HRMS Methods Research Articles

P-Terphenyl and Orsellinic Acid Derivatives from the European Polyporales Terana coerulea and Sparassis brevipes.

Investigation of the secondary metabolites of the solid-state rice cultures from the European basidiomycetes Terana coerulea and Sparassis brevipes afforded three previously undescribed secondary metabolites identified as two p-terphenyl derivatives (1 and 2) and one orsellinic acid congener (3) in addition to another known, isoeverninic acid (4). Chemical structures of the isolated compounds were elucidated through comprehensive 1D and 2D NMR spectroscopic analyses, coupled with HR-MS and other spectral methods. The isolated compounds were assessed for their cytotoxic and antimicrobial activities. Compound 1 revealed weak antimicrobial properties, whereas the inseparable mixture of 3 and 4 featured moderate cytotoxic and antimicrobial effects.

Synthesis of new piperazine‐oxadiazole derivatives and investigation of their anticancer activities

Since cancer is one of the leading causes of human death, recent research has largely focused on developing multi-target drug designs. In this study, we designed and synthesized a series of piperazine-oxadiazole derivatives as aromatase inhibitors for the treatment of cancer. Their structures were confirmed by 1H NMR, 13C NMR, HRMS and FTIR spectroscopic methods. Cytotoxicity (MTT) was performed to determine the anticancer activity of the compounds as aromatase inhibitors against breast (MCF7), fibroblast (NIH3T3) and lung (A549) cell lines. Letrazol was used as the reference agent, compound 4b exhibited a significant effect among other derivatives with a value of IC50=2.103±0.088 μM against the MCF7 cell line. Docking study showed that 4b was one of the compounds with the best pose on the aromatase. The docking study showed that 4e was one of the compounds that gave the best pose on EGFR and topoisomerase. When the aromatase, EGFR and topoisomerase docking results were compared, it was concluded that our synthesized compounds may be more effective on the Aromatase macromolecule. From the obtained evaluations of the designed batches, compound 4b appeared to be a promising agent as an aromatase inhibitor for further research and evaluation studies in the future.

Red‐Emitting Pyrazole Azo Hydrazone and Its Metal Complexes for Photophysical Probing, Latent Fingerprints, Anti‐counterfeiting, and Biological Studies

ABSTRACTThe present paper discusses the synthesis of unprecedented red‐emitting mono‐azo compound pyrazole azo fluorescent tag (PAFT) by a diazotization method, followed by an electrophilic substitution reaction. Further, the metal complex of PAFT is also prepared by refluxing the ethanolic solution of the ligand with the corresponding metal (RuCl3 and C4H6CuO4.H2O) salts under suitable experimental conditions. The synthesized fluorophore PAFT displays intense fluorescence in the aggregate state and has excellent qualities, including high purity, low cost, eco‐friendliness, and good photostability. These unique characteristics of PAFT led to the development of new fluorescence‐based technology for the in situ viewing of latent fingerprints. Various spectroscopic and analytical techniques are used to confirm the structural characteristics of the synthesized compounds, including UV–Vis, FT‐IR, (1H) NMR, HRMS, TGA, VSM, ESR, and powder XRD methods. The potency of the antibacterial activity of the compounds was evaluated. The results revealed that compound PAFT and [Ru(PAFT)Cl3] H2O showed excellent sensitivity at 0.8 μL/mL against the Gram‐positive bacteria Staphylococcus aureus.

Synthesis and characterization of new hexahydroquinoline derivatives and evaluation of their cytotoxicity, intracellular ROS production, and inhibitory effects on inflammatory mediators.

