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Journal of the American Society For... Apr 2020Gas phase modification in ESI-MS can significantly alter the charge state distribution of small peptides and proteins. The preceding paper presented a systematic...
Gas phase modification in ESI-MS can significantly alter the charge state distribution of small peptides and proteins. The preceding paper presented a systematic experimental study on this topic using Substance P and proposed a charge retention/charge depletion mechanism, explaining different gas- and liquid-phase modifications [Thinius et al. 2020, 10.1021/jasms.9b00044]. In this work, we aim to support this rational by theoretical investigations on the proton transfer processes from (multiply) charged analytes toward solvent clusters. As model systems we use small (di)amines as analytes and methanol (MeOH) and acetonitrile (ACN) as gas phase modifiers. The calculations are supported by a set of experiments using (di)amines, to bridge the gap between the present model system and Substance P used in the preceding study. Upon calculation of the thermochemical stability as well as the proton transfer pathways, we find that both ACN and MeOH form stable adduct clusters at the protonation site. MeOH can form large clusters through a chain of H-bridges, eventually lowering the barriers for proton transfer to an extent that charge transfer from the analyte to the MeOH cluster becomes feasible. ACN, however, cannot form H-bridged structures due to its aprotic nature. Hence, the charge is retained at the original protonation site, i.e., the analyte. The investigation confirms the proposed charge retention/charge depletion model. Thus, adding aprotic solvent vapors to the gas phase of an ESI source more likely yields higher charge states than using protic compounds.
Topics: Acetonitriles; Diamines; Gases; Lysine; Methanol; Models, Chemical; Protons; Spectrometry, Mass, Electrospray Ionization
PubMed: 32150409
DOI: 10.1021/jasms.9b00045 -
The Journal of Organic Chemistry Sep 2021Aiming at the valuable methylation process, readily available and inexpensive ,,,-tetramethylethylenediamine (TMEDA) was first identified as a new methyl source in...
Aiming at the valuable methylation process, readily available and inexpensive ,,,-tetramethylethylenediamine (TMEDA) was first identified as a new methyl source in photoredox-catalyzed transformation in this work. By virtue of this simple methylating reagent, a facile and practical protocol for the direct C-H methylation of -heteroarenes was developed, featuring mild reaction conditions, broad substrate scope, and scalability. Mechanistic studies disclosed that a sequential photoredox, base-assisted proton shift, fragmentation, and tautomerization process was essentially involved.
Topics: Catalysis; Ethylenediamines; Methylation; Protons
PubMed: 34344150
DOI: 10.1021/acs.joc.1c01325 -
Operative Dentistry Sep 2022This study aimed to evaluate the effect of desensitizing and conventional mouth rinses on dentin tubule occlusion. Dentin hypersensitivity was simulated by EDTA...
This study aimed to evaluate the effect of desensitizing and conventional mouth rinses on dentin tubule occlusion. Dentin hypersensitivity was simulated by EDTA application for five minutes. The specimens were randomly allocated into the following groups: desensitizing mouth rinses (Colgate Sensitive, Elmex Sensitive Professional, Listerine Advanced Defense Sensitive, Sensodyne Cool Mint); conventional mouth rinses (Colgate Plax, Elmex Caries Protection, Listerine Anticaries, Sensodyne Pronamel); a negative control (C-: distilled water); and Clinpro XT Varnish was the positive control (C+). Subsequently, the specimens were submitted to an erosive or abrasive challenge (performed separately) and to an erosive/abrasive cycling for five days (n=10 for each challenge). After treatment, challenges, and cycling, the specimens were analyzed in an environmental scanning electron microscope to verify the number of open dentin tubules (ODTs), counted by using Image J software (National Institutes of Health, Bethesda, MD, USA). Data were analyzed by the Kruskal-Wallis, Friedman and Dunn tests, with Bonferroni correction (α=0.05). Groups did not differ at baseline (p>0.05). At the post-treatment, erosion and abrasion stages, C+ was the only group that showed a reduction in ODTs compared to C-(p<0.05). In the other groups, numbers did not differ significantly from C- (p>0.05). After cycling, none of the groups exhibited significant reduction in ODTs other than C- (p>0.05); however, C+, Listerine Anticaries, and Colgate Plax had a lower number of ODTs than Listerine Sensitive and Sensodyne Pronamel. No mouth rinse was able to promote significant occlusion of the dentin tubules after treatment and the challenges. C+ was the only product that effectively promoted tubular occlusion, but this effect did not withstand several erosive and abrasive challenges.
