Electrospray Ionization Mass Spectrometry Analysis Research Articles

Unravelling structural insights into ligand-induced photoluminescence mechanisms of sulfur dots.

Sulfur dots (S-QDs) hold promise as a new category of metal-free, luminescent nanomaterials, yet their practical application faces challenges primarily due to a limited understanding of their structure and its impact on their optical properties. Herein, by employing a spectrum of aliphatic and aromatic ligands, we identify the surface structure and composition of S-QDs while delineating the pivotal role of ligands in inducing photoluminescence. Thiol-functionalized ligands, such as 4-mercapto benzoic acid and glutathione, notably promote the formation of both green and blue luminescent S-QDs, boosting a high quantum yield of up to 56%. Further investigation on the synthesis of S-QDs with 4-mercapto benzoic acid unveils the dual role of H2O2: etching sulfur powder and oxidizing the -SH group to -SO2H. These oxidized ligands passivate the S-QD surface through hydrogen bonding. Electrospray ionization mass spectrometry analysis unveils the presence of distinct sulfur species such as [S4(C6H5SO2H)4(H2O)2H]+ and [S6(C6H5SO2H)6(H2O)3H]+, while XPS analysis confirms the existence of zerovalent sulfur and oxidized sulfur species including SO32- and SO42-. Further detailed spectroscopic examination demonstrates that S-QDs predominantly exist as aggregated entities, with the emission wavelength correlating with the degree of aggregation. The absence of photoluminescence in aggregations devoid of ligands underscores the critical role of ligands in the photoluminescence genesis of S-QDs.

Genome Analysis of a Potential Novel Vibrio Species Secreting pH- and Thermo-Stable Alginate Lyase and Its Application in Producing Alginate Oligosaccharides.

Alginate lyase is an attractive biocatalyst that can specifically degrade alginate to produce oligosaccharides, showing great potential for industrial and medicinal applications. Herein, an alginate-degrading strain HB236076 was isolated from Sargassum sp. in Qionghai, Hainan, China. The low 16S rRNA gene sequence identity (<98.4%), ANI value (<71.9%), and dDDH value (<23.9%) clearly indicated that the isolate represented a potential novel species of the genus Vibrio. The genome contained two chromosomes with lengths of 3,007,948 bp and 874,895 bp, respectively, totaling 3,882,843 bp with a G+C content of 46.5%. Among 3482 genes, 3332 protein-coding genes, 116 tRNA, and 34 rRNA sequences were predicted. Analysis of the amino acid sequences showed that the strain encoded 73 carbohydrate-active enzymes (CAZymes), predicting seven PL7 (Alg1-7) and two PL17 family (Alg8, 9) alginate lyases. The extracellular alginate lyase from strain HB236076 showed the maximum activity at 50 °C and pH 7.0, with over 90% activity measured in the range of 30-60 °C and pH 6.0-10.0, exhibiting a wide range of temperature and pH activities. The enzyme also remained at more than 90% of the original activity at a wide pH range (3.0-9.0) and temperature below 50 °C for more than 2 h, demonstrating significant thermal and pH stabilities. Fe2+ had a good promoting effect on the alginate lyase activity at 10 mM, increasing by 3.5 times. Thin layer chromatography (TLC) and electrospray ionization mass spectrometry (ESI-MS) analyses suggested that alginate lyase in fermentation broth could catalyze sodium alginate to produce disaccharides and trisaccharides, which showed antimicrobial activity against Shigella dysenteriae, Aeromonas hydrophila, Staphylococcus aureus, Streptococcus agalactiae, and Escherichia coli. This research provided extended insights into the production mechanism of alginate lyase from Vibrio sp. HB236076, which was beneficial for further application in the preparation of pH-stable and thermo-stable alginate lyase and alginate oligosaccharides.

Dioxygenase Chemistry in Nucleophilic Aldehyde Deformylations Utilizing Dicopper O2-Derived Peroxide Complexes.