Inflammation is a response to injury and infection in an organism. It can be categorized as acute or chronic. Chronic inflammation is the underlying cause of many diseases such as Alzheimer disease, diabetes, rheumatoid arthritis, atherosclerosis, and cardiovascular diseases. Recent studies have proven the antiinflammatory properties of 1,4-dihydropyridines (1,4-DHPs) and their derivatives, which have many biological activities including the blocking of calcium channels. In this study, 15 compounds that are condensed derivatives of 1,4-DHPs, with the general structure of hexahydroquinoline-3-carboxylate, were synthesized. These compounds, expected to show inhibitory activity against inflammatory mediators, were obtained by the reaction of 4-(difluoromethoxy)benzaldehyde, substituted/nonsubstituted 1,3-cyclohexanedione derivatives, and appropriate alkyl acetoacetate compounds in the presence of ammonium acetate as a nitrogen source according to the Hantzsch synthesis method. The structures of the synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, and HRMS methods. The cytotoxic properties of the compounds were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method in the 3T3 cell line. Among the 15 compounds, the three compounds with the lowest levels of cytotoxic effects were selected for further experiments. Inflammation was induced by lipoxygenase and the effects of the selected compounds on the levels of reactive oxygen species, cytokines, and complement C3 and C9 regulatory proteins were investigated. It was found that the three selected compounds decreased the levels of transforming growth factor-beta 1 (TGF-β1). Among these compounds, compound 3e provided the most significant decrease in this cytokine. Moreover, 3e increased both C3 and C9 levels. Molecular modeling studies also showed that 3e had better affinity for TGF-β1. When the binding modes of these compounds in the active site of TGF-β1 were analyzed, it was found that compound 3e had hydrophobic interactions with amino acids Leu142, Tyr84, and Ile13; halogen bond interactions with Asp92; and hydrogen bond interactions with Ser89, Gly88, and Gly14 in the active binding site. Further in vitro and in vivo studies are needed to show the possible mechanism of action of compound 3e.

Synthesis of anthraquinone-based azo-metal(II) complexes as potent anti-oxidizing agents

The 3-diethylaminophenol (3-DEAP) incorporated anthraquinone mono-azo dye derivative [(E)-1-((4-(diethylamino)-2-hydroxyphenyl)diazenyl)anthracene-9,10-dione] DAAD was synthesized through an electrophilic substitution reaction. The interaction between the -OH functional group and the nitrogen atom of the azo moiety may result in intramolecular proton transfer in the DAAD. DAAD was treated with metal ions such as Co(II), Ni(II), and Cu(II) acetates in a ratio of 2 : 1 revealing an octahedral structure. Many analytical and spectroscopic methods, including UV-vis, FT-IR, (1H and 13C) NMR, HRMS, TGA, VSM, ESR, and powder XRD methods, were used to verify the structural characteristics of the compounds. Additionally, the potency of the in-vitro antioxidant properties of the ligand and its Cu(II), Ni(II), and Co(II) complexes were evaluated; the results revealed that the Co(II) complex showed a maximum percent inhibition of 85 μM against the standard ascorbic acid.

Validation of two LC[sbnd]HRMS methods for large-scale untargeted metabolomics of serum samples: Strategy to establish method fitness-for-purpose

Untargeted metabolomics by LCHRMS is a powerful tool to enhance our knowledge of pathophysiological processes. Whereas validation of a bioanalytical method is customary in most analytical chemistry fields, it is rarely performed for untargeted metabolomics. This study aimed to establish and validate an analytical platform for a long-term, clinical metabolomics study. Sample preparation was performed with an automated liquid handler and four analytical methods were developed and evaluated. The validation study spanned three batches with twelve runs using individual serum samples and various quality control samples. Data was acquired with untargeted acquisition and only metabolites identified at level 1 were evaluated. Validation parameters were set to evaluate key performance metrics relevant for the intended application: reproducibility, repeatability, stability, and identification selectivity, emphasizing dataset intrinsic variance. Concordance of semi-quantitative results between methods was evaluated to identify potential bias. Spearman rank correlation coefficients (rs) were calculated from individual serum samples. Of the four methods tested, two were selected for validation. A total of 47 and 55 metabolites (RPLC-ESI+- and HILIC-ESI−-HRMS, respectively) met specified validation criteria. Quality assurance involved system suitability testing, sample release, run release, and batch release. The median repeatability and within-run reproducibility as coefficient of variation% for metabolites that passed validation on RPLC-ESI+- and HILIC-ESI−-HRMS were 4.5 and 4.6, and 1.5 and 3.8, respectively. Metabolites that passed validation on RPLC-ESI+-HRMS had a median D-ratio of 1.91, and 89 % showed good signal intensity after ten-fold dilution. The corresponding numbers for metabolites with the HILIC-ESI−-HRMS method was 1.45 and 45 %, respectively. The rs median ({range}) for metabolites that passed validation on RPLC-ESI+- was 0.93 (N = 9 {0.69–0.98}) and on HILIC-ESI−-HRMS was 0.93 (N = 22 {0.55–1.00}). The validated methods proved fit-for-purpose and the laboratory thus demonstrated its capability to produce reliable results for a large-scale, untargeted metabolomics study. This validation not only bolsters the reliability of the assays but also significantly enhances the impact and credibility of the hypotheses generated from the studies. Therefore, this validation study serves as a benchmark in the documentation of untargeted metabolomics, potentially guiding future endeavors in the field.

