Recent progress of porous cage materials in sample preparation, chromatographic separation, and detection.

Porous cage materials with certain dimensions, sizes, shapes, and functions have been regarded as promising materials for sample preparation, chromatographic separation, and detection process. In contrast to infinite frameworks such as metal-organic frameworks or covalent organic frameworks, porous cage materials are constructed from discrete molecules containing at least one internal cavity. The well-defined cavities in porous cage materials provide opportunities for non-covalent interactions. These interactions can be programmed into the ligand design or supramolecular cage constructing using the cages as building blocks, offering various host-guest recognition with great selectivity. In this review, we desire to elucidate the fundamental principles governing the design and fabrication of porous cage materials with well-defined cavities, good solvent processability, and modifiable groups, the applications of these porous cage materials in sample preparation, chromatographic separation, and detection were discussed. The recent advantages of porous cage materials for the analysis process were summarized. We state the potential of these materials and provide an outlook for further application strategies. We expect that this review can inspire interest in the porous cage materials research area for analysis.

Dispersive hierarchically porous composites based on defective MOFs as mixed-mode stationary phases for chromatographic separation.

Defective metal-organic frameworks-based composites with excellent separation properties were obtained. The mesoporous metal-organic frameworks were selected and deliberately designed to be deficient, and they were then combined with polyacrylamide to be modified on the surface of silica microspheres. The prepared composites were employed as mixed-mode stationary phase in chromatographic separation, and they were compared to both conventional microporous metal-organic framework-based columns and commercial columns. It showed improved selectivity and retention toward both hydrophilic and hydrophobic analytes, allowing for the effective separation of nine nucleosides and nucleobases, eight alkaloids, six antibiotics, and five alkylbenzenes. Additionally, the column was used to effectively separate the active ingredients in the daring substance of honeysuckle, revealing a wide range of possible applications. For the same batch of analytes, three batches of distinct materials demonstrated consistent separation effects. It also demonstrated excellent chromatographic repeatability and stability, with relative standard deviations of the retention time and/or column efficiency being found to be less than 0.8% and 0.9%, respectively. The dispersive hierarchically porous composites were demonstrated to be effective in chromatographic separation, and the results expanded the potential uses of defective MOFs with dispersed multi-level pores.

Qualitative and Quantitative Analytical Techniques of Nucleic Acid Modification Based on Mass Spectrometry for Biomarker Discovery.

Nucleic acid modifications play important roles in biological activities and disease occurrences, and have been considered as cancer biomarkers. Due to the relatively low amount of nucleic acid modifications in biological samples, it is necessary to develop sensitive and reliable qualitative and quantitative methods to reveal the content of any modifications. In this review, the key processes affecting the qualitative and quantitative analyses are discussed, such as sample digestion, nucleoside extraction, chemical labeling, chromatographic separation, mass spectrometry detection, and data processing. The improvement of the detection sensitivity and specificity of analytical methods based on mass spectrometry makes it possible to study low-abundance modifications and their biological functions. Some typical nucleic acid modifications and their potential as biomarkers are displayed, and efforts to improve diagnostic accuracy are discussed. Future perspectives are raised for this research field.

Resin screening and process optimization for erythritol mother liquor chromatographic separation.

In order to improve the utilization value of the erythritol mother liquor, the separation and purification of the erythritol mother liquor was selected in this study. The selected chromatographic separation programme for erythritol crystallizing mother liquor is as follows: Firstly, erythritol is resolved from mannitol and arabitol with DTF-01Ca (Suqing Group) resin and then mannitol is resolved from arabitol with 99Ca/320 (Dowex) resin. At the same time, the chromatographic conditions of the DTF-01Ca (Suqing Group) and 99Ca/320 (Dowex) resins were optimized, resulting in an optimal separation temperature and mobile phase flow rate of 70 °C, 10 ml/min. On this basis, a single-column chromatographic model was used to calculate the TD model parameter (N) and the mass transfer coefficient (km ) of the separation of erythritol mother liquor by DTF-01Ca (Suqing Group) and 99Ca/320 (Dowex) resins. The adsorption isotherms, TD model parameter (N) and the mass transfer coefficient (km ) provides data references for the design and operation of the simulated moving beds (SMB) separation system for the industrial-scale separation of erythritol crystallizing mother liquor.