The chemistry of copper-dioxygen complexes is relevant to copper enzymes in biology as well as in (ligand)Cu-O2 (or Cu2-O2) species utilized in oxidative transformations. For overall energy considerations, as applicable in chemical synthesis, it is beneficial to have an appropriate atom economy; both O-atoms of O2(g) are transferred to the product(s). However, examples of such dioxygenase-type chemistry are extremely rare or not well documented. Herein, we report on nucleophilic oxidative aldehyde deformylation reactivity by the peroxo-dicopper(II) species [Cu2II(BPMPO-)(O22-)]1+ {BPMPO-H = 2,6-bis{[(bis(2-pyridylmethyl)amino]methyl}-4-methylphenol)} and [Cu2II(XYLO-)(O22-)]1+ (XYLO- = a BPMPO- analogue possessing bis(2-{2-pyridyl}ethyl)amine chelating arms). Their dicopper(I) precursors are dioxygenase catalysts. The O2(g)-derived peroxo-dicopper(II) intermediates react rapidly with aldehydes like 2-phenylpropionaldehyde (2-PPA) and cyclohexanecarboxaldehyde (CCA) in 2-methyltetrahydrofuran at -90 °C. Warming to room temperature (RT) followed by workup results in good yields of formate (HC(O)O-) along with ketones (acetophenone or cyclohexanone). Mechanistic investigation shows that [Cu2II(BPMPO-)(O22-)]1+ species initially reacts reversibly with the aldehydes to form detectable dicopper(II) peroxyhemiacetal intermediates, for which optical titrations provide the Keq (at -90 °C) of 73.6 × 102 M-1 (2-PPA) and 10.4 × 102 M-1 (CCA). In the reaction of [Cu2II(XYLO-)(O22-)]1+ with 2-PPA, product complexes characterized by single-crystal X-ray crystallography are the anticipated dicopper(I) complex, [Cu2I(XYLO-)]1+ plus a mixed-valent Cu(I)Cu(II)-formate species. Formate was further identified and confirmed by 1H NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS) analysis. Using 18O2(g)-isotope labeling the reaction produced a high yield of 18-O incorporated acetophenone as well as formate. The overall results signify that true dioxygenase reactions have occurred, supported by a thorough mechanistic investigation.

A novel bakuchiol aminoguanidine derivative induces apoptosis in human triple-negative breast cancer cells.

To synthesize new bakuchiol aminoguanidine derivatives and test their effect on viability and apoptosis of human triple-negative breast cancer (TNBC) cells. Two bakuchiol derivatives 1 and 2 were obtained by formylation and Shiff base reaction of bakuchol. The structures of derivatives 1 and 2 were identified by 1H-NMR, 13C-NMR, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) analysis. Human TNBC MDA-MB-231 cells were treated with bakuchiol and its derivatives and cell viability was measured by MTT assay. Apoptosis was detected by fluorescence microscopy and flow cytometry with Annexin V-FITC/PI staining. The expressions of apoptosis-related proteins were analyzed with Western blotting. The JC-1 and reactive oxygen species (ROS) assay kits were used to determine the effect of new bakuchiol derivatives on mitochondrial function. Based on spectroscopic analysis, a new bakuchiol schiff base derivative was elucidated as 2-{(E)-5-[(S, E)-3, 7-dimethyl-3-vinylocta-1, 6-dien-1-yl]-2-hydroxylbenzylidene} hydrazine-1-carboximidamide (derivative 2). Bakuchiol and its derivatives 1 and 2 all showed cytotoxic activity against the MDA-MB-231 cells. Derivative 2 exhibited the most potent cytotoxic activity to MDA-MB-231 cell with IC50 of (13.11±1.09), (6.91±1.78), and (2.23±1.32) μmol/L after 24, 48, and 72 h. It had low toxicity to normal mouse liver (AML-12) cells with IC50 of (31.23±1.58) μmol/L at 72 h. Fluorescence microscopy and flow cytometry demonstrated apoptosis in breast cancer cells after treating with derivative 2 in a concentration dependent manner. Western blotting showed that after derivative 2 treatment, the expression of apoptosis-related proteins cytochrome C, cleaving caspase-3 and Bax/Bcl-2 radio in MDA-MB-231 cells increased; in addition, apoptosis was associated with the decreased mitochondrial membrane potential and increased reactive oxygen species accumulation. The novel bakuchiol aminoguanidine derivative (derivative 2) is capable of inducing apoptosis in MDA-MB-231 cells, but has low toxicity to normal liver cells, suggesting that it may be used as a lead compound for an anti-TNBC agent.

