共查询到20条相似文献,搜索用时 15 毫秒
1.
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
2.
Nan Eshuis Bram J. A. van Weerdenburg Dr. Martin C. Feiters Prof. Dr. Floris P. J. T. Rutjes Prof. Dr. Sybren S. Wijmenga Dr. Marco Tessari 《Angewandte Chemie (International ed. in English)》2015,54(5):1481-1484
Signal amplification by reversible exchange (SABRE) is an emerging nuclear spin hyperpolarization technique that strongly enhances NMR signals of small molecules in solution. However, such signal enhancements have never been exploited for concentration determination, as the efficiency of SABRE can strongly vary between different substrates or even between nuclear spins in the same molecule. The first application of SABRE for the quantitative analysis of a complex mixture is now reported. Despite the inherent complexity of the system under investigation, which involves thousands of competing binding equilibria, analytes at concentrations in the low micromolar range could be quantified from single‐scan SABRE spectra using a standard‐addition approach. 相似文献
3.
Danila A. Barskiy Dr. Kirill V. Kovtunov Prof. Igor V. Koptyug Ping He Kirsten A. Groome Quinn A. Best Fan Shi Prof. Boyd M. Goodson Dr. Roman V. Shchepin Dr. Milton L. Truong Dr. Aaron M. Coffey Prof. Kevin W. Waddell Prof. Eduard Y. Chekmenev 《Chemphyschem》2014,15(18):4100-4107
By using 5.75 and 47.5 mT nuclear magnetic resonance (NMR) spectroscopy, up to 105‐fold sensitivity enhancement through signal amplification by reversible exchange (SABRE) was enabled, and subsecond temporal resolution was used to monitor an exchange reaction that resulted in the buildup and decay of hyperpolarized species after parahydrogen bubbling. We demonstrated the high‐resolution low‐field proton magnetic resonance imaging (MRI) of pyridine in a 47.5 mT magnetic field endowed by SABRE. Molecular imaging (i.e. imaging of dilute hyperpolarized substances rather than the bulk medium) was conducted in two regimes: in situ real‐time MRI of the reaction mixture (in which pyridine was hyperpolarized), and ex situ MRI (in which hyperpolarization decays) of the liquid hyperpolarized product. Low‐field (milli‐Tesla range, e.g. 5.75 and 47.5 mT used in this study) parahydrogen‐enhanced NMR and MRI, which are free from the limitations of high‐field magnetic resonance (including susceptibility‐induced gradients of the static magnetic field at phase interfaces), potentially enables new imaging applications as well as differentiation of hyperpolarized chemical species on demand by exploiting spin manipulations with static and alternating magnetic fields. 相似文献
4.
Nuclear Spin Hyperpolarization of NH2- and CH3-Substituted Pyridine and Pyrimidine Moieties by SABRE
Hyperpolarization of N-heterocycles with signal amplification by reversible exchange (SABRE) induces NMR sensitivity gains for biological molecules. Substitutions with functional groups, in particular in the ortho-position of the heterocycle, however, result in low polarization using a typical Ir catalyst with a bis-mesityl N-heterocyclic carbene ligand for SABRE, presumably due to steric hindrance. With the addition of allylamine or acetonitrile as coligands to the precatalyst chloro(1,5-cyclooctadiene)[4,5-dimethyl-1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene] iridium, the 1H signal enhancement increased in several substrates with ortho NH2 substitutions. For example, for a proton in 2,4-diaminopyrimidine, the enhancement factors increased from −7±1 to −210±20 with allylamine or to −160±10 with acetonitrile. CH3 substituted molecules yielded maximum signal enhancements of −25±7 with acetonitrile addition, which is considerably less than the corresponding NH2 substituted molecules, despite exhibiting similar steric size. With the more electron-donating NH2 substitution resulting in greater enhancement, it is concluded that steric hindrance is not the only dominant factor in determining the polarizability of the CH3 substituted compounds. The addition of allylamine increased the signal enhancement for the 290 Da trimethoprim, a molecule with a 2,4-diaminopyrimidine moiety serving as an antibacterial agent, to −70. 相似文献
5.