Electron-donating and -withdrawing groups discriminate the fluorometric sensing of phosgene.

Phosgene, diphosgene, and chlorine are called choking agents due to their acute toxicity to the respiratory system by directly attacking through inhalation and causing acute hypoxia, asphyxia and death. For these reasons, small-molecule fluorescent probes have been developed for their detection to ensure public safety. In this regard, two thiophene-based chemodosimetric fluorescent probes TCAO ((Z)-3-(4-(dimethylamino)phenyl)thiophene-2-carbaldehyde oxime) and HMBT ((Z)-4-(2-((hydroxyimino)methyl)thiophen-3-yl)benzonitrile) were designed, synthesized and characterized using 1H-NMR, 13C NMR, FT-IR spectroscopy and HRMS methods. Probe TCAO exhibited higher selectivity and sensitivity for detecting phosgene than probe HMBT. The electron-donating group (EDG) and electron-withdrawing group (EWG) play a crucial role in detecting phosgene. TCAO, bearing EDG, exhibited a fluorescence 'turn-on' response by the NGP-assisted conversion of aldoxime to the cyano group in the presence of phosgene; whereas HMBT, bearing EWG, did not show any fluorometric response. Therefore, further studies were conducted on TCAO, and the quantum yield changed from Φ = 0.043 to Φ = 0.155 in the presence of phosgene. The limit of detection for TCAO was estimated to be as low as 51 nm. In addition, onsite monitoring for visual detection was performed using the easy-to-handle paper-strip method.

Development and application of UPLC-Q-Orbitrap HRMS methods for the determination of eight metabolites of p-chloronitrobenzene in human urine

Accurate, reliable, and sensitive methods for the determination of eight metabolites of p-chloronitrobenzene (p-CNB) were developed based on ultra-performance liquid chromatography − quadrupole − orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). The free and conjugated forms of metabolites were determined before and after urine samples were hydrolyzed with acid. Subsequently, three solid phase extraction steps were used for concentration and purification. The calibration curves of the eight metabolites exhibited good linearity with an R2 of >0.999, and the precision was good as well, with the coefficient of variations of intra-day and inter-day being lower than 7.0 % and 8.5 %, respectively. Analytical accuracy for all metabolites varied within ranges of 76.0–102.9 %, and the limit of detection and limit of quantification of all the metabolites varied within ranges of 0.2–7.7 μg/L and 0.6–25.6 μg/L in human urine, respectively. In addition, the application potential of the proposed methods were evaluated by applying them to the determination of metabolites in the urine of workers exposed to p-CNB, and these results showed that these methods were accurate, reliable, and sensitive, which makes them an excellent choice for detecting the metabolites of p-CNB in the urine of exposed workers.

