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1. Parahydrogen-Based Hyperpolarization for the Masses at Millitesla Fields

   https://doi.org/10.3390/magnetochemistry11090080  

   Wibbels, Garrett L; Oladun, Clementinah; O’Hara, Tanner Y; Adelabu, Isaiah; Robinson, Joshua E; Ahmed, Firoz; Bender, Zachary T; Samoilenko, Anna; Gyesi, Joseph; Kovtunova, Larisa M; et al (September 2025, Magnetochemistry)

   Hyperpolarization (HP) techniques, such as Parahydrogen-Induced Polarization (PHIP), Signal Amplification by Reversible Exchange (SABRE), and dissolution Dynamic Nuclear Polarization (d-DNP), significantly enhance the sensitivity of nuclear magnetic resonance (NMR) spectroscopy for chemical analysis and metabolic imaging. However, the high cost of equipment, ranging from tens of thousands to millions of dollars, limits accessibility of hyperpolarization for the broad scientific community. In this work, we aim to mitigate some of the challenges by developing a cost-effective solution for parahydrogen (pH2)-based PHIP and SABRE HP methods. A custom coil-winding machine was designed to fabricate solenoid magnet coils, which were then evaluated for their magnetic field profiles, demonstrating a high degree of magnetic field homogeneity. A model 1H SABRE experiment successfully implemented the constructed solenoid, achieving efficient hyperpolarization. Additionally, the solenoid magnet can be utilized for in situ detection of hyperpolarization when integrated with a low-field NMR spectrometer, reducing the total setup cost to a few thousand dollars. These findings suggest that our approach makes HP technology more affordable and accessible, potentially broadening its applications in chemical and biomedical research, as well as educational settings involving undergraduate student researchers. This work provides a practical pathway to lower the financial barriers associated with pH2 HP setups. 

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2. Heterogeneous hydrogenation of phenylalkynes with parahydrogen: hyperpolarization, reaction selectivity, and kinetics

   https://doi.org/10.1039/c9cp02913c  

   Pokochueva, Ekaterina V.; Kovtunov, Kirill V.; Salnikov, Oleg G.; Gemeinhardt, Max E.; Kovtunova, Larisa M.; Bukhtiyarov, Valerii I.; Chekmenev, Eduard Y.; Goodson, Boyd M.; Koptyug, Igor V. (December 2019, Physical Chemistry Chemical Physics)

   Parahydrogen-induced polarization (PHIP) is a powerful technique for studying hydrogenation reactions in gas and liquid phases. Pairwise addition of parahydrogen to the hydrogenation substrate imparts nuclear spin order to reaction products, manifested as enhanced 1 H NMR signals from the nascent proton sites. Nanoscale metal catalysts immobilized on supports comprise a promising class of catalysts for producing PHIP effects; however, on such catalysts the percentage of substrates undergoing the pairwise addition route—a necessary condition for observing PHIP—is usually low. In this paper, we present a systematic study of several metal catalysts (Rh, Pt, Pd, and Ir) supported on TiO 2 in liquid-phase hydrogenation of different prototypical phenylalkynes (phenylacetylene, 1-phenyl-1-propyne, and 3-phenyl-1-propyne) with parahydrogen. Catalyst activity and selectivity were found to be affected by both the nature of the active metal and the percentage of metal loading. It was demonstrated that the optimal catalyst for production of hyperpolarized products is Rh/TiO 2 with 4 wt% metal loading, whereas Pd/TiO 2 provided the greatest selectivity for semihydrogenation of phenylalkynes. In a study of liquid-phase hydrogenation reaction kinetics, it was shown that reaction order with respect to hydrogen is nearly the same for pairwise and non-pairwise H 2 addition—consistent with a similar nature of the catalytically active sites for these reaction pathways. 

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3. PHIP hyperpolarized [1-13C]pyruvate and [1-13C]acetate esters via PH-INEPT polarization transfer monitored by 13C NMR and MRI

   https://doi.org/10.1038/s41598-021-85136-2  

   Svyatova, Alexandra; Kozinenko, Vitaly P.; Chukanov, Nikita V.; Burueva, Dudari B.; Chekmenev, Eduard Y.; Chen, Yu-Wen; Hwang, Dennis W.; Kovtunov, Kirill V.; Koptyug, Igor V. (December 2021, Scientific Reports)

   null (Ed.)

