High-resolution Mass Spectrometry Analysis Research Articles

Synthesis and Antifungal Activity Evaluation of Novel L-Carvone-Based 1,3,4-Thiadiazole-amide Derivatives as a Potential Succinate Dehydrogenase Inhibitor.

In an effort to explore new-type high-efficiency antifungal agents, 25 novel L-carvone-based 1,3,4-thiadiazole-amide derivatives were designed, synthesized, and structurally characterized by IR, 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS) analyses. The antifungal activity of the target compounds was preliminarily assayed at a concentration of 50 μg/mL, and boscalid, a commercialized fungicide identified as a succinate dehydrogenase inhibitor (SDHI), was employed as the positive control. It was found that all of the target compounds showed moderate to potent antifungal activity against the tested fungi compared to boscalid. Surprisingly, compound 4b exhibited broad-spectrum and significant inhibition activity against the growth of eight phytopathogenic strains with inhibitory rates of 67-89%. Further, the results of the EC50 value test suggested that the EC50 values of compound 4b against Physalospora piricola and Colletotrichum orbiculare were 16.33 and 18.06 μg/mL, respectively, and both of them were better than those of boscalid (16.64 and >50). Therefore, compound 4b deserves further study as a lead compound for novel fungicides. In addition, the inhibitory activity of compound 4b against succinate dehydrogenase (SDH) was evaluated as well to prove that compound 4b (IC50 = 3.38 μM) displayed higher SDH-inhibition activity than boscalid (IC50 = 7.02 μM). The binding mode of compound 4b and SDH was simulated by molecular docking and found to be similar to that of boscalid. The structure-activity relationships (SARs) of the target compounds were analyzed by establishing a 3D-QSAR model. Besides, a 4b-loaded complex 4b/CSTA on a reported L-carvone-based nanochitosan carrier CSTA containing the 1,3,4-thiadiazole-amide group was constructed, and its sustained release performance was investigated in the EtOH-H2O system (1:9, v/v). The complex 4b/CSTA exhibited preferred sustained release performance, indicating its potential for developing environmentally friendly nanofungicides.

Talaketides A−G, linear polyketides with prostate cancer cytotoxic activity from the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41027

Seven novel linear polyketides, talaketides A−G (1−7), were isolated from the rice media cultures of the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41027. Among these, talaketides A−E (1−5) represented unprecedented unsaturated linear polyketides with an epoxy ring structure. The structures, including absolute configurations of these compounds, were elucidated through detailed analyses of nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HR-MS) data, as well as electronic custom distributors (ECD) calculations. In the cytotoxicity screening against prostate cancer cell lines, talaketide E (5) demonstrated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines, with an IC50 value of 14.44 μmol·L−1 . Moreover, compound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase, ultimately inducing apoptosis. These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treatment for prostate cancer.

Administration Route Differentiation of Altrenogest via the Metabolomic LC-HRMS Analysis of Equine Urine.

Altrenogest, also known as allyltrenbolone, is a synthetic form of progesterone used therapeutically to suppress unwanted symptoms of estrus in female horses. Altrenogest affects the system by decreasing levels of endogenous gonadotrophin and luteinizing and follicle-stimulating hormones, which in turn decreases estrogen and mimics the increase of progesterone production. This results in more manageable mares for training and competition alongside male horses while improving the workplace safety of riders and handlers. However, when altrenogest is administered, prohibited steroid impurities such as trendione, trenbolone, and epitrenbolone can be detected. It has been assumed that greater concentrations of these steroid impurities are present in injectable preparations and, therefore, pose a greater risk of causing anabolic effects when administered. For this reason, and due to the necessity of this therapeutic substance for the safety of thoroughbred racing participants, a metabolomic approach investigating the differentiation of two main administration routes was conducted. Liquid chromatography high-resolution mass spectrometry analysis of equine urine samples found five sulfated compounds, estrone sulfate, testosterone sulfate, 2-methoxyestradiol sulfate, pregnenolone sulfate, and cortisol sulfate, with the potential to differentiate between oral and intramuscularly administered altrenogest using a random forest classification model. The best model results, comparing two horses' administration normalized peak area datasets, gave an AUC score of 0.965 with a confidence level of 95% (between 0.931 and 0.995). Identifications of these compounds were confirmed with assistance from the Shimadzu Insight Explore Assign feature, together with MS/MS spectrum and retention time matching of purchased and synthesized reference standards. This study proposes a new potential application for metabolomic multi-tool workflows and machine learning models in a forensic toxicological context.

