@article{kempf_koerber_plaumann_pravdivtsev_engelmann_boldt_scheffler_theis_buckenmaier_2024, title={13C MRI of hyperpolarized pyruvate at 120 μT}, volume={14}, ISSN={["2045-2322"]}, url={http://dx.doi.org/10.1038/s41598-024-54770-x}, DOI={10.1038/s41598-024-54770-x}, abstractNote={Abstract}, number={1}, journal={SCIENTIFIC REPORTS}, author={Kempf, Nicolas and Koerber, Rainer and Plaumann, Markus and Pravdivtsev, Andrey N. and Engelmann, Joern and Boldt, Johannes and Scheffler, Klaus and Theis, Thomas and Buckenmaier, Kai}, year={2024}, month={Feb} }
@article{nantogma_maissin_adelabu_abdurraheem_nelson_chukanov_salnikov_koptyug_lehmkuhl_schmidt_et al._2024, title={Carbon-13 Radiofrequency Amplification by Stimulated Emission of Radiation of the Hyperpolarized Ketone and Hemiketal Forms of Allyl [1-13C]Pyruvate}, volume={1}, ISSN={["2379-3694"]}, url={http://dx.doi.org/10.1021/acssensors.3c02075}, DOI={10.1021/acssensors.3c02075}, abstractNote={13C hyperpolarized pyruvate is an emerging MRI contrast agent for sensing molecular events in cancer and other diseases with aberrant metabolic pathways. This metabolic contrast agent can be produced via several hyperpolarization techniques. Despite remarkable success in research settings, widespread clinical adoption faces substantial roadblocks because the current sensing technology utilized to sense this contrast agent requires the excitation of 13C nuclear spins that also need to be synchronized with MRI field gradient pulses. Here, we demonstrate sensing of hyperpolarized allyl [1-13C]pyruvate via the stimulated emission of radiation that mitigates the requirements currently blocking broader adoption. Specifically, 13C Radiofrequency Amplification by Stimulated Emission of Radiation (13C RASER) was obtained after pairwise addition of parahydrogen to a pyruvate precursor, detected in a commercial inductive detector with a quality factor (Q) of 32 for sample concentrations as low as 0.125 M with 13C polarization of 4%. Moreover, parahydrogen-induced polarization allowed for the preparation of a mixture of ketone and hemiketal forms of hyperpolarized allyl [1-13C]pyruvate, which are separated by 10 ppm in 13C NMR spectra. This is a good model system to study the simultaneous 13C RASER signals of multiple 13C species. This system models the metabolic production of hyperpolarized [1-13C]lactate from hyperpolarized [1-13C]pyruvate, which has a similar chemical shift difference. Our results show that 13C RASER signals can be obtained from both species simultaneously when the emission threshold is exceeded for both species. On the other hand, when the emission threshold is exceeded only for one of the hyperpolarized species, 13C stimulated emission is confined to this species only, therefore enabling the background-free detection of individual hyperpolarized 13C signals. The reported results pave the way to novel sensing approaches of 13C hyperpolarized pyruvate, potentially unlocking hyperpolarized 13C MRI on virtually any MRI system─an attractive vision for the future molecular imaging and diagnostics.}, journal={ACS SENSORS}, author={Nantogma, Shiraz and Maissin, Henri and Adelabu, Isaiah and Abdurraheem, Abubakar and Nelson, Christopher and Chukanov, Nikita V. and Salnikov, Oleg G. and Koptyug, Igor V. and Lehmkuhl, Soren and Schmidt, Andreas B. and et al.}, year={2024}, month={Jan} }
@article{schmidt_adelabu_nelson_nantogma_kiselev_zaitsev_abdurraheem_maissin_rosen_lehmkuhl_et al._2023, title={C-13 Radiofrequency Amplification by Stimulated Emission of Radiation Threshold Sensing of Chemical Reactions}, volume={145}, ISSN={["1520-5126"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85160017400&partnerID=MN8TOARS}, DOI={10.1021/jacs.3c00776}, abstractNote={Conventional nuclear magnetic resonance (NMR) enables detection of chemicals and their transformations by exciting nuclear spin ensembles with a radio-frequency pulse followed by detection of the precessing spins at their characteristic frequencies. The detected frequencies report on chemical reactions in real time and the signal amplitudes scale with concentrations of products and reactants. Here, we employ Radiofrequency Amplification by Stimulated Emission of Radiation (RASER), a quantum phenomenon producing coherent emission of 13C signals, to detect chemical transformations. The 13C signals are emitted by the negatively hyperpolarized biomolecules without external radio frequency pulses and without any background signal from other, nonhyperpolarized spins in the ensemble. Here, we studied the hydrolysis of hyperpolarized ethyl-[1-13C]acetate to hyperpolarized [1-13C]acetate, which was analyzed as a model system by conventional NMR and 13C RASER. The chemical transformation of 13C RASER-active species leads to complete and abrupt disappearance of reactant signals and delayed, abrupt reappearance of a frequency-shifted RASER signal without destroying 13C polarization. The experimentally observed "quantum" RASER threshold is supported by simulations.}, number={20}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Schmidt, Andreas B. and Adelabu, Isaiah and Nelson, Christopher and Nantogma, Shiraz and Kiselev, Valerij G. and Zaitsev, Maxim and Abdurraheem, Abubakar and Maissin, Henri and Rosen, Matthew S. and Lehmkuhl, Soren and et al.}, year={2023}, month={May}, pages={11121–11129} }
@article{mandzhieva_adelabu_nantogma_chekmenev_theis_2023, title={Delivering Robust Proton-Only Sensing of Hyperpolarized [1,2-13C2]-Pyruvate Using Broad-Spectral-Range Nuclear Magnetic Resonance Pulse Sequences}, volume={8}, ISSN={["2379-3694"]}, url={https://doi.org/10.1021/acssensors.3c01296}, DOI={10.1021/acssensors.3c01296}, abstractNote={Hyperpolarized [1-13C]pyruvate is the leading hyperpolarized injectable contrast agent and is currently under evaluation in clinical trials for molecular imaging of metabolic diseases, including cardiovascular disease and cancer. One aspect limiting broad scalability of the technique is that hyperpolarized 13C MRI requires specialized 13C hardware and software that are not generally available on clinical MRI scanners, which employ proton-only detection. Here, we present an approach that uses pulse sequences to transfer 13C hyperpolarization to methyl protons for detection of the 13C-13C pyruvate singlet, employing proton-only excitation and detection only. The new pulse sequences are robust to the B1 and B0 magnetic field inhomogeneities. The work focuses on singlet-to-magnetization (S2M) and rotor-synchronized (R) pulses, both relying on trains of hard pulses with broad spectral width coverage designed to effectively transform hyperpolarized 13C2-singlet hyperpolarization to 1H polarization on the CH3 group of [1,2-13C2]pyruvate. This approach may enable a broader adoption of hyperpolarized MRI as a molecular imaging technique.}, number={11}, journal={ACS SENSORS}, author={Mandzhieva, Iuliia and Adelabu, Isaiah and Nantogma, Shiraz and Chekmenev, Eduard Y. and Theis, Thomas}, year={2023}, month={Nov}, pages={4101–4110} }
@article{adelabu_chowdhury_nantogma_oladun_ahmed_stilgenbauer_sadagurski_theis_goodson_chekmenev_2023, title={Efficient SABRE-SHEATH Hyperpolarization of Potent Branched-Chain-Amino-Acid Metabolic Probe [1-C-13]ketoisocaproate}, volume={13}, ISSN={["2218-1989"]}, url={https://doi.org/10.3390/metabo13020200}, DOI={10.3390/metabo13020200}, abstractNote={Efficient 13C hyperpolarization of ketoisocaproate is demonstrated in natural isotopic abundance and [1-13C]enriched forms via SABRE-SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). Parahydrogen, as the source of nuclear spin order, and ketoisocaproate undergo simultaneous chemical exchange with an Ir-IMes-based hexacoordinate complex in CD3OD. SABRE-SHEATH enables spontaneous polarization transfer from parahydrogen-derived hydrides to the 13C nucleus of transiently bound ketoisocaproate. 13C polarization values of up to 18% are achieved at the 1-13C site in 1 min in the liquid state at 30 mM substrate concentration. The efficient polarization build-up becomes possible due to favorable relaxation dynamics. Specifically, the exponential build-up time constant (14.3 ± 0.6 s) is substantially lower than the corresponding polarization decay time constant (22.8 ± 1.2 s) at the optimum polarization transfer field (0.4 microtesla) and temperature (10 °C). The experiments with natural abundance ketoisocaproate revealed polarization level on the 13C-2 site of less than 1%—i.e., one order of magnitude lower than that of the 1-13C site—which is only partially due to more-efficient relaxation dynamics in sub-microtesla fields. We rationalize the overall much lower 13C-2 polarization efficiency in part by less favorable catalyst-binding dynamics of the C-2 site. Pilot SABRE experiments at pH 4.0 (acidified sample) versus pH 6.1 (unaltered sodium [1-13C]ketoisocaproate) reveal substantial modulation of SABRE-SHEATH processes by pH, warranting future systematic pH titration studies of ketoisocaproate, as well as other structurally similar ketocarboxylate motifs including pyruvate and alpha-ketoglutarate, with the overarching goal of maximizing 13C polarization levels in these potent molecular probes. Finally, we also report on the pilot post-mortem use of HP [1-13C]ketoisocaproate in a euthanized mouse, demonstrating that SABRE-hyperpolarized 13C contrast agents hold promise for future metabolic studies.}, number={2}, journal={METABOLITES}, author={Adelabu, Isaiah and Chowdhury, Md Raduanul H. and Nantogma, Shiraz and Oladun, Clementinah and Ahmed, Firoz and Stilgenbauer, Lukas and Sadagurski, Marianna and Theis, Thomas and Goodson, Boyd M. and Chekmenev, Eduard Y.}, year={2023}, month={Feb} }
@article{lohmann_lehmkuhl_fleischer_rosen_chekmenev_theis_adams_appelt_2023, title={Exploring synchrony and chaos of parahydrogen-pumped two-compartment radio-frequency amplification by stimulated emission of radiation}, volume={108}, ISSN={["2469-9934"]}, url={https://doi.org/10.1103/PhysRevA.108.022806}, DOI={10.1103/PhysRevA.108.022806}, abstractNote={A nuclear-spin-based RASER (radio-frequency amplification by stimulated emission of radiation) is an ideal experimental system to explore nonlinear interaction phenomena of nuclear spins coupled via virtual photons to a resonator. This is due to the RASER being stable for several hours, allowing for extended observation of these phenomena. Nonlinear phenomena in multimode RASERs range from mode oscillations in synchrony, frequency shifts, frequency combs, period doublings, and even chaos. These phenomena are observed in a parahydrogen-pumped two-compartment proton RASER. In two independently pumped compartments, the separation in frequency space between the two RASER modes is precisely controlled with a magnetic field gradient. By controlling the mode separation, we can select the type of nonlinear phenomena observed. A key finding is that the ranges of mode separation where chaos and synchrony occur are very close together. The experimental results are supported by numerical simulations, based on two-mode RASER equations.}, number={2}, journal={PHYSICAL REVIEW A}, author={Lohmann, Lars and Lehmkuhl, Soeren and Fleischer, Simon and Rosen, Matthew S. and Chekmenev, Eduard Y. and Theis, Thomas and Adams, Alina and Appelt, Stephan}, year={2023}, month={Aug} }
@article{browning_macculloch_bedoya_dedesma_goodson_rosen_chekmenev_yen_tomhon_theis_2023, title={Facile hyperpolarization chemistry for molecular imaging and metabolic tracking of [1-13C]pyruvate in vivo}, url={https://doi.org/10.26434/chemrxiv-2023-4dqkx}, DOI={10.26434/chemrxiv-2023-4dqkx}, abstractNote={Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe the first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1-13C]pyruvate. A biocompatible formulation of hyperpolarized [1-13C]pyruvate was injected into healthy Sprague Dawley and Wistar rats, and metabolic conversion of pyruvate to lactate, alanine, pyruvate-hydrate, and bicarbonate was detected. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop scalable, next-generation molecular imaging.}, journal={ChemRxiv}, author={Browning, Austin and MacCulloch, Keilian and Bedoya, David Guarin and Dedesma, Carlos and Goodson, Boyd M and Rosen, Matthew S and Chekmenev, Eduard Y and Yen, Yi-Fen and TomHon, Patrick and Theis, Thomas}, year={2023}, month={Mar} }
@article{macculloch_browning_bedoya_mcbride_abdulmojeed_dedesma_goodson_rosen_chekmenev_yen_et al._2023, title={Facile hyperpolarization chemistry for molecular imaging and metabolic tracking of [1-13C]pyruvate in vivo}, volume={16-17}, ISSN={["2666-4410"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85168097895&partnerID=MN8TOARS}, DOI={10.1016/j.jmro.2023.100129}, abstractNote={Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe a first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1-13C]pyruvate. Biocompatible formulations of hyperpolarized [1-13C]pyruvate in, both, methanol-water mixtures, and ethanol-water mixtures followed by dilution with saline and catalyst filtration were prepared and injected into healthy Sprague Dawley and Wistar rats. Effective hyperpolarization-catalyst removal was performed with silica filters without major losses in hyperpolarization. Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate was detected in vivo. Pyruvate-hydrate was also observed as minor byproduct. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop safe, and scalable molecular imaging.}, journal={JOURNAL OF MAGNETIC RESONANCE OPEN}, author={Macculloch, Keilian and Browning, Austin and Bedoya, David O. Guarin and Mcbride, Stephen J. and Abdulmojeed, Mustapha B. and Dedesma, Carlos and Goodson, Boyd M. and Rosen, Matthew S. and Chekmenev, Eduard Y. and Yen, Yi-Fen and et al.}, year={2023}, month={Dec} }
@article{macculloch_browning_guarin bedoya_mcbride_abdulmojeed_dedesma_goodson_rosen_chekmenev_yen_et al._2023, title={Facile hyperpolarization chemistry for molecular imaging and metabolic tracking of [1-13C]pyruvate in vivo}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85164574839&partnerID=MN8TOARS}, DOI={10.2139/ssrn.4504262}, abstractNote={Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe a first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1-13C]pyruvate. Biocompatible formulations of hyperpolarized [1-13C]pyruvate in, both, methanol-water mixtures, and ethanol-water mixtures followed by dilution with saline and catalyst filtration were prepared and injected into healthy Sprague Dawley and Wistar rats. Effective hyperpolarization-catalyst removal was performed with silica filters without major losses in hyperpolarization. Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate was detected in vivo. Pyruvate-hydrate was also observed as minor byproduct. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop safe, and scalable molecular imaging.}, journal={SSRN}, author={MacCulloch, K. and Browning, A. and Guarin Bedoya, D.O. and McBride, S.J. and Abdulmojeed, M.B. and Dedesma, C. and Goodson, B.M. and Rosen, M.S. and Chekmenev, E.Y. and Yen, Y.-F. and et al.}, year={2023} }
