Search Results (34)

Tetraphenylethylene (TPE)–thiophene compounds are promising candidates for stimuli-responsive luminescent materials, yet systematic investigations into the influence of substitution patterns on their photophysical properties remain limited. Herein, four regioisomeric TPE–thiophene derivatives have been synthesized by systematically varying the number and positions of TPE substituents on the thiophene core. A comprehensive spectroscopic characterization reveals that substitution patterns critically modulate the photoluminescence quantum yields (PLQYs). The ortho-monosubstituted isomer exhibits the highest PLQY (52.86% in solid state) compared with the meta-monosubstituted isomer (13.87% in solid state). Interestingly, thiophenes with two or three TPEs substituted at positions 2,5 or 2,3,5 have lower PLQYs, which is rare due to the common understanding that increasing the number of AIE parts should increase the PLQY. Further single-crystal structure analyses show that the key factor impacting the PLQY is the dihedral angles of the TPE subunit, which determines the degree of intramolecular twisting. This work establishes regiochemistry as a powerful design lever for tuning TPE–thiophene photophysics, offering underlying principles for the design of TPE-based thiophene molecules with high photoluminescent performance in the future. Full article

A pyridine-fused triazapentalene shows weak fluorescence in solution and is readily accessible via nitrene-mediated cyclization. In this study, a modified Cadogan reaction was used to synthesize HetATAP 1. Palladium-catalyzed reactions have been used as post-functionalization methods. Interestingly, modified Suzuki cross-couplings with various boronic acids resulted in poor to moderate yields of HetATAPs 2–5 which were arylated at the azole moiety. Direct CH arylation of HetATAP 1 gave the products with the same regiochemistry in satisfactory yields. The structures of HetATAPs 2–5 were confirmed using NMR analysis. In addition, the photophysical properties of HetATAPs 1–5 were studied under various conditions. Particularly, the emission of HetATAPs 2–5 is enhanced in the solid and aggregate state. Full article

In this paper, we report a highly regioselective 1,3-dipolar cycloaddition (1,3-DC) reaction of nitrilimines with thioaurone derivatives that afforded the hitherto unreported spiropyrazolines. Spectroscopic and spectrometric data were utilized to confirm the structure of all products and elucidate the reaction’s regiochemistry. A mechanistic study was performed within the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311G(d,p) computational level to explain the regioselectivity observed. The electron localization function (ELF) topological analysis confirms the carbenoid-type (cb-type) mechanism of the cycloaddition reactions between nitrilimines and thioaurones. The intermolecular interactions between reagents in this reaction account for the regioselectivity observed experimentally. Full article

Peripheral blood mononuclear cells (PBMCs), including lymphocytes, are important components of the human immune system. These cells contain a diverse array of lipids, primarily glycerophospholipids (GPs) and sphingolipids (SPs), which play essential roles in cellular structure, signaling, and programmed cell death. This study presents a detailed analysis of GP and SP profiles in human PBMC samples using tandem mass spectrometry (MS/MS). Hydrophilic interaction liquid chromatography (HILIC) and electrospray ionization (ESI) coupled with linear ion-trap MS/MS were employed to investigate the diagnostic fragmentation patterns that aided in determining regiochemistry in complex lipid extracts. Specifically, the study explored the fragmentation patterns of various lipid species, including phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), their plasmalogen and lyso forms, phosphatidylserines (PSs), phosphatidylinositols (PIs), phosphatidylglycerols (PGs), sphingomyelins (SMs), and dihexosylceramides (Hex₂Cer). Our comprehensive analysis led to the characterization of over 200 distinct lipid species, significantly expanding our understanding of PBMC lipidome complexity. A freely available spreadsheet tool for simulating MS/MS spectra of GPs is provided, enhancing the accessibility and reproducibility of this research. This study advances our knowledge of PBMC lipidomes and establishes a robust analytical framework for future investigations in lipidomics. Full article