Molecular Insights into Gas-Particle Partitioning and Viscosity of Atmospheric Brown Carbon.

Biomass burning organic aerosol (BBOA), containing brown carbon chromophores, plays a critical role in atmospheric chemistry and climate forcing. However, the effects of evaporation on BBOA volatility and viscosity under different environmental conditions remain poorly understood. This study focuses on the molecular characterization of laboratory-generated BBOA proxies from wood pyrolysis emissions. The initial mixture, "pyrolysis oil (PO1)", was progressively evaporated to produce more concentrated mixtures (PO1.33, PO2, and PO3) with volume reduction factors of 1.33, 2, and 3, respectively. Chemical speciation and volatility were investigated using temperature-programmed desorption combined with direct analysis in real-time ionization and high-resolution mass spectrometry (TPD-DART-HRMS). This novel approach quantified saturation vapor pressures and enthalpies of individual species, enabling the construction of volatility basis set distributions and the quantification of gas-particle partitioning. Viscosity estimates, validated by poke-flow experiments, showed a significant increase with evaporation, slowing particle-phase diffusion and extending equilibration times. These findings suggest that highly viscous tar ball particles in aged biomass burning emissions form as semivolatile components evaporate. The study highlights the importance of evaporation processes in shaping BBOA properties, underscoring the need to incorporate these factors into atmospheric models for better predictions of BBOA aging and its environmental impact.

Enhanced removal of recalcitrant naphthenic acids through electro-cocatalytic activation of peracetic acid: Synergistic effects of multiple factors

Herein, a peracetic acid (PAA)-based electro-cocatalytic system (EC/PAA/Fe(III)) has been established for efficient degradation of 1-adamantanecarboxylic acid (ACA), which is a typical model chemical for naphthenic acids (NAs) that are abundantly present in petroleum industrial wastewater. The electric field greatly boosted the regeneration of Fe(II) to activate PAA in the system, resulting in 99.8 % removal for ACA within 20-min reaction time, with kobs of 0.3451 min−1. Results of quenching and chemical probe experiments verified the production of •CH3, CH3C(O)O•, •OH and FeIVO2+, in the EC/PAA/Fe(III) system with the FeIVO2+ identified as the primary contributor to ACA removal. The H2O2 present in the PAA solution enhanced the activation of PAA by promoting Fe(II) generation, thereby significantly improving ACA degradation efficiency. The ACA degradation byproducts and pathways were identified using the results of high resolution mass spectrometry analysis and density functional theory (DFT) calculations. Decarboxylation, hydroxy substitution, and carbonyl substitution reactions were predominant oxidation pathways of ACA decontamination. The EC/PAA/Fe(III) system demonstrated resilient degradation performance under the influence of anions and the natural water matrix for effective degradation of the commercial NAs mixture. Overall, the EC/PAA/Fe(III) system has been established with effectiveness and reliability for future remediation of NAs in petroleum industrial wastewater.

Synthesis, Characterization, and Photochemistry of a Ga2L3 Coordination Cage with Dithienylethene-Catecholate Ligands.

Two new photoswitchable dithienylethene (DTE)-catechol ligands, specifically designed for group 13 metal coordination, were synthesized via Suzuki coupling reactions from a dichloro-DTE building block, each with varying longitudinal extensions. The shorter DTE-catechol ligand did not efficiently assemble with Ga3+ metal ions; however, elongation with a phenylene-amide spacer group enabled the successful formation of a novel triply DTE-functionalized coordination [Ga2L3]6- cage. This cage represents a unique example of integrating DTE photoswitches with main group metals in a supramolecular coordination framework. The [Ga2L3]6- cage was thoroughly characterized by NMR spectroscopy, including DOSY hydrodynamic volumetric analyses, high-resolution mass spectrometry, computational DFT, and photochemical analyses. The DFT studies highlighted the structural integrity and dynamic interplay within the helicate and mesocate isomeric forms of the [Ga2L3]6- cage upon photoswitching. While the free ligands exhibited all-photonic reversible switching at up to mM concentrations upon alternating irradiation at 365 and >495 nm, the [Ga2L3]6- cage demonstrated these capabilities under dilute μM conditions, albeit with lower efficiency and fatigue resistance. This behavior highlights the intricate relationship between rigid coordination with main group metals and the flexibility of the photoswitchable DTE ligands within the [Ga2L3]6- cage.

