共查询到20条相似文献，搜索用时 0 毫秒
1.
Ryan E. Mewis Kevin D. Atkinson Michael J. Cowley Simon B. Duckett Gary G. R. Green Richard A. Green Louise A. R. Highton David Kilgour Lyrelle S. Lloyd Joost A. B. Lohman David C. Williamson 《Magnetic resonance in chemistry : MRC》2014,52(7):358-369
Hyperpolarization methods are used in NMR to overcome its inherent sensitivity problem. Herein, the biologically relevant target nicotinamide is polarized by the hyperpolarization technique signal amplification by reversible exchange. We illustrate how the polarization transfer field, and the concentrations of parahydrogen, the polarization‐transfer‐catalyst and substrate can be used to maximize signal amplification by reversible exchange effectiveness by reference to the first‐order spin system of this target. The catalyst is shown to be crucial in this process, first by facilitating the transfer of hyperpolarization from parahydrogen to nicotinamide and then by depleting the resulting polarized states through further interaction. The 15 longitudinal one, two, three and four spin order terms produced are rigorously identified and quantified using an automated flow apparatus in conjunction with NMR pulse sequences based on the only parahydrogen spectroscopy protocol. The rates of build‐up of these terms were shown to follow the order four~three > two > single spin; this order parallels their rates of relaxation. The result of these competing effects is that the less‐efficiently formed single‐spin order terms dominate at the point of measurement with the two‐spin terms having amplitudes that are an order of magnitude lower. We also complete further measurements to demonstrate that 13C NMR spectra can be readily collected where the long‐lived quaternary 13C signals appear with significant intensity. These are improved upon by using INEPT. In summary, we dissect the complexity of this method, highlighting its benefits to the NMR community and its applicability for high‐sensitivity magnetic resonance imaging detection in the future. © 2014 The Authors. Magnetic Resonance in Chemistry by John Wiley & Sons, Ltd. 相似文献
2.
Patrick M. TomHon Dr. Suyong Han Dr. Sören Lehmkuhl Prof. Stephan Appelt Prof. Eduard Y. Chekmenev Prof. Milad Abolhasani Prof. Thomas Theis 《Chemphyschem》2021,22(24):2526-2534
We introduce a Spin Transfer Automated Reactor (STAR) that produces continuous parahydrogen induced polarization (PHIP), which is stable for hours to days. We use the PHIP variant called signal amplification by reversible exchange (SABRE), which is particularly well suited to produce continuous hyperpolarization. The STAR is operated in conjunction with benchtop (1.1 T) and high field (9.4 T) NMR magnets, highlighting the versatility of this system to operate with any NMR or MRI system. The STAR uses semipermeable membranes to efficiently deliver parahydrogen into solutions at nano to milli Tesla fields, which enables 1H, 13C, and 15N hyperpolarization on a large range of substrates including drugs and metabolites. The unique features of the STAR are leveraged for important applications, including continuous hyperpolarization of metabolites, desirable for examining steady-state metabolism in vivo, as well as for continuous RASER signals suitable for the investigation of new physics. 相似文献
3.
Baptiste Joalland Nuwandi M. Ariyasingha Sren Lehmkuhl Thomas Theis Stephan Appelt Eduard Y. Chekmenev 《Angewandte Chemie (International ed. in English)》2020,59(22):8654-8660
Radio amplification by stimulated emission of radiation (RASER) was recently discovered in a low‐field NMR spectrometer incorporating a highly specialized radio‐frequency resonator, where a high degree of proton‐spin polarization was achieved by reversible parahydrogen exchange. RASER activity, which results from the coherent coupling between the nuclear spins and the inductive detector, can overcome the limits of frequency resolution in NMR. Here we show that this phenomenon is not limited to low magnetic fields or the use of resonators with high‐quality factors. We use a commercial bench‐top 1.4 T NMR spectrometer in conjunction with pairwise parahydrogen addition producing proton‐hyperpolarized molecules in the Earth's magnetic field (ALTADENA condition) or in a high magnetic field (PASADENA condition) to induce RASER without any radio‐frequency excitation pulses. The results demonstrate that RASER activity can be observed on virtually any NMR spectrometer and measures most of the important NMR parameters with high precision. 相似文献
4.
