145 research outputs found
A role for low concentration reaction intermediates in the signal amplification by reversible exchange process revealed by theory and experiment
A route to monitor the involvement of less abundant species during the catalytic transfer of hyperpolarisation from parahydrogen into a substrate is detailed. It involves probing how the degree of hyperpolarisation transfer catalysis is affected by the magnetic field experienced by the catalyst during this process as a function of temperature. The resulting data allows the ready differentiation of the roles played by hard to detect and highly reactive complexes, such as [Ir(H)2(NHC)(substrate)2(methanol)]Cl, from dominant species such as [Ir(H)2(NHC)(substrate)3]Cl. The difference in behaviour results from changes in the interligand spin-spin coupling network within the active SABRE catalysts
Using Parahydrogen to Hyperpolarize Amines, Amides, Carboxylic Acids, Alcohols, Phosphates and Carbonates
Hyperpolarization turns weak NMR and MRI responses into strong signals so normally impractical measurements are possible. We use parahydrogen here to rapidly hyperpolarize appropriate 1H, 13C, 15N and 31P responses of analytes such as NH3 and important amines such as phenylethylamine, amides such as acetamide, urea and methacrylamide, alcohols spanning methanol through octanol and glucose, the sodium salts of carboxylic acids such as acetic acid and pyruvic acid, sodium phosphate, disodium adenosine 5’triphosphate and sodium hydrogen carbonate. The associated signal gains are used to demonstrate it is possible to collect informative single-shot NMR spectra of these analytes in seconds at the micromole level in a 9.4 T observation field. To achieve these wide ranging signal gains, we first employ the Signal Amplification By Reversible Exchange (SABRE) process to hyperpolarize an amine or ammonia and then employ their exchangeable NH protons to relay polarization into the analyte without changing its identity. We found the 1H signal gains reach as high as 650-fold per proton, while for 13C, the corresponding signal gains achieved in a 1H-13C refocused INEPT experiment exceed 570-fold and those in a direct detected 13C measurement 400-fold. Thirty one examples are described to demonstrate the applicability of this technique
A Simple and Cost-efficient Technique to Generate Hyperpolarized Long-lived 15N-15N Nuclear Spin Order in a Diazine by Signal Amplification by Reversible Exchange
Signal Amplification by Reversible Exchange (SABRE) is an inexpensive and simple hyperpolarization technique and is capable of boosting Nuclear Magnetic Resonance (NMR) sensitivity by several orders of magnitude. It utilizes the reversible binding of para-hydrogen as hydride ligands and a substrate of interest to a metal catalyst to allow polarization transfer from para-hydrogen to the substrate nuclear spins. The nuclear spin lifetime of the created magnetization sets a strict upper limit on experimental timeframe. Short nuclear spin lifetimes are therefore a challenge for hyperpolarized metabolic imaging prospects. In this report we demonstrate how hyperpolarization and long nuclear spin lifetime can simultaneously be achieved in nitrogen-15 containing pyridazine and phthalazine derivatives by SABRE. These reflect two distinct classes of 15N2-coupled species with respect to their chemical symmetry and thus show different nuclear spin lifetime with the pyridazine derivative having a singlet state lifetime of ca. 2.5 minutes, produced with a signal enhancement of ca. 2,700. In contrast the phthalazine derivative yields a superior 15,000-fold enhancement at 11.7 T but has a much shorter singlet lifetime
Signal Amplification by Reversible Exchange (SABRE): : From Discovery to Diagnosis
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 due to its speed and simplicity. This minireview tracks the development of SABRE from the initial hyperpolarization of pyridine in 2009, to the point where 50% 1H polarization levels have be 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. It finishes by describing 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
Remarkable Levels of 15N Polarization Delivered through SABRE Into Unlabeled Pyridine, Pyrazine or Metronidazole Enable Single Scan NMR Quantification at the mM Level
Using SABRE hyperpolarized <sup>13</sup>C NMR to interrogate organic transformations of pyruvate
Optimisation of Pyruvate Hyperpolarisation using SABRE by Tuning the Active Magnetisation Transfer Catalyst
