Benchtop Nuclear Magnetic Resonance Spectroscopy Research Articles

Enhancing Sensitivity in the Hyphenation of High-Performance Liquid Chromatography to Benchtop Nuclear Magnetic Resonance Spectroscopy at Isocratic and Onflow Conditions.

The onflow hyphenation of high-performance liquid chromatography (HPLC) in adsorption mode with a benchtop 1H nuclear magnetic resonance (NMR) spectrometer is described for the first time. Protonated solvents and isocratic conditions are used. The sensitivity was increased by choosing suitable NMR acquisition parameter as well as optimizing injection parameters and postacquisition data processing methods. With optimized conditions, the limit of detection (LOD) and the limit of quantification (LOQ) were LOD = 0.010 g L-1 and LOQ = 0.031 g L-1 for the methoxy 1H of methyl paraben at 4.07 ppm, LOD = 0.038 g L-1 and LOQ = 0.134 g L-1 for the aromatic 1H of pentyl paraben between 7.00 and 8.50 ppm. These are expressed in injection concentration and are comparable to existing HPLC hyphenation with high-field NMR spectrometers. The analysis of a 2 g L-1 paraben mixture, far below the legal limits for usage in cosmetics, illustrates the applicability of the method. Taking advantage of the spectral resolution, chromatographically overlapping peaks are resolved using analyte-specific NMR elution traces. A methodology is detailed to facilitate the transfer of the optimized method to other (analyte) systems.

Determination of Nicotine Protonation State in E-Liquids by Low-Resolution Benchtop NMR Spectroscopy.

Over several years, e-liquids with "nicotine salts" have gained considerable popularity. These e-liquids have a low pH, at which nicotine occurs mostly in its monoprotonated form. Manufacturers usually accomplish this by the addition of an organic acid, such as levulinic acid, benzoic acid, or lactic acid. Nicotine in its protonated form can be more easily inhaled, enhancing the addictiveness and attractiveness of products. Several techniques have been described for measuring the protonation state of nicotine in e-liquids. However, nuclear magnetic resonance (NMR) spectroscopy is particularly suited for this purpose because it can be performed on unaltered e-liquids. In this article, we demonstrate the suitability of a benchtop NMR (60 MHz) instrument for determining the protonation state of nicotine in e-liquids. The method is subsequently applied to measure the protonation state of 33 commercially available e-liquids and to investigate whether the vaping process alters the protonation state of nicotine. For this purpose, the protonation state in the condensed aerosol obtained by automated vaping of different e-liquids was compared with that of the original e-liquids. Two distinct populations were observed in the protonation state of nicotine in commercial e-liquids: free-base (fraction of free-base nicotine αfb > 0.80) and protonated (αfb < 0.40). For 30 e-liquids out of 33, the information on the packaging regarding the presence of nicotine salt was in agreement with the observed protonation state. Three e-liquids contained nicotine salt, even though this was not stated on the packaging. Measuring the protonation state of nicotine before and after (machine) vaping revealed that the protonation state of e-liquids is not affected by vaping. In conclusion, it is possible to determine the nicotine protonation state with the described method. Two clusters can be distinguished in the protonation state of commercial e-liquids, and the protonation state of nicotine remains unchanged after vaping.

Quantitative at-line monitoring of enzymatic hydrolysis using benchtop diffusion nuclear magnetic resonance spectroscopy.

Benchtop diffusion nuclear magnetic resonance (NMR) spectroscopy was used to perform quantitative monitoring of enzymatic hydrolysis. The study aimed to test the feasibility of the technology to characterize enzymatic hydrolysis processes in real time. Diffusion ordered spectroscopy (DOSY) was used to measure the signal intensity and apparent self-diffusion constant of solubilized protein in hydrolysate. The NMR technique was tested on an enzymatic hydrolysis reaction of red cod, a lean white fish, by the endopeptidase alcalase at 50°C. Hydrolysate samples were manually transferred from the reaction vessel to the NMR equipment. Measurement time was approximately 3 min per time point. The signal intensity from the DOSY experiment was used to measure protein concentration and the apparent self-diffusion constant was converted into an average molecular weight and an estimated degree of hydrolysis. These values were plotted as a function of time and both the rate of solubilization and the rate of protein breakdown could be calculated. In addition to being rapid and noninvasive, DOSY using benchtop NMR spectroscopy has an advantage compared with other enzymatic hydrolysis characterization methods as it gives a direct measure of average protein size; many functional properties of proteins are strongly influenced by protein size. Therefore, a method to give protein concentration and average size in real time will allow operators to more tightly control production from enzymatic hydrolysis. Although only one type of material was tested, it is anticipated that the method should be applicable to a broad variety of enzymatic hydrolysis feedstocks.