Kirill V. Kovtunov Igor V. Koptyug Marianna Fekete Simon B. Duckett Thomas Theis Baptiste Joalland Eduard Y. Chekmenev 《Angewandte Chemie (International ed. in English)》2020,59(41):17788-17797
Imaging of gases is a major challenge for any modality including MRI. NMR and MRI signals are directly proportional to the nuclear spin density and the degree of alignment of nuclear spins with applied static magnetic field, which is called nuclear spin polarization. The level of nuclear spin polarization is typically very low, i.e., one hundred thousandth of the potential maximum at 1.5 T and a physiologically relevant temperature. As a result, MRI typically focusses on imaging highly concentrated tissue water. Hyperpolarization methods transiently increase nuclear spin polarizations up to unity, yielding corresponding gains in MRI signal level of several orders of magnitude that enable the 3D imaging of dilute biomolecules including gases. Parahydrogen‐induced polarization is a fast, highly scalable, and low‐cost hyperpolarization technique. The focus of this Minireview is to highlight selected advances in the field of parahydrogen‐induced polarization for the production of hyperpolarized compounds, which can be potentially employed as inhalable contrast agents. 相似文献
5.
Dr. Alexey S. Kiryutin Prof. Alexandra V. Yurkovskaya Prof. Konstantin L. Ivanov 《Chemphyschem》2021,22(14):1470-1477
Signal Amplification By Reversible Exchange (SABRE) is gaining increased attention as a tool to enhance weak Nuclear Magnetic Resonance (NMR) signals. In SABRE, spin order is transferred from parahydrogen (H2 in its nuclear singlet spin state) to a substrate molecule in a transient Ir-based complex. In recent years, SABRE polarization of biologically active substrates has been demonstrated, notably of metronidazole – an antibiotic and antiprotozoal drug. In this work, we study 15N SABRE polarization of metronidazole at natural isotope abundance. We are able to demonstrate significant 15N polarization reaching 15 %, which corresponds to a signal enhancement of 46,000 at 9.4 T for the nitrogen atom with lone electron pair. Additionally, the other two N-atoms can be polarized, although less efficiently. We present a detailed study of the field dependence of polarization and explain the maxima in the field dependence using the concept of coherent polarization transfer at level anti-crossings in the SABRE complex. A study of spin relaxation phenomena presented here enables optimization of the magnetic field for efficient storage of non-thermal polarization. 相似文献
6.
7.
Isaiah Adelabu Patrick TomHon Mohammad S. H. Kabir Shiraz Nantogma Mustapha Abdulmojeed Iuliia Mandzhieva Dr. Jessica Ettedgui Dr. Rolf E. Swenson Dr. Murali C. Krishna Prof. Thomas Theis Prof. Boyd M. Goodson Prof. Eduard Y. Chekmenev 《Chemphyschem》2022,23(2):e202100839
Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) is investigated to achieve rapid hyperpolarization of 13C1 spins of [1-13C]pyruvate, using parahydrogen as the source of nuclear spin order. Pyruvate exchange with an iridium polarization transfer complex can be modulated via a sensitive interplay between temperature and co-ligation of DMSO and H2O. Order-unity 13C (>50 %) polarization of catalyst-bound [1-13C]pyruvate is achieved in less than 30 s by restricting the chemical exchange of [1-13C]pyruvate at lower temperatures. On the catalyst bound pyruvate, 39 % polarization is measured using a 1.4 T NMR spectrometer, and extrapolated to >50 % at the end of build-up in situ. The highest measured polarization of a 30-mM pyruvate sample, including free and bound pyruvate is 13 % when using 20 mM DMSO and 0.5 M water in CD3OD. Efficient 13C polarization is also enabled by favorable relaxation dynamics in sub-microtesla magnetic fields, as indicated by fast polarization buildup rates compared to the T1 spin-relaxation rates (e. g., ∼0.2 s−1 versus ∼0.1 s−1, respectively, for a 6 mM catalyst-[1-13C]pyruvate sample). Finally, the catalyst-bound hyperpolarized [1-13C]pyruvate can be released rapidly by cycling the temperature and/or by optimizing the amount of water, paving the way to future biomedical applications of hyperpolarized [1-13C]pyruvate produced via comparatively fast and simple SABRE-SHEATH-based approaches. 相似文献
8.
