Recognition Of Isomers Research Articles

Simultaneous Degradation Study of Isomers in Human Plasma by HPLC-MS/MS and Application of LEDA Algorithm for Their Characterization.

This paper proposes a tandem mass spectrometry (MS/MS) approach in isomer recognition by playing in the "energetic dimension" of the experiment. The chromatographic set up (HPLC) was tuned to minimize the run time, without requiring high efficiency or resolution between the isomers. Then, the MS/MS properties were explored to solve the signal assignment by performing a series of energy resolved experiments in order to optimize the parameters, and by applying an interesting post-processing data elaboration tool (LEDA). The reliability of the new approach was evaluated, determining the accuracy and precision of the quantitative results through analysis of the isomer mixture solutions. Next, the proposed method was applied in a chemical stability study of human plasma samples through the simultaneous addition of a pair of isomers. In the studied case, only one of the isomers suffered of enzymatic hydrolysis; therefore, the influence of the stable isomer on the degradation rate of the other was verified. In order to monitor this process correctly, it must be possible to distinguish each isomer present in the sample, quantify it, and plot its degradation profile. The reported results demonstrated the effectiveness of the LEDA algorithm in separating the isomers, without chromatographic resolution, and monitoring their behavior in human plasma samples.

Simultaneous Recognition and Separation of Organic Isomers Via Cooperative Control of Pore-Inside and Pore-Outside Interactions.

Despite the desirability of organic isomer recognition and separation, current strategies are expensive and complicated. Here, a simple strategy for simultaneously recognizing and separating organic isomers using pillararene-based charge-transfer cocrystals through the cooperative control of pore-inside and pore-outside intermolecular interactions is presented. This strategy is illustrated using 1-bromobutane (1-BBU), which is often produced as an isomeric mixture with 2-bromobutane (2-BBU). According to its structure, perethylated pillar[5]arene (EtP5) and 3,5-dinitrobenzonitrile (DNB) are strategically chosen as a donor and an acceptor. As a result, their cocrystal exhibited stronger pore-inside interactions and much weaker pore-outside interactions with 1-BBU than with 2-BBU. Consequently, nearly 100% 1-BBU selectivity is achieved in two-component mixtures, even in those containing trace 1-BBU (1%), whereas free EtP5 only achieved 89.80% selectivity. The preference for linear bromoalkanes is retained in 1-bromopentane/3-bromopentane and 1-bromohexane/2-bromohexane mixtures, demonstrating the generality of this strategy. Selective adsorption of linear bromoalkanes induced a naked-eye-detectable color change from red to white. Moreover, the cocrystal are used over multiple cycles without losing selectivity.

TurboPutative: A web server for data handling and metabolite classification in untargeted metabolomics.

Untargeted metabolomics aims at measuring the entire set of metabolites in a wide range of biological samples. However, due to the high chemical diversity of metabolites that range from small to large and more complex molecules (i.e., amino acids/carbohydrates vs. phospholipids/gangliosides), the identification and characterization of the metabolome remain a major bottleneck. The first step of this process consists of searching the experimental monoisotopic mass against databases, thus resulting in a highly redundant/complex list of candidates. Despite the progress in this area, researchers are still forced to manually explore the resulting table in order to prioritize the most likely identifications for further biological interpretation or confirmation with standards. Here, we present TurboPutative (https://proteomics.cnic.es/TurboPutative/), a flexible and user-friendly web-based platform composed of four modules (Tagger, REname, RowMerger, and TPMetrics) that streamlines data handling, classification, and interpretability of untargeted LC-MS-based metabolomics data. Tagger classifies the different compounds and provides preliminary insights into the biological system studied. REname improves putative annotation handling and visualization, allowing the recognition of isomers and equivalent compounds and redundant data removal. RowMerger reduces the dataset size, facilitating the manual comparison among annotations. Finally, TPMetrics combines different datasets with feature intensity and relevant information for the researcher and calculates a score based on adduct probability and feature correlations, facilitating further identification, assessment, and interpretation of the results. The TurboPutative web application allows researchers in the metabolomics field that are dealing with massive datasets containing multiple putative annotations to reduce the number of these entries by 80%–90%, thus facilitating the extrapolation of biological knowledge and improving metabolite prioritization for subsequent pathway analysis. TurboPutative comprises a rapid, automated, and customizable workflow that can also be included in programmed bioinformatics pipelines through its RESTful API services. Users can explore the performance of each module through demo datasets supplied on the website. The platform will help the metabolomics community to speed up the arduous task of manual data curation that is required in the first steps of metabolite identification, improving the generation of biological knowledge.

