Monitoring Heterogeneously Catalyzed Hydrogenation Reactions at Elevated Pressures Using In-Line Flow NMR.

We present a novel setup that can be used for the in-line monitoring of solid-catalyzed gas-liquid reactions. The method combines the high sensitivity and resolution of a stripline NMR detector with a microfluidic network that can withstand elevated pressures. In our setup we dissolve hydrogen gas in the solvent, then flow it with the added substrate through a catalyst cartridge, and finally flow the reaction mixture directly through the stripline NMR detector. The method is quantitative and can be used to determine the solubility of hydrogen gas in liquids; it allows in-line monitoring of hydrogenation reactions and can be used to determine the reaction kinetics of these reactions. In this work, as proof of concept we demonstrate the optimization of the Pd-catalyzed hydrogenation reactions of styrene, phenylacetylene, cyclohexene, and hex-5-en-2-one in a microfluidic context.

Inline Reaction Monitoring of Amine-Catalyzed Acetylation of Benzyl Alcohol Using a Microfluidic Stripline Nuclear Magnetic Resonance Setup.

We present an in-depth study of the acetylation of benzyl alcohol in the presence of N, N-diisopropylethylamine (DIPEA) by nuclear magnetic resonance (NMR) monitoring of the reaction from 1.5 s to several minutes. We have adapted the NMR setup to be compatible to microreactor technology, scaling down the typical sample volume of commercial NMR probes (500 µL) to a microfluidic stripline setup with 150 nL detection volume. Inline spectra are obtained to monitor the kinetics and unravel the reaction mechanism of this industrially relevant reaction. The experiments are combined with conventional 2D NMR measurements to identify the reaction products. In addition, we replace DIPEA with triethylamine and pyridine to validate the reaction mechanism for different amine catalysts. In all three acetylation reactions, we find that the acetyl ammonium ion is a key intermediate. The formation of ketene is observed during the first minutes of the reaction when tertiary amines were present. The pyridine-catalyzed reaction proceeds via a different mechanism.

Continuous Flow 1H and 13C NMR Spectroscopy in Microfluidic Stripline NMR Chips.

Microfluidic stripline NMR technology not only allows for NMR experiments to be performed on small sample volumes in the submicroliter range, but also experiments can easily be performed in continuous flow because of the stripline's favorable geometry. In this study we demonstrate the possibility of dual-channel operation of a microfluidic stripline NMR setup showing one- and two-dimensional 1H, 13C and heteronuclear NMR experiments under continuous flow. We performed experiments on ethyl crotonate and menthol, using three different types of NMR chips aiming for straightforward microfluidic connectivity. The detection volumes are approximately 150 and 250 nL, while flow rates ranging from 0.5 µL/min to 15 µL/min have been employed. We show that in continuous flow the pulse delay is determined by the replenishment time of the detector volume, if the sample trajectory in the magnet toward NMR detector is long enough to polarize the spin systems. This can considerably speed up quantitative measurement of samples needing signal averaging. So it can be beneficial to perform continuous flow measurements in this setup for analysis of, e.g., reactive, unstable, or mass-limited compounds.

Spatially resolved spectroscopy using tapered stripline NMR.

Magnetic field B0 gradients are essential in modern Nuclear Magnetic Resonance spectroscopy and imaging. Although RF/B1 gradients can be used to fulfill a similar role, this is not used in common practice because of practical limitations in the design of B1 gradient coils. Here we present a new method to create B1 gradients using stripline RF coils. The conductor-width of a stripline NMR chip and the strength of its radiofrequency field are correlated, so a stripline chip can be tapered to produce any arbitrary shaped B1 field gradient. Here we show the characterization of this tapered stripline configuration and demonstrate three applications: magnetic resonance imaging on samples with nL-µL volumes, reaction monitoring of fast chemical reactions (10(-2)-10(1)s) and the compensation of B0 field gradients to obtain high-resolution spectra in inhomogeneous magnetic fields.

Analysis of mass-limited mixtures using supercritical-fluid chromatography and microcoil NMR.

A protocol is presented for offline microfluidic NMR analysis hyphenated with supercritical chromatographic separation. The method demonstrates quantitative detection with good sensitivity. Typical sample amounts of 10 nanomoles can be detected in a fast and cost-effective manner.

Direct dynamic measurement of intracellular and extracellular lactate in small-volume cell suspensions with (13)C hyperpolarised NMR.