Dr. Alexey S. Kiryutin Dr. Grit Sauer Dr. Daniel Tietze Martin Brodrecht Stephan Knecht Prof. Dr. Alexandra V. Yurkovskaya Prof. Dr. Konstantin L. Ivanov Dr. Olga Avrutina Prof. Dr. Harald Kolmar Prof. Dr. Gerd Buntkowsky 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(16):4025-4030
Two-dimensional NMR spectroscopy is one of the most important spectroscopic tools for the investigation of biological macromolecules. However, due to the low sensitivity of NMR spectroscopy, it takes usually from several minutes to many hours to record such spectra. Here, the possibility of detecting a bioactive derivative of the sunflower trypsin inhibitor-1 (SFTI-1), a tetradecapeptide, by combining parahydrogen-induced polarization (PHIP) and ultrafast 2D NMR spectroscopy is shown. The PHIP activity of the inhibitor was achieved by labeling with O-propargyl-l -tyrosine. In 1D PHIP experiments a signal enhancement of a factor of approximately 1200 compared to standard NMR was found. This enhancement permits measurement of 2D NMR correlation spectra of low-concentrated SFTI-1 in less than 10 seconds, employing ultrafast single-scan 2D NMR detection. As experimental examples PHIP-assisted ultrafast single-scan TOCSY spectra of SFTI-1 are shown. 相似文献
9.
Dr. Baptiste Joalland Nuwandi M. Ariyasingha Hassan R. Younes Shiraz Nantogma Dr. Oleg G. Salnikov Dr. Nikita V. Chukanov Dr. Kirill V. Kovtunov Prof. Igor V. Koptyug Prof. Juri G. Gelovani Prof. Eduard Y. Chekmenev 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(8):2774-2781
Many MRI contrast agents formed with the parahydrogen-induced polarization (PHIP) technique exhibit biocompatible profiles. In the context of respiratory imaging with inhalable molecular contrast agents, the development of nonflammable contrast agents would nonetheless be highly beneficial for the biomedical translation of this sensitive, high-throughput and affordable hyperpolarization technique. To this end, we assess the hydrogenation kinetics, the polarization levels and the lifetimes of PHIP hyperpolarized products (acids, ethers and esters) at various degrees of fluorine substitution. The results highlight important trends as a function of molecular structure that are instrumental for the design of new, safe contrast agents for in vivo imaging applications of the PHIP technique, with an emphasis on the highly volatile group of ethers used as inhalable anesthetics. 相似文献
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11.
Prof. Dr. Jan‐Bernd Hövener Dr. Andrey N. Pravdivtsev Dr. Bryce Kidd Prof. C. Russell Bowers Dr. Stefan Glöggler Dr. Kirill V. Kovtunov Dr. Markus Plaumann Prof. Rachel Katz‐Brull Dr. Kai Buckenmaier Prof. Alexej Jerschow Dr. Francesca Reineri Prof. Thomas Theis Prof. Roman V. Shchepin Prof. Shawn Wagner Prof. Pratip Bhattacharya Prof. Niki M. Zacharias Prof. Eduard Y. Chekmenev 《Angewandte Chemie (International ed. in English)》2018,57(35):11140-11162
Magnetic resonance (MR) is one of the most versatile and useful physical effects used for human imaging, chemical analysis, and the elucidation of molecular structures. However, its full potential is rarely used, because only a small fraction of the nuclear spin ensemble is polarized, that is, aligned with the applied static magnetic field. Hyperpolarization methods seek other means to increase the polarization and thus the MR signal. A unique source of pure spin order is the entangled singlet spin state of dihydrogen, parahydrogen (pH2), which is inherently stable and long‐lived. When brought into contact with another molecule, this “spin order on demand” allows the MR signal to be enhanced by several orders of magnitude. Considerable progress has been made in the past decade in the area of pH2‐based hyperpolarization techniques for biomedical applications. It is the goal of this Review to provide a selective overview of these developments, covering the areas of spin physics, catalysis, instrumentation, preparation of the contrast agents, and applications. 相似文献
12.