Phosphorus-doped deep eutectic solvent-derived carbon dots-modified silica as a mixed-mode stationary phase for reversed-phase and hydrophilic interaction chromatography.

In this work, phosphorus-doped carbon dots (P-DESCDs) were successfully prepared using choline chloride/lactic acid type deep eutectic solvent and phosphoric acid as ingredients, and (3-aminopropyl) trimethoxysilane was used as a bridge to graft P-DESCDs onto the silica surface to obtain a new mixed-mode stationary phase (Sil-P-DESCDs) for reversed-phase and hydrophilic interaction liquid chromatography. The successful preparation of the stationary phase was confirmed by laser scanning confocal microscopy, elemental analysis, and Fourier transform infrared spectrometry. Interestingly, the doping of phosphorus greatly improved the separation performance and hydrophilicity of the Sil-P-DESCDs column. The Sil-P-DESCDs column was found to have certain hydrophobicity, hydrogen bonding ability and shape selectivity by Tanaka and Engelhardt standard test mixtures, and a series of hydrophilic and hydrophobic compounds such as alkylbenzenes, polycyclic aromatic hydrocarbons, sulfonamides, aromatic amines, phenols, flavonoids, nucleoside bases, and alkaloids. In addition, the effects of mobile phase ratio, column temperature, flow rate, salt concentration, and pH on the retention of analytes on Sil-P-DESCDs columns were investigated. Finally, the Sil-P-DESCDs column was applied to the qualitative and quantitative analysis of calcein-7-glucoside in the real sample of medicinal Astragalus pellets, and it was found at a concentration of 0.02 mg/mL.

A simple and reliable method for separation of mineral oil/polychlorobiphenyl mixtures.

Polychlorinated biphenyls (PCBs) were broadly applied worldwide as electrical insulators in transformers and power capacitors, due to their high dielectric constant and non-flammability. They were often added to mineral oils (MOs) and used as dielectric fluids, which are nowadays classified as hazardous waste. Indeed, the Stockholm Convention aims to eliminate the use of equipment with PCB content greater than 0.005 wt-% (=50 ppm) by 2025. Accurate identification and quantification of small traces of PCBs contained in MO thus represent a great analytical challenge. To achieve this goal, a simple, cost-effective and fast chromatographic process was developed to separate PCBs from MO, allowing to obtain reliable data to determine the concentration of PCBs, reduced to 2-3 ppm. Experimental and analytical methods, such as thin layer chromatography, column chromatography as well as gas chromatography coupled with mass spectroscopy, were applied to acquire a high level of qualitative and quantitative determination of PCBs in transformer MOs.

The foundations and development of lipidomics.

For over a century, the importance of lipid metabolism in biology was recognized but difficult to mechanistically understand due to the lack of sensitive and robust technologies for identification and quantification of lipid molecular species. The enabling technological breakthroughs emerged in the 1980s with the development of soft ionization methods (Electrospray Ionization and Matrix Assisted Laser Desorption/Ionization) that could identify and quantify intact individual lipid molecular species. These soft ionization technologies laid the foundations for what was to be later named the field of lipidomics. Further innovative advances in multistage fragmentation, dramatic improvements in resolution and mass accuracy, and multiplexed sample analysis fueled the early growth of lipidomics through the early 1990s. The field exponentially grew through the use of a variety of strategic approaches, which included direct infusion, chromatographic separation, and charge-switch derivatization, which facilitated access to the low abundance species of the lipidome. In this Thematic Review, we provide a broad perspective of the foundations, enabling advances, and predicted future directions of growth of the lipidomics field.

Covalent Organic Frameworks-Based Membranes as Promising Modalities from Preparation to Separation Applications: An Overview.

