In Situ Hyperpolarization Enables 15N and 13C Benchtop NMR at Natural Isotopic Abundance.

Without employing isotopic labeling, we demonstrate the generation of 15N and 13C NMR signals for molecules containing -NH2 motifs using benchtop NMR spectrometers (1-1.4 T). Specifically, high-SNR (>50) detection of ammonia, 4-aminopyridine, benzylamine, and phenethylamine dissolved in methanol or dichloromethane is demonstrated after only 10 s of parahydrogen bubbling using signal amplification by reversible exchange and applying a pulse sequence based on spin-lock-induced crossing. Optimization of the sequence parameters allows us to achieve up to 12% 15N and 0.4% 13C polarization in situ without the need for the sample transfer typically employed in other hyperpolarization methods. Moreover, hyperpolarization is generated continuously without having to stop the parahydrogen bubbling to reset magnetization, paving the way toward fast 2D spectroscopic methods and relaxometry. The provided methodology may find application for the identification of diluted chemicals relevant to industry and research with the aid of affordable benchtop NMR spectrometers.

Functionalized Controlled Porous Glasses for Producing Radical-Free Hyperpolarized Liquids by Overhauser DNP.

Overhauser dynamic nuclear polarization (ODNP) can be used as a tool for NMR signal enhancement and happens on very short time scales. Therefore, ODNP is well suited for the measurement of fast-flowing samples, even in compact magnets, which is beneficial for the real-time monitoring of chemical reactions or processes. ODNP requires the presence of unpaired electrons in the sample, which is usually accomplished by the addition of stable radicals. However, radicals affect the nuclear relaxation times and can hamper the NMR detection. This is circumvented by immobilizing radicals in a packed bed allowing for the measurement of radical-free samples when using ex situ DNP techniques (DNP build-up and NMR detection happen at different places) and flow-induced separation of the hyperpolarized liquid from the radicals. Therefore, the synthesis of robust and chemically inert immobilized radical matrices is mandatory. In the present work, this is accomplished by immobilizing the radical glycidyloxy-tetramethylpiperidinyloxyl with a polyethyleneimine (PEI) linker on the surface of controlled porous glasses (CPG). Both the porosity of the CPGs and also the size of the PEI-linker were varied, resulting in a set of distinct radical matrices for continuous-flow ODNP. The study shows that CPGs with PEI-linkers provide robust, inert and efficient ODNP matrices.

High Flow-Rate Benchtop NMR Spectroscopy Enabled by Continuous Overhauser DNP.

Analysis of a fast-flowing liquid with NMR spectroscopy is challenging because short residence times in the magnetic field of the spectrometer result in inefficient polarization buildup and thus poor signal intensity. This is particularly problematic for benchtop NMR spectrometers because of their compact design. Therefore, in the present work, different methods to counteract this prepolarization problem in benchtop NMR spectroscopy were studied experimentally. The tests were carried out with an equimolar acetonitrile + water mixture flowing through a capillary with a 0.25 mm inner diameter at flow rates up to 2.00 mL min-1, corresponding to mean velocities of up to 0.7 m s-1. Established approaches gave only poor results at high flow rates, namely, using a prepolarization magnet, using a loopy flow cell, and using a T1 relaxation agent. To overcome this, signal enhancement by Overhauser dynamic nuclear polarization (ODNP) was used, which is based on polarization transfer from unpaired electron spins to nuclear spins and happens on very short time scales, resulting in high signal enhancements, also in fast-flowing liquids. A corresponding setup was developed and used for the studies: the line leading to the 1 T benchtop NMR spectrometer first passes through a fixed bed with a radical matrix placed in a Halbach magnet equipped with a microwave cavity to facilitate the spin transfer. With this ODNP setup, excellent results were obtained even for the highest studied flow rates. This shows that ODNP is an enabler for fast-flow benchtop NMR spectroscopy.