The Macrophage-Inducible C-type Lectin receptor (Mincle) plays a critical role in innate immune recognition and pathology, and therefore represents a promising target for vaccine adjuvants. Innovative trehalose-based Mincle agonists with improved pharmacology and potency may prove useful in the development of Th17-mediated adaptive immune responses. Herein, we report on in vitro and in silico investigations of specific Mincle ligand–receptor interactions required for the effective receptor engagement and activation of Th17-polarizing cytokines. Specifically, we employed a library of trehalose benzoate scaffolds, varying the degree of aryl lipidation and regiochemistry that produce inflammatory cytokines in a Mincle-dependent fashion. In vitro interleukin-6 (IL-6) cytokine production by human peripheral blood mononuclear cells (hPBMCs) indicated that the lipid regiochemistry is key to potency and maximum cytokine output, with the tri-substituted compounds inducing higher levels of IL-6 in hPBMCs than the di-substituted derivatives. Additionally, IL-6 production trended higher after stimulation with compounds that contained lipids ranging from five to eight carbons long, compared to shorter (below five) or longer (above eight) carbon chains, across all the substitution patterns. An analysis of the additional cytokines produced by hPBMCs revealed that compound 4d, tri-substituted and five carbons long, induced significantly greater levels of interleukin-1β (IL-1β), tumor necrosis factor- α (TNF-α), interleukin-23 (IL-23), and interferon- γ (IFN-γ) than the other compounds tested in this study. An in silico assessment of 4d highlighted the capability of this analogue to bind to the human Mincle carbohydrate recognition domain (CRD) efficiently. Together, these data highlight important structure–activity findings regarding Mincle-specific cytokine induction, generating a lead adjuvant candidate for future formulations and immunological evaluations. Full article

Methyl 4-(1,3a,6a-triazapentalen-3-yl)benzoate (TAP1) shows interesting properties as a small molecule fluorophore. In the search for post-functionalization methods, palladium-catalyzed arylation reactions were demonstrated. Direct CH arylation reactions of TAP1 with various aryl halides resulted in 3,6-diaryltriazapentalenes TAP4, although mostly in poor yields. Bromination of TAP1 followed by Suzuki coupling, on the other hand, requires a more delicate procedure, but gave arylated products with the same regiochemistry (TAP4) in moderate to good yields. The structure of 6-phenyltriazapentalene TAP4a was confirmed by crystallographic analysis. In addition, the effect of the C6 arylation on the fluorescent properties of 3-aryl-1,3a,6a-triazapentalenes was studied in dichloromethane at room temperature and in 2-methyltetrahydrofuran at 77 K, while the photophysical properties of two saponified derivatives were measured in acetonitrile. Full article

In this work, Microwave-Assisted Extraction (MAE) was proposed as an alternative and environmentally friendly technique in lipidomics to study the lipid fingerprint of soft cheeses, such as mozzarella. For method development, a first step concerning an evaluation of extraction solvents was carried out via testing three different mixtures, including methanol/ethyl acetate, isopropanol/ethyl acetate, and ethanol/ethyl acetate, at a 1:2 v/v ratio. The latter was chosen as a solvent mixture for subsequent method optimization. MAE conditions, in terms of solvent volume, time, and temperature, were explored to define their effects on extraction capability through a full factorial experimental design. The best compromise to extract more lipids at the same time was obtained with 24 mL g⁻¹ for solvent-to-solid ratio, 65 °C for temperature, and 18 min for time. Lipid analyses were conducted by UHPLC-Q-Orbitrap-MS associated with multivariate statistics. The developed lipidomic workflow allowed for the extraction of over 400 lipids grouped into 18 different subclasses. The results confirmed that MAE is a suitable technique for lipid extraction in the omics approach with high efficiency, even using low-cost and less toxic solvents. Moreover, a comprehensive structure characterization of extracted lipids, in terms of fatty acid composition and regiochemistry, was carried out. Full article

A convenient approach to substituted pyrazoles and pyridazinones based on 1,2,4-triketones is presented. Chemo- and regiocontrol in condensations of t-Bu, Ph-, 2-thienyl-, and CO₂Et-substituted 1,2,4-triketone analogs with hydrazines are described. The direction of preferential nucleophilic attack was shown to be switched depending on the substituent nature in triketone as well as the reaction conditions. The acid and temperature effects on the selectivity of condensations were revealed. Regiochemistry of heterocyclic core formation was confirmed by NMR and XRD studies. The facile construction of heterocyclic motifs bearing acetyl and (or) carbethoxy groups suggests them as promising mono- or bifunctional building blocks for subsequent transformations. Full article