Prof. Dr. Vladimir V. Zhivonitko Henrik Beer Danila O. Zakharov Dr. Jonas Bresien Prof. Dr. Axel Schulz 《Chemphyschem》2021,22(9):813-817
Biradicaloids attract attention as a novel class of reagents that can activate small molecules such as H2, ethylene and CO2. Herein, we study activation of parahydrogen (nuclear spin-0 isomer of H2) by a number of 4- and 5-membered pnictogen biradicaloids based on hetero-cyclobutanediyl [X(μ-NTer)2Z] and hetero-cyclopentanediyl [X(μ-NTer)2ZC(NDmp)] moieties (X,Z=P,As; Ter=2,6-Mes2−C6H3, Dmp=2,6-Me2−C6H3). The concerted mechanism of this reaction allowed observing strong nuclear spin hyperpolarization effects in 1H and 31P NMR experiments. Signal enhancements from two to four orders of magnitude were detected at 9.4 T depending on the structure. It is demonstrated that 4-membered biradicaloids activate H2 reversibly, leading to SABRE (signal amplification by reversible exchange) hyperpolarization of biradicaloids themselves and their H2 adducts. In contrast, the 5-membered counterparts demonstrate rather irreversible parahydrogen activation resulting in hyperpolarized H2 adducts only. Kinetic measurements provided parameters to support experimental observations. 相似文献
13.
Dr. Eleonora Cavallari Dr. Carla Carrera Prof. Silvio Aime Dr. Francesca Reineri 《Chemphyschem》2019,20(2):318-325
The kinetics of metabolic processes can be assessed, in real time by means of MR hyperpolarized (HP) metabolites. [1-13C]pyruvate, hyperpolarized by means of d-DNP, is, by far, the substrate most widely applied to the investigation of several pathologies characterized by deregulated glycolytic metabolic networks, including cancer. Hyperpolarization of [1-13C]pyruvate by means of the cost effective, fast and easy to handle PHIP-SAH (para-hydrogen induced polarization-side arm hydrogenation) method opens-up a pathway for the application of HP metabolites to a wide range of cancer-related studies. Herein, we report the first application of PHIP-SAH hyperpolarized [1-13C]pyruvate in the investigation of upregulated glycolysis in two murine breast cancer cell lines (168FARN and 4T1). The results obtained using HP pyruvate have been validated with a conventional biochemical assay and are coherent with previously-reported lactate dehydrogenase activity measured in those cells. 相似文献
14.
Ekaterina V. Pokochueva Dr. Dudari B. Burueva Dr. Oleg G. Salnikov Prof. Igor V. Koptyug 《Chemphyschem》2021,22(14):1421-1440
Parahydrogen-induced polarization with heterogeneous catalysts (HET-PHIP) has been a subject of extensive research in the last decade since its first observation in 2007. While NMR signal enhancements obtained with such catalysts are currently below those achieved with transition metal complexes in homogeneous hydrogenations in solution, this relatively new field demonstrates major prospects for a broad range of advanced fundamental and practical applications, from providing catalyst-free hyperpolarized fluids for biomedical magnetic resonance imaging (MRI) to exploring mechanisms of industrially important heterogeneous catalytic processes. This review covers the evolution of the heterogeneous catalysts used for PHIP observation, from metal complexes immobilized on solid supports to bulk metals and single-atom catalysts and discusses the general visions for maximizing the obtained NMR signal enhancements using HET-PHIP. Various practical applications of HET-PHIP, both for catalytic studies and for potential production of hyperpolarized contrast agents for MRI, are described. 相似文献
15.
