Presence Of NaHCO3 Research Articles

All-in-one fabrication of NiO nanorods/carbon-containing porous catalytic polymer membranes for persulfate-facilitated oxidation-adsorption of diclofenac in flow–through

We introduce a novel all-in-one fabrication method for porous catalytic polyethersulfone (PES) membranes containing NiO nanorods and carbon nanoparticles. This method is based on the sonochemical in situ solidification of a metal salt with NaBH4 in presence of carbon particles in a PES-containing casting-reaction solution, directly followed by membrane preparation via film casting cum phase separation. In the catalytic flow-through degradation of 20 mg/L aqueous diclofenac with persulfate as oxidant, an as-prepared NiO-carbon-PES membrane achieved a 99 % aromatic content removal degree at a residence time of only 1.6 s. In comparison, NiO and CuO membranes without carbon particles exhibited < 40 % aromatic removal degrees. The high performance was attributed to a degradation-induced adsorption, with a diclofenac removal capacity of 950 mg/g of incorporated carbon particles. We demonstrated that diclofenac is catalytically mineralized in the membrane at incorporated NiO nanorods, followed by adsorption of remaining degradation products at nearby carbon particles. Our data further suggests that reducing NiO to Ni(0) via a membrane pretreatment shifts the catalytic persulfate activation from a radicaltoa non-radical pathway, and that HCO3– can function as sacrificial electron donor for Ni(0). This completely mitigated nickel leaching from the membrane in contact to persulfate. Moreover, even in the presence of NaHCO3 and NaCl, a Ni(0)–carbon–PES membrane consistently eliminated ∼ 90 % of the total organic carbon (TOC) from a 2 mg/L diclofenac feed containing persulfate in single-pass flow-through mode (continuously for 5 h, respectively for 500 L/m2 permeate volume), with no detectable release of degradation products or any nickel leaching.

Development of dual-crosslinked Pluronic F127/Chitosan injectable hydrogels incorporating graphene nanosystems for breast cancer photothermal therapy and antibacterial applications

Nanomaterials with responsiveness to near-infrared light can mediate the photoablation of cancer cells with an exceptional spatio-temporal resolution. However, the therapeutic outcome of this modality is limited by the nanostructures’ poor tumor uptake. To address this bottleneck, it is appealing to develop injectable in situ forming hydrogels due to their capacity to perform a tumor-confined delivery of the nanomaterials with minimal off-target leakage. In particular, injectable in situ forming hydrogels based on Pluronic F127 have been emerging due to their FDA-approval status, biocompatibility, and thermosensitive sol–gel transition. Nevertheless, the application of Pluronic F127 hydrogels has been limited due to their fast dissociation in aqueous media. Such limitation may be addressed by combining the thermoresponsive sol–gel transition of Pluronic F127 with other polymers with crosslinking capabilities. In this work, a novel dual-crosslinked injectable in situ forming hydrogel based on Pluronic F127 (thermosensitive gelation) and Chitosan (ionotropic gelation in the presence of NaHCO3), loaded with Dopamine-reduced graphene oxide (DOPA-rGO; photothermal nanoagent), was developed for application in breast cancer photothermal therapy. The dual-crosslinked hydrogel incorporating DOPA-rGO showed a good injectability (through 21 G needles), in situ gelation capacity and cytocompatibility (viability > 73 %). As importantly, the dual-crosslinking improved the hydrogel’s porosity and prevented its premature degradation. After irradiation with near-infrared light, the dual-crosslinked hydrogel incorporating DOPA-rGO produced a photothermal heating (ΔT ≈ 22 °C) that reduced the breast cancer cells’ viability to just 32 %. In addition, this formulation also demonstrated a good antibacterial activity by reducing the viability of S. aureus and E. coli to 24 and 33 %, respectively. Overall, the dual-crosslinked hydrogel incorporating DOPA-rGO is a promising macroscale technology for breast cancer photothermal therapy and antimicrobial applications.

Genomic investigation and clinical correlates of the in vitro β-lactam: NaHCO3 responsiveness phenotype among methicillin-resistant Staphylococcus aureus isolates from a randomized clinical trial.