Chiral probe for mass spectrometric identification and quantitation of levodropropizine and its enantiomer, dextrodropropizine.

Acyl chlorides react rapidly with hydroxyl and amino groups in the absence of catalysts and therefore hold great promise for chiral mass spectrometry. Herein, a tandem mass spectrometry method based on derivatization with (-)-camphanic acid chloride as a simple chiral probe was developed for the highly sensitive detection and quantitation of levodropropizine and its enantiomer, namely, dextrodropropizine. The diastereomeric derivatization products were quantified based on the relative abundances of their fragment ions produced upon collision-induced dissociation in positive-ion mode. The reactive site was elucidated using nuclear magnetic resonance spectroscopy and two-dimensional total correlation spectroscopy, and the reaction mechanism was proved by stoichiometry studies. The degree of isomer recognition was investigated at different collision energies and determined as Rchiral ≈1.5. Thus, this study gives the way to the mass spectrometric identification and quantitation of levodropropizine and its enantiomer, and the developed method represents a new and practical technique for rapid and sensitive determination and quality control of enantiomers of chiral drugs.

Isomer recognition by dynamic guest-adaptive ligand rotation in a metal-organic framework with local flexibility.

Local flexibility in a metal-organic framework is intriguing for reconstructing a microenvironment to distinguish different guest molecules by emphasizing their differences. Herein, guest-adaptive flexibility is observed in a metal-organic framework for efficiently discriminating aromatic isomers. Microcrystal electron diffraction directly reveals that the anthracene rings can rotate around the single bond with the adsorption of guest molecules. Disorder transformation of the ligand enables the preferential adsorption of ethylbenzene over other xylene isomers. Especially, a coated capillary column combining single/multi-component adsorption confirms a unique separation order of ethylbenzene > p-xylene > m-xylene > o-xylene with excellent selectivities, which has not been reported in other materials. Density functional theory calculations and the calculated Hirshfeld surface of guest molecules in the framework demonstrate that a guest-induced splint-like confinement structure makes the main contribution to such separation performance. This finding will provide a rational strategy for molecular recognition utilizing the local flexibility of metal-organic frameworks.

CGAS-like receptors sense RNA and control 3\u20322\u2032-cGAMP signalling in Drosophila

Cyclic GMP–AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger cG[2′–5′]pA[3′–5′]p (2′3′-cGAMP) and controls activation of innate immunity in mammalian cells1–5. Animal genomes typically encode multiple proteins with predicted homology to cGAS6–10, but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors that are capable of recognizing divergent molecular patterns and catalysing synthesis of distinct nucleotide second messenger signals. Crystal structures of human and insect cGLRs reveal a nucleotidyltransferase signalling core shared with cGAS and a diversified primary ligand-binding surface modified with notable insertions and deletions. We demonstrate that surface remodelling of cGLRs enables altered ligand specificity and used a forward biochemical screen to identify cGLR1 as a double-stranded RNA sensor in the model organism Drosophila melanogaster. We show that RNA recognition activates Drosophila cGLR1 to synthesize the novel product cG[3′–5′]pA[2′–5′]p (3′2′-cGAMP). A crystal structure of Drosophila stimulator of interferon genes (dSTING) in complex with 3′2′-cGAMP explains selective isomer recognition, and 3′2′-cGAMP induces an enhanced antiviral state in vivo that protects from viral infection. Similar to radiation of Toll-like receptors in pathogen immunity, our results establish cGLRs as a diverse family of metazoan pattern recognition receptors.

