Parahydrogen induced hyperpolarization provides a tool for NMR metabolomics at nanomolar concentrations

Abstract

Sensitivity enhancement by parahydrogen hyperpolarization allows NMR detection and quantification of hundreds of urinary metabolites at down to nanomolar concentrations.

Determination of hydrogen exchange and relaxation parameters in PHIP complexes at micromolar concentrations

“…1) are not chemically equivalent, which, due to the distribution of p-H 2 association in time, causes rapid conversion of the singlet state to longitudinal spin order (Buljubasich et al, 2013). We have previously demonstrated that this spin order can be converted into enhanced magnetization, allowing the NMR detection of hydride signals down to sub-micromolar complex concentrations (Eshuis et al, 2015;Sellies et al, 2019). This sensitivity increase can also be used to study the exchange of p-H 2 in the iridium catalyst as well as the NMR relaxation of the hydrides and p-H 2 in solution.…”

“…1b). We have previously demonstrated that such an asymmetric complex is an ideal NMR chemosensor (Hermkens et al, 2016;Sellies et al, 2019): molecules capable of associating with the PHIP catalyst can be probed by a pair of hydride signals enhanced by ca. 3 orders of magnitude with respect to thermal NMR measured at 500 MHz.…”

“…(c) Structure of the mtz co-substrate (1-methyl-1,2,3-triazole). et al, 2015), such as biofluids (Reile et al, 2016;Sellies et al, 2019) and natural extracts (Hermkens et al, 2016(Hermkens et al, , 2018.…”

“…The NMR signal enhancements obtained by these reversible PHIP techniques result from a complex interplay of substrate exchange, para-hydrogen exchange and relaxation processes Stanbury et al, 2019). For instance, at a high field, the singlet state of para-hydrogen associating with an asymmetric complex rapidly turns into hydrides' longitudinal spin order, which can be converted into enhanced hydride magnetization by a SEPP pulse sequence (Sengstschmid et al, 1996). The resulting hydrides' signal enhancement depends, therefore, amongst others, on the para-hydrogen lifetime in solution, the rates of parahydrogen association/dissociation with/from the complex, and the NMR relaxation of the longitudinal spin order in the complex.…”

“…The resulting hydrides' signal enhancement depends, therefore, amongst others, on the para-hydrogen lifetime in solution, the rates of parahydrogen association/dissociation with/from the complex, and the NMR relaxation of the longitudinal spin order in the complex. Gaining access to these parameters is crucial in order to rationalize the observed variations in hydrides' NMR signal enhancement for different substrates (Sellies et al, 2019) or to optimally tune the chemosensing system (e.g., select the best co-substrate molecule) for specific substrates and/or experimental applications. Since some of these parameters, e.g., the hydrogen dissociation rate constant, strongly depend on the concentration of ligands in solution (Cowley et al, 2011;Appleby et al, 2015), it is important to measure them in the same dilute conditions normally encountered in PHIP NMR.…”