Synthesis, characterization and α-amylase inhibition activity of new family of tetrapodal ligands with pyrazole-tetrazole subunits

New family of tetrapodal compounds entitled 3-(bis((5-methyl-1-((2-isopentyl-2H-tetrazol-5-yl)methyl)-1H-pyrazol-3 yl)methyl)amino)propan-1-ol.(T1),2-(4-(bis((5-methyl-1-((2-propyl-2H-tetrazol-5-yl)methyl)-1H-pyrazol-3-yl)methyl)amino)phenyl)ethan-1-ol.(T2),N,N-bis((1-((2-isopentyl-2H-tetrazol-5-yl)methyl)-5-methyl-1H-pyrazol-3-yl)methyl)propan-1-amine.(T3).and.N,N-bis((1-((2-isopentyl-2H-tetrazol-5-yl)methyl)-5-methyl-1H-pyrazol-3-yl)methyl)propan-2 amine (T4) were synthesised as drug candidates to treat Type 2 diabetes. Their structures as the intermediates compounds were ensured by NMR and FTIR analysis as well as the spectrometric methods including high-resolution mass spectrometry and elemental analysis. The tetrapodal molecules were obtained in moderate yields in the range of 37–45 %. Their anti-diabetic activity was evaluated based on their α-amylase inhibition potency by determining their IC50 values. The obtained results showed that the tetrapodal compounds possess potent α−amylase inhibition activity 3 to 236 times higher than that of the acarbose, used as positive control. These findings were also supported by docking calculations.

Deciphering the key drivers of oxidative potential during ammonium nitrate-mediated aqueous-phase photoreaction of methoxyphenols

Methoxyphenols are released in abundance from lignin pyrolysis during biomass burning. Apart from being atmospheric brown carbon components that absorb solar radiation and warm the climate, methoxyphenols also undergo photoreaction in the atmospheric aqueous phase and form secondary organic aerosols (aqSOA). While efforts have been devoted to understanding chemical evolutions and climate-related optical properties of aqSOA, their potential health impacts also require timely investigations. Herein, we used the dithiothreitol (DTT) assay to investigate oxidative potential of the aqSOA formed during the 8-hr aqueous-phase photoreaction of two typical methoxyphenols, vanillin and vanillic acid, under pH 2 or 8, and with or without ammonia nitrate. The highest DTT consumption rates (RDTT) were observed for vanillin aqSOA formed in the presence of ammonia nitrate and at pH 8. At pH 2, although RDTT increased rapidly during early photoreaction, it reduced after prolonged illumination. High resolution mass spectrometry and linear regression analyses were performed to correlate the photoreaction products with the observed RDTT. Results showed that three products that present quinone, lactone and dimer structures, respectively, should be the key drivers of elevated RDTT for aqSOA formed during photoreaction of vanillin and vanillic acid alone, whereas it shifted to the nitrogen-containing aromatic compounds during their photoreaction with ammonia nitrate. Our results have revealed the role of nitrogen-containing aromatic compounds in the oxidative potential and health effects of aqSOA from biomass burning, which was rarely recognized before and warrants immediate assessments.

Investigation of cytotoxic indoleninyl-thiobarbiturate zwitterions as DNA targeting agents

A series of indoleninyl-thiobarbiturate zwitterions were synthesized in up to 83 % yields from the Knoevenagel condensation between N-substituted diformyl indolenine and thiobarbiturate. The structures were characterized by spectroscopic methods such as NMR (1H, 13C), FT-IR, high-resolution mass spectrometry (HR-MS) and elemental analysis. However, their physicochemical properties and biological activities remain elusive. Herein, results from in silico ADMET calculations and cytotoxicity predictions suggest that all zwitterions are likely to exhibit a higher bioavailability and more specific cytotoxicity than doxorubicin. The notably high predicted cytotoxicity of 2d and drug-likeness score of 2f may be linked to the position of the fused benzene ring and methoxy groups, respectively. The initial biological assessment of these compounds began with in vitro DNA-binding studies because the treatment of numerous diseases such as cancer and bacterial infections is linked to DNA interactions. Zwitterion 2f demonstrated the most significant spectral change in DNA binding studies, suggesting a possible role of the methoxy group in inducing DNA binding activity. The hypothesis that 2f interacts with DNA through groove binding was confirmed by observations made during salt-back titration and DNA denaturation experiments. It was anticipated that the non-zwitterionic 2f would interact more stably with DNA (PDB code: 453D) at the minor groove than its zwitterionic form based on molecular docking calculations and molecular dynamic (MD) simulations. Additionally, the MTT assay demonstrates that 2f is moderately cytotoxic to the human breast cancer cell line MDA-MD-231, most probably as a result of the previously stated DNA binding mechanisms. Overall, the computational and in vitro data suggest the potential application of 2f as a cytotoxic DNA-targeting agent.