NaHCO3 responsiveness is a novel phenotype where some methicillin-resistant Staphylococcus aureus (MRSA) isolates exhibit significantly lower minimal inhibitory concentrations (MIC) to oxacillin and/or cefazolin in the presence of NaHCO3. NaHCO3 responsiveness correlated with treatment response to β-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO3-responsive strains with β-lactams was associated with faster clearance of bacteremia. The CAMERA2 trial (Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus) randomly assigned participants with MRSA bloodstream infections to standard therapy, or to standard therapy plus an anti-staphylococcal β-lactam (combination therapy). For 117 CAMERA2 MRSA isolates, we determined by broth microdilution the MIC of cefazolin and oxacillin, with and without 44 mM of NaHCO3. Isolates exhibiting ≥4-fold decrease in the MIC to cefazolin or oxacillin in the presence of NaHCO3 were considered "NaHCO3-responsive" to that agent. We compared the rate of persistent bacteremia among participants who had infections caused by NaHCO3-responsive and non-responsive strains, and that were assigned to combination treatment with a β-lactam. Thirty-one percent (36/117) and 25% (21/85) of MRSA isolates were NaHCO3-responsive to cefazolin and oxacillin, respectively. The NaHCO3-responsive phenotype was significantly associated with sequence type 93, SCCmec type IVa, and mecA alleles with substitutions in positions -7 and -38 in the regulatory region. Among participants treated with a β-lactam, there was no association between the NaHCO3-responsive phenotype and persistent bacteremia (cefazolin, P = 0.82; oxacillin, P = 0.81). In patients from a randomized clinical trial with MRSA bloodstream infection, isolates with an in vitro β-lactam-NaHCO3-responsive phenotype were associated with distinctive genetic signatures, but not with a shorter duration of bacteremia among those treated with a β-lactam.

NaHCO3 impairs the growth and fruit yield of tomato plants

Underground water enriched in NaHCO3 is used in farms of the Buenos Aires province for tomato crop irrigation. This farming practice leads to salt accumulation and soil impairment after several seasons of cultivation inside the greenhouses. This work assayed the effect of NaHCO3 on tomato fruit production. Plants of the Elpida variety of Solanum lycopersicum L were grown in a hydroponic system. The presence of NaHCO3 (from 5 mM, as measured in the underground water to 10 or 20 mM) reduced K+/Na+ ratio and whole plant biomass and fruit yield; however, no effect was observed on fruit quality parameters. To test the participation of ascorbic acid in the tolerance to this stress, two slggp1 Micro-Tom mutant lines deficient in this antioxidant were used. In these experiments plants were treated with 0, 5 and 10 mM NaHCO3 causing an impairment of K+/Na+ ratio, photosynthesis, fruit yield, leaf and shoot dry weight (but without effect in root biomass) and delaying of fruit ripening time. Wild type and mutants plant responses showed no differences at stress conditions. Although NaHCO3 treatments caused a similar impairment in ascorbic acid mutants and wild type plants, these results reinforced the physiological importance of ascorbic acid levels to optimize plant growth under non-stressful conditions. Taken as a whole, the results presented here demonstrated the importance of avoiding the accumulation of this salt in greenhouse soils to optimize tomato production.

Fabrication of engineered biochar-iron oxide from date palm frond for the effective removal of cationic dye from wastewater

