Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Using ² H labelling to improve the NMR detectability of pyridine and its derivatives by SABRE.

ABSTRACT: By introducing a range of ² H labels into pyridine and the para-substituted agents, methyl isonicotinate and isonicotinamide, we significantly improve their NMR detectability in conjunction with the signal amplification by reversible exchange process. We describe how the rates of T₁ relaxation for the remaining ¹ H nuclei are increased and show how this leads to a concomitant increase in the level of ¹ H and ¹³ C hyperpolarization that can ultimately be detected.

SUBMITTER: Norcott P

PROVIDER: S-EPMC6001449 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Using 2 H labelling to improve the NMR detectability of pyridine and its derivatives by SABRE.

Norcott Philip P Burns Michael J MJ Rayner Peter J PJ Mewis Ryan E RE Duckett Simon B SB

Magnetic resonance in chemistry : MRC 20180125 7

By introducing a range of 2 H labels into pyridine and the para-substituted agents, methyl isonicotinate and isonicotinamide, we significantly improve their NMR detectability in conjunction with the signal amplification by reversible exchange process. We describe how the rates of T1 relaxation for the remaining 1 H nuclei are increased and show how this leads to a concomitant increase in the level of 1 H and 13 C hyperpolarization that can u ...[more]

PMID: 29274294

Similar Datasets

Heterogeneous Microtesla SABRE Enhancement of 15 N NMR Signals.

Project description:The hyperpolarization of heteronuclei via signal amplification by reversible exchange (SABRE) was investigated under conditions of heterogeneous catalysis and microtesla magnetic fields. Immobilization of [IrCl(COD)(IMes)], [IMes=1,3-bis(2,4,6-trimethylphenyl), imidazole-2-ylidene; COD=cyclooctadiene] catalyst onto silica particles modified with amine linkers engenders an effective heterogeneous SABRE (HET-SABRE) catalyst that was used to demonstrate a circa 100-fold enhancement of 15 N NMR signals in 15 N-pyridine at 9.4 T following parahydrogen bubbling within a magnetic shield. No 15 N NMR enhancement was observed from the supernatant liquid following catalyst separation, which along with XPS characterization supports the fact that the effects result from SABRE under heterogeneous catalytic conditions. The technique can be developed further for producing catalyst-free agents via SABRE with hyperpolarized heteronuclear spins, and thus is promising for biomedical NMR and MRI applications.

| S-EPMC5561492 | biostudies-literature

Using signal amplification by reversible exchange (SABRE) to hyperpolarise 119Sn and 29Si NMR nuclei.

Project description:The hyperpolarisation of the 119Sn and 29Si nuclei in 5-(tributylstannyl)pyrimidine (ASn) and 5-(trimethylsilyl)pyrimidine (BSi) is achieved through their reaction with [IrCl(COD)(IMes)] (1a) or [IrCl(COD)(SIMes)] (1b) and parahydrogen via the SABRE process. 1a exhibits superior activity in both cases. The two inequivalent pyrimidine proton environments of ASn readily yielded signal enhancements totalling ?2300-fold in its 1H NMR spectrum at a field strength of 9.4 T, with the corresponding 119Sn signal being 700 times stronger than normal. In contrast, BSi produced analogous 1H signal gains of ?2400-fold and a 29Si signal that could be detected with a signal to noise ratio of 200 in a single scan. These sensitivity improvements allow NMR detection within seconds using micromole amounts of substrate and illustrate the analytical potential of this approach for high-sensitivity screening. Furthermore, after extended reaction times, a series of novel iridium trimers of general form [Ir(H)2Cl(NHC)(?-pyrimidine-?N:?N')]3 precipitate from these solutions whose identity was confirmed crystallographically for BSi.

| S-EPMC5436037 | biostudies-literature

15 N MRI of SLIC-SABRE Hyperpolarized 15 N-Labelled Pyridine and Nicotinamide.

Project description:Magnetic Resonance Imaging (MRI) is a powerful non-invasive diagnostic method extensively used in biomedical studies. A significant limitation of MRI is its relatively low signal-to-noise ratio, which can be increased by hyperpolarizing nuclear spins. One promising method is Signal Amplification By Reversible Exchange (SABRE), which employs parahydrogen as a source of hyperpolarization. Recent studies demonstrated the feasibility to improve MRI sensitivity with this hyperpolarization technique. Hyperpolarized 15 N nuclei in biomolecules can potentially retain their spin alignment for tens of minutes, providing an extended time window for the utilization of the hyperpolarized compounds. In this work, we demonstrate for the first time that radio-frequency-based SABRE hyperpolarization techniques can be used to obtain 15 N MRI of biomolecule 1-15 N-nicotinamide. Two image acquisition strategies were utilized and compared: Single Point Imaging (SPI) and Fast Low Angle SHot (FLASH). These methods demonstrated opportunities of high-field SABRE for biomedical applications.

| S-EPMC6679352 | biostudies-literature

Remarkable Levels of 15N Polarization Delivered through SABRE into Unlabeled Pyridine, Pyrazine, or Metronidazole Enable Single Scan NMR Quantification at the mM Level.

