Modern Analytical Chemistry Research Articles

Network Topology Evaluation and Transitive Alignments for Molecular Networking.

Untargeted tandem mass spectrometry (MS/MS) is an essential technique in modern analytical chemistry, providing a comprehensive snapshot of chemical entities in complex samples and identifying unknowns through their fragmentation patterns. This high-throughput approach generates large data sets that can be challenging to interpret. Molecular Networks (MNs) have been developed as a computational tool to aid in the organization and visualization of complex chemical space in untargeted mass spectrometry data, thereby supporting comprehensive data analysis and interpretation. MNs group related compounds with potentially similar structures from MS/MS data by calculating all pairwise MS/MS similarities and filtering these connections to produce a MN. Such networks are instrumental in metabolomics for identifying novel metabolites, elucidating metabolic pathways, and even discovering biomarkers for disease. While MS/MS similarity metrics have been explored in the literature, the influence of network topology approaches on MN construction remains unexplored. This manuscript introduces metrics for evaluating MN construction, benchmarks state-of-the-art approaches, and proposes the Transitive Alignments approach to improve MN construction. The Transitive Alignment technique leverages the MN topology to realign MS/MS spectra of related compounds that differ by multiple structural modifications. Combining this Transitive Alignments approach with pseudoclique finding, a method for identifying highly connected groups of nodes in a network, resulted in more complete and higher-quality molecular families. Finally, we also introduce a targeted network construction technique called induced transitive alignments where we demonstrate effectiveness on a real world natural product discovery application. We release this transitive alignment technique as a high-throughput workflow that can be used by the wider research community.

Non-Invasive Disposable 2D Ti3C2Tx based Enzyme Free Electrochemical Sweat Glucose Biosensor

Modern analytical chemistry, enhanced by advancements in materials science, is crucial for cost-effectively improving measurement techniques, and making analyses more accessible and user-friendly. Disposable screen-printed electrodes have emerged as promising tools, offering miniaturization, high reproducibility, high sensitivity, rapid detection, and inherent selectivity. This study highlights the development of advanced 2D Ti3C2Tx MXene-modified disposable screen-printed gold electrodes for non-invasive, enzyme-free glucose sensing. Ti3C2Tx was synthesized using direct and in-situ etchants to achieve controlled surface chemistry. Techniques such as XRD, UV–visible spectroscopy, SEM, and TEM were employed to characterize Ti3C2Tx synthesized with different etchants. The synthesized materials were then used as working electrodes to investigate their electrocatalytic performance, tailored for continuous glucose monitoring. Upon optimization, in-situ LiF and HCl etched Li-Ti3C2Tx@SPGE exhibited a high sensitivity of 569.70 µA mM−1cm−2, followed by HF-Ti3C2Tx@SPGE and N-Ti3C2Tx@SPGE with sensitivities of 249.62 and 297.78 µA mM−1cm−2, respectively. These sensors demonstrated low limits of detection (LOD) of 5 nM, 28 nM, and 19 nM within a linear range of 5 to 350 µM. Additionally, real sweat analysis was conducted by collecting natural sweat through fast walking and evaluating sensor performance after beverage consumption. Overall, Li-Ti3C2Tx@SPGE, without any additional composition or doping, shows potential as a superior commercial sweat sensor for routine glucose monitoring. This study underscores the innovative use of 2D materials in developing highly sensitive, non-invasive sweat glucose sensors that are both effective and accessible.

Achievements and Challenges of Matrix Solid-Phase Dispersion Usage in the Extraction of Plants and Food Samples

A review of the application of matrix solid-phase dispersion (MSPD) in the extraction of biologically active compounds and impurities from plants and food samples with a particular emphasis on conventional and new types of sorbents has been provided. An overview of MSPD applications for the isolation of organic residues from biological samples, determined using chromatographic and spectroscopic techniques, has been presented. In this study, procedural solutions that may extend MSDP applicability for the extraction such as vortex-assisted, ultrasound-assisted, microwave-assisted, and extraction with a magnetic sorbent have been discussed. Special attention has been paid to MSPD sorbents including modified silica, diatomite, magnesium silicate, alumina, carbon materials (carbon nanotubes, graphene oxide, graphene, or graphite), molecularly imprinted polymers, and cyclodextrin. An important aspect of the MSPD procedure is the use of high-purity and environmentally friendly solvents for extraction (e.g., deep eutectic solvents), with such criteria being the most important for modern analytical chemistry. Many advantages of MSPD are presented, such as high recoveries, the requirement for a smaller volume of solvent, and shorter procedure times than classical methods.