Wastewater containing dye is harmful to the environment. Methylene blue (MB) dye can be removed from wastewater using low-cost, renewable adsorbents. In this study, modified biochar (Biochar-FexOy), pristine biochar and FexOy were fabricated, characterized, and investigated for their performance to remove MB dye from wastewater. The Biochar-FexOy (85.1 mg/g) showed increased adsorption capacity in comparison to biochar (60.1 mg/g) and FexOy (50 mg/g) at an optimum pH of 8 due to the increase in surface area, porosity, and deposition of metal ions on its surface for adsorption. The enhanced MB adsorption by the Biochar-FexOy can be attributed to electrostatic attraction, hydrogen bonding, π-π interactions, and possible cationic exchange as evidenced by the result of the FTIR, EDX, and XRD analysis. Moreover, the adsorption of MB dye by the Biochar-FexOy showed an antagonistic effect in the presence of NaHCO3− and NaCl salt but showed a synergistic effect in the presence of Cu (II) ions. The Langmuir and pseudo-second-order isotherm model best describe the adsorption process of MB dye over the Biochar-FexOy. The adsorption capacity was still high after 4 regeneration cycles for the Biochar-FexOy which concludes that modified biochar can be effectively utilized for dye wastewater treatment. Finally, the fixed-bed column adsorption performance demonstrated that Biochar-FexOy could be used to polish real secondary textile industry effluents prior to treatment.

Stereoselective Synthesis of New 4-Aryl-5-indolyl-1,2,4-triazole S- and N-β-Galactosides: Characterizations, X-ray Crystal Structure and Hirshfeld Surface Analysis

5-(1H-Indol-2-yl)-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 1a and 4-(4-chlorophenyl)-5-(1H-indol-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 1b were galactosylated in the presence of NaHCO3 in ethanol to produce S-galactosides 3,4, whereas, in the presence of K2CO3 in acetone they produced a mixture of S- and N-galactosides 3-6 with a higher yield of S-galactosides over the respective N-galactosides. Improvement in the yields of N-galactosides was produced by thermal migration of the galactosyl moiety from sulfur to nitrogen using fusion. β-Stereoselectivity of galactosylation was determined using the coupling constant value 3J1,2, which exceeded 9.0 Hz in all prepared galactosides. The precursors 1a and 1b alkylated with 3-bromopropan-1-ol 7 in K2CO3 and acetone produced the S-alkylated products 8 and 9, respectively. Structural determinations of new compounds 5 and 9 are presented. The phenyl and indole moieties were found to be twisted from the triazole ring mean in both compounds. For compound 5, the twist angles were 66.24° and 18.86°, respectively, while the corresponding values for 9 were in the ranges of 73.15–77.29° and 13.96–20.70°, respectively. Hence, the crystal system of 9 is triclinic while the space group is P-1. Detailed analysis of the intermolecular interactions in the crystal structure of 5 is presented using Hirshfeld calculations. The O…H, N…H, C…H, and S…H contacts appeared as red spots in the dnorm Hirshfeld surface indicating short distance intermolecular interactions. Their percentages were estimated based on the decomposition of the fingerprint plot to be 25.6, 2.4, 14.0, and 6.3%, respectively.

NiFe Foam for Oxygen-Evolution Reaction under Neutral Conditions, Electrolysis of Baking Soda Solution: Catalytic and Mechanistic Studies

NiFe oxide-based electrodes are promising compounds for oxygen-evolution reaction (OER), which is essential in metal–air batteries and water splitting. Indeed, OER is of great significance in the energy storage domain. Herein, NiFe oxide-based electrodes have been applied as effective and durable electrocatalysts in the presence of NaHCO3 (baking soda). Compared to corrosive acidic or alkaline solutions, the electrolysis of the baking soda solution toward producing oxygen and hydrogen is highly promising. Surprisingly, NiFe foam, without any anodization or modification, is an efficient and stable electrode for OER at pH= 8.5 (NaHCO3, 0.75 M). In addition, the experiments show that NiO(OH) and not Ni (bicarbonate) is the true catalyst for OER. The surface of the foam was investigated through several methods, including in situ Raman spectroscopy in the presence of NaH12/13CO3. All of the methods indicate the presence of various NiFe (hydr)oxides with different phases on the NiFe foam’s surface. For the NiFe foam at pH= 8.5 (NaHCO3, 0.75 M), the overpotentials for the onset of OER and the activity at 10 mA/cm2 are recorded at 250 and 460 mV, respectively. The Tafel plot of the electrode prepared at pH = 8.5 shows the linearity of the log(i) vs overpotential with a slope as low as 60 mV per decade. The effects of anodization potentials, electrochemically active surface areas, and a proposed mechanism for OER are also discussed. At least one possible pathway for OER could be the reaction of the electrolyte with high valent Ni ions on the surface of the electrode.