Hyperpolarised (HP) (13)C NMR allows enzymatic activity to be probed in real time in live biological systems. The use of in vitro models gives excellent control of the cellular environment, crucial in the understanding of enzyme kinetics. The increased conversion of pyruvate to lactate in cancer cells has been well studied with HP (13)C NMR. Unfortunately, the equally important metabolic step of lactate transport out of the cell remains undetected, because intracellular and extracellular lactate are measured as a single resonance. Furthermore, typical experiments must be performed using tens of millions of cells, a large amount which can lead to a costly and sometimes highly challenging growing procedure. We present a relatively simple set-up that requires as little as two million cells with the spectral resolution to separate the intracellular and extracellular lactate resonances. The set-up is tested with suspensions of prostate cancer carcinoma cells (PC3) in combination with HP [1-(13)C]pyruvate. We obtained reproducible pyruvate to lactate label fluxes of 1.2 and 1.7 nmol/s per million cells at 2.5 and 5.0 mM pyruvate concentrations. The existence of a 3-Hz chemical shift difference between intracellular and extracellular lactate enabled us to determine the lactate transport rates in PC3. We deduced a lactate export rate of 0.3 s(-1) and observed a decrease in lactate transport on addition of the lactate transport inhibitor α-cyano-4-hydroxycinnamic acid.

The role of Ni in increasing the reversibility of the hydrogen release from nanoconfined LiBH4.

Nanoconfinement and the use of catalysts are promising strategies to enhance the reversibility of hydrogen storage in light metal hydrides. We combined nanoconfinement of LiBH4 in nanoporous carbon with the addition of Ni. Samples were prepared by deposition of 5-6 nm Ni nanoparticles inside the porous carbon, followed by melt infiltration with LiBH4. The Ni addition has only a slight influence on the LiBH4 hydrogen desorption, but significantly enhances the subsequent uptake of hydrogen under mild conditions. Reversible, but limited, intercalation of Li is observed during hydrogen cycling. X-ray diffraction shows that the initial crystalline 5-6 nm Ni nanoparticles are not present anymore after melt infiltration with LiBH4. However, transmission electron microscopy showed Ni-containing nanoparticles in the samples. Extended X-ray absorption fine structure spectroscopy proved the presence of Ni(x)B phases with the Ni-B coordination numbers changing reversibly with dehydrogenation and rehydrogenation of the sample. Ni(x)B can act as a hydrogenation catalyst, but solid-state 11B NMR proved that the addition of Ni also enhanced the reversibility of the system by influencing the microstructure of the nanoconfined LiBH4 upon cycling.

A solid-state NMR and DFT study of compositional modulations in Al(x)Ga(1-x)As.

We have conducted (75)As and (69)Ga Nuclear Magnetic Resonance (NMR) experiments to investigate order/disorder in Al(x)Ga(1-x)As lift-off films with x∼ 0.297 and 0.489. We were able to identify all possible As(Al(n)Ga(4-n)) sites with n = 0-4 coordinations in (75)As NMR spectra using spin-echo experiments at 18.8 Tesla. This was achieved by employing high rf field strengths using a small solenoid coil and an NMR probe specifically designed for this purpose. Spectral deconvolution, using an evolutionary algorithm, complies with the absence of long-range order if a CuAu based order parameter is imposed. An unconstrained fit shows a deviation of the statistics imposed by this type of ordering. The occupational disorder in the Ga and Al positions is reflected in a distribution of the Electric Field Gradients (EFGs) experienced at the different arsenic sites. We established that this can be modelled by summing the effects of the first coordination sphere and a Czjzek type distribution resulting from the compositional variation in the Al/Ga sub-lattice in the higher coordination spheres. (69)Ga 3QMAS and nutation data exclude the presence of highly symmetric sites and also show a distribution in EFG. The experimentally obtained quadrupolar interactions are in good agreement with calculations based on Density Functional Theory (DFT). Using additivity of EFG tensors arising from distant charge perturbations, we could use DFT to model the EFG distributions of the n = 0-4 sites, reproducing the Czjzek and extended Czjzek distributions that were found experimentally. On the basis of these calculations we conclude that the (75)As quadrupolar interaction is sensitive to compositional modulations up to the 7th coordination shell in these systems.

Microcoil high-resolution magic angle spinning NMR spectroscopy.

We report the construction of a dual-channel microcoil nuclear magnetic resonance probehead allowing magic-angle spinning for mass-limited samples. With coils down to 235 mum inner diameter, this allows high-resolution solid-state NMR spectra to be obtained for amounts of materials of a few nanoliters. This is demonstrated by the carbon-13 spectrum of a tripeptide and a single silk rod, prepared from the silk gland of the Bombyx mori silkworm. Furthermore, the microcoil allows for radio frequency field strengths well beyond current probe technology, aiding in getting the highest possible resolution by efficiently decoupling the observed nuclei from the abundantly present proton nuclei.