Ga complexes of 8-hydroxyquinoline-2-carboxylic acid: Chemical speciation and biological activity

The binding ability of 8-hydroxyquinoline-2-carboxylic acid (8-HQA) towards Ga3+ has been investigated by ISEH+ (Ion Selective Electrode, glass electrode) potentiometric and UV/Vis spectrophotometric titrations in KCl(aq) at I = 0.2 mol dm−3 and at T = 298.15 K. Further experiments were also performed adopting both the metal (with Fe3+ as competing cation) and ligand-competition approaches (with EDTA as competing ligand). Results gave evidence of the formation of the [Ga(8-HQA)]+, [Ga(8-HQA)(OH)], [Ga(8-HQA)(OH)2]− and [Ga(8-HQA)2]− species, the latter being so far the most stable, as also confirmed by ESI-MS analysis. Experiments were also designed to determine the stability constants of the [Ga(EDTA)]− and [Ga(EDTA)(OH)]2− in the above conditions. Due to the relevance of Ga3+ hydrolysis in aqueous systems, literature data on this topic were collected and critically analyzed, providing equations for the calculation of mononuclear Ga3+ hydrolysis constants at T = 298.15 K, in different ionic media, in the ionic strength range 0 < I / mol dm−3 ≤ 1.0. The synthesis and characterization (by ElectroSpray Ionization – Mass Spectrometry (ESI-MS), Attenuated Total Reflectance - Fourier-Transform Infrared Spectroscopy (ATR-FTIR) and ThermoGravimetric Analysis (TGA)) of Ga3+/8-HQA complexes were also performed, identifying [Ga(8-HQA)2]− as the main isolated species, even in the solid state. Finally, the potential effects of 8-HQA and Ga3+/8-HQA complex towards human microbiota exposed to ionizing radiation were evaluated (namely Actinomyces viscosus, Streptococcus mutans, Streptococcus sobrinus, Pseudomonas putida, Pseudomonas fluorescens and Escherichia coli), as well as their anti-proliferative and anti-inflammatory properties. A radioprotective effect of Ga3+/8-HQA complex was observed on Actinomyces viscosus, while showing a potential radiosensitizing effect against Streptococcus mutans and Streptococcus sobrinus. No cytotoxicity on RAW264.7 murine macrophage cells was observed, neither for the free ligand or Ga3+/8-HQA complex. Nevertheless, Ga3+/8-HQA complex highlighted potential anti-inflammatory properties.

Citrus Pomace as a Source of Plant Complexes to Be Used in the Nutraceutical Field of Intestinal Inflammation.

This study aims to recover the main by-product of Citrus fruits processing, the raw pomace, known also as pastazzo, to produce plant complexes to be used in the treatment of inflammatory bowel disease (IBD). Food-grade extracts from orange (OE) and lemon (LE) pomace were obtained by ultrasound-assisted maceration. After a preliminary phytochemical and biological screening by in vitro assays, primary and secondary metabolites were characterized by proton nuclear magnetic resonance (1H-NMR) and liquid chromatography coupled to diode array detection and electrospray ionization mass spectrometry (LC-DAD-ESI-MS) analyses. The intestinal bioaccessibility and antioxidant and anti-inflammatory properties were investigated by in vitro simulated gastro-intestinal digestion followed by treatments on a lipopolysaccharide (LPS)-stimulated human colorectal adenocarcinoma cell line (Caco-2). The tight junctions-associated structural proteins (ZO-1, Claudin-1, and Occludin), transepithelial electrical resistance (TEER), reactive oxygen species (ROS)-levels, expression of some key antioxidant (CAT, NRF2 and SOD2) and inflammatory (IL-1β, IL-6, TNF-α, IL-8) genes, and pNFkB p65 nuclear translocation, were evaluated. The OE and LE digesta, which did not show any significant difference in terms of phytochemical profile, showed significant effects in protecting against the LPS-induced intestinal barrier damage, oxidative stress and inflammatory response. In conclusion, both OE and LE emerged as potential candidates for further preclinical studies on in vivo IBD models.

