Selective excitation of hydrogen doubles the yield and improves the robustness of parahydrogen-induced polarization of low-γ nuclei

Schmidt, Andreas B.; Brahms, Arne; Ellermann, Frowin; Knecht, Stephan; Berner, Stephan; Hennig, Jürgen; Elverfeldt, Dominik von; Herges, Rainer; Hövener, Jan‐Bernd; Pravdivtsev, Andrey N.

doi:10.1039/d1cp04153c

Cited by 19 publications

(37 citation statements)

References 62 publications

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“…In the literature, 13 C-polarization about 20% was reported on ethyl pyruvate. Here, pH 2 was added to vinyl pyruvate at a high field and spin order was transferred to 13 C using INEPT [56]. About 20-35% 13 C-polarization was reported in a similar experiment, where pH 2 was added at a low field and the detection took place at the high field after magnetic field variation [46,57].…”

Section: Symmetry Constraintsmentioning

confidence: 79%

Symmetry Constraints on Spin Order Transfer in Parahydrogen-Induced Polarization (PHIP)

et al. 2022

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It is well known that the association of parahydrogen (pH2) with an unsaturated molecule or a transient metalorganic complex can enhance the intensity of NMR signals; the effect is known as parahydrogen-induced polarization (PHIP). During recent decades, numerous methods were proposed for converting pH2-derived nuclear spin order to the observable magnetization of protons or other nuclei of interest, usually 13C or 15N. Here, we analyze the constraints imposed by the topological symmetry of the spin systems on the amplitude of transferred polarization. We find that in asymmetric systems, heteronuclei can be polarized to 100%. However, the amplitude drops to 75% in A2BX systems and further to 50% in A3B2X systems. The latter case is of primary importance for biological applications of PHIP using sidearm hydrogenation (PHIP-SAH). If the polarization is transferred to the same type of nuclei, i.e., 1H, symmetry constraints impose significant boundaries on the spin-order distribution. For AB, A2B, A3B, A2B2, AA’(AA’) systems, the maximum average polarization for each spin is 100%, 50%, 33.3%, 25%, and 0, respectively, (where A and B (or A’) came from pH2). Remarkably, if the polarization of all spins in a molecule is summed up, the total polarization grows asymptotically with ~1.27 and can exceed 2 in the absence of symmetry constraints (where is the number of spins). We also discuss the effect of dipole–dipole-induced pH2 spin-order distribution in heterogeneous catalysis or nematic liquid crystals. Practical examples from the literature illustrate our theoretical analysis.

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Section: Symmetry Constraintsmentioning

confidence: 79%

Symmetry Constraints on Spin Order Transfer in Parahydrogen-Induced Polarization (PHIP)

et al. 2022

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“…the spin system can be reduced to two protons and one (third) nucleus of choice, e.g., 13 C using selective deuteration [26,27] or selective excitation [42,43] . Note that because of the symmetry…”

Section: Resultsmentioning

confidence: 99%

Parahydrogen-induced polarization and spin order transfer in ethyl pyruvate at high magnetic fields

Pravdivtsev

Brahms

Ellermann

et al. 2022

Preprint

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Nuclear magnetic resonance has experienced great advances with the development and translation of hyperpolarization methods into routine procedures for fundamental and clinical studies. Here, we propose the use of a wide bore NMR for the large-scale (volume- and concentration-wise) production of hyperpolarized media using parahydrogen-induced polarization. We discuss the benefits of radio frequency-induced parahydrogen spin order transfer, we show that 100% polarization is theoretically expected in homogeneous B0 and B1 magnetic fields for a three-spin system. Moreover, we estimated that the efficiency of spin order transfer is not significantly reduced when the B1 inhomogeneity is below ±5%; recommendations for the sample size and RF coils are also given. With the latest breakthrough in high yield synthesis of 1-13C-vinyl pyruvate and its deuterated isotopologues, the high-field PHIP-SAH will gain increased attention. Some remaining challenges will be addressed shortly.

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“…[31] However, the polarization yield is still lower for allyl or propargyl precursors than for vinyl precursors. [31,36] The transfer of pH 2 -derived spin order into the polarization of a third nucleus is most efficient if there are no other nuclei interacting with pH 2 , [21,37] or if the interactions can be canceled. [38] In these cases, the spin system is effectively a three spin-1 = 2 system, and X-nuclei polarization of 100 % can be achieved.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of¹³C and²H Labeled Vinyl Pyruvate and Hyperpolarization of Pyruvate

Brahms

Pravdivtsev

Stamp

et al. 2022

Chemistry A European J

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The hyperpolarization of nuclear spins has enabled unique applications in chemistry, biophysics, and particularly metabolic imaging. Parahydrogen-induced polarization (PHIP) offers a fast and cost-efficient way of hyperpolarization. Nevertheless, PHIP lags behind dynamic nuclear polarization (DNP), which is already being evaluated in clinical studies. This shortcoming is mainly due to problems in the synthesis of the corresponding PHIP precursor molecules. The most widely used DNP tracer in clinical studies, particularly for the detection of prostate cancer, is 1-13 C-pyruvate. The ideal derivative for PHIP is the deuterated vinyl ester because the spin physics allows for 100 % polarization. Unfortunately, there is no efficient synthesis for vinyl esters of β-ketocarboxylic acids in general and pyruvate in particular. Here, we present an efficient new method for the preparation of vinyl esters, including 13 C labeled, fully deuterated vinyl pyruvate using a palladium-catalyzed procedure. Using 50 % enriched parahydrogen and mild reaction conditions, a 13 C polarization of 12 % was readily achieved; 36 % are expected with 100 % pH 2 . Higher polarization values can be potentially achieved with optimized reaction conditions.

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Selective excitation of hydrogen doubles the yield and improves the robustness of parahydrogen-induced polarization of low-γ nuclei

Abstract: We describe a new method for pulsed spin order transfer of parahydrogen-induced polarization (PHIP) that enables high polarization in incompletely 2H-labeled molecules by exciting only the desired protons in a frequency-selective manner.

Cited by 19 publications

References 62 publications

Symmetry Constraints on Spin Order Transfer in Parahydrogen-Induced Polarization (PHIP)

Symmetry Constraints on Spin Order Transfer in Parahydrogen-Induced Polarization (PHIP)

Parahydrogen-induced polarization and spin order transfer in ethyl pyruvate at high magnetic fields

Synthesis of¹³C and²H Labeled Vinyl Pyruvate and Hyperpolarization of Pyruvate

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Selective excitation of hydrogen doubles the yield and improves the robustness of parahydrogen-induced polarization of low-γ nuclei

Abstract: We describe a new method for pulsed spin order transfer of parahydrogen-induced polarization (PHIP) that enables high polarization in incompletely 2H-labeled molecules by exciting only the desired protons in a frequency-selective manner.

Cited by 19 publications

References 62 publications

Symmetry Constraints on Spin Order Transfer in Parahydrogen-Induced Polarization (PHIP)

Symmetry Constraints on Spin Order Transfer in Parahydrogen-Induced Polarization (PHIP)

Parahydrogen-induced polarization and spin order transfer in ethyl pyruvate at high magnetic fields

Synthesis of13C and2H Labeled Vinyl Pyruvate and Hyperpolarization of Pyruvate

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Synthesis of¹³C and²H Labeled Vinyl Pyruvate and Hyperpolarization of Pyruvate