LC-HRMS-based global metabolomics profiling unravels the distinct metabolic signature of lapatinib-resistant and trastuzumab-resistant HER2+ breast cancer cells

The effectiveness of lapatinib (LAP) and trastuzumab (TRZ), the first-line therapies for HER2+ breast cancer, has been limited owing to the development of acquired resistance in patients with HER2+. This study aimed to investigate the alterations in metabolic signatures in LAP-resistant HCC1954 and TRZ-resistant HCC1954 and pathways in human HER2+ breast cancer cells using liquid chromatography–high-resolution mass spectrometry (LC-HRMS) and enrichment analysis. The HCC1954 parental cells were sequentially treated 13 rounds with LAP or TRZ to develop resistant cells and then tested for their cytotoxicity using the MTT assay. Metabolites were prepared from HCC1954 parental (MBXWT), HCC1954-LAP (MBXLAP), and HCC1954-TRZ (MBXTRZ) cells prior to LC-HRMS, chemometric, enrichment, and joint pathway analyses. LAP- and TRZ-resistant cells were successfully developed from HCC1954, and 29 and 17 differentially expressed metabolites (DEMs) were identified between MBXWT-MBXLAP and MBXWT-MBXTRZ, respectively. The analysis of DEMs between MBXWT and MBXLAP revealed significant enrichment in D-amino acid metabolism, while MBXWT and MBXTRZ identified valine, leucine, isoleucine biosynthesis, ascorbate, and aldarate metabolism. Joint pathway enrichment analysis of LAP-resistant DEMs and differentially expressed genes (DEGs) showed enrichment in glutathione metabolism, while that of TRZ-resistance and DEGs showed enrichment in carbohydrate metabolism, namely pentose and glucuronate interconversions, starch and sucrose metabolism, and galactose metabolism. The findings from this study indicate considerable metabolic changes in LAP- and TRZ-resistant HCC1954 cells, which are crucial for understanding the resistance mechanisms and developing strategies to overcome these problems.

Enhanced Photocatalytic Paracetamol Degradation by NiCu-Modified TiO2 Nanotubes: Mechanistic Insights and Performance Evaluation.

Anodic TiO2 nanotube arrays decorated with Ni, Cu, and NiCu alloy thin films were investigated for the first time for the photocatalytic degradation of paracetamol in water solution under UV irradiation. Metallic co-catalysts were deposited on TiO2 nanotubes using magnetron sputtering. The influence of the metal layer composition and thickness on the photocatalytic activity was systematically studied. Photocatalytic experiments showed that only Cu-rich co-catalysts provide enhanced paracetamol degradation rates, whereas Ni-modified photocatalysts exhibit no improvement compared with unmodified TiO2. The best-performing material was obtained by sputtering a 20 nm thick film of 1:1 atomic ratio NiCu alloy: this material exhibits a reaction rate more than doubled compared with pristine TiO2, enabling the complete degradation of 10 mg L-1 of paracetamol in 8 h. The superior performance of NiCu-modified systems over pure Cu-based ones is ascribed to a Ni and Cu synergistic effect. Kinetic tests using selective holes and radical scavengers unveiled, unlike prior findings in the literature, that paracetamol undergoes direct oxidation at the photocatalyst surface via valence band holes. Finally, Chemical Oxygen Demand (COD) tests and High-Resolution Mass Spectrometry (HR-MS) analysis were conducted to assess the degree of mineralization and identify intermediates. In contrast with the existing literature, we demonstrated that the mechanistic pathway involves direct oxidation by valence band holes.