Direct and simultaneous recognition of the positional isomers of aminobenzenesulfonic acid by TIMS-TOF-MS

Positional isomer recognition is a challenging scientific issue. Fast and accurate detection of isomers is required for understanding their chemical properties. Here, we describe a method for simultaneous recognition of three positional isomers of 2-aminobenzenesulfonic acid (2-ABSA), 3-ABSA, and 4-ABSA using trapped ion mobility spectroscopy-time-of-flight mass spectrometry (TIMS-TOF-MS). The three ABSA positional isomers were recognized by measuring the different ion mobility of the ternary complexes of [β-cyclodextrin (CD)+ABSA + Li]+ or [λ-CD + ABSA + Na]+, because their different collision cross-sections or different spatial conformations. The collision-induced dissociation mechanism of the different complexes of [β-CD + ABSA + Li]+ and [λ-CD + ABSA + Na]+ using tandem mass spectrometry exhibited the same dissociation process with slightly different dissociation energies, which the smaller cross-section requires higher collision energy that means the smaller complex with tighter and more stable conformation than a larger complex for the ABSA complexes. In addition, relative quantification of the ABSA isomers was studied by measuring any two of the three ABSA isomer complexes at different molar ratio of 10:1 to 1:10 in the μM range, good linearity (R2 > 0.99) with precision between 2.14% and 2.58%, and accuracy ≥ 97.1% were obtained. The method for fast determination and recognition of ABSA positional isomers by combination with CD and alkali metal ions possesses the advantages of being simple, direct, rapid, sensitive, cost-effective, and needs no chemical derivatives or chromatographic separation before analysis. Therefore, the proposed method would be a powerful tool for the analysis of ABSA isomers or even other positional isomers.

A novel algorithm for the isomorphism detection of various kinematic chains using topological index

For mechanism design, the isomorphic kinematic chains (KCs) should be deleted to improve design efficiency. At present, most methods of isomorphism detection involve complex concepts and comparison of intermediate parameters. Moreover, when the number of components increases, it is complex and difficult to discriminate a large number of KCs in short time. However, the molecular topological index is proposed to identify isomer in organic chemistry, which shows excellent abilities for isomer recognition. In some respects, topological graph of kinematic chain is similar to chemical molecular model. Therefore, this idea is adopted to obtain extended adjacency identification index (EAID) which fits for isomorphism detection of KCs, namely KC-EAID. If two topological graphs have same KC-EAID value, then they are isomorphic. Otherwise, they are not. Three kinds of kinematic chains, including simple joints KCs, multiple joints KCs and gear-link KCs are given to verify effectiveness of this index in isomorphism detection. For KC-EAID index, it requires a few known quantities and no comparison of intermediate parameters. The algorithm only includes the calculation of matrices, which saves operation time. Therefore, KC-EAID can be used as a powerful tool for isomorphism detection in number synthesis of KCs.

Profiling and isomer recognition of phenylethanoid glycosides from Magnolia officinalis based on diagnostic/holistic fragment ions analysis coupled with chemometrics

Isomers derived from natural products are promising candidates for drug discovery. However, characterization of isomers by mass spectrometry, especially stereoisomers and positional isomers, remains a large challenge due to insufficient reference standards and isomers’ highly similar fragmentation pathways or nondistinctive ion abundances. Herein, this report presents the first proposal of a method, combining multiple diagnostic ion/neutral loss (DINL) postanalysis and especially untargeted fingerprint analysis of all fragment ions (FAAFI) by means of a home-made program and chemometrics, to profile chemical components and recognize their isomers derived from medicinal plants. As a proof-of-concept, the chemical profiling of phenylethanoid glycosides (PhGs) and their isomers, which showed remarkable neuroprotective, anti-inflammatory and immunomodulatory effects, was performed. Using DINL to extract PhGs and FAAFI to distinguish their stereoisomers and positional isomers, as many as 87 PhGs, including 14 isomers, were tentatively identified from Magnolia officinalis; in addition, 17 PhGs were unambiguously identified by comparing the retention time and MS/MS data with those of reference compounds. Under the theory of Big Data analysis, the untargeted fingerprint analysis concerning unbiased ions was sufficient to contribute to discrimination of isomers even without evident distinction occurred for main ions.