HPLC analysis of synthetic dyes in wastewater

The analysis of synthetic dyes in wastewater is an urgent task of modern analytical chemistry since an increased content of dyes in wastewater can have an adverse effect on the environment. Reverse phase high performance liquid chromatography (RP HPLC) is often used to control the content of dyes in various objects, which makes it possible to reliably determine the content of specified substances. The purpose of this work was to create and evaluate the metrological characteristics for the method of analysis of synthetic dyes in the industrial wastewater with a high content of inorganic salts. The chromatographic system used in this work was a Knauer high-pressure pump. The separation was performed on a Kromasil 100-5-C18 (w) reverse phase column (4.6 × 250 mm) in the gradient elution mode. Acetonitrile and ammonium acetate solution were used as the mobile phase. Synthetic dyes were detected on an Azura diode array detector. The paper presents the results of concentrating 10 synthetic dyes on commercially available solid phase extraction cartridges that were suitable for working with aqueous solutions with a high content of inorganic salts. For each substance, the degree of concentration from distilled and model wastewater was calculated, which varied from 2 to 98%. Among the analysed cartridges, the highest degree of concentration during operation in conditions close to real wastewater was shown by the Diapak P cartridge, at a pH of the concentrated solution equal to 4. The results of this study were used to develop and validate a method for a simultaneous detection of 10 synthetic food dyes (SFD) (E102, E104, E110, E122, E124, E129, E131, E133, E142, E151) in aqueous and organic solutions. The results of the study can be used to provide analytical control of the content of synthetic dyes in the industrial wastewater. The limit of intermediate precision of the method did not exceed 5%, and the expanded uncertainty of the measurements was less than 10%.

Keeping Analytical Chemistry Training Up-to-Date.

The undergraduate analytical chemistry curriculum serves to equip students with the knowledge and skills for work outside of classroom training. As such, instructors face a challenging task in deciding the breadth and depth of topics for their courses to ensure their syllabi can remain up-to-date with today's needs. We propose that instructors consider covering capillary electrophoresis (CE) and lab-on-a-chip (LOC) technologies in their analytical chemistry courses. Past surveys of the curriculum show a noticeable lack of emphasis on these topics, which we feel is a missed opportunity and one that holds potential for the collective benefit of instructors and students. CE and LOCs are utilized in a diverse array of fields like biochemistry, pharmaceutical production, materials science, and environmental analysis, and their applications are becoming increasingly important amidst the growing movement toward environmentally sustainable practices and green chemistry. They are also more accessible in the analytical chemistry classroom compared with typical benchtop instruments due to the flexibility of their size and cost. This makes them easier to obtain, maintain, and transport for use and demonstration purposes. Additionally, interwoven in these topics are core concepts that are fundamental to analytical chemistry; thus, covering them will inherently reinforce students' understanding of fundamental knowledge. Therefore, we believe increased coverage of CE and LOCs can better prepare undergraduates for modern analytical chemistry work in various industries and fields of research.

Sensitive, Stable, and Recyclable ZnO/Ag Nanohybrid Substrates for Surface-Enhanced Raman Scattering Metrology.

Surface-enhanced Raman scattering is a practical, noninvasive spectroscopic technique that measures chemical fingerprints for varieties of molecules in multiple applications. However, synthesizing appropriate substrates for practical, long-term applications of this method has always been a challenging task. In the present study, we show that ZnO/Ag nanohybrid substrates may act as highly stable, sensitive, and recyclable substrates for surface-enhanced Raman scattering, as illustrated by the detection of methylene blue, selected as a test dye molecule with self-cleaning functionalities. Specifically, we demonstrate the detection enhancement factor of 3.7 × 107 along with exceptional long-term stability explained in terms of the localized surface plasmon resonance from the Ag nanocrystals embedded into the chemically inert ZnO nanoparticles, constituting the nanohybrid. Significantly, these substrates can be efficiently cleaned and regenerated while maintaining their high performance upon recycling. As a result, using these substrates, up to 10-12 M detection sensitivity has been demonstrated, enabling the accuracy required in modern environmental monitoring, bioassays, and analytical chemistry. Thus, ZnO nanoparticles with embedded Ag nanocrystals constitute a novel class of advanced nanohybrid substrates for use in multiple applications of surface-enhanced Raman scattering metrology.