LC–HRMS Lipidomic Fingerprints in Serbian Cohort of Schizophrenia Patients

Schizophrenia (SCH) is a major mental illness that causes impaired cognitive function and long-term disability, so the requirements for reliable biomarkers for early diagnosis and therapy of SCH are essential. The objective of this work was an untargeted lipidomic study of serum samples from a Serbian cohort including 30 schizophrenia (SCH) patients and 31 non-psychiatric control (C) individuals by applying liquid chromatography (LC) coupled with high-resolution mass spectrometry (HRMS) and chemometric analyses. Principal component analysis (PCA) of all samples indicated no clear separation between SCH and C groups but indicated clear gender separation in the C group. Multivariate statistical analyses (PCA and orthogonal partial least squares discriminant analysis (OPLS-DA)) of gender-differentiated SCH and C groups established forty-nine differential lipids in the differentiation of male SCH (SCH-M) patients and male controls (C-M), while sixty putative biomarkers were identified in the differentiation of female SCH patients (SCH-F) and female controls (C-F). Lipidomic study of gender-differentiated groups, between SCH-M and C-M and between SCH-F and C-F groups, confirmed that lipids metabolism was altered and the content of the majority of the most affected lipid classes, glycerophospholipids (GP), sphingolipids (SP), glycerolipids (GL) and fatty acids (FA), was decreased compared to controls. From differential lipid metabolites with higher content in both SCH-M and SCH-F patients groups compared to their non-psychiatric controls, there were four common lipid molecules: ceramides Cer 34:2, and Cer 34:1, lysophosphatidylcholine LPC 16:0 and triacylglycerol TG 48:2. Significant alteration of lipids metabolism confirmed the importance of metabolic pathways in the pathogenesis of schizophrenia.

Citral: A potent inhibitor of advanced glycation end products

Advanced glycation end products (AGEs), which are produced during food processing, pose health risks to humans. This study found that citral (Cit) effectively inhibited the formation of both fluorescent and non-fluorescent AGEs in the bovine serum albumin (BSA)-glucose (Glc) system. Cit achieved an average inhibition rate of over 80 % for fluorescent AGEs and reduced the levels of N-ε-carboxymethyllysine (CML) and N-ε-carboxyethyllysine (CEL) by up to 45.85 % and 59.32 %, respectively. The comprehensive characterizations and high-resolution mass spectrometry analysis demonstrated that the carbonyl group and CC group present on Cit could compete with Glc for the amino groups on BSA, thereby reducing the formation of AGEs. Additionally, the cytotoxicity assay demonstrated that the BSA-Cit adducts were non-toxic. This research indicated that Cit was a potent and safe inhibitor of AGEs.

Divergent Reactivity of Iminyl Radicals in Four Interrupted Pathways for the Synthesis of Cyclic/Acyclic Ketones and N-Heterocycles from Vinyl Azides and Phenylacetic Acids.

Herein, we report the Ag-catalyzed substrate-controlled interrupted radical pathways of the iminyl radical. The benzylic groups played a crucial role in pathway selection involving a series of dimerization and hydrolysis, a 1,5-H shift followed by cascade radical cyclization, and direct N-(sp2)/aromatization reactions that provide access to diverse cyclic/acyclic ketones, quinolines, and phenanthridine derivatives. Contrary to previous reports, mechanistic investigations with high-resolution mass spectrometry analysis uncovered the involvement of rare azine, oxime, and β-functionalized vinyl azide intermediates.

Upconversion Luminescence in a Photostable Ion-Paired Yb-Eu Heteronuclear Complex.