Synthesis, crystal structure and anticancer activity of 4‑chloro-2-methoxybenzoic acid transition metal complexes

Seven novel transition metal complexes were synthesized from a starting material of 4‑chloro-2-methoxybenzoic acid, I: [Cu(4-Cl-2-MOBA)2(Py)2(H2O)2]; II: [Cu(4-Cl-2-MOBA)2(Imz)2]; III: [Co(4-Cl-2-MOBA)2(H2O)3.5]; IV: [Ni(4-Cl-2-MOBA)2(H2O)6]; V: [Ni(4-Cl-2-MOBA)2(DMF)]; VI: [Ni(4-Cl-2-MOBA)2(3-NH2–5-hypy)2(H2O)2O3.67] and VII: [Zn2(4-Cl-2-MOBA)3(4,4′-bipy)(Py)(HAc)]n by a one-pot, solvothermal method. All complexes were characterized by elemental analysis (EA), Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV–Vis), electrospray ionization mass spectrometry (ESI-MS) and single-crystal X-ray diffraction analysis (XRD). Single crystal XRD analyses showed that central metal ion type, auxiliary ligands and solvents acted synergistically to determine structural diversity. Complexes I-VII had cytotoxic activity towards the human tumor cell lines, A549 and SMMC-7721. Complex I showed the most potent cytotoxicity with an IC50 value of 8.976 μM for lung cancer cells and 13.94 μM for liver cancer cells.

Dual function Schiff-base as a selective fluorescence “Turn-on” sensor for Zn2+ and a colorimetric sensor for Cu2+ and Fe3+ ions

A simple and adaptable salen-based Schiff base receptor (L = 6,6′-((1E,1′E)-(cyclohexane-1,2-diylbis(azanylylidene))bis(methanylylidene))bis(2-methoxyphenol))was employed in the current study for colorimetric detection of Cu2+, Fe3+, and fluorescence detection of Zn2+ ions in a semi-aqueous solution. L could identify the three target ions among the many different cations and anions in the solution. The turn-on fluorescence signal of L to Zn2+ ions was boosted by the restriction of the intramolecular charge transfer process, and the resulting chelation enhances the fluorescence signal. The sensing mechanisms were validated using a Job’s plot, Electrospray Ionization Mass Spectrometry (ESI-MS) analysis, Nuclear Magnetic Resonance (NMR) titration experiment, and theoretical calculation investigations. The detection limits for Zn2+ were determined to be 0.038 μM, whereas Cu2+ and Fe3+ detection limits were 0.58 μM and 0.62 μM, respectively. Next, L was used to develop solid silica gel and test strips for instantaneous colorimetric and fluorescent detection of the three target ions in real time. The trace level of Cu2+ and Fe3+ in the tap and drinking water samples could be quantitatively measured using L. Eventually, applications for keypad locks and molecular logic gates were developed utilizing the receptor L.

Air-Stable Cobalt(III) and Chromium(III) Complexes as Single-Component Catalysts for the Activation of Carbon Dioxide and Epoxides.