Teaching Experimental Instrumental Analytical Chemistry Are we forming professionals, training operators or illuding students (and ourselves)?

Teaching Experimental Instrumental Analytical Chemistry Are we forming professionals, training operators or illuding students (and ourselves)?

Teaching the principles of least-cost poultry feed formulation utilizing the Solver function within a computer software workbook

A Microsoft Excel workbook, User-Friendly Feed Formulation with Data from Australia (UffdAu.xlsm), has been developed for teaching feed formulation techniques to tertiary level, university students. It runs under both Microsoft Windows and Apple iOS operating systems. The example ingredient composition matrix is based on the Australian Feed Ingredient Database to illustrate the biological and econometric principles of least-cost feed formulation. The nutrient data are based roughly on recent primary breeder company recommendations. The workbook is easily adapted to appropriate ingredients, nutrients, and prices most relevant to the students, wherever it is used. The workbook uses the linear routines of Excel's Solver add-in under the Data heading in the header Ribbon. There is a worksheet illustrating how to adapt non-linear responses such as exogenous enzymes to typical linear models using a step function. Additional worksheets illustrate how proximate analysis can be interpreted in modern analytical chemistry terms and, how various feed energy measures are related to feed composition. UffdAu.xlsm is available free of charge from the Poultry Hub Australia website (https://www.poultryhub.org).

Influence of polarity mode switching and standby times on signal stability and detection of aspirated droplet signatures in electrospray mass spectrometry

Electrospray ionization plays a central role in modern analytical chemistry. It is often used in combination with an HPLC system and is able to transfer large molecules, such as proteins and complexes, into the gas phase. A liquid solution containing the analyte is sprayed in a strong electric field. Charged droplets generated by this process release the analyte molecules which can ultimately be analyzed by the mass spectrometer system. However, the exact mechanisms of droplet generation and ion release are still not fully understood and are under investigation. Recent literature puts the focus on droplet disintegration and shows that the analyte ions are not exclusively released from the droplets within the ionization chamber but rather in the whole mass spectrometer system. Previous experiments allow the direct observation of the signatures of fragmented droplets within the analyzer region of a time-of-flight mass spectrometer: An oscilloscope was connected to a secondary electron multiplier which serves as an auxiliary ion detector, located downstream of the orthogonal acceleration stage of a time-of-flight mass spectrometer. The oscilloscope is thus able to monitor the time-resolved ion current in the mass analyzer region. Pulses of extraordinarily high ion currents are observable here which are attributed to aspirated charged droplets.This work provides insights into long-term experiments with this experimental setup. There is a focus on signal stability, in the presence of such droplet signatures. It is apparent that the standby time of the instrument between individual measurements and the time since a switch of the polarity mode, has a significant influence on the signal stability. There are also indications that the observations of droplet signatures and the MS signal stability are correlated.

LC-ESI-HRMS — lipidomics of phospholipids

Lipids are a diverse class of molecules involved in many biological functions including cell signaling or cell membrane assembly. Owing to this relevance, LC–MS/MS-based lipidomics emerged as a major field in modern analytical chemistry. Here, we thoroughly characterized the influence of MS and LC settings — of a Q Exactive HF operated in Full MS/data-dependent MS2 TOP N acquisition mode — in order to optimize the semi-quantification of polar lipids. Optimization of MS-source settings improved the signal intensity by factor 3 compared to default settings. Polar lipids were separated on an ACQUITY Premier CSH C18 reversed-phase column (100 × 2.1 mm, 1.7 µm, 130 Å) during an elution window of 28 min, leading to a sufficient number of both data points across the chromatographic peaks, as well as MS2 spectra. Analysis was carried out in positive and negative ionization mode enabling the detection of a broader spectrum of lipids and to support the structural characterization of lipids. Optimal sample preparation of biological samples was achieved by liquid–liquid extraction using MeOH/MTBE resulting in an excellent extraction recovery > 85% with an intra-day and inter-day variability < 15%. The optimized method was applied on the investigation of changes in the phospholipid pattern in plasma from human subjects supplemented with n3-PUFA (20:5 and 22:6). The strongest increase was observed for lipids bearing 20:5, while 22:4 bearing lipids were lowered. Specifically, LPC 20:5_0:0 and PC 16:0_20:5 were found to be strongest elevated, while PE 18:0_22:4 and PC 18:2_18:2 were decreased by n3-PUFA supplementation. These results were confirmed by targeted LC–MS/MS using commercially available phospholipids as standards.Graphical abstract