Covalent organic frameworks (COFs) are a promising class of porous crystalline materials made up of covalently connected and periodically protracted network topologies through organic linkers. The tailorability of organic linker and intrinsic structures endow COFs with a tunable porosity and structure, low density, facilely-tailored functionality, and large surface area, attracting increasing amount of interests in variety of research areas of membrane separations. COF-based membranes have spawned a slew of new research projects, ranging from fabrication methodologies to separation applications. Herein, we tried to emphasis the major developments in the synthetic approaches of COFs based membranes for a variety of separation applications such as, separation of gaseous mixtures, water treatment as well as separation of isomeric and chiral organic compounds. The proposed methods for fabricating COF-based continuous membranes and columns for real world applications are also thoroughly explored. Finally, a viewpoint on the future directions and remaining challenges for COF research in the area of separation is provided.

Effect of Natural Deep Eutectic Solvents on trans-Resveratrol Photo-Chemical Induced Isomerization and 2,4,6-Trihydroxyphenanthrene Electro-Cyclic Formation.

trans-Resveratrol is a natural bioactive compound with well-recognized health promoting effects. When exposed to UV light, this compound can undergo a photochemically induced trans/cis isomerization and a 6π electrochemical cyclization with the subsequent formation of 2,4,6-trihydroxyphenanthrene (THP). THP is a potentially harmful compound which can exert genotoxic effects. In this work we improved the chromatographic separation and determination of the two resveratrol isomers and of THP by using a non-commercial pentafluorophenyl stationary phase. We assessed the effect of natural deep eutectic solvents (NaDES) as possible photo-protective agents by evaluating cis-resveratrol isomer and THP formation under different UV-light exposure conditions with the aim of enhancing resveratrol photostability and inhibiting THP production. Our results demonstrate a marked photoprotective effect exerted by glycerol-containing NaDES, and in particular by proline/glycerol NaDES, which exerts a strong inhibitory effect on the photochemical isomerization of resveratrol and significantly limits the formation of the toxic derivative THP. Considering the presence of resveratrol in various commercial products, these results are of note in view of the potential genotoxic risk associated with its photochemical degradation products and in view of the need for the development of green, eco-sustainable and biocompatible resveratrol photo-stable formulations.

A Noncovalent π-Stacked Porous Organic Molecular Framework for Selective Separation of Aromatics and Cyclic Aliphatics.

Selective separation using porous adsorbents is an energy-efficient alternative to traditional separation techniques. Stacked porous organic molecular frameworks (POMFs) capable of noncovalent π⋅⋅⋅π interactions are emerging as a new kind of adsorbents that facilitate green separation. Here we report a robust porous molecular crystal (TAPM-1), which is stabilized by multiple intermolecular π⋅⋅⋅π interactions. With its long-range π-stacking, TAPM-1 has excellent hydrophobicity, thermostability, recyclability, and high selectivity for aromatics over the corresponding cyclic aliphatics. This enables TAPM-1 to serve as the stationary phase in the high-resolution gas chromatographic separation of benzene and cyclohexane or toluene and methylcyclohexane.

Rapid quantification of fatty acids in plant oils and biological samples by LC-MS.

Analysis of fatty acids (FA) in food and biological samples such as blood is indispensable in modern life sciences. We developed a rapid, sensitive and comprehensive method for the quantification of 41 saturated and unsaturated fatty acids by means of LC-MS. Optimized chromatographic separation of isobaric analytes was carried out on a C8 reversed phase analytical column (100 × 2.1 mm, 2.6 µm core-shell particle) with a total run time of 15 min with back pressure lower than 300 bar. On an old triple quadrupole instrument (3200, AB Sciex), pseudo selected reaction monitoring mode was used for quantification of the poorly fragmenting FA, yielding limits of detection of 5-100 nM. Sample preparation was carried out by removal of phospholipids and triglycerides by solid-phase extraction (non-esterified fatty acids in oils) or saponification in iso-propanol (fatty acyls). This is not only a rapid strategy for quantification of fatty acyls, but allows the direct combination with the LC-MS-based analysis of fatty acid oxidation products (eicosanoids and other oxylipins) from the same sample. The concentrations of fatty acyls determined by means of LC-MS were consistent with those from GC-FID analysis demonstrating the accuracy of the developed method. Moreover, the method shows high precisions with a low intra-day (≤ 10% for almost all fatty acids in plasma and ≤ 15% in oils) and inter-day as well as inter-operator variability (< 20%). The method was successfully applied on human plasma and edible oils. The possibility to quantify non-esterified fatty acids in samples containing an excess of triacylglycerols and phospholipids is a major strength of the described approach allowing to gain new insights in the composition of biological samples.

