Hyphenation of capillary separations with nuclear magnetic resonance spectroscopy

The hyphenation of small-volume separations to information-rich detection offers the promise of unmatched analytical information on the components of complex mixtures. Nuclear magnetic resonance (NMR) spectroscopy provides information about molecular structure, although sensitivity remains an issue for on-line NMR detection. This is especially true when hyphenating NMR to capillary separations as the observation time and analyte mass are decreased to the point where reduced information is obtained from the eluting analytes. Because of these limitations, advances in instrumental performance have a large impact on the overall performance of a separation–NMR system. Instrumental aspects and the capabilities of cLC–NMR, CEC–NMR and CE–NMR are reviewed, and applications that have used this technology highlighted. Recent trends towards small volume capillary scale separations are emphasized, as is the recent success of capillary-isotachophoresis (cITP)–NMR.     

Real-time separation of natural products by ultrafast 2D NMR coupled to on-line HPLC

Hyphenated HPLC-NMR is an extremely efficient analytical tool, which makes it possible to perform on-flow experiments where 1D NMR spectra are obtained in real time as the analytes are separated and eluted from the chromatographic column. However, it is incompatible with multidimensional NMR methods that form an indispensible tool for the study of complex mixtures. Recently, Frydman and co-workers have proposed an ultrafast 2D NMR approach, where a complete 2D NMR correlation can be recorded in a single scan, thus providing a solution to the irreversibility of hyphenated techniques. This paper presents the first implementation of on-line ultrafast HPLC-NMR. Ultrafast COSY spectra are acquired every 12 s in the course of a chromatographic run performed on a mixture of natural aromatic compounds. The results, obtained on a commercial HPLC-NMR setup, highlight the generality of the ultrafast HPLC-NMR methodology, thus opening the way to a number of applications in the numerous fields in which HPLC-NMR forms a routine analytical tool.     

高效液相色谱－核磁共振联用技术及其应用

高效液相色谱－核磁共振（ＨＰＬＣ－ＮＭＲ）在线联用技术是同时进行未知混合物的分离和结构鉴定的最好手段之一。详细介绍了在ＨＰＬＣ－ＮＭＲ联用技术中１Ｈ谱的分辨率、检测限和多重溶剂峰抑制的最新进展，并简要评述了其它分离方法与ＮＭＲ联用情况     

高效液相色谱－核磁共振联用技术及其应用

高效液相色谱－核共共振在线联用技术是同时进行未知混合物的分离和结构鉴定的量好手段之一。详细介绍了在ＨＰＬＣ－ＮＭＲ联用技术中Ｈ谱的分辨率，检测限手多重溶剂峰抑制的最新进展，并简要评述了其它分离方法与ＮＭＲ联用情况。     

NMR-based analysis of protein–ligand interactions

Physiological processes are mainly controlled by intermolecular recognition mechanisms involving protein–protein and protein–ligand (low molecular weight molecules) interactions. One of the most important tools for probing these interactions is high-field solution nuclear magnetic resonance (NMR) through protein-observed and ligand-observed experiments, where the protein receptor or the organic compounds are selectively detected. NMR binding experiments rely on comparison of NMR parameters of the free and bound states of the molecules. Ligand-observed methods are not limited by the protein molecular size and therefore have great applicability for analysing protein–ligand interactions. The use of these NMR techniques has considerably expanded in recent years, both in chemical biology and in drug discovery. We review here three major ligand-observed NMR methods that depend on the nuclear Overhauser effect—transferred nuclear Overhauser effect spectroscopy, saturation transfer difference spectroscopy and water–ligand interactions observed via gradient spectroscopy experiments—with the aim of reporting recent developments and applications for the characterization of protein–ligand complexes, including affinity measurements and structural determination.     

Organocatalysis of asymmetric epoxidation mediated by iminium salts: comments on the mechanism

Non-aqueous conditions developed for catalytic asymmetric epoxidation mediated by iminium salt organocatalysts have allowed NMR spectroscopy to be carried out on the reaction mixtures for the first time.     