Lanthanide-based upconversion molecular complexes have potential application in diverse fields and attracted considerable research interest in recent years. However, the similar coordination reactivity of lanthanide ions has constrained the designability of target molecule with well-defined structure, and many attempts obtained statistical mixtures. Herein, an ion-paired Yb-Eu heteronuclear complex [Eu(TpPy)2][Yb(ND)4] (TpPy = tris[3-(2-pyridyl)pyrazolyl]hydroborate, ND = 3-cyano-2-methyl-1,5-naphthyridin-4-olate) was designed and synthesized. Thanks to the radius difference between Eu3+ (1.07 Å) and Yb3+ (0.98 Å) ions, the hexadentate TpPy ligand was selected to coordinate with Eu3+ and the Yb3+ with a smaller radius was chelated by bidentate ND ligand. As a result, the sites of Eu3+ and Yb3+ in the complex can be clarified by high-resolution mass spectrometry and single-crystal structure analysis. Upon the excitation of Yb3+ at 980 nm, the upconversion emission of Eu3+ was realized through a cooperative sensitization process. Furthermore, [Eu(TpPy)2][Yb(ND)4] demonstrated excellent photostability during continuous high-power density 980 nm laser irradiation, with a LT95 (the time to 95% of the initial emission intensity) of 420 minutes. This work provides the first example of a pure ion-paired Yb-Eu heteronuclear complex upconversion system and may bring insights into rational design of lanthanide-based upconversion molecular complexes.

Combining High-Resolution Mass Spectrometry and Chemiluminescence Analysis to Characterize the Composition and Fate of Total N-Nitrosamines in Wastewater Treatment Plants.

Monitoring the prevalence and persistence of N-nitrosamines and their precursors in wastewater treatment plants (WWTPs) and effluent-receiving aquatic compartments is a priority for utilities practicing wastewater recycling or exploiting wastewater-impacted source waters. In this work, we developed an analytical framework that combines liquid chromatography-high-resolution mass spectrometry (LC-HRMS) with acidic triiodide-chemiluminescence analysis to characterize the composition and fate of total N-nitrosamines (TONO) and their precursors along the treatment trains of eight WWTPs in New York. Through the parallel application of LC-HRMS and chemiluminescence methods, the TONO scores for 41 N-nitrosamines containing structurally diverse substituents on their amine nitrogen were derived based on their solid-phase extraction recoveries and conversion efficiencies to nitric oxide. Correcting the compositional analysis of TONO using the TONO scores of target N-nitrosamines refined the assessment of the reduction or accumulation of TONO and their precursors across treatment steps in WWTPs. Nontargeted analysis prioritized seven additional N-nitrosamines for confirmation by reference standards, including three previously uncharacterized species: N-nitroso-tert-butylphenylamine, N-nitroso-2-pyrrolidinmethanol, and N-nitrosodesloratadine, although they only served as minor components of TONO. Overall, our study establishes an adaptable methodological framework for advancing the quantitative and qualitative analysis of specific and unknown components of TONO across water treatment and reuse scenarios.

Identifying Quinones in Complex Aqueous Environmental Media (Biochar Extracts) through Tagging with Cysteine and Cysteine-Contained Peptides and High Resolution Mass Spectrometry Analysis.

Quinones are among the most important components in natural organic matter (NOM) for redox reactions; however, no quinones in complex environmental media have been identified. To aid the identification of quinone-containing molecules in ultracomplex environmental samples, we developed a chemical tagging method that makes use of a Michael addition reaction between quinones and thiols (-SH) in cysteine (Cys) and cysteine-contained peptides (CCP). After the tagging, candidates of quinones in representative aqueous environmental samples (water extractions of biochar) were identified through high-resolution mass spectrometry (HRMS) analysis. The MS and UV spectra analysis showed rapid reactions between Cys/CCP and model quinones with β-carbon from the same benzene ring available for Michael addition. The tagging efficiency was not influenced by other co-occurring nonquinone representative compounds, including caffeic acid, cinnamic acid, and coumaric acid. Cys and CCP were used to tag quinones in water extractions of biochars, and possible candidates of quinones (20 and 53 based on tagging with Cys and CCP, respectively) were identified based on the HRMS features for products of reactions with Cys/CCP. This study has successfully demonstrated that such a Michael addition reaction can be used to tag quinones in complex environmental media and potentially determine their identities. The method will enable an in-depth understanding of the redox chemistry of NOM and its critical chemical compositions and structures.

