Density Functional Theory Study of Reaction Equilibria in Signal Amplification by Reversible Exchange.
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ABSTRACT:
SUBMITTER: Lin K
PROVIDER: S-EPMC8725239 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC6247415 | biostudies-literature
Project description:A novel variant of an iridium-based organometallic catalyst was synthesized and used to enhance the NMR signals of pyridine in a heterogeneous phase by immobilization on polymer microbead solid supports. Upon administration of parahydrogen (pH2) gas to a methanol mixture containing the HET-SABRE catalyst particles and the pyridine, up to fivefold enhancements were observed in the (1)H NMR spectra after sample transfer to high field (9.4 T). Importantly, enhancements were not due to any residual catalyst molecules in solution, thus supporting the true heterogeneity of the SABRE process. Further significant improvements may be expected by systematic optimization of experimental parameters. Moreover, the heterogeneous catalyst is easy to separate and recycle, thus opening a door to future potential applications varying from spectroscopic studies of catalysis, to imaging metabolites in the body without concern of contamination from expensive and potentially toxic metal catalysts or accompanying organic molecules.
| S-EPMC6284233 | biostudies-literature
Project description: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 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 that (i) 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.
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Project description:Hyperpolarisation methods that premagnetise agents such as pyruvate are currently receiving significant attention because they produce sensitivity gains that allow disease tracking and interrogation of cellular metabolism by magnetic resonance. Here, we communicate how signal amplification by reversible exchange (SABRE) can provide strong 13 C pyruvate signal enhancements in seconds through the formation of the novel polarisation transfer catalyst [Ir(H)2 (?2 -pyruvate)(DMSO)(IMes)]. By harnessing SABRE, strong signals for [1-13 C]- and [2-13 C]pyruvate in addition to a long-lived singlet state in the [1,2-13 C2 ] form are readily created; the latter can be observed five minutes after the initial hyperpolarisation step. We also demonstrate how this development may help with future studies of chemical reactivity.
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Project description:Signal Amplification by Reversible Exchange (SABRE), a hyperpolarization technique, has been harnessed as a powerful tool to achieve useful hyperpolarized materials by polarization transfer from parahydrogen. In this study, we systemically applied SABRE to a series of nitrile compounds, which have been rarely investigated. By performing SABRE in various magnetic fields and concentrations on nitrile compounds, we unveiled its hyperpolarization properties to maximize the spin polarization and its transfer to the next spins. Through this sequential study, we obtained a ~130-fold enhancement for several nitrile compounds, which is the highest number ever reported for the nitrile compounds. Our study revealed that the spin polarization on hydrogens decreases with longer distances from the nitrile group, and its maximum polarization is found to be approximately 70 G with 5 μL of substrates in all structures. Interestingly, more branched structures in the ligand showed less effective polarization transfer mechanisms than the structural isomers of butyronitrile and isobutyronitrile. These first systematic SABRE studies on a series of nitrile compounds will provide new opportunities for further research on the hyperpolarization of various useful nitrile materials.
| S-EPMC7435364 | biostudies-literature
Project description:Rufinamide, possessing a triazole ring, is a new antiepileptic drug (AED) relatively well-absorbed in the lower dose range (10 mg/kg per day) and is currently being used in antiepileptic medications. Triazole derivatives can interact with various enzymes and receptors in biological systems via diverse non-covalent interactions, thus inducing versatile biological effects. Strain-promoted azide-alkyne cycloaddition (SPAAC) is a significant method for obtaining triazoles, even under physiological conditions, in the absence of a copper catalyst. To confirm the progress of chemical reactions under biological conditions, research on reaction monitoring at low concentrations is essential. This promising strategy is gaining acceptance for applications in fields such as drug development and nanoscience. We investigated the optimum Ir catalyst and magnetic field for achieving maximum proton hyperpolarization transfer in triazole derivatives. These reactions were analyzed using signal amplification by reversible exchange (SABRE) to overcome the limitations of low sensitivity in nuclear magnetic resonance spectroscopy, when monitoring copper-free click reactions in real time. Finally, a more versatile copper-catalyzed click reaction was monitored in real time, using a 60 MHz benchtop NMR system, in order to analyze the reaction mechanism.
| S-EPMC10120034 | biostudies-literature
Project description:Signal amplification by reversible exchange (SABRE) is an efficient method to hyperpolarize spin-1/2 nuclei and affords signals that are orders of magnitude larger than those obtained by thermal spin polarization. Direct polarization transfer to heteronuclei such as 13C or 15N has been optimized at static microTesla fields or using coherence transfer at high field, and relies on steady state exchange with the polarization transfer catalyst dictated by chemical kinetics. Here we demonstrate that pulsing the excitation field induces complex coherent polarization transfer dynamics, but in fact pulsing with a roughly 1% duty cycle on resonance produces more magnetization than constantly being on resonance. We develop a Monte Carlo simulation approach to unravel the coherent polarization dynamics, show that existing SABRE approaches are quite inefficient in use of para-hydrogen order, and present improved sequences for efficient hyperpolarization.
| S-EPMC6344499 | biostudies-literature
Project description: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 P(15N) ≈ 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.
| S-EPMC4442667 | biostudies-literature
Project description: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 (13)C NMR spectra can be readily collected where the long-lived quaternary (13)C 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.
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Project description:Fentanyl, also known as 'jackpot', is a synthetic opiate that is 50-100 times more potent than morphine. Clandestine laboratories produce analogues of fentanyl, known as fentalogues to circumvent legislation regarding its production. Three pyridyl fentalogues were synthesized and then hyperpolarized by signal amplification by reversible exchange (SABRE) to appraise the forensic potential of the technique. A maximum enhancement of -168-fold at 1.4 T was recorded for the ortho pyridyl 1H nuclei. Studies of the activation parameters for the three fentalogues revealed that the ratio of ligand loss trans to hydride and hydride loss in the complex [Ir(IMes)(L)3(H)2]+ (IMes=1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene) ranged from 0.52 to 1.83. The fentalogue possessing the ratio closest to unity produced the largest enhancement subsequent to performing SABRE at earth's magnetic field. It was possible to hyperpolarize a pyridyl fentalogue selectively from a matrix that consisted largely of heroin (97 : 3 heroin:fentalogue) to validate the use of SABRE as a forensic tool.
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