Electrochemical recognition of nitrophenol isomers by assembly of pillar[5]arenes mutifilms

The rational design of electrochemical methods for isomer recognition is a focus of research in the molecular recognition and separation fields. In this work, a novel, rapid, and convenient electrochemical approach for recognition of nitrophenol isomers was constructed based on the alternating layer-by-layer (LbL) assembly of water-soluble cationic and anionic pillar [5]arene on a carboxylic graphene (C-Gra) modified glass carbon electrode. The electrochemical recognition of nitrophenol isomers was investigated by differential pulse voltammetry (DPV). The electrochemical results reveal that both the peak currents of m-nitrophenol (m-NP) and p-nitrophenol (p-NP) increased with the increasing of the layer number of the assembled pillar [5]arene, whereas the peak current of o-nitrophenol (o-NP) decreased with the increased layers, which demonstrated an efficient route for discriminating the nitrophenol isomers. The molecular recognition mechanism was studied by 1H NMR spectra, which indicated that the m-NP and p-NP can be included in the cavity of the pillar [5]arene host. However, the o-NP could not enter into the host of pillar [5]arene, which was ascribed to the formation of intramolecular hydrogen bond of o-NP. The LbL assembly modified GCE was used for detecting p-NP and m-NP. A low detection limit of 0.33 μM (S/N = 3) and a linear response range of 1–90 μM for p-NP were obtained by using this method. And the detection limit of 0.16 μM (S/N = 3) and a linear response range of 0.5–70 μM for m-NP were obtained. This method of LbL assembly modified GCE has potential application in molecular recognition and separation.

A rapid assay of identification for glimepiride and its cis-isomer by tandem mass spectrometry

A simple and rapid identification method of glimepiride and its cis-isomer was established for the first time. The collision-induced dissociation (CID) mass spectrometry method was used in this study. Under negative ion mode, the CID mass spectra of the deprotonated molecule ion showed two characteristic ions, m/z 364 and m/z 376, which are confirmed by the method of energy-resolved mass spectrometry (ERMS). The relative abundance of the m/z 364 of glimepiride showed lower than that of its cis-isomer, which is related to the stereo structure of glimepiride and its isomer. Zinc ion was chosen to adduct to the glimepiride and its isomer, which experimental results showed the zinc ions enhanced the degree of recognition. The RIsomer values, which evaluate the degree of the isomer recognition, were investigated at different collision energy. The quantitative determination of glimepiride was performed by using MS/MS. Aiming at the recognition of geometric isomers; this methodology shows huge potential of extended mass spectrometry method to a large number of chiral drugs and their impurity.

Distinguishing Diketopyrrolopyrrole Isomers in Single-Molecule Junctions via Reversible Stimuli-Responsive Quantum Interference.

Distinguishing structural isomers at the single-molecule level remains a challenge. We report the single-molecule recognition of two diketopyrrolopyrrole containing isomers (SDPP and SPPO) employing the mechanically controllable break junction technique. The single-molecule conductances of the two isomers are indistinguishable under normal conditions. However, reversible protonation and deprotonation of the SPPO in molecular junction result in more than 1 order of magnitude conductance change, which dramatically enhances the conductance difference between the two isomers. Theoretical study reveals that the dramatic conductance switching is due to reversible quantum interference effect. It is suggested that combination of stimuli-response and quantum interference can be an efficient strategy to enhance isomer recognition and conductance switching in single-molecule junctions.

Graphene quantum dots/β-cyclodextrin nanocomposites: A novel electrochemical chiral interface for tryptophan isomer recognition

Abstract Graphene quantum dots (GQDs) were prepared by pyrolysis of citric acid, and then incorporated into β-cyclodextrin (β-CD) via H-bonds between the oxygen-containing groups on GQDs and the hydroxyl groups on β-CD. The nanocomposites of GQDs and β-CD (GQDs/β-CD) were negatively charged due to the ionization of carboxyl groups of GQDs, and therefore they could be effectively electrodeposited onto a glassy carbon electrode (GCE). The electrodeposited GQDs/β-CD were optically active due to the introduction of β-CDs with well-defined hydrophobic central cavities, and it was employed as an electrochemical chiral interface for enantiorecognition of tryptophan (Trp) isomers.

A Promising Raman Spectroscopy Technique for the Investigation of trans and cis Cholesteryl Ester Isomers in Biological Samples.