Development of methyl 5-((cinnamoyloxy)methyl)picolinate, exploring its bio-target potential aiming at CVD mediated by multiple proteins through surface and physiochemical analysis

The emphasis on sustainable sources of drug development seems imminent with phytochemicals emerging as promising candidates due to their minimal probability of adverse effects. This study focuses on utilizing simple cinnamic acid and nicotinic acid derivatives as starting materials, employing an efficient synthetic protocol to obtain methyl 5-((cinnamoyloxy)methyl)picolinate targeting CVD mediated by multiple enzymes such as MAPK, PCSK9, MPO, SIRT1 and TNF-α. Comprehensive characterization of synthesized molecule is achieved through 1H, 13C, FT-IR, and HRMS methods. Additionally, the crystal structure was established via SC-XRD. Comparative analysis with the DFT-optimized structure identifies key nucleophilic and electrophilic regions for determining interactions with bio-targets. Notably, Compound 5 adheres to all drug-likeness criteria, further validated through screening similar pharmacophoric drugs from databases. Targeting bio-relevant areas with a specific focus on CVD drug development. The molecular docking studies elucidate ligand–protein interactions for better binding connectivity. This investigation further underscores the importance of sustainable practices, simple chemical synthesis, and computational approaches, contributing to the pursuit of eco-friendly drug development with enhanced safety profiles (MTT assay).

Design, synthesis, and biological evaluation of chalcone acetamide derivatives against triple negative breast cancer

Chalcones are chemical scaffolds found in natural products, particularly in plants, and are considered for structural diversity in medicinal chemistry for drug development. Herein, we designed and synthesised novel acetamide derivatives of chalcone, characterizing them using 1H NMR, 13C NMR, HRMS, and IR spectroscopic methods. These derivatives were then screened against human cancer cells for cytotoxicity using the SRB assay. Among the tested derivatives, 7g, with a pyrrolidine group, exhibited better cell growth inhibition activity against triple-negative breast cancer (TNBC) cells. Further assays, including SRB, colony formation, and fluorescent dye-based microscopic analysis, confirmed that 7g significantly inhibited MDA-MB-231 cell proliferation. Furthermore, 7g promoted apoptosis by upregulating cellular reactive oxygen species (ROS) levels and disrupting mitochondrial membrane potential (MMP). Elevated expression of pro-apoptotic proteins (Bax and caspase-3) and a higher Bax/Bcl-2 ratio with downregulation of anti-apoptotic (Bcl-2) protein levels were observed in TNBC cells. The above results suggest that 7g can promote cellular death through apoptotic mechanisms in TNBC cells.

Development of the Squaramide Scaffold for High Potential and Multielectron Catholytes for Use in Redox Flow Batteries.

Nonaqueous organic redox flow batteries (N-ORFBs) are a promising technology for grid-scale storage of energy generated from intermittent renewable sources. Their primary benefit over traditional aqueous RFBs is the wide electrochemical stability window of organic solvents, but the design of catholyte materials, which can exploit the upper range of this window, has proven challenging. We report herein a new class of N-ORFB catholytes in the form of squaric acid quinoxaline (SQX) and squaric acid amide (SQA) materials. Mechanistic investigation of decomposition in battery-relevant conditions via NMR, HRMS, and electrochemical methods enabled a rational design approach to optimizing these scaffolds. Three lead compounds were developed: a highly stable one-electron SQX material with an oxidation potential of 0.51 V vs Fc/Fc+ that maintained 99% of peak capacity after 102 cycles (51 h) when incorporated into a 1.58 V flow battery; a high-potential one-electron SQA material with an oxidation potential of 0.81 V vs Fc/Fc+ that demonstrated negligible loss of redox active material as measured by pre- and postcycling CV peak currents when incorporated in a 1.63 V flow battery for 110 cycles over 29 h; and a proof-of-concept two-electron SQA catholyte material with oxidation potentials of 0.48 and 0.85 V vs Fc/Fc+ that demonstrated a capacity fade of just 0.56% per hour during static H-cell cycling. These findings expand the previously reported space of high-potential catholyte materials and showcase the power of mechanistically informed synthetic design for N-ORFB materials development.

The Effect of Fermentation on the Chemical Constituents of Gastrodia Tuber Hallimasch Powder (GTHP) Estimated by UHPLC-Q-Orbitrap HRMS and HPLC.