Quantitative Analysis in Continuous-Flow ^1H Benchtop NMR Spectroscopy by Paramagnetic Relaxation Enhancement

Nuclear magnetic resonance (NMR) spectroscopy is an excellent tool for reaction and process monitoring. Process monitoring is often carried out online, where the analytic device is operated in flow mode. Benchtop NMR spectrometers are especially well-suited for these applications because they can be installed close to the studied process. However, quantitative 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, where it severely limits the flow velocity in quantitative measurements. One method for increasing polarization in continuous-flow NMR spectroscopy is paramagnetic relaxation enhancement (PRE). Here, the interaction of the studied liquid with a PRE agent significantly accelerates the buildup of nuclear polarization prior to NMR detection, which enables quantitative measurements at high flow velocities. For process monitoring applications, the synthesis of robust and chemically inert immobilized PRE agents is mandatory. This was accomplished in the present work, where a new PRE agent is tested on 12 common solvents including water, acetonitrile, 1,4-dioxane, and binary mixtures with quantitative benchtop ^1H NMR spectroscopy at 1 Tesla. The results show that the flow regime for quantitative measurements can be greatly extended by the use of the synthesized PRE agent.

Reaction monitoring via benchtop nuclear magnetic resonance spectroscopy: A practical comparison of on-line stopped-flow and continuous-flow sampling methods.

The ability for nuclear magnetic resonance (NMR) spectroscopy to provide quantitative, structurally rich information makes this spectroscopic technique an attractive reaction monitoring tool. The practicality of NMR for this type of analysis has only increased in the recent years with the influx of commercially available benchtop NMR instruments and compatible flow systems. In this study, we aim to compare 19F NMR reaction profiles acquired under both on-line continuous-flow and stopped-flow sampling methods, with modern benchtop NMR instrumentation, and two reaction systems: a homogeneous imination reaction and a biphasic activation of a carboxylic acid to acyl fluoride. Reaction trends with higher data density can be acquired with on-line continuous-flow analyses, and this work highlights that representative reaction trends can be acquired without any correction when monitoring resonances with a shorter spin-lattice relaxation time (T1), and with the used flow conditions. On-line stopped-flow analyses resulted in representative reaction trends in all cases, including the monitoring of resonances with a long T1, without the need of any correction factors. The benefit of easier data analysis, however, comes with the cost of time, as the fresh reaction solution must be flowed into the NMR system, halted, and time must be provided for spins to become polarized in the instrument's external magnetic field prior to spectral measurement. Results for one of the reactions were additionally compared with the use of a high-field NMR.

Determination of copolymer compositions in polyhydroxyalkanoates using 1H benchtop nuclear magnetic resonance spectroscopy.

Continuous research into polyhydroxyalkanoates (PHAs), biodegradable polymers which can be produced by, and harvested from, various bacteria has led to more cost-effective ways of isolating and commercializing them. As bio-based polymers, PHAs can be transformed into compostable bioplastics and utilized for a variety of applications. Often isolated as copolymers, the monomeric ratio compositions of these products greatly affect both the properties and consequently, possible end uses of these products. As such, methods of reliably characterizing these ratios are important for quality control and product development purposes. Herein, we discuss how 1H benchtop nuclear magnetic resonance (NMR) instruments can be used for the determination of monomeric ratio compositions in PHAs and compare results obtained at three different NMR field strengths: 1.40 T (60 MHz), 2.35 T (100 MHz), and 9.4 T (400 MHz).

Predicting Mandarin Fruit Acceptability: From High-Field to Benchtop NMR Spectroscopy.

Recent advances in nuclear magnetic resonance (NMR) have led to the development of low-field benchtop NMR systems with improved sensitivity and resolution suitable for use in research and quality-control laboratories. Compared to their high-resolution counterparts, their lower purchase and running costs make them a good alternative for routine use. In this article, we show the adaptation of a method for predicting the consumer acceptability of mandarins, originally reported using a high-field 400 MHz NMR spectrometer, to benchtop 60 MHz NMR systems. Our findings reveal that both instruments yield comparable results regarding sugar and citric acid levels, leading to the development of virtually identical predictive linear models. However, the lower cost of benchtop NMR systems would allow cultivators to implement this chemometric-based method as an additional tool for the selection of new cultivars.