New 2-thioxopyrimidin-4-ones capable of participating in regioselective reactions with functionally diverse hydrazonoyl chlorides towards angular regioisomers, rather than linear ones, were designed and synthesized to form stereoisomeric cis- and trans-hexahydro [1,2,4]triazolo[4,3-a]quinazolin-9-ones to be tested as antitumor candidates. The angular regiochemistry of the products was verified through crystallographic experiments and NMR studies. In addition, the regioselectivity of the reaction was found to be independent of the stereochemistry of the used 2-thioxopyrimidin-4-one. Only compound 4c demonstrated satisfactory growth inhibition against all the cancer cells used among all the produced drugs. Full article

In this work, we report an analytical procedure to investigate the lipid compositions of sheep and goat milk. This approach is based on an ion mobility–high-resolution mass spectrometric method to facilitate the identification of complex lipid species and their regiochemistry. A common triacylglycerol profile was observed for sheep and goat milk samples, while a higher abundance of medium-chain fatty acids was observed at the sn-2 position for sheep milk. Furthermore, differences can be also observed in the levels of saturated and unsaturated fatty acids at the sn-2 position. In terms of lipid classes, goat milk showed higher levels of triacylglycerols, phosphatidylinositols and ether-linked phosphatidylethanolamines, while sheep milk showed higher levels of free fatty acids, lysophosphatidylethanolamines, lysophosphocholines and non-hydroxy fatty acid-dihydrosphingosine ceramides when compared with goat milk. Full article

The search for new synthetic melanin-related pigments that maintain the antioxidant and photoprotective properties of naturally occurring dark eumelanins, while overcoming their unfavorable solubility, and molecular heterogeneity is presently a very active issue for dermo-cosmetic purposes. In this work, we explored the potential of a melanin obtained from the carboxybutanamide of a major eumelanin biosynthetic precursor, 5,6-dihydroxyindole-2-carboxylic acid (DHICA), by aerobic oxidation under slightly alkaline conditions. Analysis of the pigment by EPR, ATR-FTIR and MALDI MS indicated a substantial structural similarity to DHICA melanin, while investigation of the early intermediates confirmed unchanged regiochemistry of the oxidative coupling. The pigment exhibited a UVA–visible absorption even more intense than that of DHICA melanin, and a noticeable solubility in polar solvents of dermo-cosmetic relevance. The hydrogen- and/or electron-donor ability, and the iron (III) reducing power as determined by conventional assays provided evidence for marked antioxidant properties not merely ascribable to the more favorable solubility profile, while the inhibitory action of the radical- or photosensitized solar light-induced lipid peroxidation was more marked compared to that of DHICA melanin. Overall, these results hint at this melanin, which remarkable properties are, in part, due to the electronic effects of the carboxyamide functionality as a promising functional ingredient for dermo-cosmetic formulations. Full article

Alkynes may be regioselectively alkylated to alkenes by organocopper reagents in a reaction known as “carbocupration”, where an alkylCu(I) binds to the alkyne and transfers its organic moiety to one of the alkyne carbon atoms. Alkynes hetero-substituted with third-row elements yield alkenes with a regiochemistry opposite to that obtained when using alkynes hetero-substituted with second-row elements. Early computational investigations of his reaction mechanism have identified the importance of the organocopper counter-cation (Li⁺) to the achievement of good reaction rates, but in the subsequent two decades no further progress has been reported regarding the exploration of the mechanism or the explanation of the experimental regiochemistry. In this work, density-functional theory is used to investigate the mechanism used and to describe a model that correctly explains both the reaction rates at sub-zero temperatures and the regiochemistry profiles obtained with each of the heteroalkynes. The rate-determining step is shown to vary depending on the heterosubstituent, and the alkyl transfer is consistently shown to occur, somewhat counter-intuitively, to the alkyne carbon that is complexed by Cu rather than to the “free” alkyne carbon atom, which instead interacts with the counter-cation that stabilizes the developing electronic charge distribution. Full article