@article{nelson_schmidt_adelabu_nantogma_kiselev_abdurraheem_maissin_lehmkuhl_appelt_theis_et al._2023, title={Innentitelbild: Parahydrogen‐Induced Carbon‐13 Radiofrequency Amplification by Stimulated Emission of Radiation (Angew. Chem. 5/2023)}, url={https://doi.org/10.1002/ange.202218484}, DOI={10.1002/ange.202218484}, abstractNote={Carbon-13 radiofrequency amplification by stimulated emission of radiation (C-13 RASER) is demonstrated on a bolus of liquid hyperpolarized ethyl [1-13C]acetate, as reported by Thomas Theis, Eduard Y. Chekmenev et al. in their Communication (e202215678). Spontaneous RASER signal emissions were detected using a 1.4 T NMR spectrometer equipped with a standard radiofrequency detection coil for over three minutes. RASER detection enables new detection schemes for 13C-hyperpolarized contrast agents and particular new opportunities for next-generation molecular imaging on clinical MRI scanners.}, journal={Angewandte Chemie}, author={Nelson, Christopher and Schmidt, Andreas B. and Adelabu, Isaiah and Nantogma, Shiraz and Kiselev, Valerij G. and Abdurraheem, Abubakar and Maissin, Henri and Lehmkuhl, Sören and Appelt, Stephan and Theis, Thomas and et al.}, year={2023}, month={Jan} }
@article{nelson_schmidt_adelabu_nantogma_kiselev_abdurraheem_maissin_lehmkuhl_appelt_theis_et al._2023, title={Inside Cover: Parahydrogen‐Induced Carbon‐13 Radiofrequency Amplification by Stimulated Emission of Radiation (Angew. Chem. Int. Ed. 5/2023)}, url={https://doi.org/10.1002/anie.202218484}, DOI={10.1002/anie.202218484}, abstractNote={Carbon-13 radiofrequency amplification by stimulated emission of radiation (C-13 RASER) is demonstrated on a bolus of liquid hyperpolarized ethyl [1-13C]acetate, as reported by Thomas Theis, Eduard Y. Chekmenev et al. in their Communication (e202215678). Spontaneous RASER signal emissions were detected using a 1.4 T NMR spectrometer equipped with a standard radiofrequency detection coil for over three minutes. RASER detection enables new detection schemes for 13C-hyperpolarized contrast agents and particular new opportunities for next-generation molecular imaging on clinical MRI scanners.}, journal={Angewandte Chemie International Edition}, author={Nelson, Christopher and Schmidt, Andreas B. and Adelabu, Isaiah and Nantogma, Shiraz and Kiselev, Valerij G. and Abdurraheem, Abubakar and Maissin, Henri and Lehmkuhl, Sören and Appelt, Stephan and Theis, Thomas and et al.}, year={2023}, month={Jan} }
@article{pravdivtsev_buckenmaier_kempf_stevanato_scheffler_engelmann_plaumann_koerber_hoevener_theis_2023, title={LIGHT-SABRE Hyperpolarizes 1-13C-Pyruvate Continuously without Magnetic Field Cycling}, volume={4}, ISSN={["1932-7455"]}, url={https://doi.org/10.1021/acs.jpcc.3c01128}, DOI={10.1021/acs.jpcc.3c01128}, abstractNote={Nuclear spin hyperpolarization enables real-time observation of metabolism and intermolecular interactions in vivo. 1-13C-pyruvate is the leading hyperpolarized tracer currently under evaluation in several clinical trials as a promising molecular imaging agent. Still, the quest for a simple, fast, and efficient hyperpolarization technique is ongoing. Here, we describe that continuous, weak irradiation in the audio-frequency range of the 13C spin at the 121 μT magnetic field (approximately twice Earth’s field) enables spin order transfer from parahydrogen to 13C magnetization of 1-13C-pyruvate. These so-called LIGHT-SABRE pulses couple nuclear spin states of parahydrogen and pyruvate via the J-coupling network of reversibly exchanging Ir-complexes. Using ∼100% parahydrogen at ambient pressure, we polarized 51 mM 1-13C-pyruvate in the presence of 5.1 mM Ir-complex continuously and repeatedly to a polarization of 1.1% averaged over free and catalyst-bound pyruvate. The experiments were conducted at −8 °C, where almost exclusively bound pyruvate was observed, corresponding to an estimated 11% polarization on bound pyruvate. The obtained hyperpolarization levels closely match those obtained via SABRE-SHEATH under otherwise identical conditions. The creation of three different types of spin orders was observed: transverse 13C magnetization along the applied magnetic field, 13C z-magnetization along the main field B0, and 13C–1H zz-spin order. With a superconducting quantum interference device (SQUID) for detection, we found that the generated spin orders result from 1H–13C J-coupling interactions, which are not visible even with our narrow linewidth below 0.3 Hz and at −8 °C.}, number={14}, journal={JOURNAL OF PHYSICAL CHEMISTRY C}, author={Pravdivtsev, Andrey N. and Buckenmaier, Kai and Kempf, Nicolas and Stevanato, Gabriele and Scheffler, Klaus and Engelmann, Joern and Plaumann, Markus and Koerber, Rainer and Hoevener, Jan-Bernd and Theis, Thomas}, year={2023}, month={Apr} }
@article{pravdivtsev_buckenmaier_kempf_stevanato_scheffler_engelmann_plaumann_koerber_hövener_theis_2023, title={LIGHT-SABRE hyperpolarizes 1-13C-pyruvate continuously, without magnetic field cycling}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85149163371&partnerID=MN8TOARS}, DOI={10.48550/arXiv.2302.09299}, abstractNote={Nuclear spin hyperpolarization enables real-time observation of metabolism and intermolecular interactions in vivo. 1-13C-Pyruvate is the leading hyperpolarized tracer currently under evaluation in several clinical trials as a promising molecular imaging agent. Still, the quest for a simple, fast, and efficient hyperpolarization technique is ongoing. Here, we describe that continuous, weak irradiation in the audio-frequency range of the 13C spin at 121 {\mu}T magnetic field (\sim twiceEarth\apos s field) enables spin order transfer from parahydrogen to 13C magnetization of 1-13C-pyruvate. These so-called LIGHT-SABRE pulses couple nuclear spin states of parahydrogen and pyruvate via the J-coupling network of reversibly exchanging Ir-complexes. Using \sim 100% parahydrogen at ambient pressure, we polarized 51 mM of 1-13C-pyruvate in the presence of 5.1 mM Ir-complex continuously and repeatedly to a polarization of 1.1% averaged over free and catalyst-bound pyruvate. The experiments were conducted at -8{\deg}C), where almost exclusively bound pyruvate was observed, corresponding to an estimated 11% polarization on bound pyruvate. The obtained hyperpolarization levels closely match those obtained via SABRE-SHEATH under otherwise identical conditions. The creation of three different types of spin orders was observed: transverse 13C magnetization along the applied magnetic field, 13C z-magnetization along the main field B_0, and 13C-1H zz-spin-order. With a superconducting quantum interference device (SQUID) for detection, we found that the generated spin orders result from tiny 1H-13C J-coupling interactions, which are not visible even with our narrow linewidth below 0.3 Hz.}, journal={arXiv}, author={Pravdivtsev, A.N. and Buckenmaier, K. and Kempf, N. and Stevanato, G. and Scheffler, K. and Engelmann, J. and Plaumann, M. and Koerber, R. and Hövener, J.-B. and Theis, T.}, year={2023} }
@article{macculloch_browning_tomhon_lehmkuhl_chekmenev_theis_2023, title={Parahydrogen in Reversible Exchange Induces Long-Lived 15N Hyperpolarization of Anticancer Drugs Anastrozole and Letrozole}, volume={5}, ISSN={["1520-6882"]}, url={https://doi.org/10.1021/acs.analchem.2c04817}, DOI={10.1021/acs.analchem.2c04817}, abstractNote={Hyperpolarization modalities overcome the sensitivity limitations of NMR and unlock new applications. Signal amplification by reversible exchange (SABRE) is a particularly cheap, quick, and robust hyperpolarization modality. Here, we employ SABRE for simultaneous chemical exchange of parahydrogen and nitrile-containing anticancer drugs (letrozole or anastrozole) to enhance 15N polarization. Distinct substrates require unique optimal parameter sets, including temperature, magnetic field, or a shaped magnetic field profile. The fine tuning of these parameters for individual substrates is demonstrated here to maximize 15N polarization. After optimization, including the usage of pulsed μT fields, the 15N nuclei on common anticancer drugs, letrozole and anastrozole, can be polarized within 1-2 min. The hyperpolarization can exceed 10%, corresponding to 15N signal enhancement of over 280,000-fold at a clinically relevant magnetic field of 1 T. This sensitivity gain enables polarization studies at naturally abundant 15N enrichment level (0.4%). Moreover, the nitrile 15N sites enable long-lasting polarization storage with [15N]T1 over 9 min, enabling signal detection from a single hyperpolarization cycle for over 30 min.}, number={20}, journal={ANALYTICAL CHEMISTRY}, author={MacCulloch, Keilian and Browning, Austin and TomHon, Patrick and Lehmkuhl, Soeren and Chekmenev, Eduard Y. and Theis, Thomas}, year={2023}, month={May} }
@article{nelson_schmidt_adelabu_nantogma_kiselev_abdurraheem_maissin_lehmkuhl_appelt_theis_et al._2023, title={Parahydrogen‐Induced Carbon‐13 Radiofrequency Amplification by Stimulated Emission of Radiation}, url={https://doi.org/10.1002/ange.202215678}, DOI={10.1002/ange.202215678}, abstractNote={Abstract}, journal={Angewandte Chemie}, author={Nelson, Christopher and Schmidt, Andreas B. and Adelabu, Isaiah and Nantogma, Shiraz and Kiselev, Valerij G. and Abdurraheem, Abubakar and Maissin, Henri and Lehmkuhl, Sören and Appelt, Stephan and Theis, Thomas and et al.}, year={2023}, month={Jan} }
@article{duchowny_denninger_lohmann_theis_lehmkuhl_adams_2023, title={SABRE Hyperpolarization with up to 200 bar Parahydrogen in Standard and Quickly Removable Solvents}, volume={24}, ISSN={["1422-0067"]}, url={https://doi.org/10.3390/ijms24032465}, DOI={10.3390/ijms24032465}, abstractNote={Parahydrogen (p-H2)-based techniques are known to drastically enhance NMR signals but are usually limited by p-H2 supply. This work reports p-H2-based SABRE hyperpolarization at p-H2 pressures of hundreds of bar, far beyond the typical ten bar currently reported in the literature. A recently designed high-pressure setup was utilized to compress p-H2 gas up to 200 bar. The measurements were conducted using a sapphire high-pressure NMR tube and a 43 MHz benchtop NMR spectrometer. In standard methanol solutions, it could be shown that the signal intensities increased with pressure until they eventually reached a plateau. A polarization of about 2%, equal to a molar polarization of 1.2 mmol L−1, could be achieved for the sample with the highest substrate concentration. While the signal plateaued, the H2 solubility increased linearly with pressure from 1 to 200 bar, indicating that p-H2 availability is not the limiting factor in signal enhancement beyond a certain pressure, depending on sample composition. Furthermore, the possibility of using liquefied ethane and compressed CO2 as removable solvents for hyperpolarization was demonstrated. The use of high pressures together with quickly removable organic/non-organic solvents represents an important breakthrough in the field of hyperpolarization, advancing SABRE as a promising tool for materials science, biophysics, and molecular imaging.}, number={3}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Duchowny, Anton and Denninger, Johannes and Lohmann, Lars and Theis, Thomas and Lehmkuhl, Soeren and Adams, Alina}, year={2023}, month={Feb} }
@article{browning_macculloch_tomhon_mandzhieva_chekmenev_goodson_lehmkuhl_theis_2023, title={Spin dynamics of [1,2-C-13(2)]pyruvate hyperpolarization by parahydrogen in reversible exchange at micro Tesla fields}, volume={25}, ISSN={["1463-9084"]}, url={https://doi.org/10.1039/D3CP00843F}, DOI={10.1039/D3CP00843F}, abstractNote={The spin dynamics during SABRE of [1,2-13C2]pyruvate are detailed. An analytical model and numerical simulations are used to understand the selective formation of hyperpolarized magnetization or singlet order on the 13C2-spin pair.}, number={24}, journal={PHYSICAL CHEMISTRY CHEMICAL PHYSICS}, author={Browning, Austin and Macculloch, Keilian and TomHon, Patrick and Mandzhieva, Iuliia and Chekmenev, Eduard Y. and Goodson, Boyd M. and Lehmkuhl, Soeren and Theis, Thomas}, year={2023}, month={Jun}, pages={16446–16458} }
@article{schmidt_maissin_adelabu_nantogma_ettedgui_tomhon_goodson_theis_chekmenev_2022, title={Catalyst-Free Aqueous Hyperpolarized [1-13C]Pyruvate Obtained by Re-Dissolution Signal Amplification by Reversible Exchange}, volume={11}, ISSN={["2379-3694"]}, url={https://doi.org/10.1021/acssensors.2c01715}, DOI={10.1021/acssensors.2c01715}, abstractNote={Despite great successes in oncology, patient outcomes are often still discouraging, and hence the diagnostic imaging paradigm is increasingly shifting toward functional imaging of the pathology to better understand individual disease biology and to personalize therapies. The dissolution Dynamic Nuclear Polarization (d-DNP) hyperpolarization method has enabled unprecedented real-time MRI sensing of metabolism and tissue pH using hyperpolarized [1-13C]pyruvate as a biosensor with great potential for diagnosis and monitoring of cancer patients. However, current d-DNP is expensive and suffers from long hyperpolarization times, posing a substantial translational roadblock. Here, we report the development of Re-Dissolution Signal Amplification By Reversible Exchange (Re-D SABRE), which relies on fast and low-cost hyperpolarization of [1-13C]pyruvate by chemical exchange with parahydrogen at microtesla magnetic fields. [1-13C]pyruvate is precipitated from catalyst-containing methanol using ethyl acetate and rapidly reconstituted in aqueous media. 13C polarization of 9 ± 1% is demonstrated after redissolution in water with residual iridium mass fraction of 8.5 ± 1.5 ppm; further improvement is anticipated via process automation. Re-D SABRE makes hyperpolarized [1-13C]pyruvate biosensor available at a fraction of the cost (<$10,000) and production time (≈1 min) of currently used techniques and makes aqueous hyperpolarized [1-13C]pyruvate "ready" for in vivo applications.}, number={11}, journal={ACS SENSORS}, author={Schmidt, Andreas B. and Maissin, Henri and Adelabu, Isaiah and Nantogma, Shiraz and Ettedgui, Jessica and TomHon, Patrick and Goodson, Boyd M. and Theis, Thomas and Chekmenev, Eduard Y.}, year={2022}, month={Nov} }
@article{schmidt_bowers_buckenmaier_chekmenev_maissin_eills_ellermann_gloeggler_gordon_knecht_et al._2022, title={Instrumentation for Hydrogenative Parahydrogen-Based Hyperpolarization Techniques}, volume={1}, ISSN={["1520-6882"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85123603684&partnerID=MN8TOARS}, DOI={10.1021/acs.analchem.1c04863}, abstractNote={■ CONTENTS Analysis of pH2 Polarizers B Parahydrogen Addition B Spin-Order Transfer C Purification and Quality Assurance C Components and Capabilities of a Polarizer C Review of Published Instruments D Parahydrogen Generators D Spin Order Transfer (SOT) E SOT Conditions E SOT at Millitesla Fields G SOT Conditions G Published Setups G Challenges H SOT at Ultralow Fields (ULF) I SOT Conditions I Published Setups I Challenges I Magnetic Field Cycling (MFC) I SOT Conditions I Published Setups J Challenges L PHIP of Gases L Published Setups L Challenges M Purification M Catalyst Scavenging M Liquid−Liquid Phase Separation O Heterogeneous Catalysts O Precipitation P Other Promising Developments P PHIP-on-a-Chip P Radio Amplification by Stimulated Emission of Radiation (RASER) P PHIP-X P Toward Clinical Application P Conclusions Q Author Information Q Corresponding Authors Q Authors Q Author Contributions R Notes R Biographies R Acknowledgments S References T}, number={1}, journal={ANALYTICAL CHEMISTRY}, author={Schmidt, Andreas B. and Bowers, C. Russell and Buckenmaier, Kai and Chekmenev, Eduard Y. and Maissin, Henri and Eills, James and Ellermann, Frowin and Gloeggler, Stefan and Gordon, Jeremy W. and Knecht, Stephan and et al.}, year={2022}, month={Jan} }