Cobalt(III) and chromium(III) salophen chloride complexes were synthesized and tested for the cycloaddition of carbon dioxide (CO2) with epoxides to obtain cyclic carbonates. The cat1, cat2, cat4, and cat5 complexes presented high catalytic activity without cocatalysts and are solvent-free at 100 °C, 8 bar, and 9 h. At these conditions, the terminal epoxides (1a-1k) were successfully converted into the corresponding cyclic carbonates with a maximum conversion of ∼99%. Moreover, cat5 was highlighted due to its capability of opening internal epoxides such as limonene oxide (1l) with a 36% conversion to limonene carbonate (2l), and from cyclohexene oxide (1m), cyclic trans-cyclohexene carbonate (2m) and poly(cyclohexene carbonate) were obtained with 15% and 85% selectivity, respectively. A study of the coupling reaction mechanism was proposed with the aid of electrospray ionization mass spectrometry (ESI-MS) analysis, confirming the single-component behavior of the complexes through their ionization due to epoxide coordination. In addition, crystallographic analysis of cat1 single crystals grown in a saturated solution of pyridine helped to demonstrate that the substitution of chloride ion by pyridine ligands to form an octahedral coordination occurs (Py-cat1), supporting the proposed mechanism. Also, a recyclability study was performed for cat5, and a total turnover number of 952 was obtained with only minor losses in catalytic activity after five cycles.

Genome Analysis of Multiple Polysaccharide-Degrading Bacterium Microbulbifer thermotolerans HB226069: Determination of Alginate Lyase Activity.

Polysaccharide-degrading bacteria are key participants in the global carbon cycle and algal biomass recycling. Herein, a polysaccharide lyase-producing strain HB226069 was isolated from Sargassum sp. from Qingge Port, Hainan, China. Results of the phylogenetic of the 16S rRNA gene and genotypic analysis indicated that the isolate should be classified as Microbulbifer thermotolerans. The whole genome is a 4,021,337bp circular chromosome with a G+C content of 56.5%. Analysis of the predicted genes indicated that strain HB226069 encoded 161 carbohydrate-active enzymes (CAZymes), and abundant putative enzymes involved in polysaccharide degradation were predicted, including alginate lyase, fucosidase, agarase, xylanase, cellulase, pectate lyase, amylase, and chitinase. Three of the putative polysaccharide lyases from PL7 and PL17 families were involved in alginate degradation. The alginate lyases of strain HB226069 showed the maximum activity of 117.4 U/mL at 50°C, pH 7.0, and 0.05M FeCl3, while exhibiting the best stability at 30°C and pH 7.0. The Thin Layer Chromatography (TLC) and Electrospray Ionization Mass Spectrometry (ESI-MS) analyses indicated that the alginate oligosaccharides (AOSs) degraded by the partially purified alginate lyases contained oligosaccharides of DP2-DP5 and monosaccharide while reacting for 36h. The complete genome of M. thermotolerans HB226069 enriches our understanding of the mechanism of polysaccharide lyase production and supports its potential application in polysaccharide degradation.

Separation of indium and tin from ITO powders with short-chain dicarboxylic acid-ChCl deep eutectic solvents: Indium tin leaching and splitting mechanism

The substitution of corrosive mineral acids with green deep eutectic solvents (DESs) for extracting rare and precious metals from discarded electronic devices has a sustained appeal for developing clean hydrometallurgical processes. However, the dissolution mechanism of DESs on specific metals still requires an exhaustive understanding. In this work, short-chain dicarboxylic acid-choline chloride DESs were used to dissolve indium tin oxide (ITO) to achieve the separation of indium and tin. Kinetic and thermodynamic studies have shown that the leaching of indium and tin was considered a mixed control of diffusion and chemical reaction, with low activation energies (Ea(In) = 39.93 kJ/mol, Ea(Sn) = 39.52 kJ/mol). The electrospray ionization mass spectrometry (ESI-MS) analysis of the leaching solution and molecular orbital calculations revealed that tin was leached in the main form of [Sn4+(OH−)3(H2O)]+ cation as well as slight [Sn4+MA2−(Cl−)3]− anion, while the dominant ions of indium were [In3+(Cl−)4]− ligand as well as small amounts of [In3+MAH−(Cl−)4]2−, [In3+(MA2−)3]3− and [In3+MA2−(Cl−)2]−. The tin-containing species in the leaching solution can be completely precipitated in the form of cassiterite SnO2 through water dilution and hydrothermal treatment, in which amorphous indium-containing substances were mixed. Most of the indium was retained in the form of [In3+(Cl−)4]− in the liquid. After adjusting the pH of the solution, over 99% of the indium precipitated out as In(OH)3, and after calcination at 600 °C in air for 1 hour, In2O3 was obtained. This study unveiled the leaching mechanism of short-chain dicarboxylic acid-choline chloride DESs on ITO powders. It developed a green, simple, and mild process for potentially recovering ITO-based materials.