Hyperpolarisation techniques such as Signal Amplification By Reversible Exchange (SABRE) can deliver NMR signals several orders of magnitude larger than those derived under Boltzmann conditions. SABRE is able to catalytically transfer latent magnetisation from para-hydrogen to a substrate in reversible exchange via temporary associations with an iridium complex. It has recently been applied to the hyperpolarisation of pyruvate, a substrate often used in many in vivo MRI studies. In this work, we seek to optimise the pyruvate-13C2 signal gains delivered through SABRE by fine tuning the properties of the active polarisation transfer catalyst. We present a detailed study of the effects of varying the carbene and sulfoxide ligands on the formation and behaviour of the active [Ir(H)2(η2-pyruvate)(sulfoxide)(NHC)] catalyst to produce a rational for achieving high pyruvate signal gains in a cheap and refreshable manner. This optimisation approach allows us to achieve signal enhancements of 2140 and 2125-fold for the 1-13C and 2-13C sites respectively of sodium pyruvate-1,2-[13C2]
Exploring the hyperpolarisation of EGTA-based ligands using SABRE
The design of molecules whose magnetic resonance (MR) signals report on their biological environment is receiving attention as a route to non-invasive functional MR. Hyperpolarisation techniques improve the sensitivity of MR and enable real time low concentration MR imaging, allowing for the development of novel functional imaging methodologies. In this work, we report on the synthesis of a series of EGTAderived molecules (EGTA – ethylene glycol-bis(2-aminoethylether)-N,N,N’,N’-tetraacetic acid), whose core structures are known to bind biologically relevant metal ions in vivo, in addition to pyridyl rings that allow reversible ligation to an iridium dihydride complex. Consequently, they are amenable to hyperpolarisation through the parahydrogen-based signal amplification by reversible exchange (SABRE) process. We investigate how the proximity of EGTA and pyridine units, and the identity of the linker group, affect the SABRE hyperpolarisation attained for each agent. We also describe the effect of catalyst identity and coligand presence on these measurements and can achieve 1H NMR signal enhancements of up to 160-fold. We rationalise these results to suggest the design elements needed for probes amenable to SABRE hyperpolarisation whose MR signals might in the future report on the presence of metal ions
The Detection and Reactivity of Silanols and Silanes Using Hyperpolarized 29Si Nuclear Magnetic Resonance
Silanols and silanes are key precursors and intermediates for the synthesis of silicon-based materials. While their characterization and quantification using 29Si NMR has received significant attention, it is a technique that is limited by the low natural abundance of 29Si and its low sensitivity. Here, we describe a method using p-H2 to hyperpolarize 29Si. The observed signal enhancements, approaching 3000-fold at 11.7 T, would take many days of measurement for comparable results under Boltzmann conditions. The resulting signals are exploited to monitor the rapid reaction of tris(tert-butoxy)silanol with triflic anhydride in a T1 corrected process that allows for rapid quantification. These results demonstrate a novel route to quantify dynamic processes and intermediates in the synthesis of silicon materials
Iridium Cyclooctene Complex Forms a Hyperpolarization Transfer Catalyst Before Converting to a Binuclear C-H Bond Activation Product Responsible for Hydrogen Isotope Exchange
[IrCl(COE)2]2 ( 1 ) reacts with pyridine and H2 to form crystallo-graphically characterized IrCl(H)2(COE)(py)2 ( 2 ). 2 undergoes pyridine loss to form 16-electron IrCl(H)2(COE)(py) (3) with equivalent hydride ligands. When this reaction is studied with parahydrogen, 1 efficiently achieves the hyperpolarization of free pyridine (and nicotinamide, nicotine, 5-aminopyrimidine and 3,5-lutudine) via signal amplification by reversible exchange (SABRE) and hence reflects a simple and readily available precatayst for this process. 2 reacts further over 48 hrs at 298 K to form crystallographically characterized (Cl)(H)(py)(μ-Cl)(μ-H)(κ-μ-NC5H4)Ir(H)(py)2 (4). This dimer is shown to be active in the hydrogen isotope exchange process that is used in radiophar-maceutical preparations. Furthermore, while [Ir(H)2(COE)(py)3]PF6 ( 6 ) forms on addition of AgPF6 to 2 , its stability precludes its efficient involvement in SABRE
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