@article{nantogma_eriksson_adelabu_mandzhieva_browning_tomhon_warren_theis_goodson_chekmenev_2022, title={Interplay of Near-Zero-Field Dephasing, Rephasing, and Relaxation Dynamics and [1-C-13]Pyruvate Polarization Transfer Efficiency in Pulsed SABRE-SHEATH}, volume={11}, ISSN={["1520-5215"]}, url={https://doi.org/10.1021/acs.jpca.2c07150}, DOI={10.1021/acs.jpca.2c07150}, abstractNote={Hyperpolarized [1-13C]pyruvate is a revolutionary molecular probe enabling ultrafast metabolic MRI scans in 1 min. This technology is now under evaluation in over 30 clinical trials, which employ dissolution Dynamic Nuclear Polarization (d-DNP) to prepare a batch of the contrast agent; however, d-DNP technology is slow and expensive. The emerging SABRE-SHEATH hyperpolarization technique enables fast (under 1 min) and robust production of hyperpolarized [1-13C]pyruvate via simultaneous chemical exchange of parahydrogen and pyruvate on IrIMes hexacoordinate complexes. Here, we study the application of microtesla pulses to investigate their effect on C-13 polarization efficiency, compared to that of conventional SABRE-SHEATH employing a static field (∼0.4 μT), to provide the matching conditions of polarization transfer from parahydrogen-derived hydrides to the 13C-1 nucleus. Our results demonstrate that using square-microtesla pulses with optimized parameters can produce 13C-1 polarization levels of up to 14.8% (when detected, averaging over all resonances), corresponding to signal enhancement by over 122,000-fold at the clinically relevant field of 1.4 T. We anticipate that our results can be directly translated to other structurally similar biomolecules such as [1-13C]α-ketoglutarate and [1-13C]α-ketoisocaproate. Moreover, other more advanced pulse shapes can potentially further boost heteronuclear polarization attainable via pulsed SABRE-SHEATH.}, number={48}, journal={JOURNAL OF PHYSICAL CHEMISTRY A}, author={Nantogma, Shiraz and Eriksson, Shannon L. and Adelabu, Isaiah and Mandzhieva, Iuliia and Browning, Austin and TomHon, Patrick and Warren, Warren S. and Theis, Thomas and Goodson, Boyd M. and Chekmenev, Eduard Y.}, year={2022}, month={Nov} }
@article{nelson_schmidt_adelabu_nantogma_kiselev_abdurraheem_maissin_lehmkuhl_appelt_theis_et al._2022, title={Parahydrogen-Induced Carbon-13 Radiofrequency Amplification by Stimulated Emission of Radiation}, volume={62}, ISSN={["1521-3773"]}, url={https://doi.org/10.1002/anie.202215678}, DOI={10.1002/anie.202215678}, abstractNote={Abstract}, number={5}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Nelson, Christopher and Schmidt, Andreas B. and Adelabu, Isaiah and Nantogma, Shiraz and Kiselev, Valerij G. and Abdurraheem, Abubakar and Maissin, Henri and Lehmkuhl, Soeren and Appelt, Stephan and Theis, Thomas and et al.}, year={2022}, month={Dec} }
@article{mandzhieva_adelabu_chekmenev_theis_2022, title={Proton-Only Sensing of Hyperpolarized [1,2-C-13(2)]Pyruvate}, volume={11}, ISSN={["2379-3694"]}, url={https://doi.org/10.1021/acssensors.2c01608}, DOI={10.1021/acssensors.2c01608}, abstractNote={Hyperpolarized MRI is emerging as a next-generation molecular imaging modality that can detect metabolic transformations in real time deep inside tissue and organs. 13C-hyperpolarized pyruvate is the leading hyperpolarized contrast agent that can probe cellular energetics in real time. Currently, hyperpolarized MRI requires specialized "multinuclear" MRI scanners that have the ability to excite and detect 13C signals. The objective of this work is the development of an approach that works on conventional (i.e., proton-only) MRI systems while taking advantage of long-lived 13C hyperpolarization. The long-lived singlet state of [1,2-13C2]pyruvate is hyperpolarized with parahydrogen in reversible exchange, and subsequently, the polarization is transferred from the 13C2 spin pair to the methyl protons of pyruvate for detection. This polarization transfer is accomplished with spin-lock induced crossing pulses that are only applied to the methyl protons yet access the hyperpolarization stored in the 13C2 singlet state. Theory and first experimental demonstrations are provided for our method, which obviates 13C excitation and detection for proton sensing of 13C-hyperpolarized pyruvate with an overall experimental-polarization transfer efficiency of ∼22% versus a theoretically predicted polarization transfer efficiency of 25%.}, number={12}, journal={ACS SENSORS}, author={Mandzhieva, Iuliia and Adelabu, Isaiah and Chekmenev, Eduard Y. and Theis, Thomas}, year={2022}, month={Nov} }
@article{lehmkuhl_fleischer_lohmann_rosen_chekmenev_adams_theis_appelt_2022, title={RASER MRI: Magnetic Resonance Images formed Spontaneously exploiting Cooperative Nonlinear Interaction}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85170905745&partnerID=MN8TOARS}, DOI={10.48550/arxiv.2203.00632}, abstractNote={The spatial resolution of magnetic resonance imaging (MRI) is fundamentally limited by the width of Lorentzian point spread functions (PSF) associated with the exponential decay rate of transverse magnetization (1/T2*). Here we show a different contrast mechanism in MRI by establishing RASER (Radio-frequency Amplification by Stimulated Emission of Radiation) in imaged media. RASER imaging bursts emerge out of noise and without applying (Radio Frequency) RF pulses when placing spins with sufficient population inversion in a weak magnetic field gradient. A small difference in initial population inversion density creates a stronger image contrast than conventional MRI. This contrast is based on the cooperative nonlinear interaction between all slices. On the other hand, the cooperative nonlinear interaction gives rise to imaging artifacts, such as amplitude distortions and side lobes outside of the imaging domain. Both the contrast and the artifacts are demonstrated experimentally and predicted by simulations based on a proposed theory. This theory of RASER MRI is strongly connected to many other distinct fields related to synergetics and non-linear dynamics.}, journal={arXiv}, author={Lehmkuhl, S. and Fleischer, S. and Lohmann, L. and Rosen, M.S. and Chekmenev, E.Y. and Adams, A. and Theis, T. and Appelt, S.}, year={2022} }
@article{lehmkuhl_fleischer_lohmann_rosen_chekmenev_ada_theis_appelt_2022, title={RASER MRI: Magnetic resonance images formed spontaneously exploiting cooperative nonlinear interaction}, volume={8}, ISSN={["2375-2548"]}, url={https://doi.org/10.1126/sciadv.abp8483}, DOI={10.1126/sciadv.abp8483}, abstractNote={
The spatial resolution of magnetic resonance imaging (MRI) is limited by the width of Lorentzian point spread functions associated with the transverse relaxation rate 1/
T
2
*
. Here, we show a different contrast mechanism in MRI by establishing RASER (radio-frequency amplification by stimulated emission of radiation) in imaged media. RASER imaging bursts emerge out of noise and without applying radio-frequency pulses when placing spins with sufficient population inversion in a weak magnetic field gradient. Small local differences in initial population inversion density can create stronger image contrast than conventional MRI. This different contrast mechanism is based on the cooperative nonlinear interaction between all slices. On the other hand, the cooperative nonlinear interaction gives rise to imaging artifacts, such as amplitude distortions and side lobes outside of the imaging domain. Contrast mechanism and artifacts are explored experimentally and predicted by simulations on the basis of a proposed RASER MRI theory.
}, number={28}, journal={SCIENCE ADVANCES}, author={Lehmkuhl, Soeren and Fleischer, Simon and Lohmann, Lars and Rosen, Matthew S. and Chekmenev, Eduard Y. and Ada, Alina and Theis, Thomas and Appelt, Stephan}, year={2022}, month={Jul} }
@article{adelabu_ettedgui_joshi_nantogma_chowdhury_mcbride_theis_sabbasani_chandrasekhar_sail_et al._2022, title={Rapid C-13 Hyperpolarization of the TCA Cycle Intermediate alpha-Ketoglutarate via SABRE-SHEATH}, volume={9}, ISSN={["1520-6882"]}, url={https://doi.org/10.1021/acs.analchem.2c02160}, DOI={10.1021/acs.analchem.2c02160}, abstractNote={α-Ketoglutarate is a key biomolecule involved in a number of metabolic pathways─most notably the TCA cycle. Abnormal α-ketoglutarate metabolism has also been linked with cancer. Here, isotopic labeling was employed to synthesize [1-13C,5-12C,D4]α-ketoglutarate with the future goal of utilizing its [1-13C]-hyperpolarized state for real-time metabolic imaging of α-ketoglutarate analytes and its downstream metabolites in vivo. The signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH) hyperpolarization technique was used to create 9.7% [1-13C] polarization in 1 minute in this isotopologue. The efficient 13C hyperpolarization, which utilizes parahydrogen as the source of nuclear spin order, is also supported by favorable relaxation dynamics at 0.4 μT field (the optimal polarization transfer field): the exponential 13C polarization buildup constant Tb is 11.0 ± 0.4 s whereas the 13C polarization decay constant T1 is 18.5 ± 0.7 s. An even higher 13C polarization value of 17.3% was achieved using natural-abundance α-ketoglutarate disodium salt, with overall similar relaxation dynamics at 0.4 μT field, indicating that substrate deuteration leads only to a slight increase (∼1.2-fold) in the relaxation rates for 13C nuclei separated by three chemical bonds. Instead, the gain in polarization (natural abundance versus [1-13C]-labeled) is rationalized through the smaller heat capacity of the "spin bath" comprising available 13C spins that must be hyperpolarized by the same number of parahydrogen present in each sample, in line with previous 15N SABRE-SHEATH studies. Remarkably, the C-2 carbon was not hyperpolarized in both α-ketoglutarate isotopologues studied; this observation is in sharp contrast with previously reported SABRE-SHEATH pyruvate studies, indicating that the catalyst-binding dynamics of C-2 in α-ketoglutarate differ from that in pyruvate. We also demonstrate that 13C spectroscopic characterization of α-ketoglutarate and pyruvate analytes can be performed at natural 13C abundance with an estimated detection limit of 80 micromolar concentration × *%P13C. All in all, the fundamental studies reported here enable a wide range of research communities with a new hyperpolarized contrast agent potentially useful for metabolic imaging of brain function, cancer, and other metabolically challenging diseases.}, number={39}, journal={ANALYTICAL CHEMISTRY}, author={Adelabu, Isaiah and Ettedgui, Jessica and Joshi, Sameer M. and Nantogma, Shiraz and Chowdhury, Md Raduanul H. and McBride, Stephen and Theis, Thomas and Sabbasani, Venkata R. and Chandrasekhar, Mushti and Sail, Deepak and et al.}, year={2022}, month={Sep} }
@article{brown_mandzhieva_tomhon_theis_castellano_2022, title={Triplet Photosensitized para-Hydrogen Induced Polarization}, volume={11}, ISSN={["2374-7951"]}, url={https://doi.org/10.1021/acscentsci.2c01003}, DOI={10.1021/acscentsci.2c01003}, abstractNote={Despite its enormous utility in structural characterization, nuclear magnetic resonance (NMR) spectroscopy is inherently limited by low spin polarization. One method to address the low polarization is para-hydrogen (p-H2) induced polarization (PHIP) which uses the singlet spin isomer of H2 to generate disparate nuclear spin populations to amplify the associated NMR signals. PHIP often relies on thermal catalysis or, more infrequently, UV-activated catalytic hydrogenation. Light-activated hydrogenation enables direct and timed control over the hyperpolarization of target substrates, critical for identifying short-lived intermediates. Here, we use an established Ir(III) triplet photosensitizer (PS) to visible light sensitize the triplet ligand-field states in the d6-transition metal dihydride Ru(CO)(PPh3)3(H)2 (1). Excitation inside a 9.4 T NMR spectrometer with the PS and a 420 nm blue LED, under 3 atm of p-H2, successfully photosensitized hyperpolarization in 1 and in a range of unsaturated substrates at and below room temperature, up to 1630-fold. In otherwise identical experimental conditions without light activation, no polarization was realized in 1 or the substrates evaluated. We believe triplet-sensitized PHIP (Trip-PHIP) represents a facile experimental means for probing triplet sensitized light activation in transition metal catalysts possessing low-lying triplet ligand-field states, providing mechanistic insight of potentially tremendous value in chemical catalysis.}, number={11}, journal={ACS CENTRAL SCIENCE}, author={Brown, Emily E. and Mandzhieva, Iuliia and TomHon, Patrick M. and Theis, Thomas and Castellano, Felix N.}, year={2022}, month={Nov} }
@article{tomhon_han_lehmkuhl_appelt_chekmenev_abolhasani_theis_2021, title={A Versatile Compact Parahydrogen Membrane Reactor}, volume={10}, ISSN={["1439-7641"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85118185085&partnerID=MN8TOARS}, DOI={10.1002/cphc.202100667}, abstractNote={Abstract}, number={24}, journal={CHEMPHYSCHEM}, author={TomHon, Patrick M. and Han, Suyong and Lehmkuhl, Soren and Appelt, Stephan and Chekmenev, Eduard Y. and Abolhasani, Milad and Theis, Thomas}, year={2021}, month={Oct} }
@article{joalland_theis_appelt_chekmenev_2021, title={Background-Free Proton NMR Spectroscopy with Radiofrequency Amplification by Stimulated Emission Radiation}, volume={10}, ISSN={["1521-3773"]}, url={https://doi.org/10.1002/anie.202108939}, DOI={10.1002/anie.202108939}, abstractNote={Abstract}, number={50}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, publisher={Wiley}, author={Joalland, Baptiste and Theis, Thomas and Appelt, Stephan and Chekmenev, Eduard Y.}, year={2021}, month={Oct} }
@article{joalland_theis_appelt_chekmenev_2021, title={Background‐Free Proton NMR Spectroscopy with Radiofrequency Amplification by Stimulated Emission Radiation}, volume={9}, url={https://doi.org/10.1002/ange.202108939}, DOI={10.1002/ange.202108939}, abstractNote={Abstract}, journal={Angewandte Chemie}, publisher={Wiley}, author={Joalland, Baptiste and Theis, Thomas and Appelt, Stephan and Chekmenev, Eduard Y.}, year={2021}, month={Dec} }
@article{lin_tomhon_lehmkuhl_laasner_theis_blum_2021, title={Density Functional Theory Study of Reaction Equilibria in Signal Amplification by Reversible Exchange}, volume={9}, ISSN={["1439-7641"]}, url={https://doi.org/10.1002/cphc.202100204}, DOI={10.1002/cphc.202100204}, abstractNote={Abstract}, number={19}, journal={CHEMPHYSCHEM}, publisher={Wiley}, author={Lin, Kailai and TomHon, Patrick and Lehmkuhl, Soren and Laasner, Raul and Theis, Thomas and Blum, Volker}, year={2021}, month={Sep} }