Inside Cover: Quantitative Trace Analysis of Complex Mixtures Using SABRE Hyperpolarization (Angew. Chem. Int. Ed. 5/2015)
下载免费PDF全文
![点击此处可从《Angewandte Chemie (International ed. in English)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Nan Eshuis Bram J. A. van Weerdenburg Dr. Martin C. Feiters Prof. Dr. Floris P. J. T. Rutjes Prof. Dr. Sybren S. Wijmenga Dr. Marco Tessari 《Angewandte Chemie (International ed. in English)》2015,54(5):1372-1372
6.
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
7.
《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(31):9302-9305
DOSY is an NMR spectroscopy technique that resolves resonances according to the analytes’ diffusion coefficients. It has found use in correlating NMR signals and estimating the number of components in mixtures. Applications of DOSY in dilute mixtures are, however, held back by excessively long measurement times. We demonstrate herein, how the enhanced NMR sensitivity provided by SABRE hyperpolarization allows DOSY analysis of low‐micromolar mixtures, thus reducing the concentration requirements by at least 100‐fold. 相似文献
8.
Dr. Peter J. Rayner Prof. Dr. Simon B. Duckett 《Angewandte Chemie (International ed. in English)》2018,57(23):6742-6753
Signal amplification by reversible exchange (SABRE) turns typically weak magnetic resonance responses into strong signals making previously impractical measurements possible. This technique has gained significant popularity because of its speed and simplicity. This Minireview tracks the development of SABRE from the initial hyperpolarization of pyridine in 2009 to the point in which 50 % 1H polarization levels have been achieved in a di‐deuterio‐nicotinate, a key step in the pathway to potential clinical use. Simple routes to highly efficient 15N hyperpolarization and the creation of hyperpolarized long‐lived magnetic states are illustrated. To conclude, we describe how the recently reported SABRE‐RELAY approach offers a route for parahydrogen to hyperpolarize a much wider array of molecular scaffolds, such as amides, alcohols, carboxylic acids, and phosphates, than was previously thought possible. We predict that collectively these developments ensure that SABRE will significantly impact on both chemical analysis and the diagnosis of disease in the future. 相似文献
9.
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
10.
Dr. Ivan V. Skovpin Alexandra Svyatova Dr. Nikita Chukanov Prof. Dr. Eduard Y. Chekmenev Dr. Kirill V. Kovtunov Prof. Dr. Igor V. Koptyug 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(55):12694-12697
Signal Amplification by Reversible Exchange (SABRE) is a promising method for NMR signal enhancement and production of hyperpolarized molecules. As nuclear spin relaxation times of heteronuclei are usually much longer than those of protons, SABRE-based hyperpolarization of heteronuclei in molecules is highly important in the context of biomedical applications. In this work, we demonstrate that the SLIC-SABRE technique can be successfully used to hyperpolarize 15N nuclei in dalfampridine. The high polarization level of ca. 8 % achieved in this work made it possible to acquire 15N MR images at natural abundance of the 15N nuclei for the first time. 相似文献
11.
Dr. Andrey N. Pravdivtsev Prof. Dr. Jan-Bernd Hövener 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(32):7659-7668
The hyperpolarization of nuclear spins by using parahydrogen (pH2) is a fascinating technique that allows spin polarization and thus the magnetic resonance signal to be increased by several orders of magnitude. Entirely new applications have become available. Signal amplification by reversible exchange (SABRE) is a relatively new method that is based on the reversible exchange of a substrate, catalyst and parahydrogen. SABRE is particularly interesting for in vivo medical and industrial applications, such as fast and low-cost trace analysis or continuous signal enhancement. Ever since its discovery, many attempts have been made to model and understand SABRE, with various degrees of simplifications. In this work, we reduced the simplifications further, taking into account non-linear chemical and physical (CAP) dynamics of several multi-spin systems. A master equation was derived and realized using the MOIN open-source software. The effects of different parameters (exchange rates, concentrations, spin–spin couplings) on relaxation and the polarization level have been evaluated and the results provide interesting insights into the mechanism of SABRE. 相似文献
12.
