Paramagnetic Relaxation Agents for Enhancing Temporal Resolution and Sensitivity in Multinuclear FlowNMR Spectroscopy
Paramagnetic Relaxation Agents for Enhancing Temporal Resolution and Sensitivity in Multinuclear FlowNMR Spectroscopy
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DOI：
10.1002/chem.202300215
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发表时间：
2023-05-17
影响因子：
4.3
通讯作者：
Hintermair, Ulrich
中科院分区：
文献类型：
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作者：
Bara-Estaun, Alejandro;Harder, Marie C.;Hintermair, Ulrich
由于样品在磁场中的停留时间有限，用于反应监测的FlowNMR光谱的灵敏度通常受到低水平预磁化的影响。虽然这种内流效应对于H-1和F-19等高灵敏度核是可以容忍的，但它显著降低了P-31和C-13光谱中的信噪比，使得FlowNMR对于低浓度的低灵敏度核是不切实际的。顺磁弛豫剂（PRAs）可以增强极化和自旋晶格弛豫，消除不利的流入效应，提高信噪比。本文研究了[Co(acac)(3)], [Mn(acac)(3)], [Fe(acac)(3)](,) [Cr(acac)(3)](,) [Ni(acac)(2)](3,) [Gd(tmhd)(3)]和[Cr(tmhd)(3)]在FlowNMR应用中对催化活性过渡金属配合物的化学惰性附加约束下提高单位时间信号强度的有效性。高自旋Cr（III）乙酰丙酮酸酯是最有效的化合物，在低至10 mM的PRA浓度下，成功地将P-31 T-1值降低了4至5倍，而不会引起不良的谱宽。虽然[Cr(acac)(3)]与三苯基膦、三苯基膦氧化物和三苯基磷酸盐的混合物在80摄氏度的几个小时内表现出化学反应的迹象，但在这些条件下，体积较大的[Cr(tmhd)(3)]是稳定的，与PRA一样有效。研究了其与均相催化中常用的一系列代表性过渡金属配合物的相容性，并证明了[Cr(tmhd)(3)]在rh催化的氢甲酰化反应中显著改善H-1和P-31{H-1} FlowNMR数据质量的应用。随着PRA的加入，C-13的松弛时间减少了6倍以上，从而可以在自然丰度下通过C-13{H-1} FlowNMR光谱对底物消耗和产物形成进行定量反应监测。
Sensitivity in FlowNMR spectroscopy for reaction monitoring often suffers from low levels of pre-magnetisation due to limited residence times of the sample in the magnetic field. While this in-flow effect is tolerable for high sensitivity nuclei such as H-1 and F-19, it significantly reduces the signal-to-noise ratio in P-31 and C-13 spectra, making FlowNMR impractical for low sensititvity nuclei at low concentrations. Paramagnetic relaxation agents (PRAs), which enhance polarisation and spin-lattice relaxation, could eliminate the adverse in-flow effect and improve the signal-to-noise ratio. Herein, [Co(acac)(3)], [Mn(acac)(3)], [Fe(acac)(3)](,) [Cr(acac)(3)](,) [Ni(acac)(2)](3,) [Gd(tmhd)(3)] and [Cr(tmhd)(3)] are investigated for their effectiveness in improving signal intensity per unit time in FlowNMR applications under the additional constraint of chemical inertness towards catalytically active transition metal complexes. High-spin Cr(III) acetylacetonates emerged as the most effective compounds, successfully reducing P-31 T-1 values four- to five-fold at PRA concentrations as low as 10 mM without causing adverse line broadening. Whereas [Cr(acac)(3)] showed signs of chemical reactivity with a mixture of triphenylphosphine, triphenylphosphine oxide and triphenylphosphate over the course of several hours at 80 degrees C, the bulkier [Cr(tmhd)(3)] was stable and equally effective as a PRA under these conditions. Compatibility with a range of representative transition metal complexes often used in homogeneous catalysis has been investigated, and application of [Cr(tmhd)(3)] in significantly improving H-1 and P-31{H-1} FlowNMR data quality in a Rh-catalysed hydroformylation reaction has been demonstrated. With the PRA added, C-13 relaxation times were reduced more than six-fold, allowing quantitative reaction monitoring of substrate consumption and product formation by C-13{H-1} FlowNMR spectroscopy at natural abundance.