Analysis of Aging Products from Biofuels in Long-Term Storage.

The long-term aging processes during storage of different heating oils and their blends with biofuels including fatty acid methyl ester, hydrogenated vegetable oil, and power-to-liquids products were followed by different analytical techniques, and the aging products were analyzed. While most standard techniques are time-consuming and labor-intensive and specify only a single property, analyses by benchtop nuclear magnetic resonance spectroscopy proved to be effortless and fast. Moreover, only 0.4 mL of the sample is required for nondestructive NMR measurements. White and waxlike precipitates were found in FAME stored at a cold temperature and identified as esters of glycerol with saturated side chains by chromatographic, thermal, and spectroscopic analyses. At colder temperatures, they reversibly precipitate and can lead to system failure.

Composition analysis of natural gas by combined benchtop NMR spectroscopy and mechanistical multivariate regression

Natural gas is an essential energy source for a large variety of applications in today’s society. Forecasts predict that it will also play a vital role in decarbonizing the energy sector. The price of natural gas is determined by its calorific value, which depends on its composition. Thus, the accurate composition quantification of natural gas is essential to both producers and consumers. In this context, proton Nuclear Magnetic Resonance (NMR) spectra of pure and mixed hydrocarbon gases have been studied with a desktop spectrometer in the range between 1 to 200 bar. Although spectral linewidth, chemical shift, and relaxation times depend on pressure and composition, the hydrocarbon concentrations of binary, ternary, and an eleven-component gas mixture could be quantified by spectral analysis using Spectral Hard Modeling, a mechanistical multivariate regression. Concentrations determined for the main components at 200 bar by NMR deviated by 0.1 to 0.18 mol% from Gas Chromatography values, leading to a difference in calorific values of only 0.15%. The presented results demonstrate that benchtop NMR combined with chemometrics can quantify complex hydrocarbon-gas mixtures reliably and quickly.

Recent Applications of Benchtop Nuclear Magnetic Resonance Spectroscopy

Benchtop nuclear magnetic resonance (NMR) spectroscopy uses small permanent magnets to generate magnetic fields and therefore offers the advantages of operational simplicity and reasonable cost, presenting a viable alternative to high-field NMR spectroscopy. In particular, the use of benchtop NMR spectroscopy for rapid in-field analysis, e.g., for quality control or forensic science purposes, has attracted considerable attention. As benchtop NMR spectrometers are sufficiently compact to be operated in a fume hood, they can be efficiently used for real-time reaction and process monitoring. This review introduces the recent applications of benchtop NMR spectroscopy in diverse fields, including food science, pharmaceuticals, process and reaction monitoring, metabolomics, and polymer materials.

Identification of seven psychedelic 2,5-dimethoxy-phenylethyl-amine-based designer drugs via benchtop 1 H nuclear magnetic resonance spectroscopy.

The dissemination of spectral information of new psychoactive substances (NPS) acquired on benchtop nuclear magnetic resonance (NMR) spectrometers is of high importance considering the emerging application of such portable and accessible instruments in forensic analyses. Seven members of the 2C-X series (2C-B, 2C-C, 2C-D, 2C-E, 2C-P, 2C-T2, and 2C-T7) of NPS were analyzed via 60 MHz 1 H benchtop NMR spectroscopy and their molecular structural relations are discussed with respect to the observed proton NMR spectra.

Benchtop nuclear magnetic resonance spectroscopy in forensic chemistry.

Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique well known for its ability to elucidate structures and analyse mixtures and its quantitative nature. However, the cost and maintenance of high field NMR instruments prevent its widespread use by forensic chemists. The introduction of benchtop NMR spectrometers to the market operating at 40-80 MHz have a small footprint, are easy to use and cost much less than high field instruments, which makes them well suited to meet the needs of forensic chemists. These modern low field spectrometers are often capable of running multiple nuclei including 1 H, 13 C, 19 F and 31 P; 2D NMR experiments and advanced experiments such as solvent suppression and diffusion-ordered spectroscopy (DOSY) are possible. This has resulted in a number of publications in the area of forensic chemistry using benchtop NMR spectroscopy in the last 5 years that was previously missing from the literature. This mini review summarises this research including examples of benchtop NMR being used to identify and quantify compounds relevant to forensics and some advanced methods that may be used to overcome some of the limitations of these instruments for forensic analysis. Further validation and automation are likely required for widespread uptake of benchtop NMR in industry; however, it has been demonstrated as a useful complement to other analytical techniques commonplace of forensic laboratories.