@article{lin_tomhon_lehmkuhl_laasner_theis_blum_2021, title={Density Functional Theory Study of Reaction Equilibria in Signal Amplification by Reversible Exchange}, volume={22}, ISSN={["1439-7641"]}, url={https://doi.org/10.1002/cphc.202100678}, DOI={10.1002/cphc.202100678}, abstractNote={Abstract}, number={19}, journal={CHEMPHYSCHEM}, author={Lin, Kailai and TomHon, Patrick and Lehmkuhl, Soren and Laasner, Raul and Theis, Thomas and Blum, Volker}, year={2021}, month={Oct}, pages={1937–1938} }
@article{lin_tomhon_lehmkuhl_laasner_theis_blum_2021, title={Front Cover: Density Functional Theory Study of Reaction Equilibria in Signal Amplification by Reversible Exchange (ChemPhysChem 19/2021)}, url={https://doi.org/10.1002/cphc.202100677}, DOI={10.1002/cphc.202100677}, abstractNote={The Front Cover shows the reaction network of Signal Amplification by Reversible Exchange (SABRE), elucidated by density functional theory (DFT). More information can be found in the Article by T. Theis, V. Blum, and co-workers.}, journal={ChemPhysChem}, author={Lin, Kailai and TomHon, Patrick and Lehmkuhl, Sören and Laasner, Raul and Theis, Thomas and Blum, Volker}, year={2021}, month={Oct} }
@article{macculloch_tomhon_browning_akeroyd_lehmkuhl_chekmenev_theis_2021, title={Hyperpolarization of common antifungal agents with SABRE}, volume={6}, ISSN={["1097-458X"]}, url={https://doi.org/10.1002/mrc.5187}, DOI={10.1002/mrc.5187}, abstractNote={Abstract}, number={12}, journal={MAGNETIC RESONANCE IN CHEMISTRY}, publisher={Wiley}, author={MacCulloch, Keilian and Tomhon, Patrick and Browning, Austin and Akeroyd, Evan and Lehmkuhl, Soren and Chekmenev, Eduard Y. and Theis, Thomas}, year={2021}, month={Jun} }
@article{joalland_theis_appelt_chekmenev_2021, title={Innentitelbild: Background‐Free Proton NMR Spectroscopy with Radiofrequency Amplification by Stimulated Emission Radiation (Angew. Chem. 50/2021)}, volume={11}, url={https://doi.org/10.1002/ange.202113430}, DOI={10.1002/ange.202113430}, abstractNote={RASER (radiofrequency amplification by stimulated emission radiation) ist die Variante von Laser und Maser, die im Hochfrequenzspektralbereich arbeitet. Eduard Y. Chekmenev et al. setzen in ihrer Zuschrift auf S. 26502 61-MHz-Protonen-RASER ein, um eine robuste, untergrundfreie Detektion biomolekularer NMR-Resonanzen zu demonstrieren, selbst in den extremen Fällen von vollständig protonierten Lösungsmitteln und biologischen Flüssigkeiten. Dieser Ansatz ebnet den Weg für vielzählige hochauflösenden NMR- und In-vivo-MRT-Anwendungen zur untergrundfreien Protonendetektion hyperpolarisierter Moleküle.}, journal={Angewandte Chemie}, publisher={Wiley}, author={Joalland, Baptiste and Theis, Thomas and Appelt, Stephan and Chekmenev, Eduard Y.}, year={2021}, month={Dec} }
@article{joalland_theis_appelt_chekmenev_2021, title={Inside Cover: Background‐Free Proton NMR Spectroscopy with Radiofrequency Amplification by Stimulated Emission Radiation (Angew. Chem. Int. Ed. 50/2021)}, volume={11}, url={https://doi.org/10.1002/anie.202113430}, DOI={10.1002/anie.202113430}, abstractNote={Radiofrequency amplification by stimulated emission radiation (RASER) is the version of lasers and masers operating in the radiofrequency spectral range. In their Communication on page 26298, Eduard Y. Chekmenev and co-workers employ 61 MHz proton RASER to demonstrate robust background-free detection of biomolecular NMR resonances even in the extreme cases of fully protonated solvents and biological fluids. This approach paves the way to a wide range of high-resolution NMR and in vivo MRI applications of background-free proton detection of hyperpolarized molecules.}, journal={Angewandte Chemie International Edition}, publisher={Wiley}, author={Joalland, Baptiste and Theis, Thomas and Appelt, Stephan and Chekmenev, Eduard Y.}, year={2021}, month={Dec} }
@article{han_ramezani_tomhon_abdel-latif_epps_theis_abolhasani_2021, title={Intensified continuous extraction of switchable hydrophilicity solvents triggered by carbon dioxide}, volume={23}, ISSN={["1463-9270"]}, url={https://doi.org/10.1039/D1GC00811K}, DOI={10.1039/D1GC00811K}, abstractNote={An intensified continuous flow strategy is developed and utilized for scalable extraction of switchable hydrophilicity solvents triggered by carbon dioxide.}, number={8}, journal={GREEN CHEMISTRY}, publisher={Royal Society of Chemistry (RSC)}, author={Han, Suyong and Ramezani, Mahdi and TomHon, Patrick and Abdel-Latif, Kameel and Epps, Robert W. and Theis, Thomas and Abolhasani, Milad}, year={2021}, month={Apr}, pages={2900–2906} }
@article{arunkumar_bucher_turner_tomhon_glenn_lehmkuhl_lukin_park_rosen_theis_et al._2021, title={Micron-Scale NV-NMR Spectroscopy with Signal Amplification by Reversible Exchange}, volume={2}, ISSN={2691-3399}, url={http://dx.doi.org/10.1103/prxquantum.2.010305}, DOI={10.1103/PRXQuantum.2.010305}, abstractNote={High-resolution sensing of weak signals is implemented by means of an integrated diamond---nuclear-magnetic-resonance technique}, number={1}, journal={PRX Quantum}, publisher={American Physical Society (APS)}, author={Arunkumar, Nithya and Bucher, Dominik B. and Turner, Matthew J. and TomHon, Patrick and Glenn, David and Lehmkuhl, Sören and Lukin, Mikhail D. and Park, Hongkun and Rosen, Matthew S. and Theis, Thomas and et al.}, year={2021}, month={Jan}, pages={010305} }
@article{adelabu_tomhon_kabir_nantogma_abdulmojeed_mandzhieva_ettedgui_swenson_krishna_theis_et al._2021, title={Order-Unity C-13 Nuclear Polarization of [1-C-13]Pyruvate in Seconds and the Interplay of Water and SABRE Enhancement}, volume={23}, ISSN={["1439-7641"]}, url={https://doi.org/10.1002/cphc.202100839}, DOI={10.1002/cphc.202100839}, abstractNote={Abstract}, number={2}, journal={CHEMPHYSCHEM}, publisher={Wiley}, author={Adelabu, Isaiah and TomHon, Patrick and Kabir, Mohammad S. H. and Nantogma, Shiraz and Abdulmojeed, Mustapha and Mandzhieva, Iuliia and Ettedgui, Jessica and Swenson, Rolf E. and Krishna, Murali C. and Theis, Thomas and et al.}, year={2021}, month={Dec} }
@article{appelt_lehmkuhl_fleischer_joalland_ariyasingha_chekmenev_theis_2021, title={SABRE and PHIP pumped RASER and the route to chaos}, volume={322}, ISSN={1090-7807}, url={http://dx.doi.org/10.1016/j.jmr.2020.106815}, DOI={10.1016/j.jmr.2020.106815}, abstractNote={In a RASER (Radio-frequency Amplification by Stimulated Emission of Radiation), the fast relaxing electromagnetic modes of an LC resonator are enslaved by the slow nuclear spin motion, whose coherence decays with the transverse relaxation rate γm=1/T2∗. Such a system obeys the slaving principle, mathematically identical with the adiabatic elimination procedure, leading to multi-mode RASER equations. If the pumping rate of nuclear spin polarization Γ>>γm, a second adiabatic elimination process applies and the spectral properties of the RASER can be predicted. The resulting model is similar to the model of two non-linear coupled oscillators and predicts the observed RASER phenomena, including frequency combs and mode collapse. If the second adiabatic elimination is not applicable, mode collapse is completely absent and successive period doubling processes and chaos occur at very high population inversions. We compare these theoretical predictions with experimental results from a PHIP (Para-Hydrogen Induced Polarization) pumped 1H RASER. Moreover, in SABRE (Signal Amplification By Reversible Exchange) pumped 1H experiments, RASER revivals are observed long after the parahydrogen pumping source has been switched off. All these findings shed light onto the links between NMR spectroscopy, RASER physics, synergetics and chaos theory. Several new applications are envisioned in the fields of quantum sensor technology, structure investigation or magnetic resonance imaging (MRI).}, journal={Journal of Magnetic Resonance}, publisher={Elsevier BV}, author={Appelt, Stephan and Lehmkuhl, Sören and Fleischer, Simon and Joalland, Baptiste and Ariyasingha, Nuwandi M. and Chekmenev, Eduard Y. and Theis, Thomas}, year={2021}, month={Jan}, pages={106815} }
@article{tomhon_abdulmojeed_adelabu_nantogma_kabir_lehmkuhl_chekmenev_theis_2021, title={Temperature Cycling Enables Efficient 13C SABRE-SHEATH Hyperpolarization and Imaging of [1-13C]Pyruvate}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85126204617&partnerID=MN8TOARS}, DOI={10.26434/chemrxiv-2021-cpz32}, abstractNote={Current metabolic imaging in humans is dominated by positron emission tomography (PET) methods. An emerging non-ionizing alternative for molecular imaging is hyperpolarized MRI. In particular, imaging of hyperpolarized 13C-pyruvate is a leading candidate because pyruvate is innocuous and has a central role in metabolism. However, simi-lar to PET, hyperpolarized MRI with dynamic nuclear polarization (DNP) is complex, costly and requires complex in-frastructure. In contrast, signal amplification by reversible exchange (SABRE) is a fast, cheap, and scalable hyperpo-larization technique. In particular, SABRE in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) transfers polarization from parahydrogen to 13C in pyruvate, however, to date, SABRE-SHEATH of 13C-pyruvate was limited in polarization levels relative to DNP (1.7% with SABRE-SHEATH vs. ~60% with DNP). Here we introduce a temperature cycling method for SABRE-SHEATH that enables >10% polarization on [1-13C]pyruvate, sufficient for successful in vivo experiments. First, at lower temperatures, ~20% polarization is accumulated on SABRE-catalyst bound pyruvate, which is subsequently released into free pyruvate in solution at elevated temperatures. We take ad-vantage of the achieved polarization to demonstrate first 13C pyruvate images with a cryogen-free MRI system operat-ed at 1 T. This illustrates that inexpensive hyperpolarization methods can be combined with low-cost MRI systems to obtain a broadly available, yet highly sensitive metabolic imaging platform.}, journal={ChemRxiv}, author={TomHon, Patrick and Abdulmojeed, Mustapha and Adelabu, Isaiah and Nantogma, Shiraz and Kabir, Mohammad Shah Hafez and Lehmkuhl, Sören and Chekmenev, Eduard Y. and Theis, Thomas}, year={2021} }
@article{tomhon_abdulmojeed_adelabu_nantogma_kabir_lehmkuhl_chekmenev_theis_2021, title={Temperature Cycling Enables Efficient C-13 SABRE-SHEATH Hyperpolarization and Imaging of [1-C-13]-Pyruvate}, volume={12}, ISSN={["1520-5126"]}, url={https://doi.org/10.1021/jacs.1c09581}, DOI={10.1021/jacs.1c09581}, abstractNote={Molecular metabolic imaging in humans is dominated by positron emission tomography (PET). An emerging nonionizing alternative is hyperpolarized MRI of 13C-pyruvate, which is innocuous and has a central role in metabolism. However, similar to PET, hyperpolarized MRI with dissolution dynamic nuclear polarization (d-DNP) is complex costly, and requires significant infrastructure. In contrast, Signal Amplification By Reversible Exchange (SABRE) is a fast, cheap, and scalable hyperpolarization technique. SABRE in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) can transfer polarization from parahydrogen to 13C in pyruvate; however, polarization levels remained low relative to d-DNP (1.7% with SABRE-SHEATH versus ≈60% with DNP). Here we introduce a temperature cycling method for SABRE-SHEATH that enables >10% polarization on [1-13C]-pyruvate, sufficient for successful in vivo experiments. First, at lower temperatures, ≈20% polarization is accumulated on SABRE catalyst-bound pyruvate, which is released into free pyruvate at elevated temperatures. A kinetic model of differential equations is developed that explains this effect and characterizes critical relaxation and buildup parameters. With the large polarization, we demonstrate the first 13C pyruvate images with a cryogen-free MRI system operated at 1.5 T, illustrating that inexpensive hyperpolarization methods can be combined with low-cost MRI systems to obtain a broadly available, yet highly sensitive metabolic imaging platform.}, number={1}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, publisher={American Chemical Society (ACS)}, author={TomHon, Patrick and Abdulmojeed, Mustapha and Adelabu, Isaiah and Nantogma, Shiraz and Kabir, Mohammad Shah Hafez and Lehmkuhl, Soren and Chekmenev, Eduard Y. and Theis, Thomas}, year={2021}, month={Dec} }
@article{park_zhang_bae_theis_warren_wang_2020, title={Application of 15N2-Diazirines as a Versatile Platform for Hyperpolarization of Biological Molecules by d-DNP}, volume={31}, ISSN={1043-1802 1520-4812}, url={http://dx.doi.org/10.1021/acs.bioconjchem.0c00028}, DOI={10.1021/acs.bioconjchem.0c00028}, abstractNote={15N2-Diazirines represent an attractive class of imaging tags for hyperpolarized magnetic resonance imaging (HP-MRI), offering desirable biocompatibility, ease of incorporation into a variety of molecules, and ability to deliver long-lasting polarization. We have recently established hyperpolarization of 15N2-diazirines in organic solvents using SABRE-Shield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH). Yet, the current challenge of SABRE-SHEATH in water, specifically poor polarization efficiency, presents a barrier in examining practical use of 15N2-diazirines for HP-MRI. Herein, we show that efficient polarization of diverse 15N2-diazirine-labeled molecules in water can be readily achieved by dissolution dynamic nuclear polarization (d-DNP), a hyperpo-larization technique used in clinical practice. Hyperpolarization by d-DNP also demonstrates greater enhancement for long-lasting 15N signals, in comparison with SABRE-SHEATH. Various biologically important molecules are studied in this work, including amino acid, sugar, and drug compounds, demonstrating great potential of 15N2-diazirines as molecular tags in broad biomedical and clinical applications.}, number={3}, journal={Bioconjugate Chemistry}, publisher={American Chemical Society (ACS)}, author={Park, Hyejin and Zhang, Guannan and Bae, Junu and Theis, Thomas and Warren, Warren S. and Wang, Qiu}, year={2020}, month={Feb}, pages={537–541} }
@article{tomhon_akeroyd_lehmkuhl_chekmenev_theis_2020, title={Automated pneumatic shuttle for magnetic field cycling and parahydrogen hyperpolarized multidimensional NMR}, volume={312}, ISSN={1090-7807}, url={http://dx.doi.org/10.1016/j.jmr.2020.106700}, DOI={10.1016/j.jmr.2020.106700}, abstractNote={We present a simple-to-implement pneumatic sample shuttle for automation of magnetic field cycling and multidimensional NMR. The shuttle system is robust allowing automation of hyperpolarized and non-hyperpolarized measurements, including variable field lifetime measurements, SABRE polarization optimization, and SABRE multidimensional experiments. Relaxation-protected singlet states are evaluated by variable-field T1 and TS measurements. Automated shuttling facilitates characterization of hyperpolarization dynamics, field dependence and polarization buildup rates. Furthermore, reproducible hyperpolarization levels at every shuttling event enables automated 2D hyperpolarized NMR, including the first inverse 15N/1H HSQC. We uncover binding mechanisms of the catalytic species through cross peaks that are not accessible in standard one-dimensional hyperpolarized experiments. The simple design of the shuttling setup interfaced with standard TTL signals allows easy adaptation to any standard NMR magnet.}, journal={Journal of Magnetic Resonance}, publisher={Elsevier BV}, author={TomHon, Patrick and Akeroyd, Evan and Lehmkuhl, Sören and Chekmenev, Eduard Y. and Theis, Thomas}, year={2020}, month={Mar}, pages={106700} }