Role of the NaHCO3 Transporter MpsABC in the NaHCO3-β-Lactam-Responsive Phenotype in Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are an increasing concern due to their intrinsic resistance to most standard-of-care β-lactam antibiotics. Recent studies of clinical isolates have documented a novel phenotype, termed NaHCO3 responsiveness, in which a substantial proportion of MRSA strains exhibit enhanced susceptibility to β-lactams such as cefazolin and oxacillin in the presence of NaHCO3. A bicarbonate transporter, MpsAB (membrane potential-generating system), was recently found in S. aureus, where it plays a role in concentrating NaHCO3 for anaplerotic pathways. Here, we investigated the role of MpsAB in mediating the NaHCO3 responsiveness phenotype. Radiolabeled NaH14CO3 uptake profiling revealed significantly higher accumulation in NaHCO3-responsive vs nonresponsive MRSA strains when grown in ambient air. In contrast, under 5% CO2 conditions, NaHCO3-responsive (but not nonresponsive) strains exhibited repressed uptake. Oxacillin MICs were measured in four prototype strains and their mpsABC deletion mutants in the presence of NaHCO3 supplementation under 5% CO2 conditions. NaHCO3-mediated reductions in oxacillin MICs were observed in the responsive parental strains but not in mpsABC deletion mutants. No significant impact on oxacillin MICs was observed in the nonresponsive strains under the same conditions. Transcriptional and translational studies were carried out using both quantitative reverse transcription-PCR (qRT-PCR) and mpsA-green fluorescent protein (GFP) fusion constructs; these investigations showed that mpsA expression and translation were significantly upregulated during mid-exponential-phase growth in oxacillin-NaHCO3-supplemented medium in responsive versus nonresponsive strains. Taken together, these data show that the NaHCO3 transporter MpsABC is a key contributor to the NaHCO3-β-lactam responsiveness phenotype in MRSA. IMPORTANCE MRSA infections are increasingly difficult to treat, due in part to their resistance to most β-lactam antibiotics. A novel and relatively common phenotype, termed NaHCO3 responsiveness, has been identified in which MRSA strains show increased susceptibility in vitro and in vivo to β-lactams in the presence of NaHCO3. A recently described S. aureus NaHCO3 transporter, MpsAB, is involved in intracellular NaHCO3 concentration for anaplerotic pathways. We investigated the role of MpsAB in mediating the NaHCO3 responsiveness phenotype in four prototype MRSA strains (two responsive and two nonresponsive). We demonstrated that MpsABC is an important contributor to the NaHCO3-β-lactam responsiveness phenotype. Our study adds to the growing body of well-defined characteristics of this novel phenotype, which could potentially translate to alternative targets for MRSA treatment using β-lactams.

Comparison of four digestion protocols on the physical characteristics of gastric digesta from cooked couscous using the Human Gastric Simulator.

In vitro digestion is widely employed in food, nutraceutical and pharmaceutical research, and numerous in vitro gastric digestion protocols have been proposed, with a wide range of experimental conditions. Differences in the simulated gastric fluids (pH, mineral content, enzyme type and enzyme activity) of different digestion protocols may alter the results for the digestion of the same meal. This study aimed to investigate how variations in the gastric secretion rate and composition in four in vitro digestion protocols (Infogest Riddet, Infogest Semi-dynamic, UC Davis and United States Pharmacopeia) impacted the physical properties of the emptied gastric digesta. Cooked couscous was used as a model meal and subjected to simulated gastric digestion using a dynamic gastric model, the Human Gastric Simulator (HGS). The digesta were collected from the outlet of the HGS after 15, 30, 60, 90, 120, 150, or 180 min. The gastric emptying of dry matter, pH, rheological properties, and particle size were evaluated. The digestion protocol significantly influenced the solid content and moisture content of the digesta (p < 0.001), particles per gram of dry matter (p < 0.0001), gastric emptying of dry matter (p < 0.003), shear stress at 0.45 s-1 and consistency coefficient (p < 0.0001). The presence of NaHCO3 in the Infogest Riddet and Infogest Semi-dynamic gastric secretions provided an additional buffering effect and increased the digesta pH during gastric digestion. Similarly, the inclusion of mucin in the UC Davis protocol resulted in a higher flow and viscoelastic properties of the emptied digesta. The highest dilution of gastric content in the United States Pharmacopeia (USP) protocol resulted in larger particles emptied from the HGS and the longest gastric emptying half-time of all digestion protocols. These findings provide new insights into the impact of digestion protocols on the digesta properties, which can be beneficial for the design and standardization of in vitro digestion models.