Incorporating Benchtop NMR Spectrometers in the Undergraduate Lab: Understanding Resolution and Circumventing Second-Order Effects

Nuclear magnetic resonance (NMR) spectroscopy is commonly introduced to students in the classroom, but its hands-on use in undergraduate laboratories is far less common. The significant costs to purchase and maintain a traditional high-field NMR spectrometer means that many institutions cannot offer this service to their students. Benchtop NMR spectrometers represent a very powerful alternative at a fraction of the cost and laboratory footprint. However, concerns about resolution and managing second-order effects can hamper its incorporation into the undergraduate curricula. Herein, we describe how resolution at the benchtop level differs from traditional high-field instruments and provide a thorough, tabulated list of 204 molecules which exhibit little to no second-order effects at the lower magnetic fields utilized in benchtop NMR spectroscopy.

Organic Reaction Monitoring of a Glycine Derivative Using Signal Amplification by Reversible Exchange-Hyperpolarized Benchtop Nuclear Magnetic Resonance Spectroscopy.

Currently, signal amplification by reversible exchange (SABRE) using para-hydrogen is an attractive method of hyperpolarization for overcoming the sensitivity problems of nuclear magnetic resonance (NMR) spectroscopy. Additionally, SABRE, using the spin order of para-hydrogen, can be applied in reaction monitoring processes for organic chemistry reactions where a small amount of reactant exists. The organic reaction monitoring system created by integrating SABRE and benchtop NMR is the ideal combination for monitoring a reaction and identifying the small amounts of materials in the middle of the reaction. We used a laboratory-built setup, prepared materials by synthesis, and showed that the products obtained by esterification of glycine were also active in SABRE. The products, which were synthesized esterified glycine with nicotinoyl chloride hydrochloride, were observed with a reaction monitoring system. The maximum SABRE enhancement among them (approximately 147-fold) validated the use of this method. This study is the first example of the monitoring of this organic reaction by SABRE and benchtop NMR. It will open new possibilities for applying this system to many other organic reactions and also provide more fruitful future applications such as drug discovery and mechanism study.

Benchtop 19 F NMR spectroscopy as a practical tool for testing of remedial technologies for the degradation of perfluorooctanoic acid, a persistent organic pollutant.

The development of effective remedial technologies for the destruction of environmental pollutants requires the ability to clearly monitor degradation processes. Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for understanding reaction progress; however, practical considerations often restrict the application of NMR spectroscopy as a tool to better understand the degradation of environmental pollutants. Chief among these restrictions is the limited access smaller environmental research labs and remediation companies have to suitable NMR facilities. Benchtop NMR spectroscopy is a low-cost and user-friendly approach to acquire much of the same information as conventional nuclear magnetic resonance (NMR) spectroscopy, albeit with reduced sensitivity and resolution. This paper explores the practical application of benchtop NMR spectroscopy to understand the degradation of perfluorooctanoic acid using sodium persulfate, a common reagent for the destruction of groundwater contaminants. It is found that Benchtop 19 F NMR spectroscopy is able to monitor the complete degradation of perfluorooctanoic acid into fluoride; however, the observation of intermediate degradation products formed, which can be observed using a conventional NMR spectrometer, cannot be readily distinguished from the parent compound when measurements are performed using the benchtop instrument. Under certain reaction conditions, the formation of fluorinated structures that are resistant to further degradation is readily observed. Overall, it is shown that benchtop 19 F NMR spectroscopy has potential as a quick and reliable tool to assist in the development of remedial technologies for the degradation of fluorinated contaminants.

Low-field benchtop NMR spectroscopy: status and prospects in natural product analysis†.

