Separation Of Isomers Research Articles

Tailoring molecular diffusion in core‐shell zeolite imidazolate framework composites realizes efficient kinetic separation of xylene isomers

The separation of xylene isomers is a critical and energy‐intensive process in the petrochemical industry, primarily due to their closely similar molecular structures and boiling points. In this work, we report the synthesis and application of a novel core‐shell zeolitic imidazolate framework (ZIF) composite, ZIF‐65@ZIF‐67, designed to significantly enhance the kinetic separation of xylene isomers through a synergistic "shell‐gated diffusion and core‐facilitated transport" strategy. The external ZIF‐67 shell selectively restricts the diffusion of larger isomers (MX and OX), while the internal ZIF‐65 core accelerates the diffusion of PX, thereby amplifying the diffusion differences among the isomers. This architecture yields remarkable improvements in both selectivity and diffusion rates, as demonstrated by vapor‐phase adsorption studies and molecular dynamics simulations. The ZIF‐65@ZIF‐67 composite exhibits up to 12.5 times higher PX/OX selectivity in liquid‐phase adsorption and 3.4 times higher dynamic selectivity in fixed‐column breakthrough experiments compared to the individual ZIF components. Theoretical simulations further corroborate the heterogeneous diffusion control mechanism, revealing the time‐dependent diffusion regulation within the core‐shell architecture. This work underscores the great potential of core‐shell MOF composites in optimizing molecular sieving processes for industrially significant separations and highlights a new route for enhancing kinetic separation efficiency in complex multicomponent systems.

Tailoring molecular diffusion in core-shell zeolite imidazolate framework composites realizes efficient kinetic separation of xylene isomers.

The separation of xylene isomers is a critical and energy-intensive process in the petrochemical industry, primarily due to their closely similar molecular structures and boiling points. In this work, we report the synthesis and application of a novel core-shell zeolitic imidazolate framework (ZIF) composite, ZIF-65@ZIF-67, designed to significantly enhance the kinetic separation of xylene isomers through a synergistic "shell-gated diffusion and core-facilitated transport" strategy. The external ZIF-67 shell selectively restricts the diffusion of larger isomers (MX and OX), while the internal ZIF-65 core accelerates the diffusion of PX, thereby amplifying the diffusion differences among the isomers. This architecture yields remarkable improvements in both selectivity and diffusion rates, as demonstrated by vapor-phase adsorption studies and molecular dynamics simulations. The ZIF-65@ZIF-67 composite exhibits up to 12.5 times higher PX/OX selectivity in liquid-phase adsorption and 3.4 times higher dynamic selectivity in fixed-column breakthrough experiments compared to the individual ZIF components. Theoretical simulations further corroborate the heterogeneous diffusion control mechanism, revealing the time-dependent diffusion regulation within the core-shell architecture. This work underscores the great potential of core-shell MOF composites in optimizing molecular sieving processes for industrially significant separations and highlights a new route for enhancing kinetic separation efficiency in complex multicomponent systems.

Characterization of Sugammadex-Related Isomeric Cyclodextrin Impurities Using Cyclic Ion Mobility High-Resolution Mass Spectrometry.

Cyclic ion mobility-mass spectrometry (cIM-MS) is a powerful technique for separating and identifying isomeric mixtures of compounds. When coupled with chromatography, cIM-MS creates a multidimensional separation system, with high resolving power and peak capacity. In this study, we report the cyclic ion mobility separation and high-resolution mass spectrometry identification of four regioisomers of a Sugammadex-related impurity, abbreviated as Di-OH-SGM. Separation using multipass cyclic ion mobility was achieved by selecting the [M + 2Na]2+ ion, while other adducts, such as [M + Na]+, [M + 2H]2+, [M + H + Na]2+, and [M - 2H]2- did not yield isomer separation. Two methods were developed for ion mobility separation of the isomers: a conventional multipass method and a slicing method. Isomer assignment was based on the characteristic fragment ions. The collision cross section values (cTWCCSN2) of the resolved cyclodextrin isomers were also determined. Ion mobility separation of structurally different fragment ions was demonstrated. Additionally, by coupling cIM-MS with reversed-phase liquid chromatography (HPLC-cIM-MS), two-dimensional separation of the isomers was achieved. The isomers, separated using HPLC-cIM-MS, were identified with the same approach as with cIM-MS alone, and their elution order provided insights into their relative hydrophobicity.