Influence of Sodium Bicarbonate on Wall Teichoic Acid Synthesis and β-Lactam Sensitization in NaHCO3-Responsive and Nonresponsive Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) strains pose major treatment challenges due to their innate resistance to most β-lactams under standard in vitro antimicrobial susceptibility testing conditions. A novel phenotype among MRSA, termed "NaHCO3 responsiveness," where certain strains display increased susceptibility to β-lactams in the presence of NaHCO3, has been identified among a relatively large proportion of MRSA isolates. One underlying mechanism of NaHCO3 responsiveness appears to be related to decreased expression and altered functionality of several genes and proteins involved in cell wall synthesis and maturation. Here, we studied the impact of NaHCO3 on wall teichoic acid (WTA) synthesis, a process intimately linked to peptidoglycan (PG) synthesis and functionality, in NaHCO3-responsive versus -nonresponsive MRSA isolates. NaHCO3 sensitized responsive MRSA strains to cefuroxime, a specific penicillin-binding protein 2 (PBP2)-inhibitory β-lactam known to synergize with early WTA synthesis inhibitors (e.g., ticlopidine). Combining cefuroxime with ticlopidine with or without NaHCO3 suggested that these latter two agents target the same step in WTA synthesis. Further, NaHCO3 decreased the abundance and molecular weight of WTA only in responsive strains. Additionally, NaHCO3 stimulated increased autolysis and aberrant cell division in responsive strains, two phenotypes associated with disruption of WTA synthesis. Of note, studies of key genes involved in the WTA biosynthetic pathway (e.g., tarO, tarG, dltA, and fmtA) indicated that the inhibitory impact of NaHCO3 on WTA biosynthesis in responsive strains likely occurred posttranslationally. IMPORTANCE MRSA is generally viewed as resistant to standard β-lactam antibiotics. However, a NaHCO3-responsive phenotype is observed in a substantial proportion of clinical MRSA strains in vitro, i.e., isolates which demonstrate enhanced susceptibility to standard β-lactam antibiotics (e.g., oxacillin) in the presence of NaHCO3. This phenotype correlates with increased MRSA clearance in vivo by standard β-lactam antibiotics, suggesting that patients with infections caused by such MRSA strains might be amenable to treatment with β-lactams. The mechanism(s) behind this phenotype is not fully understood but appears to involve mecA-PBP2a production and maturation axes. Our study adds significantly to this body of knowledge in terms of additional mechanistic targets of NaHCO3 in selected MRSA strains. This investigation demonstrates that NaHCO3 has direct impacts on S. aureus wall teichoic acid biosynthesis in NaHCO3-responsive MRSA. These findings provide an additional target for new agents being designed to synergistically kill MRSA using β-lactam antibiotics.

Можливе значення аденілатциклазного сигнального шляху в синтезі оксиду азоту мітохондріями міометрія

