 13 C, and 15 N signal enhancement have been previously communicated (29)(30)(31)(32)(33). In this work we undertake the SABRE process in the solvents methanol-d 4 or ethanol-d 6 at a field of 65 G unless otherwise stated and use a 400-MHz or 9.4-T field for the final measurement step.…”

“…We are currently using this approach to optimally polarize the 13 C and 15 N nuclei of a range of substrates with long magnetization lifetimes. It should be noted that in recent reports hyperpolarized 15 N and 1 H NMR signals can be detected over 15 min after their creation by harnessing SABRE in conjunction with long-lived singlet states, which reflects a further route to extend this approach (43,44).…”

“…The development of this technique is, therefore, fraught with experimental challenges because fresh samples are needed for each study. Furthermore, the use of NMR spectroscopy as an analytical tool would benefit substantially if materials could be rapidly characterized at lower concentrations than is currently possible (13)(14)(15).…”

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

“…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 ]…”

2D NMR Trace Analysis by Continuous Hyperpolarization at High Magnetic Field

“…[3] However,f ast 1 Hrelaxation has so far limited the application of dissolution-DNP to heteronuclear NMR (mainly 13 C), which, for natural systems,r equires relatively high analyte concentrations (typically millimolar). In contrast, SABRE allows NMR detection at sub-micromolar concentration, [4] albeit limited to species that can reversibly bind to an iridium-based metal complex in solution, as already shown for nucleobases, [5] amino acids, [6] drugs, [7] and tagged oligopeptides. [8] Furthermore,asSABRE relies on the reversible interactions of para-hydrogen (p-H 2 )a nd substrate molecules at the metal complex, fast sample repolarization is possible by bubbling p-H 2 through solution.…”