Lipid geometry is an important issue in biology and medicine. The cis-trans geometry conversion of double bonds in lipids is an endogenous process that can be mediated by sulfur-centered free radicals. Trans isomers of polyunsaturated fatty acids can be used as biological markers of free radical stress, and their presence in biological samples can be determined by synthesis and characterization of appropriate reference compounds. Fractions of plasma lipids, such as cholesteryl linoleate and arachidonate esters, are interesting targets because of their connection with membrane phospholipid turnover and their roles in cardiovascular health. In this context, Raman spectroscopy can provide a useful contribution, since Raman analysis can be performed directly on the lipid extracts without any derivatization reaction, is nondestructive, and can rapidly supply biochemical information. This study focused on the build up of Raman spectral libraries of different cis and trans isomers of cholesteryl esters to be used as references for the examination of complex biological samples and to facilitate isomer recognition. Unsaturated cholesteryl esters obtained by chemical synthesis and with different alkyl chain lengths, double bond numbers, or both, were analyzed. The potential of Raman analysis for trans isomer detection in biological samples was successfully tested on some cholesteryl ester lipid fractions from human serum. The data suggest promising applications of Raman spectroscopy in metabolomics and lipidomics.

Construction and isomer recognition of polyoxometalates functionalized by 1,2-dimethylimidazole alkane templates

Eleven novel inorganic–organic hybrid polyoxometallates, namely, [1,2-bis(1,2-dimethylimidazole)methane]3[β-HMo8O26]2·[H3O+]2·7H2O (1), [1,2-bis(1,2-dimethylimidazole)ethane]2[β-Mo8O26]·H2O (2), [1,2-bis(1,2-dimethylimidazole)propane]2[α-Mo8O26] (3), [1,2-bis(1,2-dimethylimidazole)butane]2[γ-Mo8O26] (4), [1, 2-bis(1,2-dimethylimidazole) pentane]3[β-Mo8O26]2[H3O+]2 (5), [1,2-bis(1,2-dimethylimidazole) hexane]4[β-Mo8O26]2 (6), [1,2-bis(1,2-dimethylimidazole)heptane][Mo6O19] (7), [1,2-bis(1,2-dimethylimidazole) octane] [Mo6O19] (8), [1,3,5-tris[(1,2-dimethylimidazole-3-iumyl)benzene)]2[β-Mo8O26]1.5·2H2O (9), [1,3,5-tris[(1,2-dimethylimidazole-3-iumyl)-2,4,6-trimethyl benzene)]4 [α-Mo8O26]2 [Mo6O19]2·4H2O (10), [1,3,5-tris[imidazol-1-ylmethyl)-2,4,6-trimethyl benzene)]2 [β-Mo8O26] [Mo6O19] (11) were synthesized by the cation-templated self-assembly with octamolybdate or hexamolybdate anions under hydrothermal reaction conditions. Crystal data analysis revealed that these compounds were all composed of discrete organic cations and polyacid anions interacted by electrostatic and hydrogen bond interactions. Interestingly in these compounds the anion fraction could take on [β-Mo8O26]4− cluster, α-[Mo8O26]4− cluster, γ-[Mo8O26]4− cluster, [Mo6O19]2− cluster or two mixing kinds of polyoxomolybdate anions with the modification of lengths of alkane components or change the valence configuration of the templates.

Templated fabrication, isomer recognition of series of 1,1′-(alkane-1,ω-diyl)-bis(3-methylimidazolium)-induced polyoxometalates (ω = 1–11)

Eleven novel polyoxometalates, namely [1,1′-(alkane-1,ω-diyl)-bis(3-methylimidazolium)]m [Mo8O26][nH3O+]·xH2O (ω=1–11; m=1, 1.5, 2; n=0, 1; x=0, 1, 2) were synthesized by the self-assembly with octamolybdate anions under hydrothermal reaction conditions. The crystal data analysis revealed that these compounds were all composed of discrete methylimidazolium cations and polyacid anions [Mo8O26]4− interacted by electrostatic interactions and hydrogen bonds. Interestingly, the anions of these compounds took on single [β-Mo8O26]4− cluster, twin [β-Mo8O26]4− clusters, a δ-[Mo8O26]4− cluster and a rare 1D 1/∞[β-Mo8O26]4− polymeric chain with the modification of lengths of alkane components.