To compare the effect of fermentation on the chemical constituents of Gastrodia Tuder Halimasch Powder (GTHP), to establish its fingerprinting and multicomponent content determination, and to provide a basis for the processing, handling, and clinical application of this herb. Ultra-high-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to conduct a preliminary analysis of the chemical constituents in GTHP before and after fermentation. High-performance liquid chromatography (HPLC) was used to determine some major differential components of GTHP and establish fingerprints. Cluster analysis (CA), and principal component analysis (PCA) were employed for comprehensive evaluation. Seventy-nine compounds were identified, including flavonoids, organic acids, nucleosides, terpenoids, and others. The CA and PCA results showed that ten samples were divided into three groups. Through standard control and HPLC analysis, 10 compounds were identified from 22 peaks, namely uracil, guanosine, adenosine, 5-hydroxymethylfurfural (5-HMF), daidzin, genistin, glycitein, daidzein, genistein, and ergosterol. After fermentation, GTHP exhibited significantly higher contents of uracil, guanosine, adenosine, 5-hydroxymethylfurfural, and ergosterol and significantly lower genistein and daidzein contents. The UHPLC-Q-Orbitrap HRMS and HPLC methods can effectively identify a variety of chemical components before and after the fermentation of GTHP. This study provides a valuable reference for further research on the rational clinical application and quality control improvement of GTHP.

Synthesis of photo- and ionochromic N-acylated 2-(aminomethylene)benzo[b]thiophene-3(2Н)-ones with a terminal phenanthroline group.

A series of novel photo- and ionochromic N-acylated 2-(aminomethylene)benzo[b]thiophene-3(2Н)-ones with a terminal phenanthroline receptor substituent was synthesized. Upon irradiation in acetonitrile or DMSO with light of 436 nm, they underwent Z-E isomerization of the C=C bond, followed by very fast N→O migration of the acyl group and the formation of nonemissive O-acylated isomers. These isomers were isolated preparatively and fully characterized by IR, 1H, and 13C NMR spectroscopy as well as HRMS and XRD methods. The reverse thermal reaction was catalyzed by protonic acids. N-Acylated compounds exclusively with Fe2+ formed nonfluorescent complexes with a contrast naked-eye effect: a color change of the solutions from yellow to dark orange. Subsequent selective interaction with AcO- led to the restoration of the initial absorption and emission properties. Thus, the obtained compounds represent dual-mode "on-off-on" switches of optical and fluorescent properties under sequential exposure to light and H+ or sequential addition of Fe2+ and AcO- ions.

A thiophene-linked terpyridine based phenanthridine chemoreceptor for Cd2+ and Cr3+ selective ratiometric fluorescence detection in environmental water and rice samples

BackgroundThe studied materials, Cadmium (Cd2+) and Chromium (Cr3+) are highly toxic, and it focuses on investigating various environmental sources, such as industrial processes and waste water. When quantities of Cr3+ and Cd2+ exceed the allowable limit, biological toxicity and hazardous environmental pollution are unavoidable. In order to address this problem, we introduce 5-(5-(4-([2,2':6′,2″-terpyridin]-4′-yl) phenyl) thiophen-2-yl)-7,8,13,14-tetrahydrodibenzo [a,i] phenanthridine (TPTP), a dual-emission response chemosensor that employs a colorimetric and fluorescence turn-on approach for the rapid, sensitive, and discriminate detection of Cr3+ and Cd2+ ions. ResultsWe created a newly designed luminous TPTP sensor based on intramolecular charge transfer (ICT). TPTP sensor probe specifically determined Cr3+ and Cd2+ ions with an immediate colour shift from cyan to green and orange in CH3CN: H2O (6:4) solvent solution. The permissible level set by the Environmental Protection Agency (EPA) of the United States for the presence of Cr3+ and Cd2+ ions in drinking water was higher than the detection level of 3.5 and 9.7 nM, by this sensor respectively. NMR titrations, HRMS, and theoretical calculation methods were employed to examine the accurate sensing processes of TPTP and complexes. SignificanceThis is an effective method of detecting Cr3+ and Cd2+ ions in an environmental system using a ratiometric methodology. In addition, TPTP was used to determine the concentration of Cr3+ and Cd2+ ions in natural water and food samples. Fluorescent bio-imaging studies revealed that the present sensor TPTP could identify Cr3+ and Cd2+ ions inside living HeLa cells. A paper kit analysis has been done on TPTP, which has a time-to-result of less than 1 s and offers a cost-effective assay. As a result, the platform offers portability.