A Novel Bisquaternary Ammonium Compound as an Anion Sensor-ESI-MS and Fluorescence Study.

Electrospray ionization mass spectrometry (ESI-MS) analysis is frequently associated with noncovalent adduct formation, both in positive and negative modes. Anion binding and sensing by mass spectrometry, notably more challenging compared to cation binding, will have major research potential with the development of appropriate sensors. Here, we demonstrated identification of stable bisquaternary dication adducts with trifluoroacetate (TFA-), Cl- and HSO4- in positive-mode ESI-MS analysis. The observed adducts were stable in MS/MS mode, leading to the formation of characteristic fragment ions containing a covalently bound anion, which requires bond reorganization. This phenomenon was confirmed by computational methods. Furthermore, given that anion detection and anion sensor chemistry have gained significant prominence in chemistry, we conducted an analysis of the fluorescent properties of bisquaternary ammonium compound as a potential anion sensor.

G-Quadruplex Structure in the ATP-Binding DNA Aptamer Strongly Modulates Ligand Binding Activity.

Secondary structures formed by single-stranded DNA aptamers can allow for the binding of small-molecule ligands. Some of these secondary structures are highly stable in solution and are great candidates for use in the development of molecular tools for biomarker detection, environmental monitoring, and others. In this paper, we explored adenosine triphosphate (ATP)-binding aptamers for the simultaneous detection of two small-molecule ligands: adenosine triphosphate (ATP) and thioflavin T (ThT). The aptamer can form a G-quadruplex (G4) structure with two G-quartets, and our results show that each of these quartets is equally involved in binding. Using fluorescently labeled and label-free methods, we further explored the role of the G4 motif in modulating the ligand binding property of the aptamer by making two extended variants that can form three or four G-quartet G4 structures. Through equilibrium binding and electrospray ionization mass spectrometry (ESI-MS) analysis, we observed a stronger affinity of aptamers to ATP by the variant G4 constructs relative to the native aptamer (Kd range of 0.040-0.042 μM for variants as compared to 0.15 μM for the native ATP aptamer). Additionally, we observed a dual binding of ThT and ATP to the G4 constructs in the label-free and ESI-MS analyses. These findings together suggest that the G4 motif in the ATP aptamer is a critical structural element that is required for optimum ATP binding and can be modulated for the binding of multiple ligands. These findings are instrumental for designing smart molecular tools for a wide range of applications, including biomarker monitoring and ligand binding studies.

Identification and nitric oxide production inhibitory activity of phenolic derivatives from the trunks of Gnetum latifolium

Phytochemical investigation of the trunks from Gnetum latifolium led to the isolation of a novel phenolic glucoside, 2E-2,4-di-(3,4-dihydroxyphenyl)but-2-en-1-yl-O-β-D-glucopyranoside (1), along with five known stilbene derivatives (2–6). Their structures were determined mainly using high-resolution electrospray ionisation mass spectrometry and nuclear magnetic resonance spectroscopic analyses, followed by comparisons of observed spectral data with reported values. The novel compound 1 in G. latifolium was found to be useful as a chemotaxonomic marker. Biological evaluation revealed that compound 6 had remarkable inhibitory effects on nitric oxide production, with a half-maximal inhibitory concentration (IC50) value of 4.85 ± 0.20 µM, which was much higher than that of the positive control dexamethasone (IC50 = 14.20 ± 0.54 µM).