Stephan Berner Andreas B. Schmidt Mirko Zimmermann Dr. Andrey N. Pravdivtsev Dr. Stefan Glöggler Prof. Dr. Dr. h.c. Jürgen Hennig PD Dr. Dominik von Elverfeldt Prof. Dr. Jan-Bernd Hövener 《ChemistryOpen》2019,8(6):728-736
The signal enhancement provided by the hyperpolarization of nuclear spins of biological molecules is a highly promising technique for diagnostic imaging. To date, most 13C-contrast agents had to be polarized in an extra, complex or cost intensive polarizer. Recently, the in situ hyperpolarization of a 13C contrast agent to >20 % was demonstrated without a polarizer but within the bore of an MRI system. This approach addresses some of the challenges of MRI with hyperpolarized tracers, i. e. elevated cost, long production times, and loss of polarization during transfer to the detection site. Here, we demonstrate the first hyperpolarization of a biomolecule in aqueous solution in the bore of an MRI at field strength of 7 T within seconds. The 13C nucleus of 1-13C, 2,3-2H2-succinate was polarized to 11 % corresponding to a signal enhancement of approximately 18.000. Interesting effects during the process of the hydrogenation reaction which lead to a significant loss of polarization have been observed. 相似文献
13.
14.
Single‐Scan Multidimensional NMR Analysis of Mixtures at Sub‐Millimolar Concentrations by using SABRE Hyperpolarization
下载免费PDF全文
![点击此处可从《Chemphyschem》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Dr. Valeria Daniele Dr. François‐Xavier Legrand Dr. Patrick Berthault Dr. Jean‐Nicolas Dumez Dr. Gaspard Huber 《Chemphyschem》2015,16(16):3413-3417
Signal amplification by reversible exchange (SABRE) is a promising method to increase the sensitivity of nuclear magnetic resonance (NMR) experiments. However, SABRE‐enhanced 1H NMR signals are short lived, and SABRE is often used to record 1D NMR spectra only. When the sample of interest is a complex mixture, this results in severe overlaps for 1H spectra. In addition, the use of a co‐substrate, whose signals may obscure the 1H spectra, is currently the most efficient way to lower the detection limit of SABRE experiments. Here, we describe an approach to obtain clean, SABRE‐hyperpolarized 2D 1H NMR spectra of mixtures of small molecules at sub‐millimolar concentrations in a single scan. The method relies on the use of para‐hydrogen together with a deuterated co‐substrate for hyperpolarization and ultrafast 2D NMR for acquisition. It is applicable to all substrates that can be polarized with SABRE. 相似文献
15.
In recent years the NMR hyperpolarisation method signal amplification by reversible exchange (SABRE) has been applied to multiple substrates of potential interest for in vivo investigation. Unfortunately, SABRE commonly requires an iridium-containing catalyst that is unsuitable for biomedical applications. This report utilizes inductively coupled plasma-optical emission spectroscopy (ICP-OES) to investigate the potential use of metal scavengers to remove the iridium catalytic species from the solution. The most sensitive iridium emission line at 224.268 nm was used in the analysis. We report the effects of varying functionality, chain length, and scavenger support identity on iridium scavenging efficiency. The impact of varying the quantity of scavenger utilized is reported for the three scavengers with the highest iridium removed from initial investigations: 3-aminopropyl (S1), 3-(imidazole-1-yl)propyl (S4), and 2-(2-pyridyl) (S5) functionalized silica gels. Exposure of an activated SABRE sample (1.6 mg mL−1 of iridium catalyst) to 10 mg of the most promising scavenger (S5) resulted in <1 ppm of iridium being detectable by ICP-OES after 2 min of exposure. We propose that combining the approach described herein with other recently reported approaches, such as catalyst separated-SABRE (CASH-SABRE), would enable the rapid preparation of a biocompatible SABRE hyperpolarized bolus. 相似文献
16.