Kinetic Separation of Butane Isomers Using a Formate Metal-Organic Framework.

n-butane (n-C4H10) and isobutane (i-C4H10) are important raw materials in chemical industry. The separation of the two hydrocarbon isomers via distillation is challenging and energy-consuming. Herein we report the adsorption behavior of a microporous cobalt formate framework [Co3(HCOO)6] for potential kinetic separation of butane isomers. Under ambient condition, [Co3(HCOO)6] shows near adsorption capacity for n-C4H10 (1.77 mmol g-1) and i-C4H10 (1.36 mmol g-1) with different adsorption kinetics. Study on the adsorption kinetic for butane indicates that the smaller isomer is adsorbed at a higher diffusion rate, resulting in a high kinetic selectivity of 193 for n-C4H10/i-C4H10 separation. Analyses of adsorption kinetics and breakthrough experiment have validated the separation potential of [Co3(HCOO)6] for butane purification.

Quality by Design-Steered Chromatographic Separation and Identification of the Geometric Isomers of Capsiate by Reversed-Phase HPLC and LC-MS.

Quality by Design-Steered Chromatographic Separation and Identification of the Geometric Isomers of Capsiate by Reversed-Phase HPLC and LC-MS.

Robust Aluminum-Based Metal–Organic Framework Adsorbents with Heteroatom-Functionalized Nanochannels for Hexane Isomer Separation

Robust Aluminum-Based Metal–Organic Framework Adsorbents with Heteroatom-Functionalized Nanochannels for Hexane Isomer Separation

Fluorine-rich poly(arylene amine) membranes for the separation of liquid aliphatic compounds.

We explored the potential for membrane materials to reduce energy and carbon requirements for the separation of aliphatic hydrocarbon feedstocks and products. We developed a series of fluorine-rich poly(arylene amine) polymer membranes that feature rigid polymer backbones with segregated perfluoroalkyl side chains. This combination imbues the polymers with resistance to dilation induced by hydrocarbon immersion without the loss of solution-based membrane fabrication techniques. These materials exhibit good separation of liquid-phase alkane isomers at ambient temperatures. The integration of these polymeric membranes into fuel and chemical feedstock separation processes was investigated in a series of experiments. Technoeconomic analyses based on these experiments indicate that the best-performing membrane materials can substantially reduce the energy costs and associated carbon emissions of hydrocarbon separations (two to 10 times, depending on product specifications).

Nanospace Engineering for C8 Aromatic Isomer Separation.

C8 aromatic isomers, namely para-xylene (PX), meta-xylene (MX), ortho-xylene (OX), and ethylbenzene (EB), are essential industrial chemicals with a wide range of applications. The effective separation of these isomers is crucial across various sectors, including petrochemicals, pharmaceuticals, and polymer manufacturing. Traditional separation methods, such as distillation and solvent extraction, are energy-intensive. In contrast, selective adsorption has emerged as an efficient technique for separating C8 aromatic isomers, in which nanospace engineering offers promising strategies to address existing challenges by precisely tailoring the structures and properties of porous materials at the nanoscale. This review explores the application of nanospace engineering in modifying the pore structures and characteristics of diverse porous materials─including zeolites, metal-organic frameworks (MOFs), covalent organic frameworks (COFs), and other porous substances─to enhance their performance in C8 aromatic isomer separation. Additionally, this review provides a comprehensive summary of how different separation techniques, temperature fluctuations, enthalpy/entropy considerations, and desorption processes influence separation efficiency. It also presents a forward-looking perspective on remaining challenges and potential opportunities for advancing C8 aromatic isomer separation.

