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通过在水性介质中可逆交换的信号放大实现抗寄生虫药物奥硝唑的N超极化。

N hyperpolarisation of the antiprotozoal drug ornidazole by Signal Amplification By Reversible Exchange in aqueous medium.

作者信息

Iali Wissam, Moustafa Gamal A I, Dagys Laurynas, Roy Soumya S

机构信息

Department of Chemistry, King Fahd University of Petroleum and Minerals (KFUPM), Dhahran, Saudi Arabia.

Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, Egypt.

出版信息

Magn Reson Chem. 2021 Dec;59(12):1199-1207. doi: 10.1002/mrc.5144. Epub 2021 Mar 8.

Abstract

Signal amplification by reversible exchange (SABRE) offers a cost-effective route to boost nuclear magnetic resonance (NMR) signal by several orders of magnitude by employing readily available para-hydrogen as a source of hyperpolarisation. Although H spins have been the natural choice of SABRE hyperpolarisation since its inception due to its simplicity and accessibility, limited spin lifetimes of H makes it harder to employ them in a range of time-dependent NMR experiments. Heteronuclear spins, for example, C and N, in general have much longer T lifetimes and thereby are found to be more suitable for hyperpolarised biological applications as demonstrated previously by para-hydrogen induced polarisation (PHIP) and dynamic nuclear polarisation (DNP). In this study we demonstrate a simple procedure to enhance N signal of an antibiotic drug ornidazole by up to 71,000-folds with net N polarisation reaching ~23%. Further, the effect of co-ligand strategy is studied in conjunction with the optimum field transfer protocols and consequently achieving N hyperpolarised spin lifetime of >3 min at low field. Finally, we present a convenient route to harness the hyperpolarised solution in aqueous medium free from catalyst contamination leading to a strong N signal detection for an extended duration of time.

摘要

通过可逆交换进行信号放大(SABRE)提供了一种经济高效的途径,通过使用 readily available 的仲氢作为超极化源,将核磁共振(NMR)信号提高几个数量级。尽管自 SABRE 超极化技术诞生以来,由于其简单性和可及性,H 自旋一直是其自然选择,但 H 自旋的有限自旋寿命使得在一系列与时间相关的 NMR 实验中使用它们变得更加困难。例如,异核自旋 C 和 N,通常具有长得多的 T 寿命,因此如先前通过仲氢诱导极化(PHIP)和动态核极化(DNP)所证明的,它们被发现更适合用于超极化生物应用。在本研究中,我们展示了一种简单的方法,可将抗生素药物奥硝唑的 N 信号增强高达 71,000 倍,净 N 极化达到约 23%。此外,结合最佳场转移协议研究了共配体策略的效果,从而在低场下实现了大于 3 分钟的 N 超极化自旋寿命。最后,我们提出了一种便捷的途径,在无催化剂污染的水性介质中利用超极化溶液,从而在延长的时间内实现强 N 信号检测。

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