Optimizing the Composition of the Substrate Enhances the Performance of Peroxidase-like Nanozymes in Colorimetric Assays: A Case Study of Prussian Blue and 3,3'-Diaminobenzidine.

One of the emerging trends in modern analytical and bioanalytical chemistry involves the substitution of enzyme labels (such as horseradish peroxidase) with nanozymes (nanoparticles possessing enzyme-like catalytic activity). Since enzymes and nanozymes typically operate through different catalytic mechanisms, it is expected that optimal reaction conditions will also differ. The optimization of substrates for nanozymes usually focuses on determining the ideal pH and temperature. However, in some cases, even this step is overlooked, and commercial substrate formulations designed for enzymes are utilized. This paper demonstrates that not only the pH but also the composition of the substrate buffer, including the buffer species and additives, significantly impact the analytical signal generated by nanozymes. The presence of enhancers such as imidazole in commercial substrates diminishes the catalytic activity of nanozymes, which is demonstrated herein through the use of 3,3'-diaminobenzidine (DAB) and Prussian Blue as a model chromogenic substrate and nanozyme. Conversely, a simple modification to the substrate buffer greatly enhances the performance of nanozymes. Specifically, in this paper, it is demonstrated that buffers such as citrate, MES, HEPES, and TRIS, containing 1.5-2 M NaCl or NH4Cl, substantially increase DAB oxidation by Prussian Blue and yield a higher signal compared to commercial DAB formulations. The central message of this paper is that the optimization of substrate composition should be an integral step in the development of nanozyme-based assays. Herein, a step-by-step optimization of the DAB substrate composition for Prussian Blue nanozymes is presented. The optimized substrate outperforms commercial formulations in terms of efficiency. The effectiveness of the optimized DAB substrate is affirmed through its application in several commonly used immunostaining techniques, including tissue staining, Western blotting assays of immunoglobulins, and dot blot assays of antibodies against SARS-CoV-2.

SR-Unet: A Super-Resolution Algorithm for Ion Trap Mass Spectrometers Based on the Deep Neural Network.

The mass spectrometer is an important tool for modern chemical analysis and detection. Especially, the emergence of miniature mass spectrometers has provided new tools for field analysis and detection. The resolution of a mass spectrometer reflects the ability of the instrument to discriminate between adjacent mass-to-charge ratio ions, and the higher the resolution, the better the discrimination of complex mixtures. Quadrupole ion traps are generally considered as a low-resolution mass spectrometry method, but they have gained wide attention and development in recent years because of their suitability for miniaturization and high qualitative capability. For an ion trap mass spectrometer, the mass sensitivity and resolution can be mutually constrained and need to be balanced by setting an appropriate scanning speed. In this study, a super-resolution U-net algorithm (SR-Unet) is proposed for ion trap mass spectrometry, which can estimate the possible ions from the overlapping ion peaks of low-resolution spectra and improve the equivalent resolution while ensuring sufficient sensitivity and analysis speed of the instrument. By determining the mass spectra of a linear ion trap mass spectrometer (LTQ XL) in Turbo and Normal scan modes, the same unit mass resolution as that at a scan speed of 16,667 Da/s was successfully obtained at 125,000 Da/s. Also, the experiments demonstrated that the algorithm is capable of the mass-to-charge ratio and instrument migration. SR-Unet can be migrated and applied to a miniature mass spectrometer for cruise detection of volatile organic compounds (VOCs), and the identification of VOC species in Photochemical Assessment Monitoring Stations (PAMS) was improved from 31 to 50 species with the same monitoring and analysis speed requirement. Further, super-unit mass resolution peptide detection was achieved on a miniature mass spectrometer with the help of the SR-Unet algorithm, which reduced the full width at half-maxima (FWHM) of bradykinin divalent ions (m/z 531) from 0.35 to 0.15 Da at a scan speed of 375 Da/s and improved the equivalent resolution to 3540. The proposed method provides a new idea to enhance the field mixture detection capability of miniature ion trap mass spectrometers.