Dr. Ben. J. Tickner Dr. Fadi Ahwal Dr. Adrian C. Whitwood Prof. Simon B. Duckett 《Chemphyschem》2021,22(1):13-17
The substrate scope of sulfoxide-containing magnetisation transfer catalysts is extended to hyperpolarize α-ketoisocaproate and α-ketoisocaproate-1-[13C]. This is achieved by forming [Ir(H)2(κ2-ketoisocaproate)(N-heterocyclic carbene)(sulfoxide)] which transfers latent magnetism from p-H2 via the signal amplification by reversible exchange (SABRE) process. The effect of polarization transfer field on the formation of enhanced 13C magnetization is evaluated. Consequently, performing SABRE in a 0.5 μT field enabled most efficient magnetisation transfer. 13C NMR signals for α-ketoisocaproate-1-[13C] in methanol-d4 are up to 985-fold more intense than their traditional Boltzmann derived signal intensity (0.8 % 13C polarisation). Single crystal X-ray diffraction reveals the formation of the novel catalyst decomposition products [Ir(μ-H)(H)2(IMes)(SO(Ph)(Me)2)]2 and [(Ir(H)2(IMes)(SO(Me)2))2(μ-S)] when the sulfoxides methylphenylsulfoxide and dimethylsulfoxide are used respectively. 相似文献
16.
Dr. Kai Buckenmaier Prof. Dr. Klaus Scheffler Dr. Markus Plaumann Paul Fehling Prof. Dr. Johannes Bernarding Dr. Matthias Rudolph Dr. Christoph Back Prof. Dr. Dieter Koelle Prof. Dr. Reinhold Kleiner Prof. Dr. Jan-Bernd Hövener Dr. Andrey N. Pravdivtsev 《Chemphyschem》2019,20(21):2823-2829
The development of hyperpolarization technologies enabled several yet exotic NMR applications at low and ultra-low fields (ULF), where without hyperpolarization even the detection of a signal from analytes is a challenge. Herein, we present a method for the simultaneous excitation and observation of homo- and heteronuclear multiple quantum coherences (from zero up to the third-order), which give an additional degree of freedom for ULF NMR experiments, where the chemical shift variation is negligible. The approach is based on heteronuclear correlated spectroscopy (COSY); its combination with a phase-cycling scheme allows the selective observation of multiple quantum coherences of different orders. The nonequilibrium spin state and multiple spin orders are generated by signal amplification by reversible exchange (SABRE) and detected at ULF with a superconducting quantum interference device (SQUID)-based NMR system. 相似文献
17.
Dr. Nikita V. Chukanov Dr. Oleg G. Salnikov Ivan A. Trofimov Mohammad S. H. Kabir Dr. Kirill V. Kovtunov Prof. Igor V. Koptyug Prof. Eduard Y. Chekmenev 《Chemphyschem》2021,22(10):960-967
Signal Amplification by Reversible Exchange (SABRE) technique enables nuclear spin hyperpolarization of wide range of compounds using parahydrogen. Here we present the synthetic approach to prepare 15N-labeled [15N]dalfampridine (4-amino[15N]pyridine) utilized as a drug to reduce the symptoms of multiple sclerosis. The synthesized compound was hyperpolarized using SABRE at microtesla magnetic fields (SABRE-SHEATH technique) with up to 2.0 % 15N polarization. The 7-hour-long activation of SABRE pre-catalyst [Ir(IMes)(COD)Cl] in the presence of [15N]dalfampridine can be remedied by the use of pyridine co-ligand for catalyst activation while retaining the 15N polarization levels of [15N]dalfampridine. The effects of experimental conditions such as polarization transfer magnetic field, temperature, concentration, parahydrogen flow rate and pressure on 15N polarization levels of free and equatorial catalyst-bound [15N]dalfampridine were investigated. Moreover, we studied 15N polarization build-up and decay at magnetic field of less than 0.04 μT as well as 15N polarization decay at the Earth's magnetic field and at 1.4 T. 相似文献
18.