@article{arunkumar_bucher_turner_tomhon_glenn_lehmkuhl_lukin_park_rosen_theis_et al._2020, title={Micron-scale SABRE-enhanced NV-NMR Spectroscopy}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85170127843&partnerID=MN8TOARS}, DOI={10.48550/arxiv.2006.03910}, journal={arXiv}, author={Arunkumar, N. and Bucher, D.B. and Turner, M.J. and TomHon, P. and Glenn, D. and Lehmkuhl, S. and Lukin, M.D. and Park, H. and Rosen, M.S. and Theis, T. and et al.}, year={2020} }
@article{micron-scale sabre-enhanced nv-nmr spectroscopy_2020, year={2020}, month={Jun} }
@article{kovtunov_koptyug_fekete_duckett_theis_joalland_chekmenev_2020, title={Parahydrogen‐Induced Hyperpolarization of Gases}, volume={59}, ISSN={1433-7851 1521-3773}, url={http://dx.doi.org/10.1002/anie.201915306}, DOI={10.1002/anie.201915306}, abstractNote={Abstract}, number={41}, journal={Angewandte Chemie International Edition}, publisher={Wiley}, author={Kovtunov, Kirill V. and Koptyug, Igor V. and Fekete, Marianna and Duckett, Simon B. and Theis, Thomas and Joalland, Baptiste and Chekmenev, Eduard Y.}, year={2020}, month={Aug}, pages={17788–17797} }
@article{joalland_ariyasingha_lehmkuhl_theis_appelt_chekmenev_2020, title={Parahydrogen‐Induced Radio Amplification by Stimulated Emission of Radiation}, volume={59}, ISSN={1433-7851 1521-3773}, url={http://dx.doi.org/10.1002/anie.201916597}, DOI={10.1002/anie.201916597}, abstractNote={Abstract}, number={22}, journal={Angewandte Chemie International Edition}, publisher={Wiley}, author={Joalland, Baptiste and Ariyasingha, Nuwandi M. and Lehmkuhl, Sören and Theis, Thomas and Appelt, Stephan and Chekmenev, Eduard Y.}, year={2020}, month={Mar}, pages={8654–8660} }
@article{joalland_ariyasingha_lehmkuhl_theis_appelt_chekmenev_2020, title={Parahydrogen‐Induced Radio Amplification by Stimulated Emission of Radiation}, volume={132}, url={https://doi.org/10.1002/ange.201916597}, DOI={10.1002/ange.201916597}, abstractNote={Abstract}, number={22}, journal={Angewandte Chemie}, publisher={Wiley}, author={Joalland, Baptiste and Ariyasingha, Nuwandi M. and Lehmkuhl, Sören and Theis, Thomas and Appelt, Stephan and Chekmenev, Eduard Y.}, year={2020}, month={May}, pages={8732–8738} }
@article{kovtunov_koptyug_fekete_duckett_theis_joalland_chekmenev_2020, title={Parawasserstoff‐induzierte Hyperpolarisation von Gasen}, volume={132}, ISSN={0044-8249 1521-3757}, url={http://dx.doi.org/10.1002/ange.201915306}, DOI={10.1002/ange.201915306}, abstractNote={Abstract}, number={41}, journal={Angewandte Chemie}, publisher={Wiley}, author={Kovtunov, Kirill V. and Koptyug, Igor V. and Fekete, Marianna and Duckett, Simon B. and Theis, Thomas and Joalland, Baptiste and Chekmenev, Eduard Y.}, year={2020}, month={Aug}, pages={17940–17949} }
@article{colell_logan_zhou_lindale_laasner_shchepin_chekmenev_blum_warren_malcolmson_et al._2020, title={Rational ligand choice extends the SABRE substrate scope}, volume={56}, ISSN={1359-7345 1364-548X}, url={http://dx.doi.org/10.1039/D0CC01330G}, DOI={10.1039/d0cc01330g}, abstractNote={Here we report on chelating ligands for Signal Amplification By Reversible Exchange (SABRE) catalysts that permit hyperpolarisation on otherwise sterically hindered substrates.}, number={65}, journal={Chemical Communications}, publisher={Royal Society of Chemistry (RSC)}, author={Colell, Johannes F. P. and Logan, Angus W. J. and Zhou, Zijian and Lindale, Jacob R. and Laasner, Raul and Shchepin, Roman V. and Chekmenev, Eduard Y. and Blum, Volker and Warren, Warren S. and Malcolmson, Steven J. and et al.}, year={2020}, pages={9336–9339} }
@article{lehmkuhl_suefke_kentner_yen_blümich_rosen_appelt_theis_2020, title={SABRE polarized low field rare-spin spectroscopy}, volume={152}, ISSN={0021-9606 1089-7690}, url={http://dx.doi.org/10.1063/5.0002412}, DOI={10.1063/5.0002412}, abstractNote={High-field nuclear magnetic resonance (NMR) spectroscopy is an indispensable technique for identification and characterization of chemicals and biomolecular structures. In the vast majority of NMR experiments, nuclear spin polarization arises from thermalization in multi-Tesla magnetic fields produced by superconducting magnets. In contrast, NMR instruments operating at low magnetic fields are emerging as a compact, inexpensive, and highly accessible alternative but suffer from low thermal polarization at a low field strength and consequently a low signal. However, certain hyperpolarization techniques create high polarization levels on target molecules independent of magnetic fields, giving low-field NMR a significant sensitivity boost. In this study, SABRE (Signal Amplification By Reversible Exchange) was combined with high homogeneity electromagnets operating at mT fields, enabling high resolution 1H, 13C, 15N, and 19F spectra to be detected with a single scan at magnetic fields between 1 mT and 10 mT. Chemical specificity is attained at mT magnetic fields with complex, highly resolved spectra. Most spectra are in the strong coupling regime where J-couplings are on the order of chemical shift differences. The spectra and the hyperpolarization spin dynamics are simulated with SPINACH. The simulations start from the parahydrogen singlet in the bound complex and include both chemical exchange and spin evolution at these mT fields. The simulations qualitatively match the experimental spectra and are used to identify the spin order terms formed during mT SABRE. The combination of low field NMR instruments with SABRE polarization results in sensitive measurements, even for rare spins with low gyromagnetic ratios at low magnetic fields.}, number={18}, journal={The Journal of Chemical Physics}, publisher={AIP Publishing}, author={Lehmkuhl, Sören and Suefke, Martin and Kentner, Arne and Yen, Yi-Fen and Blümich, Bernhard and Rosen, Matthew S. and Appelt, Stephan and Theis, Thomas}, year={2020}, month={May}, pages={184202} }
@article{shchepin_birchall_chukanov_kovtunov_koptyug_theis_warren_gelovani_goodson_shokouhi_et al._2019, title={Hyperpolarizing Concentrated Metronidazole
15
NO
2
Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime}, volume={25}, ISSN={0947-6539 1521-3765}, url={http://dx.doi.org/10.1002/chem.201901192}, DOI={10.1002/chem.201901192}, abstractNote={Abstract}, number={37}, journal={Chemistry – A European Journal}, publisher={Wiley}, author={Shchepin, Roman V. and Birchall, Jonathan R. and Chukanov, Nikita V. and Kovtunov, Kirill V. and Koptyug, Igor V. and Theis, Thomas and Warren, Warren S. and Gelovani, Juri G. and Goodson, Boyd M. and Shokouhi, Sepideh and et al.}, year={2019}, month={Jul}, pages={8829–8836} }
@article{glachet_marzag_saraiva rosa_colell_zhang_warren_franck_theis_reboul_2019, title={Iodonitrene in Action: Direct Transformation of Amino Acids into Terminal Diazirines and15N2-Diazirines and Their Application as Hyperpolarized Markers}, volume={141}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/jacs.9b07035}, DOI={10.1021/jacs.9b07035}, abstractNote={A one-pot metal-free conversion of unprotected amino acids to terminal diazirines has been developed using phenyliodonium diacetate (PIDA) and ammonia. This PIDA mediated transformation occurs via three consecutive reactions and involves an iodonitrene intermediate. This method is tolerant to most functional groups found on the lateral chain of amino acids, it is operationally simple, and can be scaled up to provide multigram quantities of diazirine. Interestingly, we also demonstrated that this transformation could be applied to dipeptides without racemization. Furthermore, 14N2 and 15N2 isotopomers can be obtained, emphasizing a key trans-imination step when using 15NH3. In addition, we report the first experimental observation of 14N/15N isotopomers directly creating an asymmetric carbon. Finally, the 15N2-diazirine from L-tyrosine was hyperpolarized by a parahydrogen-based method (SABRE-SHEATH), demonstrating the products utility as hyperpolarized molecular tag.}, number={34}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Glachet, Thomas and Marzag, Hamid and Saraiva Rosa, Nathalie and Colell, Johannes F. P. and Zhang, Guannan and Warren, Warren S. and Franck, Xavier and Theis, Thomas and Reboul, Vincent}, year={2019}, month={Aug}, pages={13689–13696} }
@inbook{goodson_kidd_hövener_schröder_theis_whiting_chekmenev_2019, place={San Diego, CA}, edition={3rd}, title={Nuclear Magnetic Resonance Spectroscopy Techniques: Hyperpolarization for Sensitivity Enhancement}, ISBN={9780081019849}, url={http://dx.doi.org/10.1016/B978-0-12-409547-2.14072-7}, DOI={10.1016/B978-0-12-409547-2.14072-7}, abstractNote={Nuclear spin polarization can be significantly enhanced through a process called hyperpolarization, resulting in up to several orders increase of the nuclear spin polarization (compared to equilibrium thermal polarization) with concomitant gains in NMR spectroscopic and imaging signals. Here, we describe the leading techniques for NMR hyperpolarization: dynamic nuclear polarization (DNP), spin exchange optical pumping (SEOP), parahydrogen induced polarization (PHIP), and signal amplification by reversible exchange (SABRE). We also discuss key features of and schemes associated with NMR spectroscopic detection in the context of NMR hyperpolarization applications.}, booktitle={Encyclopedia of Analytical Science}, publisher={Elsevier}, author={Goodson, Boyd M. and Kidd, Bryce and Hövener, Jan-Bernd and Schröder, Leif and Theis, Thomas and Whiting, Nicholas and Chekmenev, Eduard Y.}, editor={Worsfold, Paul and Townshend, Alan and Poole, Colin and Miró, ManuelEditors}, year={2019}, pages={168–181} }
@article{ariyasingha_lindale_eriksson_clark_theis_shchepin_chukanov_kovtunov_koptyug_warren_et al._2019, title={Quasi-Resonance Fluorine-19 Signal Amplification by Reversible Exchange}, volume={10}, ISSN={1948-7185 1948-7185}, url={http://dx.doi.org/10.1021/acs.jpclett.9b01505}, DOI={10.1021/acs.jpclett.9b01505}, abstractNote={We report on an extension of the QUASi-Resonance (QUASR) pulse sequence used for Signal Amplification by Reversible Exchange (SABRE), showing that we may target distantly J-coupled 19F-spins. Polarization transfer from the parahydrogen-derived hydrides to the 19F nucleus is accomplished via weak five-bond J-couplings using a shaped QUASi-Resonance (QUASR) radio-frequency pulse at a 0.05 T magnetic field. The net result is the direct generation of hyperpolarized 19F z-magnetization, derived from the parahydrogen singlet order. An accumulation of 19F polarization on the free ligand is achieved with subsequent repetition of this pulse sequence. The hyperpolarized 19F signal exhibits clear dependence on the pulse length, irradiation frequency, and delay time in a manner similar to that reported for 15N QUASR-SABRE. Moreover, the hyperpolarized 19F signals of 3-19F-14N-pyridine and 3-19F-15N-pyridine isotopologues are similar, suggesting (i) that polarization transfer via QUASR-SABRE is irrespective of the nitrogen isotopologue, and (ii) the presence or absence of the spin-1/2 15N nucleus has no impact on the efficiency of QUASR-SABRE polarization transfer. Although optimization of polarization transfer efficiency to 19F (P19F~0.1%) was not the goal of this study, we show that high-field SABRE can be efficient and broadly applicable for direct hyperpolarization of 19F spins.}, number={15}, journal={The Journal of Physical Chemistry Letters}, publisher={American Chemical Society (ACS)}, author={Ariyasingha, Nuwandi M. and Lindale, Jacob R. and Eriksson, Shannon L. and Clark, Grayson P. and Theis, Thomas and Shchepin, Roman V. and Chukanov, Nikita V. and Kovtunov, Kirill V. and Koptyug, Igor V. and Warren, Warren S. and et al.}, year={2019}, month={Jul}, pages={4229–4236} }
@article{tanner_lindale_eriksson_zhou_colell_theis_warren_2019, title={Selective hyperpolarization of heteronuclear singlet states via pulsed microtesla SABRE}, volume={151}, ISSN={0021-9606 1089-7690}, url={http://dx.doi.org/10.1063/1.5108644}, DOI={10.1063/1.5108644}, abstractNote={Signal Amplification By Reversible Exchange (SABRE) and its heteronuclear variant SABRE in SHield Enables Alignment Transfer to Heteronuclei create large nuclear magnetization in target ligands, exploiting level crossings in an iridium catalyst that transiently binds both the ligands and parahydrogen. This requires a specific, small magnetic field to match Zeeman splittings to scalar couplings. Here, we explore a different strategy, direct creation of heteronuclear singlet states in the target ligands, which produces enhanced signals at other field strengths, including zero field. We also show that pulsed methods (including pulsed field nulling) coherently and selectively pump such singlets, affording a significant enhancement on the resulting hyperpolarization.}, number={4}, journal={The Journal of Chemical Physics}, publisher={AIP Publishing}, author={Tanner, Christian P. N. and Lindale, Jacob R. and Eriksson, Shannon L. and Zhou, Zijian and Colell, Johannes F. P. and Theis, Thomas and Warren, Warren S.}, year={2019}, month={Jul}, pages={044201} }
@article{zhang_colell_glachet_lindale_reboul_theis_warren_2019, title={Terminal Diazirines Enable Reverse Polarization Transfer from
15
N
2
Singlets}, volume={58}, ISBN={1521-3773}, ISSN={1433-7851 1521-3773}, url={http://dx.doi.org/10.1002/anie.201904026}, DOI={10.1002/anie.201904026}, abstractNote={Abstract}, number={32}, journal={Angewandte Chemie International Edition}, publisher={Wiley}, author={Zhang, Guannan and Colell, Johannes F. P. and Glachet, Thomas and Lindale, Jacob R. and Reboul, Vincent and Theis, Thomas and Warren, Warren S.}, year={2019}, month={Aug}, pages={11118–11124} }
@article{zhang_colell_glachet_lindale_reboul_theis_warren_2019, title={Terminal Diazirines Enable Reverse Polarization Transfer from 15N2 Singlets}, url={https://doi.org/10.1002/ange.201904026}, DOI={10.1002/ange.201904026}, abstractNote={Abstract}, journal={Angewandte Chemie}, author={Zhang, Guannan and Colell, Johannes F. P. and Glachet, Thomas and Lindale, Jacob R. and Reboul, Vincent and Theis, Thomas and Warren, Warren S.}, year={2019}, month={Aug} }
@article{lindale_eriksson_tanner_zhou_colell_zhang_bae_chekmenev_theis_warren_2019, title={Unveiling coherently driven hyperpolarization dynamics in signal amplification by reversible exchange}, volume={10}, ISSN={2041-1723}, url={http://dx.doi.org/10.1038/s41467-019-08298-8}, DOI={10.1038/s41467-019-08298-8}, abstractNote={Abstract}, number={1}, journal={Nature Communications}, publisher={Springer Science and Business Media LLC}, author={Lindale, Jacob R. and Eriksson, Shannon L. and Tanner, Christian P. N. and Zhou, Zijian and Colell, Johannes F. P. and Zhang, Guannan and Bae, Junu and Chekmenev, Eduard Y. and Theis, Thomas and Warren, Warren S.}, year={2019}, month={Jan} }
@article{bae_zhou_theis_warren_wang_2018, title={15N4-1,2,4,5-tetrazines as potential molecular tags: Integrating bioorthogonal chemistry with hyperpolarization and unearthing para-N2}, volume={4}, ISSN={2375-2548}, url={http://dx.doi.org/10.1126/sciadv.aar2978}, DOI={10.1126/sciadv.aar2978}, abstractNote={
A bioorthogonal reaction–based HP-MR strategy affords novel hyperpolarized products from tetrazine, including
para
-
15
N
2
gas.