Disentangling Reaction Processes of Zeolites within Single-Oriented Channels

Establishing structure–reactivity relationships for specific channel orientations of zeolites is vital to developing new, superior materials for various applications, including oil and gas conversion processes. Herein, a well-defined model system was developed to build structure–reactivity relationships for specific zeolite-channel orientations during various catalytic reaction processes, for example, the methanol- and ethanol-to-hydrocarbons (MTH and ETH) process as well as oligomerization reactions. The entrapped and effluent hydrocarbons from single-oriented zeolite ZSM-5 channels during the MTH process were monitored by using operando UV/Vis diffuse reflectance spectroscopy (DRS) and on-line mass spectrometry (MS), respectively. The results reveal that the straight channels favor the formation of internal coke, promoting the aromatic cycle. Furthermore, the sinusoidal channels produce aromatics, (e.g., toluene) that further grow into larger polyaromatics (e.g., graphitic coke) leading to deactivation of the zeolites. This underscores the importance of careful engineering of materials to suppress coke formation and tune product distribution by rational control of the location of zeolite acid sites and crystallographic orientations.     

Absolute Minimal Sampling of Homonuclear 2D NMR TOCSY Spectra for High-Throughput Applications of Complex Mixtures

Modern applications of 2D NMR spectroscopy to diagnostic screening, metabolomics, quality control, and other high-throughput applications are often limited by the time-consuming sampling requirements along the indirect time domain t₁. 2D total correlation spectroscopy (TOCSY) provides unique spin connectivity information for the analysis of a large number of compounds in complex mixtures, but standard methods typically require >100 t₁ increments for an accurate spectral reconstruction, rendering these experiments ineffective for high-throughput applications. For a complex metabolite mixture it is demonstrated that absolute minimal sampling (AMS), based on direct fitting of resonance frequencies and amplitudes in the time domain, yields an accurate spectral reconstruction of TOCSY spectra using as few as 16 t₁ points. This permits the rapid collection of homonuclear 2D NMR experiments at high resolution with measurement times that previously were only the realm of 1D experiments.     

Online Reaction Monitoring with Fast and Flow-Compatible Diffusion NMR Spectroscopy

Online monitoring by flow NMR spectroscopy is a powerful approach to study chemical reactions and processes, which can provide mechanistic understanding, and drive optimisations. However, some of the most useful methods for mixture analysis and reaction monitoring are not directly applicable in flow conditions. This is the case of classic diffusion-ordered NMR spectroscopy (DOSY) methods, which can be used to separate the spectral information for mixture's components. We describe a fast and flow-compatible diffusion NMR experiment that makes it possible to collect accurate diffusion data for samples flowing at up to 3 mL/min. We use it to monitor the synthesis of a Schiff base with a flow-tube with a time resolution of approximately 2 minutes. The one-shot flow-compatible diffusion NMR described here open many avenues for reaction monitoring applications.     

分子筛上糖类催化转化的核磁共振研究

葡萄糖、 果糖和木糖等糖类是一类重要的绿色生物质资源, 其高效利用是生物质转化的重要研究方向. 具有Lewis酸性的分子筛在糖类催化转化中表现出优异的性能, 对其活性中心结构、 性质以及反应机理的认识是糖类高效转化研究中亟待解决的关键科学问题. 核磁共振是分子筛上活性中心表征和反应机理研究的重要手段. 本文讨论了先进核磁共振技术与方法在分子筛上糖类转化反应中的应用, 包括催化剂活性中心表征、 催化转化反应机理研究和催化反应产物分析3个方面, 总结了核磁共振在糖类转化反应研究中所取得的新进展并对其未来发展方向进行了展望.     

TReNDS—Software for reaction monitoring with time-resolved non-uniform sampling

NMR spectroscopy, used routinely for structure elucidation, has also become a widely applied tool for process and reaction monitoring. However, the most informative of NMR methods—correlation experiments—are often useless in this kind of applications. The traditional sampling of a multidimensional FID is usually time-consuming, and thus, the reaction-monitoring toolbox was practically limited to 1D experiments (with rare exceptions, e.g., single-scan or fast-sampling experiments). Recently, the technique of time-resolved non-uniform sampling (TR-NUS) has been proposed, which allows to use standard multidimensional pulse sequences preserving the temporal resolution close to that achievable in 1D experiments. However, the method existed only as a prototype and did not allow on-the-fly processing during the reaction. In this paper, we introduce TReNDS: free, user-friendly software kit for acquisition and processing of TR-NUS data. The program works on Bruker, Agilent, and Magritek spectrometers, allowing to carry out up to four experiments with interleaved TR-NUS. The performance of the program is demonstrated on the example of enzymatic hydrolysis of sucrose.     