A chiral porous organic cage–modified restricted-access material achieves online analysis of serum samples containing enantiomers and positional isomers

Restricted-access materials (RAMs) allow biological samples to directly enter the chromatographic column for analysis owing to the steric exclusion function ability for biomolecules and extraction function for small-molecule analytes, which promoting the development of rapid, efficient, and automated in vivo drug analysis. Few reports on chiral RAMs that have been used to analyze enantiomers and positional isomers in serum by direct injection in currently. In this study, a chiral porous organic cage material RCC3 was innovatively introduced into the inner surface of silica gel and modified the outer surface with polyethylene glycol to prepare a novel type of chiral RAM-RCC3, and reported the use of chiral RAM-RCC3 as a stationary phase for the separation of chiral compounds and positional isomers in blank serum using high-performance liquid chromatography. The novel RAM-RCC3 column exhibited good performance in the online analysis of nine enantiomers and five positional isomers in serum samples. The effects of analyte mass, temperature, and composition of the mobile phase on the separation of o-, m-, and p-nitrophenol in serum samples using the RAM-RCC3 column were also investigated. Even after 300 injections, the RAM-RCC3 column exhibited good reproducibility and stability. These results indicate the potential of the chiral RAM-RCC3 column as a stationary phase for direct injection analysis of both chiral separation and positional isomers in biological samples, which also rendering it suitable to be further developed as a new type of RAM for online analysis of various small molecules in biological samples.

Synergistic global and local flexibilities in Zr-based metal-organic frameworks enable sequential sieving of hexane isomers.

Separating hexane isomers based on the branching degree is crucial for their efficient utilization in the petrochemical industry, yet remains challenging due to their similar properties. Here we report a temperature-responsive Zr-based metal-organic framework, Zr-fum-FA, capable of sequentially sieving linear, mono-, and di-branched hexane isomers. Notably, the pore structure of Zr-fum-FA dynamically transforms from segmented triangular channels to an integrated rhombic configuration as the temperature increases, leading to distinct sieving effects. At low temperatures, the narrow triangular pores allow the exclusive adsorption of n-hexane while excluding branched isomers. In contrast, the expanded rhombic pores at high temperatures enable the sieving of mono- and di-branched isomers. Mechanistic studies reveal that this unique dual-sieving behavior originates from the synergistic effects of the global framework flexibility and the local dynamics of pendent hydroxyl groups. Furthermore, we demonstrate the decoupling of global and local flexibilities via two strategies: incorporating steric hindrance to dampen the global framework dynamics and enhancing the metal node rigidity to limit the local vibrations. These findings not only provide a promising adsorbent for the challenging separation of hexane isomers but also offer rational design principles for harnessing flexibility in MOFs.

Chiral supercritical fluid chromatography of monoacylglycerol and diacylglycerol enantiomers in biological samples: Adjusting selectivity via column coupling.

The distinction of lipid isomers is gaining more attention in lipidomics due to their different biochemical properties in the organism. Herein, we aimed to develop a method for the analysis of monoacylglycerol (MG) and diacylglycerol (DG) enantiomers in biological samples using chiral supercritical fluid chromatography and mass spectrometry (SFC-MS). Amylose-based chiral columns showed a certain degree of separation of MG and DG isomers, but low selectivity for the acylglycerol classes in total lipid extracts, which could not be improved by modifier composition or other chromatographic conditions. The coelution of MG and DG enantiomers with highly concentrated triacylglycerols (TGs) negatively affected their MS determination based on the peak area ratio, therefore the interclass selectivity of chiral SFC was adjusted by coupling with an achiral column. The connection of the amylose tris-(3,5-dimethylphenylcarbamate) chiral column with octadecyl achiral column using a methanol as a modifier provided an excellent interclass separation of acylglycerols with the resolution of 5.53 and 15.17 for oleic acid-based MG/DG and DG/TG classes, respectively. The developed method enabled the determination of MG and DG enantiomers in complex total lipid extracts of biological samples in a 15 min gradient without time-consuming sample prefractionation. Chiral SFC-MS analysis of egg yolk, human plasma, and porcine brain samples showed different ratios of enantiomers, suggesting their unique roles within each sample type.

Detection and application of 40 piperazine compounds in hair suitable for rapid separation of isomers.