Direct Injection Electrospray Ionization Mass Spectrometry (ESI-MS) Analysis of Proteins with High Matrix Content:Utilizing Taylor-Aris Dispersion.

This is the first work demonstrating the utility of the Taylor-Aris (TA) dispersion in avoiding serious interference issues commonly occurring in the electrospray ionization-mass spectrometric (ESI-MS) determination of therapeutic protein pharmaceuticals undergoing no pre-separation or sample purification. It was also pointed out that the TA dispersion conditions and its analytical utilization for proteomics can be easily accomplished in a commercial CE-MS instrument. In the proposed Taylor-Aris dispersion-assisted mass spectrometry (TADA-MS) analysis 0.5 μL sample is injected into a 65 cm long 50 μm i.d. capillary and pumped with 1 bar toward the MS. The procedure is efficient for the direct injection analysis of components having low diffusion coefficients (proteins) that are present in complex matrices of small organic and inorganic compounds.

Direct Injection Electrospray Ionization Mass Spectrometry (ESI‐MS) Analysis of Proteins with High Matrix Content:Utilizing Taylor–Aris Dispersion

AbstractThis is the first work demonstrating the utility of the Taylor–Aris (TA) dispersion in avoiding serious interference issues commonly occurring in the electrospray ionization‐mass spectrometric (ESI‐MS) determination of therapeutic protein pharmaceuticals undergoing no pre‐separation or sample purification. It was also pointed out that the TA dispersion conditions and its analytical utilization for proteomics can be easily accomplished in a commercial CE‐MS instrument. In the proposed Taylor–Aris dispersion‐assisted mass spectrometry (TADA‐MS) analysis 0.5 μL sample is injected into a 65 cm long 50 μm i.d. capillary and pumped with 1 bar toward the MS. The procedure is efficient for the direct injection analysis of components having low diffusion coefficients (proteins) that are present in complex matrices of small organic and inorganic compounds.

Rivastigmine nasal spray for the treatment of Alzheimer’s Disease: Olfactory deposition and brain delivery

Alzheimer’s disease (AD) is characterized by a gradual decline in cognitive function and memory impairment, significantly impacting the daily lives of patients. Rivastigmine (RHT), a cholinesterase inhibitor, is used to treat mild to moderate AD via oral administration. However, oral administration is associated with slow absorption rate and severe systemic side effects. RHT nasal spray (RHT-ns), as a nose-to-brain delivery system, is more promising for AD management due to its efficient brain delivery and reduced peripheral exposure. This study constructed RHT-ns for enhancing AD treatment efficacy, and meanwhile the correlation between drug olfactory deposition and drug entering into the brain was explored. A 3D-printed nasal cast was employed to quantify the drug olfactory deposition. Brain delivery of RHT-ns was quantified using fluorescence tracking and Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) analysis, which showed a good correlation to the olfactory deposition. F2 (containing 1% (w/v) viscosity modifier Avicel® RC-591) with high olfactory deposition and drug brain delivery was further investigated for pharmacodynamics study. F2 exhibited superiority in AD treatment over the commercially available oral formulation. In summary, the present study showed the successful development of RHT-ns with improved olfactory deposition and enhanced brain delivery. It might provide new insight into the design and development of nose-to-brain systems for the treatment of AD.

Cobalt pyridyl complexes against drug-resistant bacteria: Synthesis, characterization, antibacterial properties, mode of action, and molecular docking studies