Development and applications of deep eutectic solvent derived functional materials in chromatographic separation.

Deep eutectic solvents have received increasing attention over the past decade, and the green and versatile nature makes them important media for developing environmentally friendly and sustainable technologies. In addition to act as green alternatives to traditional organic solvents, deep eutectic solvents offer tremendous opportunities to produce different kinds of emerging functional materials. The present review highlights the recent development and applications of deep functional materials based on deep eutectic solvents as novel adsorbents for diverse analytes in complex matrices. The type, preparation, and unique properties of deep eutectic solvents, the synthesis of deep eutectic solvent derived materials, as well as their applications in chromatographic separation are described. We aim to demonstrate that deep eutectic solvents not only allow the design of eco-friendly extraction processes but also open straightforward access to advanced materials in sample preparation.

Methods of Lipidomic Analysis: Extraction, Derivatization, Separation, and Identification of Lipids.

Lipidomics refers to the large-scale study of pathways and networks of cellular lipids in biological systems. A lipidomic analysis often involves the identification and quantification of the thousands of cellular lipid molecular species within a complex biological sample and therefore requires a well optimized method for lipid profiling. In this chapter, the methods for lipidomic analysis, including sample collection and preparation, lipid derivatization and separation, mass spectrometric identification of lipids, data processing and interpretation, and quality control, are overviewed.

Fabrication of two-dimensional metal-organic framework nanosheets/PDA composites as mixed-mode stationary phase for chromatographic separation.

The synthesis of two-dimensional metal-organic frameworks (2D MOFs)/polymer core-shell composites is reported which were composed of polydopamine modified 2D Zr-1,3,5-(4-carboxylphenyl)-benzene (2D Zr-BTB) nanosheets and silica microspheres via a double-solvent approach. In this way, the composites were obtained under the condition of two solvents with different polarities to avoid agglomeration and uneven modification of most MOFs particles on the surface of the silica, existing inevitably in the one-pot method. Compared with the reported MOFs@silica composites adopting one-pot solvent method, the prepared composites exhibited significantly enhanced separation performance for sulfonamides, antibiotics, nucleosides, and polycyclic aromatic hydrocarbons compounds. Furthermore, the retention mechanisms were demonstrated by studying the relationships of chromatographic retention factors of tested analytes versus a variety of parameters under RPLC and HILIC modes, respectively. The superior chromatographic repeatability and stability were validated through the relative standard deviations of the retention time and/or column efficiency, which were found to be less than 0.8% and 0.9%, respectively. The material showed efficient separation ability for several types of compounds and provided another selectivity for preparing composites based on 2D MOFs nanosheets and other functional molecules.

One-Pot and Shape-Controlled Synthesis of Organic Cages.

Organic cages are fascinating because of their well-defined 3D cavities, excellent stability, and accessible post-modification. However, the synthesis is normally realized by fragment coupling approach in low yields. Herein, we report one-pot, gram-scale and shape-controlled synthesis of two covalent organic cages (box-shaped [4]cage and triangular prism-shaped [2]cage) in yields of 46 % and 52 %, involving direct condensation of triangular 1,3,5-tris(2,4-dimethoxyphenyl)benzene monomer with paraformaldehyde and isobutyraldehyde, respectively. The cages can convert into high-yielding per-hydroxylated analogues. The [2]cage can be utilized as gas chromatographic stationary phase for high-resolution separation of benzene/cyclohexane and toluene/methylcyclohexane. By changing the central moiety of the triangular monomer and/or aldehyde, this synthetic method would have the potential to be a general strategy to access diverse cages with tunable shape, size, and electronic properties.

Preparation and application of novel MIL-101(Cr) composite in liquid chromatographic separation of aromatic compounds: experimental and computational insights.