A simple and sensitive procedure, using benzylpiperazine-D7 (BZP-D7) as an internal standard, has been developed and validated for the qualitative and quantitative analysis of 40 piperazines in hair. Drugs were extracted from 20 mg of hair with 0.5 mL of methanol containing 1 ng/mL BZP-D7. After ultrasonication, centrifugation and filtration, the supernatant was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) operating in the multiple reaction monitoring mode. Piperazine-type substances were separated in 10 min on a T3 column using a mobile phase gradient composed of A (water, formic acid 0.1 %, acetonitrile 5 %, and 20 mmol/L ammonium acetate) and B (acetonitrile). The developed and validated method showed good selectivity, sensitivity (limit of detection: 0.5-20 pg/mg and lower limit of quantitation: 5-20 pg/mg), linearity (R2 > 0.99), accuracy, precision, and dilution integrity. The method also showed good recovery and acceptable matrix effects for most of the targeted compounds. This analytical approach was successfully applied for the identification and quantification of piperazine-type substances in hair from rat and guinea pig.

Separation of isomers of chiral thiourea derivatives by spontaneous resolution and rationale of molecular recognition

Enrichment of enantiomers during crystallization of racemic thiourea is investigated. The spontaneous resolution of chiral thiourea by preferential crystallization is attributed to theromodynamic stability when molecules of identical chirality bind...

New insights into the N-glycomes of Dictyostelium species.

Dictyostelia are cellular slime molds, a group of Amoebozoa, that form multicellular fruiting bodies out of aggregating cells able of differentiating into resistant spore forms. In previous studies on Dictyostelium discoideum, it was demonstrated that their N-glycans, as in most eukaryotes, derive from the Glc3Man9GlcNAc2-PP-Dol precursor; however, unique glyco-epitopes, including intersecting GlcNAc, core α1,3-fucosylation, sulphation and methylphosphorylation, were detected. In the present study, we have examined the N-glycans of two other Dictyostelium species, D. purpureum, whose genome is also sequenced, and D. giganteum. The detailed glycomic analysis of their fruiting bodies was based on isomeric separation of the glycan structures by HPLC, followed by mass spectrometry in combination with enzymatic digests and chemical treatments. Two features absent from the 'model' dictyostelid D. discoideum were found: especially in D. purpureum, a long linear galactose arm β1,4-linked to the β1,4-N-acetylglucosamine on the 'lower' A-branch of its oligo-mannosylated structures could be identified. In contrast, neutral N-glycans with multiple fucose residues attached to terminal mannoses were found in D. giganteum. All three species have common modifications on their anionic N-glycans: while (methyl)phosphorylated residues are always associated with terminal mannose residues, the sulphation position differs. While D. discoideum has 6-sulphation of subterminal mannose residues, D. giganteum and D. purpureum may rather have 2-sulphation of core α1,6-mannose. Overall, we have discovered species-specific glycan variations and our data will contribute to future comparative and functional studies on these three species within the same genus.

Differential Mobility Spectrometry Acoustic Ejection Mass Spectrometer System for Screening Isomerization-Mediating Enzyme Drug Targets.

We report the first implementation of ion mobility mass spectrometry combined with an ultrahigh throughput sample introduction technology for high-throughput screening (HTS). The system integrates differential mobility spectrometry (DMS) with acoustic ejection mass spectrometry (AEMS), termed DAEMS, enabling the simultaneous quantitation of structural isomers that are the substrates and products of isomerase-mediated reactions in intermediary metabolism. We demonstrate this potential by comparing DAEMS to a luminescence assay for the isoform of phosphoglycerate mutase (iPGM) distinctively present in pathogens, offering an opportunity as a drug target for a variety of microbial and parasite borne diseases. The metabolome consists of many structural isomers that require for separation a mobility resolving power of more than 300. Resolving powers measured in collision cross-section space of 1588 and 1948 for 2- and 3-phosphoglycerate and the citrate/isocitrate isomeric pairs, respectively, are shown. These are the highest reported ion mobility resolving powers for molecules from the metabolome reported to date. The potential for DAEMS as a generalized screening tool is demonstrated with the separation of the substrates and products of two additional isomerases that present as potential therapeutic targets, chorismate mutase and triosephosphate isomerase. The separations are achieved at speeds compatible with the sample introduction rates of AEMS providing sufficient data points to integrate the peaks for quantitation without the use of internal standards. DMS hyphenated with acoustic sample ejection MS provides a unique solution to high-throughput mass spectrometry applications where separation of isomers and other types of isobaric overlaps are required.