Topics: Benzoates; Dentin; Dentin Desensitizing Agents; Diamines; Edetic Acid; Fluorides; Microscopy, Electron, Scanning; Mouthwashes; Sodium Dodecyl Sulfate; Sodium Fluoride; Water
PubMed: 36026699
DOI: 10.2341/21-043-L -
Colloids and Surfaces. B, Biointerfaces Feb 2020Curcumin is a powerful scavenger of reactive oxygen species and could prevent the corneal cells from oxidative damage. However, the clinical efficacy of curcumin is...
Curcumin is a powerful scavenger of reactive oxygen species and could prevent the corneal cells from oxidative damage. However, the clinical efficacy of curcumin is limited by its low aqueous solubility and stability, leading to poor bioavailability. β-cyclodextrin, with a hydrophilic surface and a hydrophobic cavity and self-assembling properties, can form inclusion complexes with lipophilic drugs such as curcumin for ocular delivery. We synthesized ethylene diamine (EDA)-modified β-cyclodextrin and prepared the curcumin complexation using the solvent evaporation method. The EDA-β-cyclodextrin provided a better thermodynamic stability and higher complex yield for curcumin complexes, compared to β-cyclodextrin, which were demonstrated on the analysis of their van't Hoff plots and phase solubility diagrams. We characterized EDA-β-cyclodextrin curcumin nanoparticles and determined that the EDA modified β-cyclodextrin is a more suitable carrier than parental β-cyclodextrin, using FT-IR, XRD, TEM, and analyses of solubility and storage stability. In addition, the curcumin-EDA-β-cyclodextrin nanoparticles had better in vitro corneal penetration and 3 -h cumulative flux in a porcine cornea experiment, and displayed an improved biocompatibility, confirmed by the histological examination of porcine corneas and cell viability of bovine corneal epithelial cells. These results together revealed a role of EDA modification in the β-cyclodextrin carrier, including the improvement of curcumin complex formation, thermodynamic properties, cytotoxicity, and the in vitro corneal penetration. The EDA-β-cyclodextrin inclusion can provide curcumin a higher degree of aqueous solubility and corneal permeability.
Topics: Animals; Cornea; Curcumin; Drug Delivery Systems; Ethylenediamines; Nanoparticles; Particle Size; Solubility; Surface Properties; Swine; beta-Cyclodextrins
PubMed: 31862560
DOI: 10.1016/j.colsurfb.2019.110726 -
Food Science and Technology... Oct 2022The influence of temperatures (18, 22 and 26 °C), salt (60, 70 and 80 g/kg) and starter culture (0, 0.025 and 0.050 g/kg) on physico-chemical and microbiological...
The influence of temperatures (18, 22 and 26 °C), salt (60, 70 and 80 g/kg) and starter culture (0, 0.025 and 0.050 g/kg) on physico-chemical and microbiological changes during fermentation in cabbage heads were investigated. The experiment was set up in industrial conditions, samples were taken after 0, 5, 12, 27 and 62 days in order to determine the changes in color, texture, biogenic amines content, microbiological parameters, pH, a, total sugar content, total acidity and salt content. Analysis of variance and Principal component analysis were applied to get a better overview of differences between samples and the similarities between different fermentation conditions. Significant color changes and softening of cabbage tissue did not occurred during the entire fermentation process. Cadaverine was not detected in samples containing starter culture, also the results were in range for maximum allowed putrescine and cadaverine doses for all cabbage samples. Total number of molds increased, contrary to number of yeasts on the last examined day in comparison with raw cabbage sample. Enterobacteriaceae were not detected after 5 fermentation day, while sharp increase of lactic acid bacteria number occurred until 12 day, and on the 12 fermentation day was in range of 7.82 to 9.84 log cfu/g. The fermentation process led to decrease in pH, a and total sugar content, meanwhile total acidity 0.54%-0.89% and salt content 2.08%-3.19% in the cabbage heads increased, in comparison with raw sample where results for total acidity and salt content were 0.13% and 0.05%, respectively. Additionally, according Principal component analysis, temperature of fermentation had the greatest influence on the fermentation process, followed by the application of starter culture and then concentration of added salt.
