Pulse-Programmable Magnetic Field Sweeping of Parahydrogen-Induced Polarization by Side Arm Hydrogenation

Abstract

Among the hyperpolarization techniques geared toward in vivo magnetic resonance imaging, parahydrogen-induced polarization (PHIP) shows promise due to its low cost and fast speed of contrast agent preparation. The synthesis of 13 C-labeled, unsaturated precursors to perform PHIP by side arm hydrogenation has recently opened new possibilities for metabolic imaging owing to the biological compatibility of the reaction products, although the polarization transfer between the parahydrogen-derived protons and the 13 C heteronucleus must yet to be better understood, characterized, and eventually optimized. In this realm, a new experimental strategy incorporating pulse-programmable magnetic field cycling has been developed. The approach is evaluated by measuring the 13 C polarization of ethyl acetate-1-13 C, i.e. the product of pairwise addition of parahydrogen to vinyl acetate-1-13 C, resulting from zero-crossing magnetic field sweeps of various durations, amplitudes, and step sizes. The results demonstrate (i) the profound effect these parameters have on the 1 H to 13 C polarization transfer efficiency and (ii) the high reproducibility of the technique.

Synthesis and 15N NMR Signal Amplification by Reversible Exchange of [15N]Dalfampridine at Microtesla Magnetic Fields

“…In PHIP, the symmetry of p‐H 2 molecule is broken via pairwise p‐H 2 addition to an asymmetric unsaturated precursor molecule [4,16] . The requirement to have an unsaturated precursor limits the range of compounds which can be hyperpolarized using PHIP, although [1‐ 13 C]pyruvate and other metabolically relevant biomolecules have been successfully hyperpolarized [17–22] . In contrast, SABRE technique allows one to hyperpolarize compounds without their chemical modification [7] .…”

Chemical Reaction Monitoring using Zero‐Field Nuclear Magnetic Resonance Enables Study of Heterogeneous Samples in Metal Containers

“…In PHIP, the singlet spin order of parahydrogen can be converted into enhanced (nonequilibrium) nuclear magnetization of the hydrogenation product if p‐H 2 is added in a pairwise manner to an unsaturated precursor using a suitable hydrogenation catalyst . Spin‐polarization levels of a few to a few tens of % can be achieved with PHIP depending on experimental implementation . In ZULF NMR experiments, enhanced signals can be observed if there is a heteronuclear spin present in the molecule which renders the parahydrogen‐derived protons magnetically inequivalent …”

“…[40] Spin-polarization levels of afew to af ew tens of %c an be achieved with PHIP depending on experimental implementation. [41][42][43][44][45][46][47][48] In ZULF NMR experiments,enhanced signals can be observed if there is aheteronuclear spin present in the molecule which renders the parahydrogen-derived protons magnetically inequivalent. [32] In this work we study two-step hydrogenation of an unsaturated precursor molecule with para-enriched hydrogen gas using ZULF NMR.…”

Chemical Reaction Monitoring Using Zero-Field Nuclear Magnetic Resonance Enables Study of Heterogeneous Samples in Metal Containers

“…In PHIP, the singlet spin order of parahydrogen can be converted into enhanced (nonequilibrium) nuclear magnetization of the hydrogenation product if p-H2 is added in a pairwise manner to an unsaturated precursor using a suitable hydrogenation catalyst [39]. Spin-polarization levels of a few to a few tens of % can be achieved with PHIP depending on experimental implementation [40][41][42][43][44][45][46][47]. In ZULF NMR experiments, enhanced signals can be observed if there is a heteronuclear spin present in the molecule which renders the parahydrogen-derived protons magnetically inequivalent [31].…”