Propane- d6 Heterogeneously Hyperpolarized by Parahydrogen

Abstract

Long-lived spin states of hyperpolarized propane-d₆ gas were demonstrated following pairwise addition of parahydrogen gas to propene-d₆ using heterogeneous parahydrogen-induced polarization (HET-PHIP). Hyperpolarized molecules were synthesized using Rh/TiO₂ solid catalyst with 1.6 nm Rh nanoparticles. Hyperpolarized (P_H ∼ 1%) propane-d₆ was detected at high magnetic field (9.4 T) spectroscopically and by high-resolution 3D gradient-echo MRI (4.7 T) as the gas flowed through the radiofrequency coil with a spatial and temporal resolution of 0.5 × 0.5 × 0.5 mm³ and 17.7 s, respectively. Stopped-flow hyperpolarized propane-d₆ gas was also detected at 0.0475 T with an observed nuclear spin polarization of P_H ∼ 0.1% and a relatively long lifetime with T_1,eff = 6.0 ± 0.3 s. Importantly, it was shown that the hyperpolarized protons of the deuterated product obtained via pairwise parahydrogen addition could be detected directly at low magnetic field. Importantly, the relatively long low-field T_1,eff of HP propane-d₆ gas is not susceptible to paramagnetic impurities as tested by exposure to ∼0.2 atm oxygen. This long lifetime and nontoxic nature of propane gas could be useful for bioimaging applications including potentially pulmonary low-field MRI. The feasibility of high-resolution low-field 2D gradient-echo MRI was demonstrated with 0.88 × 0.88 mm² spatial and ∼0.7 s temporal resolution, respectively, at 0.0475 T.

Figure 1

ALTADENA single-scan NMR spectroscopy of HP propane-d₆ with detection at 9.4 T: (a) experimental setup diagram, (b) the diagram of pairwise addition of p-H₂ (shown as H_A – H_B) to propene-d₆ resulting in propane-d₆, (c) T₁ measurements for thermally polarized propane-d₆ by the inversion–recovery method at 9.4 T, (d) ALTADENA spectrum of HP propane-d₆ with ε(app,flow) = 100 ± 5 with respect to the spectrum (e) of stopped thermally polarized propane-d₆ gas, where unequal thermal resonances for CHD and CD₂H protons are formed due to fast H–D exchange reaction over the metal surface of heterogeneous catalyst, and (f) 32-scan spectrum of thermally polarized propene-d₆ gas showing residual ¹H proton signals in propene-d₆ groups.

Figure 2

High-resolution 3D gradient echo (GRE) MRI at 4.7 T. (a) 3D MRI of flowing ∼20 mM HP propane gas with 0.5 × 0.5 × 0.5 mm³ spatial and 17.7 s temporal resolution with 32 × 32 × 32 mm³ field of view. (b) The corresponding image of still thermally polarized 55 M tap water and (c) photograph of spiral phantom used for MRI imaging studies shown in (a) and (b). Signal-to-noise ratio (SNR) values are provided for representative voxels marked with white asterisk (*).

Figure 3

PASADENA NMR spectroscopy of HP propane-d₆ with detection at 9.4 T: (a) experimental setup diagram, (b) PASADENA spectrum (8 averages) of HP propane-d₆, and (c) 32-scan spectrum of thermally polarized propane-d₆ gas. The inset scheme shows pairwise addition of p-H₂ (shown as H_A – H_B) to propene-d₆ resulting in propane-d₆.

Figure 4

Reaction mechanism of pairwise addition of p-H₂ to propene-d₆ and dehydrogenation leading to the observation of PASADENA signals in partially deuterated propenes: (a) pathways of hydrogenation/dehydrogenation reactions leading to incorporation of p-H₂ (shown as H_A – H_B) into partially deuterated propenes and (b) scaled (×25) spectrum shown in Figure 3b.

Figure 5

Stopped-flow NMR spectroscopy of hyperpolarized propane-d₆ gas at 0.0475 T. (a) Experimental setup diagram and (b) (left) single-scan NMR spectrum of HP propane-d₆ after pairwise addition of p-H₂ to propene-d₆ in Earth magnetic field. The inset shows the decay of HP signal measured with a small-angle RF excitation pulse (α = 7°); (middle) the corresponding spectrum of thermally polarized water, and (right) the corresponding spectrum of HP propane. It should be noted that the effect of 7° RF excitation pulse on magnetization is negligible (>99% of residual polarization is retained after each RF pulse) conveniently allowing in situ direct monitoring of exponential signal decay, i.e., T₁ measurement.^,,

Figure 6

Calculated ¹H NMR spectra of HP propane and its isotopomers after pairwise addition of p-H₂ to corresponding propenes in a chemical reaction performed at 0.0475 T magnetic field. (a) The spectrum calculated for propane-d₆. (b) The weighted sum of the spectra of propane and [3-¹³C]propane (it is assumed that the two hydrogen atoms inherited from p-H₂ are in positions 1 and 2 in the propane molecule). The contribution of [3-¹³C]propane was multiplied by 0.011 to take into account ¹³C natural abundance. Note the different vertical scales for the two spectra.

Figure 7

Subsecond single-average nonslice-selective 2D MRI of 150 mM HP propane-d₆ (∼2 mL volume) at 0.0475 T with 0.88 × 0.88 mm² spatial and ∼0.7 s temporal resolution with 28 × 28 mm² field of view. The same batch of HP propane was used for subsequent 2D MRI scans every 3 s. Note that propane-d₆ images are more intense in the center due to greater sample depth in the center of the phantom variable cylindrical shape. The image on the right shows the corresponding 2D image (8 averages) of 55 M thermally polarized water (∼2.8 mL volume).