Thiazole-derived pyrazin-2-carbohydrazide chemosensors: Colorimetric & photoluminescent detection of silver ions for theoretical, environmental, and cell imaging

In this work, a simple and versatile chemosensor receptor TZPYZ was synthesized through the combination of thiazole with pyrazine-2-carbohydrazide, resulting in a confirmed chemical structure via various analytical techniques including FT-IR, 1H, and 13C Nuclear Magnetic Resonance Spectroscopy, as well as High-Resolution Mass Spectroscopy analysis. TZPYZ exhibits specific colorimetric and photoluminescent responses to Ag+ ions in a solvent solution consisting of DMSO and H2O (7:3, v/v). Upon addition of Ag+ ions, noticeable changes in absorption spectra occur, resulting in a visible color change from pale yellow to blue. Additionally, an enhanced emission intensity with wavelength at 523 nm, when excited at 410 nm. Notably, TZPYZ demonstrated exceptional selectivity for Ag+ ions over other metal cations, achieving a detection limit (LOD) of 10.6 × 10−9 M and 6.74 × 10−9 M and using the UV–visible & photoluminescent titration method. Interference studies indicated minimal disruption from other metal ions on emission at 523 nm, highlighting TZPYZ discerning capability for Ag+ ions. With a binding affinity of 3.622 × 10−11 M−1, TZPYZ proved effective in detecting Ag+ ions across various water samples, showcasing its practical utility. The mechanism of interaction between TZPYZ and Ag+ ions was investigated using various experimental techniques, including Job’s plot, Benesi-Hildebrand investigations, 1H NMR, and HRMS analysis. Test strips coated with TZPYZ showed selective detection of Ag+ ions, indicating its potential for on-site applications. Furthermore, DFT computations provided insights into the structural and electronic properties of TZPYZ and its complex with Ag+ ions, further elucidating the binding mechanism and stability of the complex. In addition, TZPYZ demonstrated compatibility with biological systems, as fluorescence imaging tests on MCF-7 breast cancer cells confirmed both its non-cytotoxic nature and its proficiency in detecting intracellular silver ions. Based on these findings, TZPYZ is highlighted as a highly sensitive and selective chemosensor for Ag+ ions, with promising applications in environmental analysis and bioimaging.

8-(2-Methoxyphenyl)-6-methyl-2-(1-methyl-1H-benzo[d]imidazol-2-yl)quinoline

For very first time, we report the synthesis of 8-(2-methoxyphenyl)-6-methyl-2-(1-methyl-1H-benzo[d]imidazol-2-yl)quinoline 1. This was achieved in several steps, including usage of the Suzuki reaction for functionalization of 2-(1H-benzo[d]imidazol-2-yl)quinoline moiety. The new compound exhibits blue fluorescence. Its structure was confirmed with 1D and 2D NMR spectroscopy, IR spectroscopy, high-resolution mass spectrometry and X-ray analysis.

Detecting M-Protein via Mass Spectrometry and Affinity Beads: Enrichment With Mixed Kappa-Lambda Beads Enables Prompt Application in Clinical Laboratories.

Detecting monoclonal protein (M-protein), a hallmark of plasma cell disorders, traditionally relies on methods such as protein electrophoresis, immune-electrophoresis, and immunofixation electrophoresis (IFE). Mass spectrometry (MS)-based methods, such as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and electrospray ionization-quadrupole time-of-flight (ESI-qTOF) MS, have emerged as sensitive methods. We explored the M-protein-detection efficacies of different MS techniques. To isolate immunoglobulin and light chain proteins, six types of beads (IgG, IgA, IgM, kappa, lambda, and mixed kappa and lambda) were used to prepare samples along with CaptureSelect nanobody affinity beads (NBs). After purification, both MALDI-TOF MS and liquid chromatography coupled with Synapt G2 ESI-qTOF high-resolution MS analysis were performed. We purified 25 normal and 25 abnormal IFE samples using NBs and MALDI-TOF MS (NB-MALDI-TOF). Abnormal samples showed monoclonal peaks, whereas normal samples showed polyclonal peaks. The IgG and mixed kappa and lambda beads showed monoclonal peaks following the use of daratumumab (an IgG/kappa type of monoclonal antibody) with both MALDI-TOF and ESI-qTOF MS analysis. The limits of detection for MALDI-TOF MS and ESI-qTOF MS were established as 0.1 g/dL and 0.025 g/dL, respectively. NB-MALDI-TOF and IFE exhibited comparable sensitivity and specificity (92% and 92%, respectively). NBs for M-protein detection, particularly with mixed kappa-lambda beads, identified monoclonal peaks with both MALDI-TOF and ESI-qTOF analyses. Qualitative analysis using MALDI-TOF yielded results comparable with that of IFE. NB-MALDI-TOF might be used as an alternative method to replace conventional tests (such as IFE) to detect M-protein with high sensitivity.