Dr. Oleg G. Salnikov Dr. Nikita V. Chukanov Dr. Larisa M. Kovtunova Prof. Valerii I. Bukhtiyarov Dr. Kirill V. Kovtunov Prof. Roman V. Shchepin Prof. Igor V. Koptyug Prof. Eduard Y. Chekmenev 《Chemphyschem》2021,22(13):1389-1396
Magnetic resonance imaging of [1-13C]hyperpolarized carboxylates (most notably, [1-13C]pyruvate) allows one to visualize abnormal metabolism in tumors and other pathologies. Herein, we investigate the efficiency of 1H and 13C hyperpolarization of acetate and pyruvate esters with ethyl, propyl and allyl alcoholic moieties using heterogeneous hydrogenation of corresponding vinyl, allyl and propargyl precursors in isotopically unlabeled and 1-13C-enriched forms with parahydrogen over Rh/TiO2 catalysts in methanol-d4 and in D2O. The maximum obtained 1H polarization was 0.6±0.2 % (for propyl acetate in CD3OD), while the highest 13C polarization was 0.10±0.03 % (for ethyl acetate in CD3OD). Hyperpolarization of acetate esters surpassed that of pyruvates, while esters with a triple carbon-carbon bond in unsaturated alcoholic moiety were less efficient as parahydrogen-induced polarization precursors than esters with a double bond. Among the compounds studied, the maximum 1H and 13C NMR signal intensities were observed for propyl acetate. Ethyl acetate yielded slightly less intense NMR signals which were dramatically greater than those of other esters under study. 相似文献
19.
Jing Yang Peng Wang Prof. Dr. Jan G. Korvink Prof. Dr. Jürgen J. Brandner Dr. Sören Lehmkuhl 《Chemphyschem》2023,24(14):e202300204
A RASER (Radio Amplification by Stimulated Emission of Radiation) facilitates the study of nonlinear phenomena, as well as the determination of NMR parameters with high precision. To achieve maximum sensitivity in the desired operating mode, it is crucial to control the RASER over long periods of time. So far, this was only possible at ultra-low magnetic fields. Here, we introduce a way to control the operating regime of a RASER at a magnetic field of 1.45 T. We employ a continuous-flow RASER, pumped by PHIP (ParaHydrogen Induced Polarization). The hydrogenation of vinyl acetate (VA) with parahydrogen provides the required negative polarization on the methyl group of the product ethyl acetate (EA). The protons within the methyl group, separated by a 7 Hz J-coupling, are RASER active. This system demonstrates five RASER phenomena: inequivalent and equivalent amplitudes in the “normal NMR mode”, period doublings, frequency combs, and chaos. The experiments match with simulations based on a theoretical model of two nonlinear-coupled RASER modes. We predict the RASER regime at set conditions and visualize the prediction in a bifurcation diagram. 相似文献
20.
Parahydrogen hyperpolarization has emerged as a promising tool for sensitivity-enhanced NMR metabolomics. It allows resolution and quantification of NMR signals of certain classes of low-abundance metabolites that would otherwise be undetectable. Applications have been implemented in pharmacokinetics and doping drug detection, demonstrating the versatility of the technique. Yet, in order for the method to be adopted by the analytical community, certain limitations have to be understood and overcome. One such question is NMR signal assignment. At present, the only reliable way to establish the identity of an analyte that gives rise to certain parahydrogen hyperpolarized NMR signals is internal standard addition, which can be laborious. Herein we show that analogously to regular NMR metabolomics, generating libraries of hyperpolarized analyte signals is a viable way to address this limitation. We present hyperpolarized spectral data of adenosines and give an early example of identifying them from a urine sample with the small library. Doing so, we verify the detectability of a class of diagnostically valuable metabolites: adenosine and its derivatives, some of which are cancer biomarkers, and some are central to cellular energy management (e.g., ATP). 相似文献