Project description:While many drugs and metabolites contain nitrogen, harnessing their diagnostic 15N NMR signature for their characterization is underutilized because of inherent detection difficulties. Here, we demonstrate how precise ultralow field signal amplification by reversible exchange (±0.2 mG) in conjunction parahydrogen and an iridium precatalyst of the form IrCl(COD)(NHC) with the coligand d9-benzylamine allows the naturally abundant 15N NMR signatures of pyridine, pyrazine, metronidazole, and acetonitrile to be readily detected at 9.4 T in single NMR observations through >50% 15N polarization levels. These signals allow for rapid and precise reagent quantification via a response that varies linearly over the 2-70 mM concentration range.

| S-EPMC7277555 | biostudies-literature

SABRE hyperpolarization enables high-sensitivity 1H and 13C benchtop NMR spectroscopy.

Project description:Benchtop NMR spectrometers operating with low magnetic fields of 1-2 T at sub-ppm resolution show great promise as analytical platforms that can be used outside the traditional laboratory environment for industrial process monitoring. One current limitation that reduces the uptake of benchtop NMR is associated with the detection fields' reduced sensitivity. Here we demonstrate how para-hydrogen (p-H2) based signal amplification by reversible exchange (SABRE), a simple to achieve hyperpolarization technique, enhances agent detectability within the environment of a benchtop (1 T) NMR spectrometer so that informative 1H and 13C NMR spectra can be readily recorded for low-concentration analytes. SABRE-derived 1H NMR signal enhancements of up to 17 000-fold, corresponding to 1H polarization levels of P = 5.9%, were achieved for 26 mM pyridine in d4-methanol in a matter of seconds. Comparable enhancement levels can be achieved in both deuterated and protio solvents but now the SABRE-enhanced analyte signals dominate due to the comparatively weak thermally-polarized solvent response. The SABRE approach also enables the acquisition of 13C NMR spectra of analytes at natural isotopic abundance in a single scan as evidenced by hyperpolarized 13C NMR spectra of tens of millimolar concentrations of 4-methylpyridine. Now the associated signal enhancement factors are up to 45 500 fold (P = 4.0%) and achieved in just 15 s. Integration of an automated SABRE polarization system with the benchtop NMR spectrometer framework produces renewable and reproducible NMR signal enhancements that can be exploited for the collection of multi-dimensional NMR spectra, exemplified here by a SABRE-enhanced 2D COSY NMR spectrum.

| S-EPMC6040279 | biostudies-literature

Reaction Monitoring Using SABRE-Hyperpolarized Benchtop (1 T) NMR Spectroscopy.

Project description:The conversion of [IrCl(COD)(IMes)] (COD = cis, cis-1,5-cyclooctadiene, IMes = 1,3-bis(2,4,6-trimethyl-phenyl)imidazole-2-ylidene) in the presence of an excess of para-hydrogen ( p-H2) and a substrate (4-aminopyridine (4-AP) or 4-methylpyridine (4-MP)) into [Ir(H)2(IMes)(substrate)3]Cl is monitored by 1H NMR spectroscopy using a benchtop (1 T) spectrometer in conjunction with the p-H2-based hyperpolarization technique signal amplification by reversible exchange (SABRE). A series of single-shot 1H NMR measurements are used to monitor the chemical changes that take place in solution through the lifetime of the hyperpolarized response. Non-hyperpolarized high-field 1H NMR control measurements were also undertaken to confirm that the observed time-dependent changes relate directly to the underlying chemical evolution. The formation of [Ir(H)2(IMes)(substrate)3]Cl is further linked to the hydrogen isotope exchange (HIE) reaction, which leads to the incorporation of deuterium into the ortho positions of 4-AP, where the source of deuterium is the solvent, methanol- d4. Comparable reaction monitoring results are achieved at both high-field (9.4 T) and low-field (1 T). It is notable that the low sensitivity of the benchtop (1 T) NMR enables the use of protio solvents, which when used here allows the effects of catalyst formation and substrate deuteration to be separated. Collectively, these methods illustrate how low-cost low-field NMR measurements provide unique insight into a complex catalytic process through a combination of hyperpolarization and relaxation data.

| S-EPMC6892580 | biostudies-literature

15N Hyperpolarization by Reversible Exchange Using SABRE-SHEATH.