Application of a new method for simultaneous phase and baseline correction of NMR signals (SINC)

Recently, we presented a new approach for simultaneous phase and baseline correction of nuclear magnetic resonance (NMR) signals (SINC) that is based on multiobjective optimization. The algorithm can automatically correct large sets of NMR spectra, which are commonly acquired when reactions and processes are monitored with NMR spectroscopy. The aim of the algorithm is to provide spectra that can be evaluated quantitatively, for example, to calculate the composition of a mixture or the extent of reaction. In this work, the SINC algorithm is tested in three different studies. In an in-house comparison study, spectra of different mixtures were corrected both with the SINC method and manually by different experienced users. The study shows that the results of the different users vary significantly and that their average uncertainty of the composition measurement is larger than the uncertainty obtained when the spectra are corrected with the SINC method. By means of a dilution study, we demonstrate that the SINC method is also applicable for the correction of spectra with low signal-to-noise ratio. Furthermore, a large set of NMR spectra that was acquired to follow a reaction was corrected with the SINC method. Even in this system, where the areas of the peaks and their chemical shifts changed during the course of reaction, the SINC method corrected the spectra robustly. The results show that this method is especially suited to correct large sets of NMR spectra and it is thus an important contribution for the automation of the evaluation of NMR spectra.     

High-resolution NMR spectroscopy under the fume hood

This work reports the possibility to acquire high-resolution (1)H NMR spectra with a fist-sized NMR magnet directly installed under the fume hood. The small NMR sensor based on permanent magnets was used to monitor the trimerization of propionaldehyde catalyzed by indium trichloride in real time by continuously circulating the reaction mixture through the magnet bore in a closed loop with the help of a peristaltic pump. Thanks to the chemical selectivity of NMR spectroscopy the progress of the reaction can be monitored on-line by determining the concentrations of both reactant and product from the area under their respective lines in the NMR spectra as a function of time. This in situ measurement demonstrates that NMR probes can be used in chemistry laboratories, e.g. for reaction optimization, or installed at specific points of interest along industrial process lines. Therefore, it will open the door for the implementation of feedback control based on spectroscopic NMR data.     

Mechanisms and Beyond: Elucidation of Fluxional Dynamics by Exchange NMR Spectroscopy

Detailed mechanistic information is crucial to our understanding of reaction pathways and selectivity. Dynamic exchange NMR techniques, in particular 2D exchange spectroscopy (EXSY) and its modifications, provide indispensable intricate information on the mechanisms of organic and inorganic reactions and other phenomena, for example, the dynamics of interfacial processes. In this Review, key results from exchange NMR studies of small molecules over the last few decades are systemised and discussed. After a brief introduction to the theory, the key types of dynamic processes are identified and fundamental examples given of intra- and intermolecular reactions, which, in turn, could involve, or not, bond-making and bond-breaking events. Following that logic, internal molecular rotation, intramolecular stereomutation and molecular recognition will first be considered because they do not typically involve bond breaking. Then, rearrangements, substitution-type reactions, cyclisations, additions and other processes affecting chemical bonds will be discussed. Finally, interfacial molecular dynamics and unexpected combinations of different types of fluxional processes will also be highlighted. How exchange NMR spectroscopy helps to identify conformational changes, coordination and molecular recognition processes as well as quantify reaction energy barriers and extract detailed mechanistic information by using reaction rate theory in conjunction with computational techniques will be shown.     

New direct 11B NMR-based analysis of organoboranes through their potassium borohydrides

Representative organoborane mixtures were quantitatively converted to their borohydrides through their reaction with activated KH (KH), permitting their detailed analysis by (11)B NMR. Through the treatment of commercial KH with a THF solution of lithium aluminum hydride (LAH), a dramatic change in the surface morphology results as revealed by scanning electron microscopy (SEM). Energy dispersed spectroscopy (EDS) was employed to reveal that the LAH treatment deposits a significant amount of an unknown aluminum-containing species on the surface of the KH, which imparts a unique reactivity to the KH. Even highly hindered organoboranes are quantitatively converted to their borohydrides by replacing electronegative groups (e.g., OR, halogen) with hydrogen, retaining only the carbon ligation. Through this simple KH treatment, complex organoborane reaction mixtures are converted to the corresponding borohydrides whose (11)B NMR spectra normally exhibit resolved signals for the individual species present. The integration of these signals provides quantitative information on the relative amounts of each component of the mixture. New generalities for the effect of alpha-, beta-, and gamma-substituents have also been determined that provide a new, simple technique for the determination of the isomeric distribution in organoborane mixtures resulting from common organoborane processes (e.g., hydroboration). Moreover, the (1)H-coupled (11)B NMR spectra of these mixtures reveal the extent of alkylation for each species present. Representative organoboranes were examined by this new technique permitting a simple and convenient quantitative analysis of the regio- and diastereomeric composition of a variety of asymmetric organoborane processes. Previously unknown details of pinene-based hydroborations and reductions are revealed for the first time employing the KH (11)B NMR technique.     