This study describes the synthesis and characterization of four cobalt complexes using diverse physicochemical techniques. Notably, the co-grinding method was predominantly employed, resulting in higher yields and increased purity of the products. Thermal studies provided insights into the stability of the cobalt complexes, with dichoro-bis-4-((4-nitrophenoxy)methyl)pyridine cobalt(II) (CoL4) demonstrating the highest stability based on transformations and high melting points. High resolution electrospray ionization mass spectrometry (HRESI-MS) analysis further confirmed the successful synthesis of the cobalt complexes, reinforcing the characterization results. The dichloro-bis(pyridin-4ylmethyl-4aminobenzoate) cobalt (II) (CoL3) exhibited a cis tetrahedral structure with a high-symmetry monoclinic crystal system and a primitive lattice centering of an I2/a space group. The cobalt complexes displayed enhanced activity against Gram-negative bacteria, particularly Klebsiella pneumoniae, with some exhibiting potent bacteriostatic effects against Multidrug resistant K. pneumoniae (MDR-K. pneumoniae). Additionally, dichoro-bis-(4-[(pyridin-4-yl)methoxy] aniline) cobalt(II) (CoL2) and CoL3 were found to disrupt the folate biosynthesis of K. pneumoniae and Methicillin resistant Staphylococcus aureus (MRSA), respectively. Moreover, 4-chloromethylpyridinium tetrachlorocobaltate (II) (Co4PY-H), dichloro-bis-4-picolyl cobalt (II) (Co4PY), CoL2, and CoL3 showed significant disruption of the cell membrane integrity of K. pneumoniae, with CoL3 also affecting MRSA's cell membrane. Lastly, molecular docking calculations provided compelling evidence supporting the experimental modes of action of these active complexes.

Aluminum ion intercalation in mesoporous multilayer carbocatalysts promotes the conversion of glucose to 5-hydroxymethylfurfural.

In this study, an efficient modification strategy was proposed by facile loading of trace aluminum ions and p-toluene sulfonic acid (p-TSA) in carbon materials to improve their catalytic activity. p-TSA is then proven to regulate the carbonization process and promote the formation of mesoporous and multilayer structures. The hexa-coordinated aluminum structure is characterized by 1H-27Al solid-state nuclear magnetic resonance (SSNMR) and X-ray photoelectron spectroscopy, which serves as the Lewis-Brønsted acid site in carbocatalysts. Accordingly, the resulting catalyst facilitates a yield of ∼70% for converting glucose to 5-hydroxymethylfurfural (HMF) with a maximum carbon balance of around 91.4% at 150 °C in 6 h. In situ NMR, electrospray ionization mass spectrometry and isotope labeling analysis reveal that the hexa-coordinated aluminum sites promote the isomerization of glucose, and the sulfonic groups facilitate the subsequent dehydration and rehydration of fructose and levoglucosan intermediates. Kinetic models further indicate the decreased energy barrier for glucose conversion over the Al3+/p-TSA intercalated carbocatalyst. This work provides a promising strategy for engineering waste-derived carbocatalysts toward effectively converting carbohydrates to precursors of biofuels and bioplastics.

Design, synthesis and antibacterial activity evaluation of ebselen derivatives in NDM-1 producing bacteria.

New Delhi-β-lactamase-1 (NDM-1) is a type of metal-β-lactamase. NDM-1-expressing bacteria can spread rapidly across the globe via plasmid transfer, which greatly undermines the clinical efficacy of the carbapenem. Research on NDM-1 inhibitors has attracted extensive attention. However, there are currently no clinically available NDM-1 inhibitors. Our research group has reported that 1,2-benzisoselenazol-3(2H)-one derivatives as covalent NDM-1 inhibitors can restore the efficacy of meropenem (Mem) against NDM-1 producing strains. In this study, 22 compounds were designed and synthesized, which restored the Mem susceptibility of NDM-1-expressing Escherichia coli. and its minimum inhibitory concentration (MIC) was reduced by 2-16 times. Representative compound A4 showed significant synergistic antibacterial activity against NDM-1-producing carbapenem-resistant Enterobacteriaceae (CRE) isolates. The in vitro NDM-1 enzyme inhibitory activity test showed that the IC50 was 1.26 ± 0.37 μM, which had low cytotoxicity. When combined with meropenem, it showed good combined antibacterial activity. Electrospray ionization mass spectrometry (ESI-MS) analysis demonstrates that compound A4 covalently binds to NDM-1 enzyme. In summary, compound A4 is a potent NDM-1 covalent inhibitor and provides a potential lead compound for drug development in resistant bacteria.