A novel composite material of SiO2@dSiO2@MIL-101(Cr) was synthesized via SiO2@dSiO2 as the core and MIL-101(Cr) as the shell to separate aromatic compounds. The laboratory prepared column gave rise to the baseline separation of xylene, dichlorobenzene isomers, phthalate esters, nitrobenzene, and acetophenone with high column efficiency (e.g., 109,050 plates m-1 for methyl phthalate) and good precision (e.g., 0.02-0.05%, 0.24-0.34%, 0.14-0.18%, and 0.11-0.13% corresponding to the relative standard deviation of retention time, peak area, peak height, and half peak width for xylene isomers, respectively). The calculation of thermodynamic parameters demonstrated that the separation of o-xylene, nitrobenzene, acetophenone, and p-dichlorobenzene was controlled by positive ∆H and ∆S. Although the separation of aromatic compounds by a MOF packed column has been reported in many studies, the knowledge regarding their separation mechanism at atomic level is still very limited. In this study, we integrate fully atomistic molecular dynamics simulation and binding free energy calculation to investigate the separation mechanism of aromatic compounds by MIL-101(Cr). The investigation provides a base for separation of more and other compounds in the future. Graphical abstract.

Purification and Characterization of Antioxidant Peptides of Pseudosciaena crocea Protein Hydrolysates.

Two peptides with antioxidant activity were isolated from Pseudosciaena crocea proteins. Pseudosciaena crocea muscle was hydrolyzed with neutral protease to obtain Pseudosciaena crocea protein hydrolysates (PCPH). After ultrafiltration through molecular weight cut-off membranes of 10, 5 and 3 kDa and assessment of free radical scavenging ability, the fraction (PCPH-IV) with the highest antioxidant activity was obtained. Several purification steps, i.e., ion exchange chromatography, gel filtration chromatography and reversed phase high performance liquid chromatography, were applied to further purify PCPH-IV. Two antioxidant peptides with the amino acid sequences Ser-Arg-Cys-His-Val and Pro-Glu-His-Trp were finally identified by LC-MS/MS.

Separation and identification of indene-C70 bisadduct isomers.

Following an initial work on the isolation of a single geometric isomer from an indene-C70 bisadduct (IC70BA) mixture, we report the full fractionation and identification of the bisadduct species in the material. Eleven fractions of IC70BA isomers were separated by high-performance liquid chromatography. A number of fractions contained relatively pure isomer species and their configuration were deduced using a variety of analytical techniques including (1)H and (13)C NMR and UV-vis spectroscopy. The electrochemical properties and the organic solar cell device performance were investigated for fractions where a reasonable quantity of sample could be isolated.

Method development for the determination of 24S-hydroxycholesterol in human plasma without derivatization by high-performance liquid chromatography with tandem mass spectrometry in atmospheric pressure chemical ionization mode.

We developed a highly sensitive and specific high-performance liquid chromatography with tandem mass spectrometry method with an atmospheric pressure chemical ionization interface to determine 24S-hydroxycholesterol, a major metabolite of cholesterol formed by cytochrome P450 family 46A1, in human plasma without any derivatization step. Phosphate buffered saline including 1% Tween 80 was used as the surrogate matrix for preparation of calibration curves and quality control samples. The saponification process to convert esterified 24S-hydroxycholesterol to free sterols was optimized, followed by liquid-liquid extraction using hexane. Chromatographic separation of 24S-hydroxycholesterol from other isobaric endogenous oxysterols was successfully achieved with gradient mobile phase comprised of 0.1% propionic acid and acetonitrile using L-column2 ODS (2 µm, 2.1 mm id × 150 mm). This assay was capable of determining 24S-hydroxycholesterol in human plasma (200 µL) ranging from 1 to 100 ng/mL with acceptable intra- and inter-day precision and accuracy. The potential risk of in vitro formation of 24S-hydroxycholesterol by oxidation from endogenous cholesterol in human plasma was found to be negligible. The stability of 24S-hydroxycholesterol in relevant solvents and human plasma was confirmed. This method was successfully applied to quantify the plasma concentrations of 24S-hydroxycholesterol in male and female volunteers.

Engineering aspects of rate-related processes in food manufacturing.

Many rate-related phenomena occur in food manufacturing processes. This review addresses four of them, all of which are topics that the author has studied in order to design food manufacturing processes that are favorable from the standpoint of food engineering. They include chromatographic separation through continuous separation with a simulated moving adsorber, lipid oxidation kinetics in emulsions and microencapsulated systems, kinetic analysis and extraction in subcritical water, and water migration in pasta.