}, number={3}, journal={Science Advances}, publisher={American Association for the Advancement of Science (AAAS)}, author={Bae, Junu and Zhou, Zijian and Theis, Thomas and Warren, Warren S. and Wang, Qiu}, year={2018}, month={Mar}, pages={eaar2978} }
@article{hövener_pravdivtsev_kidd_bowers_glöggler_kovtunov_plaumann_katz-brull_buckenmaier_jerschow_et al._2018, title={Parahydrogen-Based Hyperpolarization for Biomedicine}, volume={57}, ISSN={1433-7851}, url={http://dx.doi.org/10.1002/anie.201711842}, DOI={10.1002/anie.201711842}, abstractNote={Abstract}, number={35}, journal={Angewandte Chemie International Edition}, publisher={Wiley}, author={Hövener, Jan-Bernd and Pravdivtsev, Andrey N. and Kidd, Bryce and Bowers, C. Russell and Glöggler, Stefan and Kovtunov, Kirill V. and Plaumann, Markus and Katz-Brull, Rachel and Buckenmaier, Kai and Jerschow, Alexej and et al.}, year={2018}, month={Aug}, pages={11140–11162} }
@article{hövener_pravdivtsev_kidd_bowers_glöggler_kovtunov_plaumann_katz-brull_buckenmaier_jerschow_et al._2018, title={Parawasserstoff-basierte Hyperpolarisierung für die Biomedizin}, volume={130}, ISSN={0044-8249}, url={http://dx.doi.org/10.1002/ange.201711842}, DOI={10.1002/ange.201711842}, abstractNote={Abstract}, number={35}, journal={Angewandte Chemie}, publisher={Wiley}, author={Hövener, Jan-Bernd and Pravdivtsev, Andrey N. and Kidd, Bryce and Bowers, C. Russell and Glöggler, Stefan and Kovtunov, Kirill V. and Plaumann, Markus and Katz-Brull, Rachel and Buckenmaier, Kai and Jerschow, Alexej and et al.}, year={2018}, month={Aug}, pages={11310–11333} }
@article{theis_ariyasingha_shchepin_lindale_warren_chekmenev_2018, title={Quasi-Resonance Signal Amplification by Reversible Exchange}, volume={9}, ISSN={1948-7185}, url={http://dx.doi.org/10.1021/acs.jpclett.8b02669}, DOI={10.1021/acs.jpclett.8b02669}, abstractNote={Here we present the feasibility of NMR signal amplification by reversible exchange (SABRE) using radio frequency irradiation at low magnetic field (0.05 T) in the regime where the chemical shifts of free and catalyst-bound species are similar. In SABRE, the 15N-containing substrate and parahydrogen perform simultaneous chemical exchange on an iridium hexacoordinate complex. A shaped spin-lock induced crossing (SLIC) radio frequency pulse sequence followed by a delay is applied at quasi-resonance (QUASR) conditions of 15N spins of a 15N-enriched substrate. As a result of this pulse sequence application, 15N z-magnetization is created from the spin order of parahydrogen-derived hyperpolarized hydrides. The repetition of the pulse sequence block consisting of a shaped radio frequency pulse and the delay leads to the buildup of 15N magnetization. The modulation of this effect by the irradiation frequency, pulse duration and amplitude, delay duration, and number of pumping cycles was demonstrated. Pyridine-15N, acetonitrile-15N, and metronidazole-15N2-13C2 substrates were studied representing three classes of compounds (five- and six-membered heterocycles and nitrile), showing the wide applicability of the technique. Metronidazole-15N2-13C2 is an FDA-approved antibiotic that can be injected in large quantities, promising noninvasive and accurate hypoxia sensing. The 15N hyperpolarization levels attained with QUASR-SABRE on metronidazole-15N2-13C2 were more than 2-fold greater than those with SABRE-SHEATH (SABRE in shield enables alignment transfer to heteronuclei), demonstrating that QUASR-SABRE can deliver significantly more efficient means of SABRE hyperpolarization.}, number={20}, journal={The Journal of Physical Chemistry Letters}, publisher={American Chemical Society (ACS)}, author={Theis, Thomas and Ariyasingha, Nuwandi M. and Shchepin, Roman V. and Lindale, Jacob R. and Warren, Warren S. and Chekmenev, Eduard Y.}, year={2018}, month={Oct}, pages={6136–6142} }
@article{shen_logan_colell_bae_ortiz_theis_warren_malcolmson_wang_2017, title={Cover Picture: Diazirines as Potential Molecular Imaging Tags: Probing the Requirements for Efficient and Long‐Lived SABRE‐Induced Hyperpolarization (Angew. Chem. Int. Ed. 40/2017)}, url={https://doi.org/10.1002/anie.201707296}, DOI={10.1002/anie.201707296}, abstractNote={Diazirines are an attractive class of potential molecular tags for magnetic resonance imaging owing to their biocompatibility and ease of incorporation into a large variety of molecules. In their Communication on page 12112 ff., W. S. Warren, S. J. Malcolmson, Q. Wang, and co-workers show with a 15N2-diazirine-containing choline derivative that 15N2-diazirine motifs are capable of supporting long-lasting polarization by the simple SABRE-SHEATH hyperpolarization method, making then promising as tags for NMR/MRI imaging. Diazirines are an attractive class of potential molecular tags for magnetic resonance imaging owing to their biocompatibility and ease of incorporation into a large variety of molecules. In their Communication on page 12112 ff., W. S. Warren, S. J. Malcolmson, Q. Wang, and co-workers show with a 15N2-diazirine-containing choline derivative that 15N2-diazirine motifs are capable of supporting long-lasting polarization by the simple SABRE-SHEATH hyperpolarization method, making then promising as tags for NMR/MRI imaging. Polymeric Vesicles Natural Product Synthesis Nitrile Synthesis}, journal={Angewandte Chemie International Edition}, author={Shen, Kun and Logan, Angus W. J. and Colell, Johannes F. P. and Bae, Junu and Ortiz, Gerardo X., Jr. and Theis, Thomas and Warren, Warren S. and Malcolmson, Steven J. and Wang, Qiu}, year={2017}, month={Sep} }
@article{shen_logan_colell_bae_ortiz_theis_warren_malcolmson_wang_2017, title={Diazirines as Potential Molecular Imaging Tags: Probing the Requirements for Efficient and Long-Lived SABRE-Induced Hyperpolarization}, volume={56}, ISSN={1433-7851}, url={http://dx.doi.org/10.1002/anie.201704970}, DOI={10.1002/anie.201704970}, abstractNote={Abstract}, number={40}, journal={Angewandte Chemie International Edition}, publisher={Wiley}, author={Shen, Kun and Logan, Angus W. J. and Colell, Johannes F. P. and Bae, Junu and Ortiz, Gerardo X., Jr. and Theis, Thomas and Warren, Warren S. and Malcolmson, Steven J. and Wang, Qiu}, year={2017}, month={Jul}, pages={12112–12116} }
@article{shen_logan_colell_bae_ortiz_theis_warren_malcolmson_wang_2017, title={Diazirines as Potential Molecular Imaging Tags: Probing the Requirements for Efficient and Long‐Lived SABRE‐Induced Hyperpolarization}, volume={129}, url={https://doi.org/10.1002/ange.201704970}, DOI={10.1002/ange.201704970}, abstractNote={Abstract}, number={40}, journal={Angewandte Chemie}, publisher={Wiley}, author={Shen, Kun and Logan, Angus W. J. and Colell, Johannes F. P. and Bae, Junu and Ortiz, Gerardo X., Jr. and Theis, Thomas and Warren, Warren S. and Malcolmson, Steven J. and Wang, Qiu}, year={2017}, month={Sep}, pages={12280–12284} }
@article{colell_emondts_logan_shen_bae_shchepin_ortiz_spannring_wang_malcolmson_et al._2017, title={Direct Hyperpolarization of Nitrogen-15 in Aqueous Media with Parahydrogen in Reversible Exchange}, volume={139}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/jacs.7b00569}, DOI={10.1021/jacs.7b00569}, abstractNote={Signal amplification by reversible exchange (SABRE) is an inexpensive, fast, and even continuous hyperpolarization technique that uses para-hydrogen as hyperpolarization source. However, current SABRE faces a number of stumbling blocks for translation to biochemical and clinical settings. Difficulties include inefficient polarization in water, relatively short-lived 1H-polarization, and relatively limited substrate scope. Here we use a water-soluble polarization transfer catalyst to hyperpolarize nitrogen-15 in a variety of molecules with SABRE-SHEATH (SABRE in shield enables alignment transfer to heteronuclei). This strategy works in pure H2O or D2O solutions, on substrates that could not be hyperpolarized in traditional 1H-SABRE experiments, and we record 15N T1 relaxation times of up to 2 min.}, number={23}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Colell, Johannes F. P. and Emondts, Meike and Logan, Angus W. J. and Shen, Kun and Bae, Junu and Shchepin, Roman V. and Ortiz, Gerardo X., Jr. and Spannring, Peter and Wang, Qiu and Malcolmson, Steven J. and et al.}, year={2017}, month={May}, pages={7761–7767} }
@article{colell_logan_zhou_shchepin_barskiy_ortiz_wang_malcolmson_chekmenev_warren_et al._2017, title={Generalizing, Extending, and Maximizing Nitrogen-15 Hyperpolarization Induced by Parahydrogen in Reversible Exchange}, volume={121}, ISSN={1932-7447 1932-7455}, url={http://dx.doi.org/10.1021/acs.jpcc.6b12097}, DOI={10.1021/acs.jpcc.6b12097}, abstractNote={Signal Amplification by Reversible Exchange (SABRE) is a fast and convenient NMR hyperpolarization method that uses cheap and readily available para-hydrogen as a hyperpolarization source. SABRE can hyperpolarize protons and heteronuclei. Here we focus on the heteronuclear variant introduced as SABRE-SHEATH (SABRE in SHield Enables Alignment Transfer to Heteronuclei) and nitrogen-15 targets in particular. We show that 15N-SABRE works more efficiently and on a wider range of substrates than 1H-SABRE, greatly generalizing the SABRE approach. In addition, we show that nitrogen-15 offers significantly extended T1 times of up to 12 minutes. Long T1 times enable higher hyperpolarization levels but also hold the promise of hyperpolarized molecular imaging for several tens of minutes. Detailed characterization and optimization are presented, leading to nitrogen-15 polarization levels in excess of 10% on several compounds.}, number={12}, journal={The Journal of Physical Chemistry C}, publisher={American Chemical Society (ACS)}, author={Colell, Johannes F. P. and Logan, Angus W. J. and Zhou, Zijian and Shchepin, Roman V. and Barskiy, Danila A. and Ortiz, Gerardo X., Jr. and Wang, Qiu and Malcolmson, Steven J. and Chekmenev, Eduard Y. and Warren, Warren S. and et al.}, year={2017}, month={Feb}, pages={6626–6634} }
@article{tayler_theis_sjolander_blanchard_kentner_pustelny_pines_budker_2017, title={Instrumentation for nuclear magnetic resonance in zero and ultralow magnetic field}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85170948908&partnerID=MN8TOARS}, DOI={10.48550/arxiv.1705.04489}, journal={arXiv}, author={Tayler, M.C.D. and Theis, T. and Sjolander, T.F. and Blanchard, J.W. and Kentner, A. and Pustelny, S. and Pines, A. and Budker, D.}, year={2017} }
@article{tayler_theis_sjolander_blanchard_kentner_pustelny_pines_budker_2017, title={Invited Review Article: Instrumentation for nuclear magnetic resonance in zero and ultralow magnetic field}, volume={88}, ISSN={0034-6748 1089-7623}, url={http://dx.doi.org/10.1063/1.5003347}, DOI={10.1063/1.5003347}, abstractNote={We review experimental techniques in our laboratory for nuclear magnetic resonance (NMR) in zero and ultralow magnetic field (below 0.1 μT) where detection is based on a low-cost, non-cryogenic, spin-exchange relaxation free 87Rb atomic magnetometer. The typical sensitivity is 20-30 fT/Hz1/2 for signal frequencies below 1 kHz and NMR linewidths range from Hz all the way down to tens of mHz. These features enable precision measurements of chemically informative nuclear spin-spin couplings as well as nuclear spin precession in ultralow magnetic fields.}, number={9}, journal={Review of Scientific Instruments}, publisher={AIP Publishing}, author={Tayler, Michael C. D. and Theis, Thomas and Sjolander, Tobias F. and Blanchard, John W. and Kentner, Arne and Pustelny, Szymon and Pines, Alexander and Budker, Dmitry}, year={2017}, month={Sep}, pages={091101} }
@article{zhou_yu_colell_laasner_logan_barskiy_shchepin_chekmenev_blum_warren_et al._2017, title={Long-Lived 13C2 Nuclear Spin States Hyperpolarized by Parahydrogen in Reversible Exchange at Microtesla Fields}, volume={8}, ISSN={1948-7185}, url={http://dx.doi.org/10.1021/acs.jpclett.7b00987}, DOI={10.1021/acs.jpclett.7b00987}, abstractNote={Parahydrogen is an inexpensive and readily available source of hyperpolarization used to enhance magnetic resonance signals by up to four orders of magnitude above thermal signals obtained at ∼10 T. A significant challenge for applications is fast signal decay after hyperpolarization. Here we use parahydrogen-based polarization transfer catalysis at microtesla fields (first introduced as SABRE-SHEATH) to hyperpolarize 13C2 spin pairs and find decay time constants of 12 s for magnetization at 0.3 mT, which are extended to 2 min at that same field, when long-lived singlet states are hyperpolarized instead. Enhancements over thermal at 8.5 T are between 30 and 170 fold (0.02 to 0.12% polarization). We control the spin dynamics of polarization transfer by choice of microtesla field, allowing for deliberate hyperpolarization of either magnetization or long-lived singlet states. Density functional theory calculations and experimental evidence identify two energetically close mechanisms for polarization transfer: First, a model that involves direct binding of the 13C2 pair to the polarization transfer catalyst and, second, a model transferring polarization through auxiliary protons in substrates.}, number={13}, journal={The Journal of Physical Chemistry Letters}, publisher={American Chemical Society (ACS)}, author={Zhou, Zijian and Yu, Jin and Colell, Johannes F. P. and Laasner, Raul and Logan, Angus and Barskiy, Danila A. and Shchepin, Roman V. and Chekmenev, Eduard Y. and Blum, Volker and Warren, Warren S. and et al.}, year={2017}, month={Jun}, pages={3008–3014} }