Biogas Production—The Effect of the Zinc Concentration on the Profile of Volatile Fatty Acids in Fermentation Mixtures

The development of renewable energy sources is one of the most important paths for today’s economy to follow. Currently, the process of obtaining energy from the combustion of methane extracted by methane fermentation is gaining importance. To improve its efficiency and the speed of the fermentation process and enzyme activation, this study analyzed the effect of the addition of zinc as a micronutrient to fermentation processes using corn silage. The zinc concentration in the fermenter required to stimulate fermentation processes was determined. Studies were conducted to determine inhibitory and toxic concentrations. The determination of the influence of zinc ions on the VFA profile and the value of the carbon-to-methane conversion coefficient is important for the economic aspects of obtaining biogas with the highest methane content. The carbon-to-methane conversion factor and the effect of the addition of zinc on the value of this factor were determined. During the course of the research, modern analytical chemistry methods and techniques were used. The purpose of this study was to determine the optimal concentration of zinc in the digester to maximize the methane yield of the fermentation process.

The Significance of System Suitability in High-Performance Liquid Chromatography (HPLC) Analysis: Ensuring Accurate and Reliable Results

High-Performance Liquid Chromatography (HPLC) has emerged as a fundamental technique in modern analytical chemistry, serving as a powerful tool for the separation, identification, and quantification of [1] diverse compounds. One critical aspect that ensures the validity and credibility of HPLC results is the concept of system suitability. This abstract highlights the importance of system suitability in HPLC analysis, emphasizing its role in ensuring accurate and reliable results. System suitability is a set of pre-defined criteria that evaluate the performance of the HPLCsystem, encompassing factors such as resolution, peak symmetry, tailing factor, retention time, and peak area reproducibility. Adhering to these criteria is essential for consistent and precise analyses, as they confirm that the instrument is operating optimally and capable of generating dependable data

Nonlinear dimensionality reduction methods for potentiometric multisensor systems data analysis

AbstractElectrochemical multisensor systems were proven to be a very perspective research direction in modern analytical chemistry. The multisensor approach assumes an employment of cross‐sensitive chemical sensors in combination with multivariate data processing methods. Dimensionality reduction of the data obtained from multisensor systems is a very important step and it is mostly based on the traditional tools of chemometrics, such as Principal Component Analysis (PCA). In case of chemically complex samples, the response of multisensor systems may have a complex nonlinear nature and the use of linear modelling methods does not seem optimal. However, the potential of nonlinear dimensionality reduction methods in the processing of multisensor data has not yet been systematically studied. In this report we aim to fill this gap and assess the performance of various nonlinear dimensionality reduction tools: Isomap, Self‐Organizing Kohonen Maps, and Autoencoder. These methods were explored using three datasets from potentiometric multisensor systems obtained in various real applications. It was shown that nonlinear dimensionality reduction methods give the possibility to obtain additional and more detailed information about the analyzed objects/processes compared to PCA. However, calculation time for nonlinear dimensionality reduction methods essentially exceeds that for PCA, and it can be a limiting factor for application of such algorithms.

Does modern chemical analysis allow the identification of passive cannabis smokers?

Does modern chemical analysis allow the identification of passive cannabis smokers?

Martin Heinrich Klaproth (1743-1817), a Great, Somewhat Forgotten, Chemist

For various reasons, some of them linked to the evolution of the historiography of Chemistry, many recognized and important chemists in their time – and in ours, because of the legacy they left – are relegated to some degree of oblivion. One of these chemists, dead just over 200 years ago, is Martin Heinrich Klaproth (1743-1817), a key figure in the transition from phlogiston theory to Lavoisier’s new chemistry and one of the creators of modern analytical chemistry, an empiricist who discovered many elements and polymorphism, author of remarkable chemical and mineralogical analyses and creator of archaeometry. This article presents the life, training and scientific production of a great, but less remembered, chemist, crossing the frontiers of Chemistry in many cases.

Miniaturized matrix solid-phase dispersion and solid-phase clear-up combined with capillary electrophoresis for efficient determination of trace bioactive components in complicated sample matrix: Take Wubi Shanyao Pill as an example.