Since a couple of years, low-field (LF) nuclear magnetic resonance (NMR) spectrometers (40-100 MHz) have re-entered the market. They are used for various purposes including analyses of natural products. Similar to high-field instruments (300-1200 MHz), modern LF instruments can measure multiple nuclei and record two-dimensional (2D) NMR spectra. To review the commercial availability as well as applications, advantages, limitations, and prospects of LF-NMR spectrometers for the purpose of natural products analysis. Commercial LF instruments were compared. A literature search was performed for articles using and discussing modern LF-NMR. Next, the articles relevant to natural products were read and summarised. Seventy articles were reviewed. Most appeared in 2018 and 2019. Low costs and ease of operation are most often mentioned as reasons for using LF-NMR. As the spectral resolution of LF instruments is limited, they are not used for structure elucidation of new natural products but rather applied for quality control (QC), forensics, food and health research, process control and teaching. Chemometric data handling is valuable. LF-NMR is a rapidly developing niche and new instruments keep being introduced.

Online monitoring of enzymatic hydrolysis of marine by-products using benchtop nuclear magnetic resonance spectroscopy

Enzymatic hydrolysis is becoming a more commonly used method to create high value products from traditionally low value marine by-products. However, improvement to processing is hampered by a lack of ways to characterize the reaction in real time. Current methods of analysis rely on taking offline samples, deactivating the enzymes, and performing analysis on the products afterwards. Nuclear magnetic resonance benchtop spectroscopy was investigated as a method for online process monitoring of enzymatic hydrolysis. Online and offline NMR measurements were performed for enzymatic hydrolysis reactions on red cod, salmon and shrimp. Both the online and offline measurements were able to follow the reaction process and showed good agreement in their calculated reaction rate. Application of the methodology to several types of raw materials indicates the technique is robust with regards to sample type. Advantages and disadvantages of low-field versus high-field NMR spectroscopy are discussed as well as practical considerations needed in order to apply the method industrially.

Real-time benchtop NMR spectroscopy for the online monitoring of sucrose hydrolysis

The online monitoring of chemical reactions by using benchtop Nuclear Magnetic Resonance (NMR) spectroscopy has become increasingly attractive for the past few years. The use of quantitative online NMR spectroscopy is a promising alternative to traditional analytical methods with its rapid, quantitative and non-invasive nature that makes it applicable to complex and diverse biochemical mixtures like food systems. In this study, sucrose hydrolysis by invertase was chosen as a model reaction for online monitoring. Rather than conventional NMR spectroscopy experiments that rely on the use of deuterated water, the benchtop setting allows working in protonated solvents, and tailored water suppression techniques were used to make quantification more accurate. For the hydrolysis reaction, a 10% sucrose solution was hydrolyzed. The kinetic constants determined by the fractional conversion model were comparable to the results obtained in other studies. Quantitative online NMR spectroscopy can be considered as a promising tool for monitoring food processes in a continuous mode.

Reaction Monitoring by Benchtop NMR Spectroscopy Using a Novel Stationary Flow Reactor Setup

A flow reactor setup for noninvasive monitoring of reactions using a compact benchtop nuclear magnetic resonance (NMR) spectrometer is presented, in which a tubular flow reactor is inserted into th...

Synthesis of α-fluoro-α,β-unsaturated esters monitored by 1D and 2D benchtop NMR spectroscopy.

For optimization and control of pharmaceutically and industrially important reactions, chemical information is required in real time. Instrument size, handling, and operation costs are important criteria to be considered when choosing a suitable analytical method apart from sensitivity and resolution. This present study explores the use of a robust and compact nuclear magnetic resonance (NMR) spectrometer to monitor the stereo-selective formation of α-fluoro-α,β-unsaturated esters from α-fluoro-β-keto esters via deprotonation and deacylation in real time. These compounds are precursors of various pharmaceutically active substances. The real-time study revealed the deprotonation and deacylation steps of the reaction. The reaction was studied at temperatures ranging from 293 to 333K by interleaved one-dimensional 1 H and 19 F and two-dimensional 1 H-1 H COSY experiments. The kinetic rate constants were evaluated using a pseudo first-order kinetic model. The activation energies for the deprotonation and deacylation steps were determined to 28±2 and 63.5±8kJ/mol, respectively. This showed that the deprotonation step is fast compared with the deacylation step and that the deacylation step determines the rate of the overall reaction. The reaction was repeated three times at 293K to monitor the repeatability and stability of the system. The compact NMR spectrometer provided detailed information on the mechanism and kinetics of the reaction, which is essential for optimizing the synthetic routes for stepwise syntheses of pharmaceutically active substances.