@article{shchepin_jaigirdar_theis_warren_goodson_chekmenev_2017, title={Spin Relays Enable Efficient Long-Range Heteronuclear Signal Amplification by Reversible Exchange}, volume={121}, url={https://doi.org/10.1021/acs.jpcc.7b11485}, DOI={10.1021/acs.jpcc.7b11485}, abstractNote={A systematic experimental study is reported on the polarization transfer to distant spins, which do not directly bind to the polarization transfer complexes employed in Signal Amplification By Reversible Exchange (SABRE) experiments. Both, long-range transfer to protons and long-range transfer to heteronuclei i.e. 13C and 15N are examined. Selective destruction of hyperpolarization on 1H, 13C, and 15N sites is employed, followed by their re-hyperpolarization from neighboring spins within the molecules of interest (pyridine for 1H studies and metronidazole-15N2-13C2 for 13C and 15N studies). We conclude that long-range sites can be efficiently hyperpolarized when a network of spin-½ nuclei enables relayed polarization transfer (i.e. via short-range interactions between sites). In case of proton SABRE in the milli-Tesla regime, a relay network consisting of protons only is sufficient. However, in case 13C and 15N are targeted (i.e. via SABRE in SHield Enables Alignment Transfer to Heteronuclei or SABRE-SHEATH experiment), the presence of a heteronuclear network (e.g. consisting of 15N) enables a relay mechanism that is significantly more efficient than the direct transfer of spin order from para-H2-derived hydrides.}, number={51}, journal={The Journal of Physical Chemistry C}, publisher={American Chemical Society (ACS)}, author={Shchepin, Roman V. and Jaigirdar, Lamya and Theis, Thomas and Warren, Warren S. and Goodson, Boyd M. and Chekmenev, Eduard Y.}, year={2017}, month={Dec}, pages={28425–28434} }
@article{barskiy_shchepin_tanner_colell_goodson_theis_warren_chekmenev_2017, title={The Absence of Quadrupolar Nuclei Facilitates Efficient13C Hyperpolarization via Reversible Exchange with Parahydrogen}, volume={18}, ISSN={1439-4235}, url={http://dx.doi.org/10.1002/cphc.201700416}, DOI={10.1002/cphc.201700416}, abstractNote={Abstract}, number={12}, journal={ChemPhysChem}, publisher={Wiley}, author={Barskiy, Danila A. and Shchepin, Roman V. and Tanner, Christian P. N. and Colell, Johannes F. P. and Goodson, Boyd M. and Theis, Thomas and Warren, Warren S. and Chekmenev, Eduard Y.}, year={2017}, month={May}, pages={1493–1498} }
@article{shen_logan_colell_bae_ortiz_theis_warren_malcolmson_wang_2017, title={Titelbild: Diazirines as Potential Molecular Imaging Tags: Probing the Requirements for Efficient and Long‐Lived SABRE‐Induced Hyperpolarization (Angew. Chem. 40/2017)}, url={https://doi.org/10.1002/ange.201707296}, DOI={10.1002/ange.201707296}, abstractNote={Diazirine sind dank ihrer Biokompatibilität und ihres leichten Einbaus in verschiedenartige Verbindungen aussichtsreiche molekulare Marker für Kernspintomographie und NMR-Spektroskopie. In ihrer Zuschrift auf S. 12280 zeigen W. S. Warren, S. J. Malcolmson, Q. Wang und Mitarbeiter anhand eines entsprechenden Cholinderivats, dass 15N2-Diazirin-Motive eine lang anhaltende Polarisation durch die einfache SABRE-SHEATH-Hyperpolarisationsmethode unterstützen. Diazirine sind dank ihrer Biokompatibilität und ihres leichten Einbaus in verschiedenartige Verbindungen aussichtsreiche molekulare Marker für Kernspintomographie und NMR-Spektroskopie. In ihrer Zuschrift auf S. 12280 zeigen W. S. Warren, S. J. Malcolmson, Q. Wang und Mitarbeiter anhand eines entsprechenden Cholinderivats, dass 15N2-Diazirin-Motive eine lang anhaltende Polarisation durch die einfache SABRE-SHEATH-Hyperpolarisationsmethode unterstützen. Polymervesikel Naturstoffsynthese Nitrilsynthese}, journal={Angewandte Chemie}, author={Shen, Kun and Logan, Angus W. J. and Colell, Johannes F. P. and Bae, Junu and Ortiz, Gerardo X., Jr. and Theis, Thomas and Warren, Warren S. and Malcolmson, Steven J. and Wang, Qiu}, year={2017}, month={Sep} }
@article{shchepin_goodson_theis_warren_chekmenev_2017, title={Toward Hyperpolarized 19F Molecular Imaging via Reversible Exchange with Parahydrogen}, volume={18}, ISSN={1439-4235}, url={http://dx.doi.org/10.1002/cphc.201700594}, DOI={10.1002/cphc.201700594}, abstractNote={Abstract}, number={15}, journal={ChemPhysChem}, publisher={Wiley}, author={Shchepin, Roman V. and Goodson, Boyd M. and Theis, Thomas and Warren, Warren S. and Chekmenev, Eduard Y.}, year={2017}, month={Jun}, pages={1961–1965} }
@article{shchepin_barskiy_coffey_theis_shi_warren_goodson_chekmenev_2016, title={15N Hyperpolarization of Imidazole-15N2 for Magnetic Resonance pH Sensing via SABRE-SHEATH}, volume={1}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84983493215&partnerID=MN8TOARS}, DOI={10.1021/acssensors.6b00231}, abstractNote={15N nuclear spins of imidazole-15N2 were hyperpolarized using NMR signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). A 15N NMR signal enhancement of ∼2000-fold at 9.4 T is reported using parahydrogen gas (∼50% para-) and ∼0.1 M imidazole-15N2 in methanol:aqueous buffer (∼1:1). Proton binding to a 15N site of imidazole occurs at physiological pH (pKa ∼ 7.0), and the binding event changes the 15N isotropic chemical shift by ∼30 ppm. These properties are ideal for in vivo pH sensing. Additionally, imidazoles have low toxicity and are readily incorporated into a wide range of biomolecules. 15N-Imidazole SABRE-SHEATH hyperpolarization potentially enables pH sensing on scales ranging from peptide and protein molecules to living organisms.}, number={6}, journal={ACS Sensors}, publisher={American Chemical Society (ACS)}, author={Shchepin, Roman V. and Barskiy, Danila A. and Coffey, Aaron M. and Theis, Thomas and Shi, Fan and Warren, Warren S. and Goodson, Boyd M. and Chekmenev, Eduard Y.}, year={2016}, month={Apr}, pages={640–644} }
@article{zhou_claytor_warren_theis_2016, title={Accessing long lived 1H states via 2H couplings}, volume={263}, url={https://doi.org/10.1016/j.jmr.2015.12.020}, DOI={10.1016/j.jmr.2015.12.020}, abstractNote={In this paper we demonstrate long-lived states involving a pair of chemically equivalent protons, with lifetimes ∼30 times T1 up to a total lifetime of ∼117s at high field (8.45T). This is demonstrated on trans-ethylene-d2 in solution, where magnetic inequivalence gives access to the long-lived states. It is shown that the remaining J-coupling between the two quadrupolar deuterium spins, JQQ, splits the conditions for optimally generating proton singlet states. Detailed simulations of the spin evolution are performed, shedding light on the coherent evolution during singlet-triplet conversion as well as on the incoherent evolution that causes relaxation. Subsequently, the simulations are compared with experimental results validating the theoretical insights. Possible applications include storage of hyperpolarization in the proton long-lived state. Of particular interest may be utilization of parahydrogen induced polarization to directly induce the examined long-lived states.}, journal={Journal of Magnetic Resonance}, publisher={Elsevier BV}, author={Zhou, Zijian and Claytor, Kevin and Warren, Warren S. and Theis, Thomas}, year={2016}, month={Feb}, pages={108–115} }
@article{theis_ortiz_logan_claytor_feng_huhn_blum_malcolmson_chekmenev_wang_et al._2016, title={Direct and cost-efficient hyperpolarization of long-lived nuclear spin states on universal 15N2-diazirine molecular tags}, volume={2}, url={https://doi.org/10.1126/sciadv.1501438}, DOI={10.1126/sciadv.1501438}, abstractNote={More than 10,000-fold enhanced magnetic resonance signals with >20-min signal lifetimes on universal biomolecular markers.}, number={3}, journal={Science Advances}, publisher={American Association for the Advancement of Science (AAAS)}, author={Theis, T. and Ortiz, G. X. and Logan, A. W. J. and Claytor, K. E. and Feng, Y. and Huhn, W. P. and Blum, V. and Malcolmson, S. J. and Chekmenev, E. Y. and Wang, Q. and et al.}, year={2016}, month={Mar}, pages={e1501438–e1501438} }
@article{logan_theis_colell_warren_malcolmson_2016, title={Hyperpolarization of Nitrogen-15 Schiff Bases by Reversible Exchange Catalysis with para-Hydrogen}, volume={22}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84976871360&partnerID=MN8TOARS}, DOI={10.1002/chem.201602393}, abstractNote={Abstract}, number={31}, journal={Chemistry - A European Journal}, publisher={Wiley-Blackwell}, author={Logan, Angus W. J. and Theis, Thomas and Colell, Johannes F. P. and Warren, Warren S. and Malcolmson, Steven J.}, year={2016}, month={Jun}, pages={10777–10781} }
@article{barskiy_shchepin_coffey_theis_warren_goodson_chekmenev_2016, title={Over 20%15N Hyperpolarization in Under One Minute for Metronidazole, an Antibiotic and Hypoxia Probe}, volume={138}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84979021827&partnerID=MN8TOARS}, DOI={10.1021/jacs.6b04784}, abstractNote={Direct NMR hyperpolarization of naturally abundant 15N sites in metronidazole is demonstrated using SABRE-SHEATH (Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). In only a few tens of seconds, nuclear spin polarization P15N of up to ∼24% is achieved using parahydrogen with 80% para fraction corresponding to P15N ≈ 32% if ∼100% parahydrogen were employed (which would translate to a signal enhancement of ∼0.1-million-fold at 9.4 T). In addition to this demonstration on the directly binding 15N site (using J2H-15N), we also hyperpolarized more distant 15N sites in metronidazole using longer-range spin–spin couplings (J4H-15N and J5H-15N). Taken together, these results significantly expand the range of molecular structures and sites amenable to hyperpolarization via low-cost parahydrogen-based methods. In particular, hyperpolarized nitroimidazole and its derivatives have powerful potential applications such as direct in vivo imaging of mechanisms of action or hypoxia sensing.}, number={26}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Barskiy, Danila A. and Shchepin, Roman V. and Coffey, Aaron M. and Theis, Thomas and Warren, Warren S. and Goodson, Boyd M. and Chekmenev, Eduard Y.}, year={2016}, month={Jul}, pages={8080–8083} }
@article{truong_theis_coffey_shchepin_waddell_shi_goodson_warren_chekmenev_2015, title={15N Hyperpolarization by Reversible Exchange Using SABRE-SHEATH}, volume={119}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84928548186&partnerID=MN8TOARS}, DOI={10.1021/acs.jpcc.5b01799}, abstractNote={NMR signal amplification by reversible exchange (SABRE) is a NMR hyperpolarization technique that enables nuclear spin polarization enhancement of molecules via concurrent chemical exchange of a target substrate and parahydrogen (the source of spin order) on an iridium catalyst. Recently, we demonstrated that conducting SABRE in microtesla fields provided by a magnetic shield enables up to 10% 15N-polarization (Theis, T.; et al. J. Am. Chem. Soc.2015, 137, 1404). Hyperpolarization on 15N (and heteronuclei in general) may be advantageous because of the long-lived nature of the hyperpolarization on 15N relative to the short-lived hyperpolarization of protons conventionally hyperpolarized by SABRE, in addition to wider chemical shift dispersion and absence of background signal. Here we show that these unprecedented polarization levels enable 15N magnetic resonance imaging. We also present a theoretical model for the hyperpolarization transfer to heteronuclei, and detail key parameters that should be optimized for efficient 15N-hyperpolarization. The effects of parahydrogen pressure, flow rate, sample temperature, catalyst-to-substrate ratio, relaxation time (T1), and reversible oxygen quenching are studied on a test system of 15N-pyridine in methanol-d4. Moreover, we demonstrate the first proof-of-principle 13C-hyperpolarization using this method. This simple hyperpolarization scheme only requires access to parahydrogen and a magnetic shield, and it provides large enough signal gains to enable one of the first 15N images (2 × 2 mm2 resolution). Importantly, this method enables hyperpolarization of molecular sites with NMR T1 relaxation times suitable for biomedical imaging and spectroscopy.}, number={16}, journal={The Journal of Physical Chemistry C}, publisher={American Chemical Society (ACS)}, author={Truong, Milton L. and Theis, Thomas and Coffey, Aaron M. and Shchepin, Roman V. and Waddell, Kevin W. and Shi, Fan and Goodson, Boyd M. and Warren, Warren S. and Chekmenev, Eduard Y.}, year={2015}, month={Apr}, pages={8786–8797} }
@article{shchepin_truong_theis_coffey_shi_waddell_warren_goodson_chekmenev_2015, title={Hyperpolarization of “Neat” Liquids by NMR Signal Amplification by Reversible Exchange}, volume={6}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84930202261&partnerID=MN8TOARS}, DOI={10.1021/acs.jpclett.5b00782}, abstractNote={We report NMR Signal Amplification by Reversible Exchange (SABRE) hyperpolarization of the rare isotopes in “neat” liquids, each composed only of an otherwise pure target compound with isotopic natural abundance (n.a.) and millimolar concentrations of dissolved catalyst. Pyridine (Py) or Py derivatives are studied at 0.4% isotopic natural abundance 15N, deuterated, 15N enriched, and in various combinations using the SABRE-SHEATH variant (microTesla magnetic fields to permit direct 15N polarization from parahydrogen via reversible binding and exchange with an Ir catalyst). We find that the dilute n.a. 15N spin bath in Py still channels spin order from parahydrogen to dilute 15N spins, without polarization losses due to the presence of 14N or 2H. We demonstrate P15N ≈ 1% (a gain of 2900 fold relative to thermal polarization at 9.4 T) at high substrate concentrations. This fundamental finding has a significant practical benefit for screening potentially hyperpolarizable contrast agents without labeling. The capability of screening at n.a. level of 15N is demonstrated on examples of mono- and dimethyl-substituted Py (picolines and lutidines previously identified as promising pH sensors), showing that the presence of a methyl group in the ortho position significantly decreases SABRE hyperpolarization.}, number={10}, journal={The Journal of Physical Chemistry Letters}, publisher={American Chemical Society (ACS)}, author={Shchepin, Roman V. and Truong, Milton L. and Theis, Thomas and Coffey, Aaron M. and Shi, Fan and Waddell, Kevin W. and Warren, Warren S. and Goodson, Boyd M. and Chekmenev, Eduard Y.}, year={2015}, month={May}, pages={1961–1967} }