NO synthase activity (mtNOS) in uterine smooth muscle mitochondria under the action of the cAMP/protein kinase A signaling system modulators was studied. The experiments were performed on isolated mitochondria from rat myometrium using the NO-sensitive fluorescent probe DAF-FM-DA. NO synthesis in mitochondria was increased by adenylate cyclase activators NaHCO3 (30 mM) and forskolin (10 μM), as well as phosphodiesterase inhibitor caffeine (1 mM). The addition of ATP (0.5-5 mM) caused a slight increase in nitric oxide synthesis. The effect of ATP was enhanced in the presence of NaHCO3 and caffeine. The intensity of NO formation in mitochondria decreased by approximately 50 % in the case of inhibition of adenylate cyclase activity by the compound KH7 (25 μM). In the presence of the protein kinase A inhibitor PKI (10 nM) NO synthesis in mitochondria was also significantly reduced. When the constitutive NO-synthase inhibitor L-NAME (100 μM) was introduced into the incubation medium, the stimulating effect of the studied compounds on NO synthesis in mitochondria was not observed. These data suggests a possible dependence of mtNOS function on the activity of the cAMP/protein kinase A signaling system in smooth muscle mitochondria.

The NaHCO3-Responsive Phenotype in Methicillin-Resistant Staphylococcus aureus (MRSA) Is Influenced by mecA Genotype.

ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) strains are a leading cause of many invasive clinical syndromes, and pose treatment difficulties due to their in vitro resistance to most β-lactams on standard laboratory testing. A novel phenotype frequently identified in MRSA strains, termed ‘NaHCO3-responsiveness’, is a property whereby strains are susceptible in vitro to many β-lactams in the presence of NaHCO3. Specific mecA genotypes, repression of mecA/PBP2a expression and perturbed maturation of PBP2a by NaHCO3 have all been associated with this phenotype. The aim of this study was to define the relationship between specific mecA genotypes and PBP2a substitutions, on the one hand, with NaHCO3-responsiveness in vitro. Mutations were made in the mecA ribosomal binding site (RBS -7) and at amino acid position 246 of its coding region in parental strains MW2 (NaHCO3-responsive) and C36 (NaHCO3- nonresponsive) to generate ‘swap’ variants, each harboring the other’s mecA-RBS/coding region genotypes. Successful swaps were confirmed by both sequencing, as well as predicted swap of in vitro penicillin-clavulanate susceptibility phenotypes. MW2 swap variants harboring the nonresponsive mecA genotypes became NaHCO3-nonresponsive (resistant to the β-lactam, oxacillin [OXA]), in the presence of NaHCO3. Moreover, these swap variants had lost NaHCO3-mediated repression of mecA/PBP2a expression. In contrast, C36 swap variants harboring the NaHCO3-responsive mecA genotypes remained NaHCO3-nonresponsive phenotypically, and still exhibited nonrepressible mecA/PBP2a expression. These data demonstrate that in addition to the mecA genotype, NaHCO3-responsiveness may also depend on strain-specific genetic backgrounds.

Transient Chemical Activation of Covalent Bonds for Healing of Kinetically Stable and Multifunctional Organohydrogels

Transient Chemical Activation of Covalent Bonds for Healing of Kinetically Stable and Multifunctional Organohydrogels

Impacts of NaHCO3 on β-Lactam Binding to PBP2a Protein Variants Associated with the NaHCO3-Responsive versus NaHCO3-Non-Responsive Phenotypes.

Methicillin-resistant Staphylococcus aureus (MRSA) regulates resistance to β-lactams via preferential production of an alternative penicillin-binding protein (PBP), PBP2a. PBP2a binds many β-lactam antibiotics with less affinity than PBPs which are predominant in methicillin-susceptible (MSSA) strains. A novel, rather frequent in vitro phenotype was recently identified among clinical MRSA bloodstream isolates, termed “NaHCO3-responsiveness”. This phenotype features β-lactam susceptibility of certain MRSA strains only in the presence of NaHCO3. Two distinct PBP2a variants, 246G and 246E, have been linked to the NaHCO3-responsive and NaHCO3-non-responsive MRSA phenotypes, respectively. To determine the mechanistic impact of PBP2a variants on β-lactam susceptibility, binding profiles of a fluorescent penicillin probe (Bocillin-FL) to each purified PBP2a variant were assessed and compared to whole-cell binding profiles characterized by flow cytometry in the presence vs. absence of NaHCO3. These investigations revealed that NaHCO3 differentially influenced the binding of the fluorescent penicillin, Bocillin-FL, to the PBP2a variants, with binding intensity and rate of binding significantly enhanced in the 246G compared to the 246E variant. Of note, the NaHCO3-β-lactam (oxacillin)-responsive JE2 strain, which natively harbors the 246G variant, had enhanced Bocillin-FL whole-cell binding following exposure to NaHCO3. This NaHCO3-mediated increase in whole-cell Bocillin-FL binding was not observed in the NaHCO3-non-responsive parental strain, COL, which contains the 246E PBP2a variant. Surprisingly, genetic swaps of the mecA coding sites between JE2 and COL did not alter the NaHCO3-enhanced binding seen in JE2 vs. COL. These data suggest that the non-coding regions of mecA may be involved in NaHCO3-responsiveness. This investigation also provides strong evidence that the NaHCO3-responsive phenotype in MRSA may involve NaHCO3-mediated increases in both initial cell surface β-lactam binding, as well as ultimate PBP2a binding of β-lactams.