Two new azamacrocycle-based stationary phases for high-performance liquid chromatography: Preparation and comparative evaluation

In this paper, two new azamacrocycle-bonded stationary phases for high-performance liquid chromatography are described. The new phases were prepared by respectively coupling a 14-membered Curtis macrocycle and a 30-membered hexaazaannulene to γ-chloropropyltrimethoxylsilane-modified silica and characterized by elemental analysis and infrared spectroscopy. To understand the effects of the structures of the azamacrocyles and their functional groups upon the retention and separation, the chromatographic behaviors of the two stationary phases were compared by eluting alkylbenzenes, polycyclic aromatic hydrocarbons (PAHs) and aromatic amines. The two new phases demonstrated unique selectivity and fine chromatographic performance, which were guaranteed by multiple interactions, including hydrophobic, hydrogen-bonding, π–π and dipole-induced dipole interactions between stationary phase and solutes. On the other hand, the difference between the structures of embedded azamacrocyles did lead to remarkable dissimilarity in the shape and planarity recognition of isomers, which was highlighted by the 30-membered hexaazaannulene-bonded phases’ superiority over 14-membered tetraazamacrocycle-bonded phases’ in discriminating specific PAHs. With a wide range of probes, the linear solvation energy relationship model was also applied to evaluate the chromatographic properties of the two stationary phases, further verifying the chromatographic results.

De la construcción del conocimiento científico a su enseñanza. Distintas explicaciones sobre la estructura del benceno

Reviewing the historical development to represent a compound, in this case benzene, displays the different theories that struggled to give the best explanations, showing a dynamic vision for the scientific knowledge construction. The elemental composition and the establishment of the empirical formula, the recognition of isomers, the chemical reactivity, the availability of new technological devices and chemical bond theories (the structural theory, atomic theories, valence bond theory and molecular orbital theory) are the main factors that influenced knowledge about the structure of benzene. This work can be useful in teachers’ training and perhaps enlightens on some students learning difficulties. This also is a useful model for future research that teachers can develop with their students including the meta-scientific knowledge actively in the classroom.

Rapid recognition of isomers of monochlorobiphenyls at trace levels by surface-enhanced Raman scattering using Ag nanorods as a substrate

Isomers and homologues of organic pollutants are hard to distinguish-especially in trace amounts-due to the similarities in their physical and chemical properties. We report here that by identifying the Raman characteristics of isomers of monochlorobiphenyls, these compounds can be recognized, even at trace levels, by using the surface-enhance Raman scattering method with silver nanorods as a substrate. When dissolved in acetone, 2-, 3-, and 4-chlorobiphenyls were detected at a concentration of 10−8 mol/L, at which their characteristic Raman peaks were visible. This study may provide a fast, simple, and sensitive method for the detection and recognition of organic pollutants such as polychlorinated biphenyls.

Old Drugs, New Tricks: The Effect of Molecule−Ion Interactions on the Precipitation−Dissolution Equilibrium of Lithium Carbonate in Aqueous Solution and on the Chiral Recognition of Cyclodextrins to d-,l-Tryptophan

In the present work, the influence of molecule-ion interactions on the precipitation-dissolution equilibrium of a typical inorganic drug, lithium carbonate (Li2CO3), in water and on the chiral recognition behaviors and binding abilities of alpha-, beta-, gamma-, and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (CD) to D- and L-tryptophan (Trp) was investigated. Our results revealed that the solubility of Li2CO3 was increased to a large extent and the phase solubility diagram of Li2CO3 belonged to the AN type. This finding provided a new insight into the link between molecule-ion interactions and precipitation-dissolution equilibriums of poorly dissolving inorganic salts. Furthermore, despite having a negative effect on the isomer recognition behaviors, the molecule-ion interaction between CDs and Li2CO3 effectively increased the binding abilities of these CDs to both D- and L-Trp synchronously. The observation gave an important implication that buffer solutions consisting of inorganic salts are used with caution in molecular recognition fields between host and guest or between acceptor and donor. Further analyses confirmed the interaction among Li2CO3, beta-CD, and L-Trp using an electrospray ionization mass spectrum.