Topics: Biogenic Amines; Brassica; Cadaverine; Fermentation; Food Microbiology; Nitriles; Putrescine; Sodium Chloride; Sodium Chloride, Dietary; Sugars; Temperature
PubMed: 34565206
DOI: 10.1177/10820132211036308 -
CNS Drugs Mar 2022Major depressive disorder (MDD) is a leading cause of disability worldwide and less than one-third of patients with MDD achieve stable remission of symptoms, despite...
Major depressive disorder (MDD) is a leading cause of disability worldwide and less than one-third of patients with MDD achieve stable remission of symptoms, despite currently available treatments. Although MDD represents a serious health problem, a complete understanding of the neurobiological mechanisms underlying this condition continues to be elusive. Accumulating evidence from preclinical and animal studies provides support for the antidepressant potential of modulators of KCNQ voltage-gated potassium (K) channels. KCNQ K channels, through regulation of neuronal excitability and activity, contribute to neurophysiological mechanisms underlying stress resilience, and represent potential targets of drug discovery for depression. The present article focuses on the pharmacology and efficacy of KCNQ2/3 K channel openers as novel therapeutic agents for depressive disorders from initial studies conducted on animal models showing depressive-like behaviors to recent work in humans that examines the potential for KCNQ2/3 channel modulators as novel antidepressants. Data from preclinical work suggest that KCNQ-type Kchannels are an active mediator of stress resilience and KCNQ2/3 K channel openers show antidepressant efficacy. Similarly, evidence from clinical trials conducted in patients with MDD using the KCNQ2/3 channel opener ezogabine (retigabine) showed significant improvements in depressive symptoms and anhedonia. Overall, KCNQ channel openers appear a promising target for the development of novel therapeutics for the treatment of psychiatric disorders and specifically for MDD.
Topics: Animals; Antidepressive Agents; Depressive Disorder, Major; Humans; KCNQ Potassium Channels; Phenylenediamines
PubMed: 35258812
DOI: 10.1007/s40263-021-00885-y -
Journal of Trace Elements in Medicine... Dec 2021Zinc is an essential trace element having manifold functions within living cells. Zinc deficiency but also zinc excess impairs cell-specific functions whereas a balanced...
INTRODUCTION
Zinc is an essential trace element having manifold functions within living cells. Zinc deficiency but also zinc excess impairs cell-specific functions whereas a balanced zinc level is required for an adequate cell behavior.
MATERIAL AND METHODS
This study deals with the impact of cellular priming due to stimulation with interleukin (IL)-1, IL-2, IL-4, IL-6 or the chemokine CXCL12a and its subsequent influence on the intracellular free zinc concentration. Since cellular priming and activation is essential for proper immunological reactions, and across that highly cell-type specific, we investigated T cells, B cells, and peripheral blood mononuclear cells (PBMCs). Additionally, alterations of the intracellular zinc content was investigated by inducing zinc deficiency using the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine (TPEN) with subsequent re-supplementation of zinc, hence generating an intracellular zinc flux. Evaluation of zinc staining with FluoZin3-AM, Zinpyr-1 and Zinquin was done by flow cytometry or by fluorescence microscopy.
RESULTS
Our results indicate that cellular priming for different periods of time (10 minutes/one hour) causes decreased intracellular free zinc concentrations in the FluoZin3-AM staining and increased zinc concentrations stained with Zinpyr-1. Furthermore, zinc supplementation after induced zinc deficiency leads to a fast and excessive rise of the intracellular free zinc levels in most cellular compartments.
CONCLUSION
Our study emphasizes the importance of zinc homeostasis and zinc distribution during cellular priming and for certain signaling cascades especially in T and B cells. Moreover, we demonstrated that zinc re-supplementation of zinc deficient cells results in significantly elevated intracellular free zinc concentrations compared to untreated controls. Hence, this underlines the need of a balanced zinc homeostasis for proper immune cell function.
Topics: Chelating Agents; Ethylenediamines; Leukocytes, Mononuclear; T-Lymphocytes; Trace Elements; Zinc
PubMed: 34562730
DOI: 10.1016/j.jtemb.2021.126864 -
Journal of Natural Products Jun 2022Four new indole--mannopyranoside alkaloids, neopetrosins A-D (-), together with one new diamine alkaloid, haliclorensin D (), were isolated from the marine sponge... (Review)
Review
Four new indole--mannopyranoside alkaloids, neopetrosins A-D (-), together with one new diamine alkaloid, haliclorensin D (), were isolated from the marine sponge collected off Xisha Island in the South China Sea. Their structures and absolute configurations were determined by spectroscopic analysis, single-crystal X-ray diffraction, calculated electronic circular dichroism (ECD), and DP4+ probability analyses. Compounds , , and exhibited in vivo hepatoprotective activity in a zebrafish model at a concentration of 20 μM.