Analysis of alkyl-anthraquinone derivatives from hydrogen peroxide industrial process, using LC × LC-HRMS with shifting gradients.

The characterization of industrial working solutions containing numerous structurally related compounds and isomers requires the use of two-dimensional liquid chromatography coupled with high-resolution mass spectrometry (LC × LC-HRMS). The separation of alkyl-anthraquinone derivatives produced during hydrogen peroxide production was achieved by coupling a biphenyl and a C18 in the first and second dimensions, combined with the use of continuous shifting gradients in the second dimension (2D). The use of shifting gradients offers a significant advantage over regular gradients, with a 20% increase in occupancy and better separation of isomers eluted within the same modulation. Additionally, MS spectra were improved by reducing ion suppression in the source. The analysis of the industrial solutions produced a list of 226 peaks with 75 different molar masses, thereby confirming the presence of many isomers. The excellent repeatability of the retention times (within ±0.28 s in the second dimension) enabled the method to be used to study the differences between production batches, which were divided into two groups according to their measured hydrogen peroxide yield. Using multivariate statistical tools on the area of each peak, a total of 191 variables, including 11 clusters of insufficiently resolved isomers, were studied by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). A simple Wilcoxon test performed on the most pertinent variables was able to confirm that 28 peaks could be used to monitor the industrial process. This work highlighted the efficacy of combining a very powerful separation technique with the implementation of two simple statistical tests to rapidly identity a set of discriminant markers in a highly complex industrial mixture.

A highly sensitive UHPLC-MS/MS method for determining 15 designer LSD analogs in biological samples with application to stability studies.

In recent years, the rise in the synthesis and distribution of LSD analogs in illicit drug markets, commonly referred to as "designer psychedelics", has contributed to increased recreational use. This trend has resulted in a rising number of global reports, with law enforcement increasingly detecting these compounds in blotter papers and biological samples. In the presented paper, an UHPLC-QqQ-MS/MS method was developed for trace determination (fg mL-1) of LSD, its designer analogs (ALD-52, AL-LAD, LAMPA, LSM-775, LSZ, MiPLA, 1B-LSD, 1cP-LSD, 1cP-MiPLA, 1P-LSD, 1P-MiPLA, 1V-LSD and 2-Bromo-LSD) and its metabolite (2-oxo-3-OH-LSD) with simultaneous separation of structural isomers. Biological samples were prepared using liquid-liquid extraction (LLE) at pH 9 (with ethyl acetate); quantification was performed in multiple reaction monitoring (MRM) mode. LSD-d3 was used as an internal standard. The limit of quantification (LOQ) for all substances was 0.5 pg mL-1. Precision and accuracy did not exceed 15.8% and ±14.4%, respectively. Recovery and matrix effect values were 80.6-118.6% and ±19.4%. A stability study was conducted over 30 days under different storage conditions (25 °C, 4 °C and -20 °C) for blood, urine, plasma, and serum, collected in various test tube configurations and with different preservative agents. It was found that the collection of samples in NaF can effectively stabilize LSD analogs and minimize the conversion of N1-substituted compounds to LSD or MiPLA. The presented method is the most sensitive to date for analyzing designer LSD analogs in biological samples, with potential for routine clinical and forensic use, enhancing detection of emerging illicit compounds. By examining the mass spectra (QTOF-MS/MS) obtained in this study and reviewing the literature on analytical characterization of LSD analogs, we proposed fragmentation patterns to aid in future identification of new designer LSD analogs (NPS).

An Adaptive Metal-Organic Framework Discriminates Xylene Isomers by Shape-Responsive Deformation.