Absolute Minimal Sampling of Homonuclear 2D NMR TOCSY Spectra for High‐Throughput Applications of Complex Mixtures

Modern applications of 2D NMR spectroscopy to diagnostic screening, metabolomics, quality control, and other high‐throughput applications are often limited by the time‐consuming sampling requirements along the indirect time domain t ₁. 2D total correlation spectroscopy (TOCSY) provides unique spin connectivity information for the analysis of a large number of compounds in complex mixtures, but standard methods typically require >100 t ₁ increments for an accurate spectral reconstruction, rendering these experiments ineffective for high‐throughput applications. For a complex metabolite mixture it is demonstrated that absolute minimal sampling (AMS), based on direct fitting of resonance frequencies and amplitudes in the time domain, yields an accurate spectral reconstruction of TOCSY spectra using as few as 16 t ₁ points. This permits the rapid collection of homonuclear 2D NMR experiments at high resolution with measurement times that previously were only the realm of 1D experiments.     

Computational studies of room temperature ionic liquid-water mixtures

Room temperature ionic liquids (IL) have been used in numerous applications in chemistry. Addition of water alters many of their properties making it possible to custom design solvents for specific applications. Along with experiments, computational studies using various approaches have provided key insights into the structure and dynamics of IL systems, as well as aggregate formation and phase behavior of the IL/water mixtures. These systems provide computational challenges since ILs and IL/water mixtures are viscous liquids with intrinsically slow processes and structural organization over surprisingly large length scales, which push the limits of applicability of the available techniques. Recent developments in the studies of IL/water mixtures using computational methodologies are reviewed and the future prospects for the field are briefly discussed.     

Hydrothermal Synthesis of Metal Silicates

Organically templated metal phosphates have been extensively studied because of interesting structural chemistry and potential applications in catalysis. However, in most cases the organic templates cannot be removed without collapse of the frameworks. This is in contrast to the high thermal stability and extensive applications of zeolites in refinery and petrochemical processes.Therefore, studies have been directed to the synthesis of transition metal silicates to produce more stable frameworks. Our synthetic methods are twofold, namely mild hydrothermal reactions in Teflon-lined autoclaves at 100-200 ℃ using organic amines as templates and high-temperature,high-pressure hydrothermal reactions in gold ampoules contained in a high-pressure reaction vessel at ca. 550 ℃ and 150 Mpa using alkali metal cations as templates. In this presentation I will report the high-temperature, high-pressure hydrothermal synthesis, crystal structures, and solid-state NMR spectroscopy of a number of new silicates of indium, uranium, and transition metals.     

SBA‐15‐Oxynitrides as a Solid‐Base Catalyst: Effect of Nitridation Temperature on Catalytic Activity

Solid bases, such as SBA‐15‐oxynitrides, have attracted considerable interest for potential applications as catalysts in important industrial processes. Reported herein is that by simply tuning the temperature of nitridation (ammonolysis), the catalytic activity of these solid bases can be enhanced. Solid‐state NMR spectroscopy and XPS studies provided the reasoning behind this change in activity.     

In situ solid-state NMR for heterogeneous catalysis: a joint experimental and theoretical approach

In situ solid-state NMR is a well-established tool for investigations of the structures of the adsorbed reactants, intermediates and products on the surface of solid catalysts. The techniques allow identifications of both the active sites such as acidic sites and reaction processes after introduction of adsorbates and reactants inside an NMR rotor under magic angle spinning (MAS). The in situ solid-state NMR studies of the reactions can be achieved in two ways, i.e. under batch-like or continuous-flow conditions. The former technique is low cost and accessible to the commercial instrument while the latter one is close to the real catalytic reactions on the solids. This critical review describes the research progress on the in situ solid-state NMR techniques and the applications in heterogeneous catalysis under batch-like and continuous-flow conditions in recent years. Some typical probe molecules are summarized here to detect the Br?nsted and Lewis acidic sites by MAS NMR. The catalytic reactions discussed in this review include methane aromatization, olefin selective oxidation and olefin metathesis on the metal oxide-containing zeolites. With combining the in situ MAS NMR spectroscopy and the density functional theoretical (DFT) calculations, the intermediates on the catalyst can be identified, and the reaction mechanism is revealed. Reaction kinetic analysis in the nanospace instead of in the bulk state can also be performed by employing laser-enhanced MAS NMR techniques in the in situ flow mode (163 references).