@article{theis_truong_coffey_shchepin_waddell_shi_goodson_warren_chekmenev_2015, title={Microtesla SABRE Enables 10% Nitrogen-15 Nuclear Spin Polarization}, volume={137}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84922471897&partnerID=MN8TOARS}, DOI={10.1021/ja512242d}, abstractNote={Parahydrogen is demonstrated to efficiently transfer its nuclear spin hyperpolarization to nitrogen-15 in pyridine and nicotinamide (vitamin B3 amide) by conducting “signal amplification by reversible exchange” (SABRE) at microtesla fields within a magnetic shield. Following transfer of the sample from the magnetic shield chamber to a conventional NMR spectrometer, the 15N NMR signals for these molecules are enhanced by ∼30,000- and ∼20,000-fold at 9.4 T, corresponding to ∼10% and ∼7% nuclear spin polarization, respectively. This method, dubbed “SABRE in shield enables alignment transfer to heteronuclei” or “SABRE-SHEATH”, promises to be a simple, cost-effective way to hyperpolarize heteronuclei. It may be particularly useful for in vivo applications because of longer hyperpolarization lifetimes, lack of background signal, and facile chemical-shift discrimination of different species.}, number={4}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Theis, Thomas and Truong, Milton L. and Coffey, Aaron M. and Shchepin, Roman V. and Waddell, Kevin W. and Shi, Fan and Goodson, Boyd M. and Warren, Warren S. and Chekmenev, Eduard Y.}, year={2015}, month={Jan}, pages={1404–1407} }
@article{claytor_theis_feng_yu_gooden_warren_2014, title={Accessing Long-Lived Disconnected Spin-1/2 Eigenstates through Spins > 1/2}, volume={136}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja505792j}, DOI={10.1021/ja505792j}, abstractNote={Pairs of chemically equivalent (or nearly equivalent) spin-1/2 nuclei have been shown to create disconnected eigenstates that are very long-lived compared with the lifetime of pure magnetization (T1). Here the classes of molecules known to have accessible long-lived states are extended to include those with chemically equivalent spin-1/2 nuclei accessed by coupling to nuclei with spin > 1/2, in this case deuterium. At first, this appears surprising because the quadrupolar interactions present in nuclei with spin > 1/2 are known to cause fast relaxation. Yet it is shown that scalar couplings between deuterium and carbon can guide population into and out of long-lived states, i.e., those immune from the dominant relaxation mechanisms. This implies that it may be practical to consider compounds with (13)C pairs directly bound to deuterium (or even (14)N) as candidates for storage of polarization. In addition, experiments show that simple deuteration of molecules with (13)C pairs at their natural abundance is sufficient for successful lifetime measurements.}, number={43}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Claytor, Kevin and Theis, Thomas and Feng, Yesu and Yu, Jin and Gooden, David and Warren, Warren S.}, year={2014}, month={Oct}, pages={15118–15121} }
@article{türschmann_colell_theis_blümich_appelt_2014, title={Analysis of parahydrogen polarized spin system in low magnetic fields}, volume={16}, ISSN={1463-9076 1463-9084}, url={http://dx.doi.org/10.1039/c4cp01807a}, DOI={10.1039/c4cp01807a}, abstractNote={Parahydrogen polarized spin systems allow for structure determination even in low magnetic fields of a few millitesla and enable efficient polarization transfer to rare heteronuclei.}, number={29}, journal={Physical Chemistry Chemical Physics}, publisher={Royal Society of Chemistry (RSC)}, author={Türschmann, P. and Colell, J. and Theis, T. and Blümich, B. and Appelt, S.}, year={2014}, pages={15411–15421} }
@article{theis_feng_wu_warren_2014, title={Composite and shaped pulses for efficient and robust pumping of disconnected eigenstates in magnetic resonance}, volume={140}, ISSN={0021-9606 1089-7690}, url={http://dx.doi.org/10.1063/1.4851337}, DOI={10.1063/1.4851337}, abstractNote={Hyperpolarization methods, which can enhance nuclear spin signals by orders of magnitude, open up important new opportunities in magnetic resonance. However, many of these applications are limited by spin lattice relaxation, which typically destroys the hyperpolarization in seconds. Significant lifetime enhancements have been found with “disconnected eigenstates” such as the singlet state between a pair of nearly equivalent spins, or the “singlet-singlet” state involving two pairs of chemically equivalent spins; the challenge is to populate these states (for example, from thermal equilibrium magnetization or hyperpolarization) and to later recall the population into observable signal. Existing methods for populating these states are limited by either excess energy dissipation or high sensitivity to inhomogeneities. Here we overcome the limitations by extending recent work using continuous-wave irradiation to include composite and adiabatic pulse excitations. Traditional composite and adiabatic pulses fail completely in this problem because the interactions driving the transitions are fundamentally different, but the new shapes we introduce can move population between accessible and disconnected eigenstates over a wide range of radio-frequency (RF) amplitudes and offsets while depositing insignificant amounts of power.}, number={1}, journal={The Journal of Chemical Physics}, publisher={AIP Publishing}, author={Theis, T. and Feng, Y. and Wu, T. and Warren, W. S.}, year={2014}, month={Jan}, pages={014201} }
@article{theis_truong_coffey_chekmenev_warren_2014, title={LIGHT-SABRE enables efficient in-magnet catalytic hyperpolarization}, volume={248}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84907976450&partnerID=MN8TOARS}, DOI={10.1016/j.jmr.2014.09.005}, abstractNote={Nuclear spin hyperpolarization overcomes the sensitivity limitations of traditional NMR and MRI, but the most general method demonstrated to date (dynamic nuclear polarization) has significant limitations in scalability, cost, and complex apparatus design. As an alternative, signal amplification by reversible exchange (SABRE) of parahydrogen on transition metal catalysts can hyperpolarize a variety of substrates, but to date this scheme has required transfer of the sample to low magnetic field or very strong RF irradiation. Here we demonstrate “Low-Irradiation Generation of High Tesla-SABRE” (LIGHT-SABRE) which works with simple pulse sequences and low power deposition; it should be usable at any magnetic field and for hyperpolarization of many different nuclei. This approach could drastically reduce the cost and complexity of producing hyperpolarized molecules.}, journal={Journal of Magnetic Resonance}, publisher={Elsevier BV}, author={Theis, Thomas and Truong, Milton and Coffey, Aaron M. and Chekmenev, Eduard Y. and Warren, Warren S.}, year={2014}, month={Nov}, pages={23–26} }
@article{light-sabre enables efficient in-magnet catalytic hyperpolarization_2014, url={http://www.sciencedirect.com/science/article/pii/S1090780714002420}, journal={Journal of Magnetic Resonance}, year={2014}, month={Oct} }
@article{emondts_ledbetter_pustelny_theis_patton_blanchard_butler_budker_pines_2014, title={Long-Lived Heteronuclear Spin-Singlet States in Liquids at a Zero Magnetic field}, volume={112}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84894424254&partnerID=MN8TOARS}, DOI={10.1103/physrevlett.112.077601}, abstractNote={We report an observation of long-lived spin-singlet states in a 13C-1H spin pair in a zero magnetic field. In 13C-labeled formic acid, we observe spin-singlet lifetimes as long as 37 s, about a factor of 3 longer than the T1 lifetime of dipole polarization in the triplet state. In contrast to common high-field experiments, the observed coherence is a singlet-triplet coherence with a lifetime T2 longer than the T1 lifetime of dipole polarization in the triplet manifold. Moreover, we demonstrate that heteronuclear singlet states formed between a 1H and a 13C nucleus can exhibit longer lifetimes than the respective triplet states even in the presence of additional spins that couple to the spin pair of interest. Although long-lived homonuclear spin-singlet states have been extensively studied, this is the first experimental observation of analogous singlet states in heteronuclear spin pairs.}, number={7}, journal={Phys. Rev. Lett.}, author={Emondts, M. and Ledbetter, M. P. and Pustelny, S. and Theis, T. and Patton, B. and Blanchard, J. W. and Butler, M. C. and Budker, D. and Pines, A.}, year={2014}, month={Feb} }
@article{feng_theis_wu_claytor_warren_2014, title={Long-lived polarization protected by symmetry}, volume={141}, ISSN={0021-9606 1089-7690}, url={http://dx.doi.org/10.1063/1.4896895}, DOI={10.1063/1.4896895}, abstractNote={In this paper we elucidate, theoretically and experimentally, molecular motifs which permit Long-Lived Polarization Protected by Symmetry (LOLIPOPS). The basic assembly principle starts from a pair of chemically equivalent nuclei supporting a long-lived singlet state and is completed by coupling to additional pairs of spins. LOLIPOPS can be created in various sizes; here we review four-spin systems, introduce a group theory analysis of six-spin systems, and explore eight-spin systems by simulation. The focus is on AA′XnX′n spin systems, where typically the A spins are 15N or 13C and X spins are protons. We describe the symmetry of the accessed states, we detail the pulse sequences used to access these states, we quantify the fraction of polarization that can be stored as LOLIPOPS, we elucidate how to access the protected states from A or from X polarization and we examine the behavior of these spin systems upon introduction of a small chemical shift difference.}, number={13}, journal={The Journal of Chemical Physics}, publisher={AIP Publishing}, author={Feng, Yesu and Theis, Thomas and Wu, Tung-Lin and Claytor, Kevin and Warren, Warren S.}, year={2014}, month={Oct}, pages={134307} }
@article{claytor_theis_feng_warren_2014, title={Measuring long-lived 13C2 state lifetimes at natural abundance}, volume={239}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84892739097&partnerID=MN8TOARS}, DOI={10.1016/j.jmr.2013.12.009}, abstractNote={Long-lived disconnected eigenstates (for example, the singlet state in a system with two nearly equivalent carbons, or the singlet–singlet state in a system with two chemically equivalent carbons and two chemically equivalent hydrogens) hold the potential to drastically extend the lifetime of hyperpolarization in molecular tracers for in vivo magnetic resonance imaging (MRI). However, a first-principles calculation of the expected lifetime (and thus selection of potential imaging agents) is made very difficult because of the large variety of relevant intra- and intermolecular relaxation mechanisms. As a result, all previous measurements relied on costly and time consuming syntheses of 13C labeled compounds. Here we show that it is possible to determine 13C singlet state lifetimes by detecting the naturally abundant doubly-labeled species. This approach allows for rapid and low cost screening of potential molecular biomarkers bearing long-lived states.}, journal={Journal of Magnetic Resonance}, publisher={Elsevier BV}, author={Claytor, Kevin and Theis, Thomas and Feng, Yesu and Warren, Warren}, year={2014}, month={Feb}, pages={81–86} }
@article{theis_blanchard_butler_ledbetter_budker_pines_2013, title={Chemical analysis using J-coupling multiplets in zero-field NMR}, volume={580}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84880924575&partnerID=MN8TOARS}, DOI={10.1016/j.cplett.2013.06.042}, abstractNote={Zero-field nuclear magnetic resonance (NMR) spectroscopy is emerging as a new, potentially portable, and cost-effective NMR modality with the ability to provide information-rich, high-resolution spectra. We present simple rules for analysis of zero-field NMR spectra based on first-order perturbation theory and the addition of angular momenta. These rules allow for the prediction of observed spectral lines without numerical simulation. Results are presented for a few small organic molecules with characteristic spin topologies, demonstrating unambiguous assignment of peaks, highlighting the potential of zero-field NMR as a tool for chemical identification.}, journal={Chemical Physics Letters}, publisher={Elsevier BV}, author={Theis, Thomas and Blanchard, John W. and Butler, Mark C. and Ledbetter, Micah P. and Budker, Dmitry and Pines, Alexander}, year={2013}, month={Aug}, pages={160–165} }
@article{colell_türschmann_glöggler_schleker_theis_ledbetter_budker_pines_blümich_appelt_2013, title={Fundamental Aspects of Parahydrogen Enhanced Low-Field Nuclear Magnetic Resonance}, volume={110}, url={http://dx.doi.org/10.1103/physrevlett.110.137602}, DOI={10.1103/physrevlett.110.137602}, abstractNote={We report new phenomena in low-field 1H nuclear magnetic resonance (NMR) spectroscopy using parahydrogen induced polarization (PHIP), enabling determination of chemical shift differences, δν, and the scalar coupling constant J. NMR experiments performed with thermal polarization in millitesla magnetic fields do not allow the determination of scalar coupling constants for homonuclear coupled spins in the inverse weak coupling regime (δν