Accurate quantitative analysis of trace analytes in a complicated matrix is a challenge in modern analytical chemistry. An appropriate analytical method is considered to be one of the most common gaps during the whole process. In this study, a green and efficient strategy based on miniaturized matrix solid-phase dispersion and solid-phase extraction combined with capillary electrophoresis was first proposed for extracting, purifying and determining target analytes from complicated matrix, using Wubi Shanyao Pill as an example. In detail, 60mg of samples were dispersed on MCM-48 to obtain high yields of analytes, then the extract was purified with a solid-phase extraction cartridge. Finally, four analytes in the purified sample solution were determined by capillary electrophoresis. The parameters affecting the extraction efficiency of matrix solid-phase dispersion, purification efficiency of solid-phase extraction and separation effect of capillary electrophoresis were investigated. Under the optimized conditions, all analytes demonstrated satisfactory linearity (R2 >0.9983). What's more, the superior green potential of the developed method for the determination of complex samples was confirmed by the Analytical GREEnness Metric Approach. The established method was successfully applied in the accurate determination of target analytes in Wubi Shanyao Pill and thus provided reliable, sensitive, and efficient strategy support for its quality control.

Development and Validation of Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Determination of Tramadol and Its Phase I and II Metabolites in Human Urine

Tramadol (TD) has been prescribed frequently in many countries for more than 40 years, but there is a risk of its misuse and trafficking. As a result, drug analysis has numerous legal and socially relevant implications, making it an essential part of modern analytical chemistry. Thus, the method for the detection of TD and its phase I and phase II metabolites in human urine has been developed and validated using a rapid and efficient approach combining liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization. The sample preparation was best performed using dispersive liquid–liquid microextraction. Analysis was performed using an HyPRITY Cl8 column, and isocratic elution with methanol: water (35:65) with 0.2% formic acid was used. TD and its metabolites were detected at 264.2 (TD/M0) with a base peak at 58.2, 250.3758 (M1), 250.3124 (M2), 236.3976 (M3), 222.5361 (M4), and 236.4475 (M5) m/z peaks. TD showed linearity between 0.1 and 160 ng/mL (R2 = 0.9981). The accuracy ranged from 95.56 to 100.21% for the three concentration levels, while the between- and within-day RSD ranged from 1.58 to 3.92%. The absolute TD recovery was 96.29, 96.91, and 94.31% for the concentrations of 5, 50, and 150 ng/mL, respectively. TD’s phase I metabolites, M1–5 along with nine phase II metabolites, such as sulfo- and glucurono-conjugated metabolites, oxidative TD derivatives, and sulfo-conjugated metabolites were also identified in the urine samples. The pharmacokinetics and metabolism data given provide information for the design of possible future research disorders, evaluating drug mechanism and neurotoxicity and for the effective application screening of TD.

Phosphodiester Stationary Phases as Universal Chromatographic Materials for Separation in RP LC, HILIC, and Pure Aqueous Mobile Phase.

Modern analytical chemistry techniques meet the need for greater attention to ecological and economic aspects. It is becoming necessary to seek solutions to reduce harmful waste production, especially in large quantities. High-performance liquid chromatography is a technique widely used in many industries, including mainly pharmaceuticals, and requires an approach to reduce the significant amount of organic solvent waste. One of the green chemistry solutions is using environmentally benign substitutes, such as pure water, supercritical dioxide, and ethanol. Our work focuses on the preparation and application of new stationary phases with embedded hydrophilic groups for separations using pure water in liquid chromatography. Polar-embedded stationary phases are obtained by attaching a phosphodiester group and 4 different hydrophobic molecules. The studies consisted of hydrophobicity measurements, concentration dependence of retention of the organic additive to the mobile phase, and chromatographic separations of polar and non-polar substance mixtures in RP-LC and HILIC systems. Three mixtures were studied: purine alkaloids, benzene, and polycyclic aromatic hydrocarbons and nucleosides. The stationary phases interact differently with the analytes depending on the attached hydrophobic group. It is possible to use pure water to separate each mixture under study. It is also significant that it has been possible to separate a mixture of completely non-polar compounds using pure water for the first time. The research being carried out is crucial in synthesizing new polar-embedded stationary phases, providing work versatility and high environmental performance.