Design, synthesis and biological evaluation of new series of benzotriazole-pyrazole clubbed thiazole hybrids as bioactive heterocycles: Antibacterial, antifungal, antioxidant, cytotoxicity study

The need for novel heterocyclic compounds with robust biological action is a result of the emergence of numerous pandemics and microbial resistance. To search antibacterial and antifungal lead compounds, a series of novel (E)-2-(2-((5-(1H-benzo[d][1,2,3]triazol-1-yl)-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazinyl)-4-(aryl)thiazole derivatives were synthesized via three component reaction between 5-(1H-benzo[d][1,2,3]triazol-1-yl)-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, thiosemicabazide and various substituted phenacyl bromides. The newly synthesized benzotriazole-pyrazole clubbed thiazole hybrids were characterized by FT-IR, 1H NMR, 13C NMR and HRMS methods. The synthesized compounds were screened for antibacterial activity against E. coli, B. subtilis, B. megaterium, and S. aureus and antifungal activity against A. niger, A. oryzae, Rhizophus spp., and C. albicans. All thiazole derivatives exhibited potent antibacterial and antifungal action against all tested strains. Besides, % radical scavenging activity was also evaluated and results showed good antioxidant potential of the synthesized compounds. The cytotoxicity study revealed that synthesized compounds has no to less toxicity as compared to standard Triton X-100.

Trifluoromethyl-substituted 2,8-diaryl-imidazo[1,2-a][1,8]naphthyridines: Synthesis, remarkable optical emission, and redox and thermal properties

A novel series of thirteen examples of 2,8-diaryl-4-(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridines (6) was synthesized at 21–96% yields, in which 2,8-diaryl = C6H5, 4-BrC6H4, 4-OMeC6H4, 4-CF3C6H4, and 2-naphtyl by intermolecular and regioselective [3+2] cyclocondensation reaction of a series of selected 7-aryl-2-amino-5-(trifluoromethyl)-[1,8]naphthyridines (3) with 1-aryl-2-bromo-ethanones (5). Aromatic amines 3 and bromo ethanones 5 were obtained by previously reported methods, which reacted 2,6-diamino-pyridine (2) with 4-aryl-4-methoxy-1,1,1-trifluorobut-3-en-2-ones (1) to obtain 3 and some acetophenones 4 with elemental bromo to synthesize 5. All new compounds 6 were fully characterized by 1H-, 13C, 19F NMR and IR spectroscopy, SC-XRD, and HRMS methods. The optical and electrochemical properties of the derivatives were determined by UV–Vis, steady-state and time-resolved fluorescence emission (solution and solid state), TD-DFT calculations, and redox potential and discussed, indicating a dependence of the substitution position in the heterocyclic core. In addition, the TGA experiments showed that compounds 6 presented good thermal stability at the 150–300 °C range.