Facile One-Pot Preparation of 5-Substituted 4-Iodo-1-tosylpyrazoles from N-Propargyl-N′-tosylhydrazines through Iodocyclization

AbstractTreatment of N-propargyl-N′-tosylhydrazines with molecular iodine (I2) in the presence of NaHCO3 under warming conditions gave efficiently the corresponding 5-substituted 4-iodo-1-tosylpyrazoles in good to moderate yields. In addition, the same reaction in the presence of acetic acid generated the corresponding 5-aryl-4-iodopyrazoles in moderate yields. The reactions are simple and efficient transition-metal-free methods for the preparation of 5-substituted 4-iodo­pyrazole unit.

Stability of hydrotalcite (Mg-Al layered double hydroxide) in presence of different anions

MgO contained in cementitious materials is experimentally observed to precipitate as poorly crystalline hydrotalcite (Mg-Al LDH). However, the geochemical modelling of hydrotalcite is challenging due to the lack of consistent thermodynamic dataset for this phase. Hydrotalcites with Mg/Al = 2 were synthesised in the presence of NaHCO3, NaCl, Na2SO4, NaNO3, and NaOH. Mass balance, XRD and FT-IR indicated the incorporation of the anions in the interlayer together with some carbonate. The crystallinity of the phase increased depending on the anion: SO42− < Cl− < NO3− < OH− < CO32−. An in-situ increase of temperature monitored by XRD and TGA showed that the stability of the hydrotalcite structure with temperature also depended on the incorporated anion. The solubility products were calculated based on the solution analysis of samples re-equilibrated at different temperatures, while the entropy and heat capacity were obtained from the additivity method or the molar volume. A simple solid-solution model for hydrotalcite containing CO3, OH, SO4, Cl and NO3 is suggested.

Impact of Bicarbonate-β-Lactam Exposures on Methicillin-Resistant Staphylococcus aureus (MRSA) Gene Expression in Bicarbonate-β-Lactam-Responsive vs. Non-Responsive Strains.

Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a difficult clinical treatment issue. Recently, a novel phenotype was discovered amongst selected MRSA which exhibited enhanced β-lactam susceptibility in vitro in the presence of NaHCO3 (termed ‘NaHCO3-responsiveness’). This increased β-lactam susceptibility phenotype has been verified in both ex vivo and in vivo models. Mechanistic studies to-date have implicated NaHCO3-mediated repression of genes involved in the production, as well as maturation, of the alternative penicillin-binding protein (PBP) 2a, a necessary component of MRSA β-lactam resistance. Herein, we utilized RNA-sequencing (RNA-seq) to identify genes that were differentially expressed in NaHCO3-responsive (MRSA 11/11) vs. non-responsive (COL) strains, in the presence vs. absence of NaHCO3-β-lactam co-exposures. These investigations revealed that NaHCO3 selectively repressed the expression of a cadre of genes in strain 11/11 known to be a part of the sigB-sarA-agr regulon, as well as a number of genes involved in the anchoring of cell wall proteins in MRSA. Moreover, several genes related to autolysis, cell division, and cell wall biosynthesis/remodeling, were also selectively impacted by NaHCO3-OXA exposure in the NaHCO3-responsive strain MRSA 11/11. These outcomes provide an important framework for further studies to mechanistically verify the functional relevance of these genetic perturbations to the NaHCO3-responsiveness phenotype in MRSA.