Project description: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.

| S-EPMC4419867 | biostudies-literature

Quantification of hyperpolarisation efficiency in SABRE and SABRE-Relay enhanced NMR spectroscopy.

Project description:para-Hydrogen (p-H2) induced polarisation (PHIP) is an increasingly popular method for sensitivity enhancement in NMR spectroscopy. Its growing popularity is due in part to the introduction of the signal amplification by reversible exchange (SABRE) method that generates renewable hyperpolarisation in target analytes in seconds. A key benefit of PHIP and SABRE is that p-H2 can be relatively easily and cheaply produced, with costs increasing with the desired level of p-H2 purity. In this work, the efficiency of the SABRE polarisation transfer is explored by measuring the level of analyte hyperpolarisation as a function of the level of p-H2 enrichment. A linear relationship was found between p-H2 enrichment and analyte 1H hyperpolarisation for a range of molecules, polarisation transfer catalysts, NMR detection fields and for both the SABRE and SABRE-Relay transfer mechanisms over the range 29-99% p-H2 purity. The gradient of these linear relationships were related to a simple theoretical model to define an overall efficiency parameter, E, that quantifies the net fraction of the available p-H2 polarisation that is transferred to the target analyte. We find that the efficiency of SABRE is independent of the NMR detection field and exceeds E = 20% for methyl-4,6-d2-nicotinate when using a previously optimised catalyst system. For the SABRE-Relay transfer mechanism, efficiencies of up to E = 1% were found for 1H polarisation of 1-propanol, when ammonia was used as the polarisation carrier.

| S-EPMC6202922 | biostudies-literature

Antimycobacterial activity of nitrogen heterocycles derivatives: 7-(pyridine-4-yl)-indolizine derivatives. Part VII8-12.

Project description:A series of 13 compounds having a monoindolizine mono-salt skeleton was designed and synthesised in order to evaluate their antimycobacterial activity. The synthesis is efficient, involving only three steps: two alkylations and one 3 + 2 dipolar cycloaddition. The antimicrobial activity against Mycobacterium tuberculosis H37Rv grown under aerobic conditions was evaluated, eight compounds showing a very good antimycobacterial activity. SAR correlation reveals a certain influence of the R substituent from the para position of benzoyl moiety at position 3 of indolizine. The most active five compounds passed the second stage of anti-TB testing, the assay demonstrating that they are potent against both replicating and non-replicating Mtb, have a bactericidal mechanism of action, are active against drug-resistant Mtb strains, present a moderate to good activity against nontuberculous mycobacteria, a good intracellular activity, and a moderate to high cytotoxicity. For one compound showing a promising anti-TB profile, a complete ADMET study has been performed.

| S-EPMC6021032 | biostudies-literature

Harnessing polarisation transfer to indazole and imidazole through signal amplification by reversible exchange to improve their NMR detectability.

Project description:The signal amplification by reversible exchange (SABRE) approach has been used to hyperpolarise the substrates indazole and imidazole in the presence of the co-ligand acetonitrile through the action of the precataysts [IrCl(COD)(IMes)] and [IrCl(COD)(SIMes)]. 2 H-labelled forms of these catalysts were also examined. Our comparison of the two precatalysts [IrCl(COD)(IMes)] and [IrCl(COD)(SIMes)], coupled with 2 H labelling of the N-heterocyclic carbene and associated relaxation and polarisation field variation studies, demonstrates the critical and collective role these parameters play in controlling the efficiency of signal amplification by reversible exchange. Ultimately, with imidazole, a 700-fold1 H signal gain per proton is produced at 400 MHz, whilst for indazole, a 90-fold increase per proton is achieved. The co-ligand acetonitrile proved to optimally exhibit a 190-fold signal gain per proton in these measurements, with the associated studies revealing the importance the substrate plays in controlling this value. Copyright © 2017 The Authors. Magnetic Resonance in Chemistry published by John Wiley & Sons Ltd.

| S-EPMC5599957 | biostudies-literature