The separation of xylene isomers, especially para-xylene, is a crucial but challenging process in the chemical industry due to their similar molecular dimensions. Here, a flexible metal-organic framework, Ni(ina)2, (ina = isonicotinic acid) is employed to effectively discriminate xylene isomers. The adsorbent with adaptive deformation accommodates the shapes of isomer molecules, thereby translating their subtle shape differences into characteristic framework deformation energies. Through a combination of multiple local flexibility behaviors, Ni(ina)2 exhibits guest-specific structural transformations that energetically favor para-xylene over other isomers. Single-crystal X-ray diffraction, in situ powder X-ray diffraction, and theoretical investigations validate this "adaptive fitting" mechanism, where the degree of structural deformation scales with the mismatch between the molecular shape and pore geometry. As a result, Ni(ina)2 achieves exceptional para-xylene selectivity in both liquid and vapor phase separations, maintaining a high para-xylene purity and productivity. This work demonstrates a novel strategy of exploiting framework flexibility to address challenging molecular separations and provides fresh insights into the design of selective adsorbents.

Forensic Aspects of Designer LSD Analogs Identification by GC-MS (EI) and UV Spectroscopy.

Lysergic acid diethylamide (LSD) analogs, often referred to as new psychoactive substances, are synthesized to mimic controlled substances while evading drug regulations. This study emphasizes the challenges of identifying these compounds, particularly their isomeric forms. Gas chromatography-mass spectrometry (GC-MS) and UV spectroscopy were employed to analyze 13 LSD analogs. The effects of different solvents on the detection of these analogs were analyzed, demonstrating that solvents like diethyl ether, tert-butyl methyl ether, dichloromethane and acetone provided the best sensitivity and stability. Methanol, on the other hand, causes alcoholysis of many LSD analogs, which may lead to false results. Additionally, effective chromatographic separation of isomers was established, including LSD, MiPLA, LAMPA, 1P-LSD and 1P-MiPLA, as well as 1cP-LSD and 1cP-MiPLA, which is crucial for accurate identification. The elution order of the determined compounds with the use of developed chromatographic method was as follows: LSD, MiPLA, LAMPA, AL-LAD, LSZ, 2-Br-LSD, ALD-52, 1P-LSD, 1P-MiPLA, 1B-LSD, 1V-LSD, 1cP-LSD and 1cP-MiPLA. Differences in ion ratios observed in mass spectrometry (MS) were also analyzed to distinguish between closely related compounds. Several key ions for LSD analogs were able to be identified, including 221, 208, 207, 196, 194, 192, 181, 167, 154, 152 and 128 m/z. In analogs with an N-diethyl group (or variants like N-methyl-propyl in LAMPA or N-methyl-isopropyl in MiPLA), mass spectra showed fragments 100, 72 and 58 m/z. For LSZ, the cyclic group at R1 produces ions 98 and 70 m/z. Analogs with an N6 allyl group (e.g., AL-LAD) show a characteristic ion 247 m/z. This method allows for the correct differentiation of structural isomers based on their unique ion fragmentation patterns and relative intensities. UV spectroscopy was used as a supplementary tool for screening, though it has limitations in analyzing complex mixtures. This work contributes to the forensic identification of designer LSD analogs, ensuring reliable detection for legal and toxicological investigations.

Studying Structural Details in Complex Samples: II. High Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) Coupled to High Resolution Tandem Mass Spectrometry (MS/MS).

The elucidation of structural motifs in extremely complex mixtures is very difficult since the standard methods for structural elucidation are not capable to provide significant information on a single molecule. The best method for the analysis of complex mixtures is ultrahigh resolution mass spectrometry, but the utilization of this method alone does not provide significant information about structural details. Here, a combination with a separation method is necessary. While chromatography is a well-established technique, it has some disadvantages in regard to the separation of complex mixtures, as often no separation of individual isomers is possible. Therefore, here the combination of an ion mobility separation with ultrahigh resolution mass spectrometry is evaluated. As a sample matrix, crude oil is used because it is an excellent matrix to develop new analytical techniques on complex samples. Crude oil is the most complex natural sample known, but only little information is available on the structural identity or functionalities due to a high number of structural isomers or isobars. A lab-built APPI/APLI-FAIMS source was revised to optimize ion transmission and used to follow up on the ion mobility of crude oil constituents after photoionization. An MS/MS approach using collision-induced dissociation (CID) was used to elucidate structural motifs of the transmitted isomers.