A Combined Phenotypic-Genotypic Predictive Algorithm for In Vitro Detection of Bicarbonate: β-Lactam Sensitization among Methicillin-Resistant Staphylococcus aureus (MRSA).

Antimicrobial susceptibility testing (AST) is routinely used to establish predictive antibiotic resistance metrics to guide the treatment of bacterial pathogens. Recently, a novel phenotype termed “bicarbonate (NaHCO3)-responsiveness” was identified in a relatively high frequency of clinical MRSA strains, wherein isolates demonstrate in vitro “susceptibility” to standard β-lactams (oxacillin [OXA]; cefazolin [CFZ]) in the presence of NaHCO3, and in vivo susceptibility to these β-lactams in experimental endocarditis models. We investigated whether a targeted phenotypic-genotypic screening of MRSA could rule in or rule out NaHCO3 susceptibility upfront. We studied 30 well-characterized clinical MRSA bloodstream isolates, including 15 MIC-susceptible to CFZ and OXA in NaHCO3-supplemented Mueller–Hinton Broth (MHB); and 15 MIC-resistant to both β-lactams in this media. Using a two-tiered strategy, isolates were first screened by standard disk diffusion for susceptibility to a combination of amoxicillin-clavulanate [AMC]. Isolates then underwent genomic sequence typing: MLST (clonal complex [CC]); agr; SCCmec; and mecA promoter and coding region. The combination of AMC disk susceptibility testing plus mecA and spa genotyping was able to predict MRSA strains that were more or less likely to be NaHCO3-responsive in vitro, with a high degree of sensitivity and specificity. Validation of this screening algorithm was performed in six strains from the overall cohort using an ex vivo model of endocarditis. This ex vivo model recapitulated the in vitro predictions of NaHCO3-responsiveness vs. nonresponsiveness above in five of the six strains.

Ameliorating Effect of Bicarbonate on Salinity Induced Changes in the Growth, Nutrient Status, Cell Constituents and Photosynthetic Attributes of Microalga Chlorella vulgaris

The cells of Chlorella vulgaris exhibited NaCl (0-400mM) induced decrease in the growth, protein, chlorophyll, carbohydrate and total organic carbon, whereas total lipid and proline content increased with rising level of NaCl. Addition of NaHCO3 (20mM) exhibited antagonistic effect against the adverse effect of salinity on the growth, level of macromolecules except proline. The SEM-EDS analysis of NaCl treated cells exhibited morphological variations as well as reduced accumulation of Na and Cl due to the presence of NaHCO3. The results on chlorophyll fluorescence induction kinetics revealed NaCl induced decline in the photosynthetic performance and quantum yield, while non-photochemical quenching of chlorophyll was enhanced, particularly at lower concentrations of NaCl. Addition of NaHCO3 to NaCl treated cells exhibited further increase in the non-photochemical quenching values. Thus, these results demonstrated that adverse impact of NaCl on the C. vulgaris cells was significantly mitigated in the presence of bicarbonate.

Facile preparation of 3-aryl-4-iodoisoquinolines from N-(o-Arylethynyl)benzyl p-toluenesulfonamides with iodine and base

Abstract Treatment of N-(o-arylethynyl)benzyl p-toluenesulfonamides with molecular iodine in the presence of NaHCO3 at 60 °C, followed by the reaction with tBuOK at room temperature gave 3-aryl-4-iodoisoquinolines in good yields. 4-Iodo-3-phenylisoquinoline, which is one of the obtained 3-aryl-4-iodoisoquinolines, was further transformed into isoquinoline derivatives smoothly. The present approach is a novel one-pot method for the preparation of 3-aryl-4-iodoisoquinolines from N-(o-arylethynyl)benzyl p-toluenesulfonamides under transition-metal-free conditions. © 2021 Elsevier Science. All rights reserved.