Synthesis and Biological Evaluation of Nitro-substituted chalcones as potent Antibacterial and Antifungal agents

In recent years, complications of micro-organisms, which becomes drug-resistant, have extended dreadful level across the globe. One of the significant challenges in drug discovery to overcome the increased development of drug resistance is developing novel chemical moieties that advantageously comprise chemical features different from existing chemical entities. This communication presents the synthesis, docking, and antibacterial and antifungal evaluation of nitro chalcones. New series of nitro substituted chalcone derivatives (1-12) were synthesized via Claisen-Schmidt condensation using substituted acetophenone and various substituted benzaldehydes in the presence of base and ethanol. Spectral analysis of the synthesized compounds was carried out using 1H-NMR, IR, 13C-NMR and HRMS methods. Synthesized derivatives were evaluated for antimicrobial potency via the microdilution method against two Gram-positive and two Gram-negative bacterial strains and two fungal strains. All compounds showed promising antimicrobial potency. However, compound 6 was the most potent derivative of the series against all the tested antibacterial strains. Compounds 10 and 12 were found to be the most potent analogues of the series against all the tested antifungal strains. All the synthesized derivatives had good antifungal potency in comparison to the antibacterial potency. Based on the preliminary study results, the study concluded that the synthesized chalcones derivatives promise antimicrobial activity that may be further investigated to achieve antimicrobial lead.

An AIE mechanism-based fluorescent probe for relay recognition of HSO3−/H2O2 and its application in food detection and bioimaging

In view of the important physiological role of HSO3− and H2O2, it is of great significance to develop fluorescent probes to detect HSO3− and H2O2 in aqueous medium. We herein report a new fluorescent probe (E)-3-(2-(4-(1,2,2-triphenylvinyl)styryl)benzo [d]thiazol-3-ium-3-yl)propane-1-sulfonate (TPE-y) possessing benzothiazolium salt based on tetraphenylethene (TPE) moiety with aggregation-induced emission (AIE) characteristics. TPE-y can sequentially recognize HSO3− and H2O2 through colorimetric and fluorescence dual-channel response in HEPES (pH = 7.4, 1% DMSO) buffer solution, and exhibits high sensitivity and selectivity, a large Stokes shift (189 nm), as well as a wide applicable pH range. The detection limits of TPE-y and TPE-y-HSO3 for HSO3− and H2O2 are 3.52 μM and 0.15 μM, respectively. The recognition mechanism is verified by 1H NMR and HRMS methods. Furthermore, TPE-y can detect HSO3− in sugar samples, and can image exogenous HSO3− and H2O2 in living MCF-7 cells. TPE-y can relay detect HSO3− and H2O2, which is of great significance to maintain the redox balance in organisms.

Design and Synthesis of (3-Phenylisoxazol-5-yl)methanimine Derivatives as Hepatitis B Virus Inhibitors.

Series of (3-phenylisoxazol-5-yl)methanimine derivatives were synthesized, and evaluated for anti-hepatitis B virus (HBV) activity in vitro. Half of them more effectively inhibited HBsAg than 3TC, and more favor to inhibit secretion of HBeAg than to HBsAg. Part of the compounds with significant inhibition on HBeAg were also effectively inhibit replication of HBV DNA. Compound (E)-3-(4-fluorophenyl)-5-((2-phenylhydrazineylidene)methyl)isoxazole inhibited excellently HBeAg with IC50 in 0.65 μM (3TC(Lamivudine) in 189.90 μM), inhibited HBV DNA in 20.52 μM (3TC in 26.23 μM). Structures of compounds were determined by NMR and HRMS methods, and chlorination on phenyl ring of phenylisoxazol-5-yl was confirmed by X-ray diffraction analysis, and the structure-activity relationships (SARs) of the derivatives was discussed. This work provided a new class of potent non-nucleoside anti-HBV agents.

Effects of Substituents on the Photophysical/Photobiological Properties of Mono-Substituted Corroles.

The trans-A2B-corrole series was prepared starting with 5-(pentafluorophenyl)dipyrromethene, which was then reacted with respective aryl-substituted aldehyde by Gryko synthesis. It was further characterized by HRMS and electrochemical methods. In addition, we investigated experimental photophysical properties (absorption, emission by steady-state and time-resolved fluorescence) in several solvents and TDDFT calculations, aggregation, photostability and reactive oxygen species generation (ROS), which are relevant when selecting photosensitizers used in photodynamic therapy and many other photo-applications. In addition, we also evaluated the biomolecule-binding properties with CT-DNA and HSA by spectroscopy, viscometry and molecular docking calculations assays.