Andrey N. Pravdivtsev Prof. Alexandra V. Yurkovskaya Prof. Hans‐Martin Vieth Dr. Konstantin L. Ivanov Prof. Robert Kaptein 《Chemphyschem》2013,14(14):3327-3331
Various hyperpolarization methods are able to enhance the sensitivity of nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) by several orders of magnitude. Among these methods are para‐hydrogen‐induced polarization (PHIP) and signal amplification by reversible exchange (SABRE), which exploit the strong nuclear alignment of para‐hydrogen. Several SABRE experiments have been reported but, so far, it has not been possible to account for the experimentally observed sign and magnetic‐field dependence of substrate polarization. Herein, we present an analysis based on level anti‐crossings (LACs), which provides a complete understanding of the SABRE effect. The field‐dependence of both net and anti‐phase polarization is measured for several ligands, which can be reproduced by the theory. The similar SABRE field‐dependence for different ligands is also explained. In general, the LAC concept allows complex spin dynamics to be unraveled, and is crucial for optimizing the performance of novel hyperpolarization methods in NMR and MRI techniques. 相似文献
17.
Dr. Thomas B. R. Robertson Dr. Nicolas Gilbert Dr. Oliver B. Sutcliffe Dr. Ryan E. Mewis 《Chemphyschem》2021,22(11):1059-1064
Mirfentanil, a fentanyl derivative that is a μ-opioid partial agonist, is hyperpolarised via Signal Amplification By Reversible Exchange (SABRE), a para-hydrogen-based technique. [Ir(IMes)(COD)Cl] (IMes=1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene, COD=cyclooctadiene) was employed as the polarisation transfer catalyst. Following polarisation transfer at 6.5 mT, the pyrazine-protons were enhanced by 78-fold (polarisation, P=0.04 %). The complex [Ir(IMes)(H)2(mirfentanil)2(MeOH)]+ is proposed to form based on the observation of two hydrides at δ −22.9 (trans to mirfentanil) and −24.7 (trans to methanol). In a mixture of mirfentanil and heroin, the former could be detected using SABRE at concentrations less than 1 % w/w. At the lowest concentration analyzed, the amount of mirfentanil present was 0.18 mg (812 μM) and produced a signal enhancement of −867-fold (P=0.42 %). following polarisation transfer at 6.5 mT. 相似文献
18.
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
19.
Max E. Gemeinhardt Miranda N. Limbach Thomas R. Gebhardt Clark W. Eriksson Shannon L. Eriksson Jacob R. Lindale Elysia A. Goodson Warren S. Warren Eduard Y. Chekmenev Boyd M. Goodson 《Angewandte Chemie (International ed. in English)》2020,59(1):418-423
Herein, we demonstrate “direct” 13C hyperpolarization of 13C‐acetate via signal amplification by reversible exchange (SABRE). The standard SABRE homogeneous catalyst [Ir‐IMes; [IrCl(COD)(IMes)], (IMes=1,3‐bis(2,4,6‐trimethylphenyl), imidazole‐2‐ylidene; COD=cyclooctadiene)] was first activated in the presence of an auxiliary substrate (pyridine) in alcohol. Following addition of sodium 1‐13C‐acetate, parahydrogen bubbling within a microtesla magnetic field (i.e. under conditions of SABRE in shield enables alignment transfer to heteronuclei, SABRE‐SHEATH) resulted in positive enhancements of up to ≈100‐fold in the 13C NMR signal compared to thermal equilibrium at 9.4 T. The present results are consistent with a mechanism of “direct” transfer of spin order from parahydrogen to 13C spins of acetate weakly bound to the catalyst, under conditions of fast exchange with respect to the 13C acetate resonance, but we find that relaxation dynamics at microtesla fields alter the optimal matching from the traditional SABRE‐SHEATH picture. Further development of this approach could lead to new ways to rapidly, cheaply, and simply hyperpolarize a broad range of substrates (e.g. metabolites with carboxyl groups) for various applications, including biomedical NMR and MRI of cellular and in vivo metabolism. 相似文献
20.
Back Cover: Single‐Scan Multidimensional NMR Analysis of Mixtures at Sub‐Millimolar Concentrations by using SABRE Hyperpolarization (ChemPhysChem 16/2015)
下载免费PDF全文
![点击此处可从《Chemphyschem》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Dr. Valeria Daniele Dr. François‐Xavier Legrand Dr. Patrick Berthault Dr. Jean‐Nicolas Dumez Dr. Gaspard Huber 《Chemphyschem》2015,16(16):3535-3535