   Abstract Parahydrogen-induced polarization of 13 C nuclei by side-arm hydrogenation (PHIP-SAH) for [1- 13 C]acetate and [1- 13 C]pyruvate esters with application of PH-INEPT-type pulse sequences for 1 H to 13 C polarization transfer is reported, and its efficiency is compared with that of polarization transfer based on magnetic field cycling (MFC). The pulse-sequence transfer approach may have its merits in some applications because the entire hyperpolarization procedure is implemented directly in an NMR or MRI instrument, whereas MFC requires a controlled field variation at low magnetic fields. Optimization of the PH-INEPT-type transfer sequences resulted in 13 C polarization values of 0.66 ± 0.04% and 0.19 ± 0.02% for allyl [1- 13 C]pyruvate and ethyl [1- 13 C]acetate, respectively, which is lower than the corresponding polarization levels obtained with MFC for 1 H to 13 C polarization transfer (3.95 ± 0.05% and 0.65 ± 0.05% for allyl [1- 13 C]pyruvate and ethyl [1- 13 C]acetate, respectively). Nevertheless, a significant 13 C NMR signal enhancement with respect to thermal polarization allowed us to perform 13 C MR imaging of both biologically relevant hyperpolarized molecules which can be used to produce useful contrast agents for the in vivo imaging applications. 

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4. Intermolecular Nuclear Spin Hyperpolarization Transfer via Cross‐Relaxation Triggers RASER of Solute Molecules

   https://doi.org/10.1002/anie.2865398  

   Trofimov, Ivan A; Yi, Anna P; Salnikov, Oleg G; Pravdivtsev, Andrey N; de_Maissin, Henri; Chekmenev, Eduard Y; Hövener, Jan‐Bernd; Schmidt, Andreas B; Koptyug, Igor V (May 2026, Angewandte Chemie International Edition)

   Radiofrequency amplification by stimulated emission of radiation (RASER) is a phenomenon that is observed in systems of nuclear spins with strong inverse polarization beyond the thermal equilibrium. RASER is of fundamental interest and also possesses several features of possible practical importance, such as very narrow NMR lines and background‐free detection. However, so far, the effect was limited to molecules directly polarized by corresponding hyperpolarization techniques. In this work, we found that strongly hyperpolarized allylic compounds transferred polarization via nuclear Overhauser effect (NOE) to other solutes, triggering their RASER. In stark contrast to previous observations, the parahydrogen addition and intermolecular NOE transfer engendered RASER (PAINTER) does not require direct hyperpolarization of the target molecule. This way polarized and detected solutes had 10–20 times narrower lines compared to their classical NMR spectra, providing a useful analysis tool for various molecules beyond standard NMR limitations. 

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5. High‐Efficiency Trifluoromethyl‐Methionine Incorporation into Cyclophilin A by Cell‐Free Synthesis for ¹⁹ F NMR Studies

   https://doi.org/10.1002/anie.202419709  

   Zhu, Wenkai; Monnie, Christina M; Kitoka, Kristīne; Gronenborn, Angela M (February 2025, Angewandte Chemie International Edition)

   Abstract Fluorine‐19 NMR spectroscopy has emerged as a powerful tool for studying protein structure, dynamics, and interactions. Of particular interest is the exploitation of trifluoromethyl (tfm) groups, given their high sensitivity and superior transverse relaxation properties, compared to single fluorine atoms. However, biosynthetic incorporation of tfm‐bearing amino acids remains challenging due to cytotoxicity and incompatibility with natural tRNA synthetases. Here, we report on overcoming this challenge using cell‐free synthesis, incorporating trifluoromethyl‐methionine (tfmM) into the protein Cyclophilin A (CypA) with remarkably high efficiency, impossible via biosynthetic means. Importantly, we demonstrate that tfmM CypA binds a native substrate, the N‐terminal domain of HIV‐1 capsid protein (HIV‐1 CA‐NTD), and retains peptidyl prolylcis/transisomerase activity. It also binds the peptide inhibitor Cyclosporine A (CsA) with the same affinity as non‐labeled, wild‐type CypA. Furthermore, we show that¹⁹F isotope shifts and¹⁹F solvent paramagnetic relaxation enhancements (PREs) provide valuable structural information on surface exposure. Taken together, our study illustrates that tfmM can be readily incorporated into proteins at very high levels by cell‐free synthesis without disturbing protein structure and function, significantly expanding the scope of¹⁹F NMR spectroscopy for studying protein structure and dynamics. 

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