Topics: Alkaloids; Animals; Antineoplastic Agents; China; Diamines; Indoles; Mannose; Molecular Structure; Porifera; Zebrafish
PubMed: 35650516
DOI: 10.1021/acs.jnatprod.2c00292 -
ACS Synthetic Biology Nov 2021Diamines serve as major platform chemicals that can be employed to a variety of industrial scenarios, particularly as monomers for polymer synthesis. High-throughput...
Diamines serve as major platform chemicals that can be employed to a variety of industrial scenarios, particularly as monomers for polymer synthesis. High-throughput sensors for diamine biosynthesis can greatly improve the biological production of diamines. Here, we identified and characterized a transcription factor-driven biosensor for putrescine and cadaverine in . The transcriptional TetR-family regulatory protein CgmR (CGL2612) is used for the specific detection of diamine compounds. This study also improved the dynamic range and the sensitivity to putrescine by systematically optimizing genetic components of pSenPut. By a single cell-based screening strategy for a library of CgmR with random mutations, this study obtained the most sensitive variant CgmR, which possessed an experimentally determined limit of detection (LoD) of ≤0.2 mM, a K of 11.4 mM, and a utility of 720. Using this highly sensitive putrescine biosensor pSenPut, we demonstrated that CgmRI can be used as a sensor to detect putrescine produced biologically in a system. This high sensitivity and the range of CgmR will be an influential tool for rewiring metabolic circuits and facilitating the directed evolution of recombinant strains toward the biological synthesis of diamine compounds.
Topics: Biosensing Techniques; Corynebacterium glutamicum; Diamines; Metabolic Engineering; Mutation; Transcription Factors
PubMed: 34662101
DOI: 10.1021/acssynbio.1c00363 -
Photodiagnosis and Photodynamic Therapy Jun 2022To appraise the efficacy of photodynamic therapy (PDT) and conventional regime (NaOCl) following three chelating agents ethylene diamine tetraacetic acid (EDTA), Green...
Radicular canal disinfection using photodynamic therapy and sodium hypochlorite following three chelating agents' green tea extract, grape extract, and EDTA on the push-out bond strength of epoxy resin-based sealer.
AIM
To appraise the efficacy of photodynamic therapy (PDT) and conventional regime (NaOCl) following three chelating agents ethylene diamine tetraacetic acid (EDTA), Green tea extract (GTE), grape extract (GE) on pushout bond strength (PBS) of epoxy resin-based sealer with root dentin.
MATERIAL AND METHODS
60 single-rooted human teeth were prepped using a ProTaper system and cleansed using photodynamic therapy (PDT) and 5% NaOCl (n = 30 each). Samples in each group PDT and 5% NaOCl were further divided into 6 sub-group (n = 10) based on the chelating agents used: 17% EDTA, GTE, and GE. Gutta-percha and AH Plus were used to obturate the canals. The push-out test was used to determine bond strength, and ANOVA was used to conduct statistical analysis while failure patterns were classified as adhesive, cohesive, or mixed. The Chi-squared test was used to examine the different failure modes at a significance level of 0.05.
RESULTS
NaOCl disinfection, when applied with naturally derived reducing agents (17% EDTA, GTE, and GE) demonstrated significantly higher PBS compared to PDT when used with chelating agents (17% EDTA, GTE, and GE) (p < 0.05). The most predominant failure mode was an adhesive failure when root dentin was disinfected with PDT while NaOCl treatment showed a high percentage of cohesive failure.
CONCLUSION
Radicular canal disinfection with sodium hypochlorite following three chelating agents (Green tea extract, Grape extract, and Ethylene diamine tetraacetic acid) exhibited better push-out bond strength bonded to radicular dentin with epoxy resin-based sealer.
Topics: Chelating Agents; Dentin; Disinfection; Edetic Acid; Epoxy Resins; Ethylenes; Humans; Materials Testing; Photochemotherapy; Plant Extracts; Root Canal Irrigants; Root Canal Preparation; Sodium Hypochlorite; Tea; Vitis
PubMed: 35288318
DOI: 10.1016/j.pdpdt.2022.102809