¹⁵N Magnetic Resonance Hyperpolarization via the Reaction of Parahydrogen with ¹⁵N-Propargylcholine

Abstract

(15)N-Propargylcholine has been synthesized and hydrogenated with para-H(2). Through the application of a field cycling procedure, parahydrogen spin order is transferred to the (15)N resonance. Among the different isomers formed upon hydrogenation of (15)N-propargylcholine, only the nontransposed derivative contributes to the observed N-15 enhanced emission signal. The parahydrogen-induced polarization factor is about 3000. The precise identification of the isomer responsible for the observed (15)N enhancement has been attained through a retro-INEPT ((15)N-(1)H) experiment. T(1) of the hyperpolarized (15)N resonance has been estimated to be ca. 150 s, i.e., similar to that reported for the parent propargylcholine (144 s). Experimental results are accompanied by theoretical calculations that stress the role of scalar coupling constants (J(HN) and J(HH)) and of the field dependence in the formation of the observed (15)N polarized signal. Insights into the good cellular uptake of the compound have been gained.

Efficient Transformation of Parahydrogen Spin Order into Heteronuclear Magnetization

“…Hyper-SHIELDED should perform particularly well in molecules with small asymmetries such as ethylamine, diethyamine, and choline (Figure 3 inset). 20,21 …”

ParaHydrogen Induced Polarization of 13C carboxylate resonance in acetate and pyruvate

“…Among them, succinate 14,15 and phospho-lactate 16,17 are the only metabolites for which good hyperpolarization level has been achieved until now. Alternative routes have been proposed to achieve PHIP on biologically relevant molecules by functionalizing the substrates of interest with moieties capable of hydrogenation [18][19][20] . However, the structural modifications introduced by the unsaturated group may significantly alter their biological behaviour with respect to the native substrates.…”

“…4). When the deuterated propargylic alcohol was used (2-d 2 propargylic alcohol) 19 polarization transfer to 13 C carboxylate signal was not obtained (spectrum in Supplementary Fig. 3).…”

A pulse programmable parahydrogen polarizer using a tunable electromagnet and dual channel NMR spectrometer

“…At low fields where protons are strongly coupled, the resultant singlet-state is fully preserved, but in order to be harnessed for biomedical applications, it is generally necessary to transform this spin order into net magnetization. The most common scenario is to transform this singlet-state into net heteronuclear magnetization on a long-lived nucleus such as a carbonyl- 13 C, but numerous other spin-systems and storage nuclei [60, 72] have been used and many further as yet undiscovered systems await. These experimental demands combined with the capability to detect NMR signals at the time of reaction favor spectrometer-based control networks where radiofrequency, acquisition, and valve actuation can be programmed and tuned from a central interface.…”

“…The device described here used radiofrequency (RF) pulses to transfer parahydrogen spin order; this is sometimes referred to as pulsed PHIP ( i.e . relying on RF pulses in a static magnetic field) [52, 53] versus alternative magnetic field cycling (MFC) methods [24, 37, 60]. While both methods have been shown to yield high polarizations, pulsed methods holding the sample stationary at a fixed magnetic field were pursued here rather than the alternative of either modulating the static field or moving the sample relative to the magnetic fields.…”