Quinazolinone and isoxazoline systems have attracted much attention due to their interesting pharmacological properties. The association of these two pharmacophores in a single hybrid structure can boost the biological activity or bring a new one. Inspired by this new paradigm, in the present work we report the synthesis and spectroscopic characterization of new quinazolinone–isoxazoline hybrids. The target compounds were obtained via 1,3-dipolar cycloaddition reactions of arylnitriloxides and N-allylquinazolinone. The synthesized compounds were characterized using spectroscopic techniques such as IR, 1D NMR (1H and 13C), 2D NMR (COSY and HSQC), and high-resolution mass spectrometry (HRMS). The spectral data show that this reaction leads only to the 3,5-disubstituted isoxazoline regioisomer, and that the observed regiochemistry is not affected by the nature of the substituents in the phenyl ring of the dipole. In addition, a theoretical study was performed using density functional theory (DFT) to support the experimental results in regard to the regiochemistry of the studied reactions. The computational mechanistic study was in good agreement with the experimental data. Full article

Vindoline and catharanthine are the major alkaloids of Catharanthus roseus and are extracted in large quantities to prepare the pharmaceutically important Vinca type alkaloids vincaleukoblastine, vincristine and navelbine. The higher yield of vindoline relative to catharanthine makes it an attractive substrate for developing new chemistry and adding value to the plant. In this context, we have reacted vindoline with a selection of electrophiles among which benzoquinone. Conditions were developed to optimize the synthesis of a mono-adduct, of five bis-adducts, and of tri-adducts and tetra-adducts, several of these adducts being mixtures of conformational isomers. Copper(II) was added to the reactions to promote reoxidation of the intermediate hydroquinones and simplify the reaction products. The structures were solved by spectroscopic means and by symmetry considerations. Among the bis-isomers, the 2,3-diadduct consists of three unseparable species, two major ones with an axis of symmetry, thus giving a single set of signals and existing as two different species with indistinguishable NMR spectra. The third and minor isomer has no symmetry and therefore exhibits nonequivalence in the signals of the two vindoline moieties. These isomers are designated as syn (minor) and anti (major) and there exists a high energy barrier between them making their interconversion difficult. DFT calculations on simplified model compounds demonstrate that the syn-anti interconversion is not possible at room temperature on the NMR chemical shift time scale. These molecules are not rigid and calculations showed a back-and-forth conrotatory motion of the two vindolines. This “windshield wiper” effect is responsible for the observation of exchange correlations in the NOESY spectra. The same phenomenon is observed with the higher molecular weight adducts, which are also mixtures of rotational isomers. The same lack of rotations between syn and anti isomers is responsible for the formation of four tri-adducts and of seven tetra-adducts. On a biological standpoint, the mono adduct displayed anti-inflammatory properties at the 5 μM level while the di-adducts and tri-adducts showed moderate cytotoxicity against Au565, and HeLa cancer cell lines. Full article

The annulation reactions of 8-quinolinesulfenyl halides with natural products and alkenes affording new water-soluble [1,4]thiazino[2,3,4-ij]quinolin-4-ium derivatives in high or quantitative yields are developed in this study. The reactions with styrene derivatives and terminal alkenes including allyl arenes proceed in a regioselective manner but with the opposite regiochemistry. The reactions with terminal alkenes including allyl arenes occur in an anti-Markovnikov fashion (regarding addition of the 8-quinolinesulfenyl electrophile to the double bond) to give 2-organyl-2H,3H-[1,4]thiazino[2,3,4-ij]quinolin-4-ium halides, while the reactions with styrene derivatives proceed in a Markovnikov fashion, leading to 3-substituted condensed heterocyclic compounds. In general, styrene derivatives demonstrate higher reactivity in the annulation reactions compared to the terminal alkenes. Antimicrobial activity of novel water-soluble compounds against Enterococcus durans, Bacillus subtilis and Escherichia coli are evaluated. The compounds with high antimicrobial activity are found. The annulation products of the reactions of 8-quinolinesulfenyl halides with 1H-indene, eugenol, methyl eugenol and 1-heptene, are superior in their activity compared to the antibiotic gentamicin. Full article