Semicontinuous production of lactic acid from cheese whey using integrated membrane reactor

Semicontinuous production of lactic acid from cheese whey using free cells of Bifidobacterium longum with and without nanofiltration was studied. For the semicontinuous fermentation without membrane separation, the lactic acid productivity of the second and third runs is much lower than the first run. The semicontinuous fermentation with nanoseparation was run semicontinuously for 72 h with lactic acid to be harvested every 24 h using a nanofiltration membrane unit. The cells and unutilized lactose were kept in the reactor and mixed with newly added cheese whey in the subsequent runs. Slight increase in the lactic acid productivity was observed in the second and third runs during the semicontinuous fermentation with nanofiltration. It can be concluded that nanoseparation could improve the lactic acid productivity of the semicontinuous fermentation process.     

Solution Thermodynamics of Piroxicam in some Ethanol + Water Mixtures and Correlation with the Jouyban–Acree Model

The solubility of piroxicam (PIR) in several ethanol + water mixtures was determined at five temperatures from 293.15 to 313.15 K. The thermodynamic functions; Gibbs energy, enthalpy, and entropy of solution and of mixing were obtained from these solubility data and the drug properties of fusion by using the van’t Hoff and Gibbs equations. The greatest solubility value was obtained in pure ethanol. A non-linear enthalpy–entropy relationship was observed from a plot of enthalpy versus Gibbs energy of solution. Accordingly, the driving mechanism for PIR solubility in water-rich mixtures is the entropy, probably due to water-structure loss around the drug’s non-polar moieties by ethanol, whereas, in ethanol-rich mixtures the driving mechanism is the enthalpy, probably due to better PIR solvation by the co-solvent molecules. The solubilities and the derived thermodynamic properties in mixed solvents were correlated using the Jouyban–Acree model.     

Engineering and Kinetic Stabilization of the Therapeutic Enzyme Anabeana variabilis Phenylalanine Ammonia Lyase

Anabeana variabilis phenylalanine ammonia lyase has just recently been discovered and introduced in clinical trials of phenylketonuria enzyme replacement therapy for its outstanding kinetic properties. In the present study, kinetic stabilization of this therapeutically important enzyme has been explored by introduction of a disulfide bond into the structure. Site-directed mutagenesis was performed with quick-change PCR method. Recombinant wild-type and mutated enzymes were expressed in Escherichia coli, and his-tagged proteins were affinity purified. Formation of disulfide bond was confirmed by Ellman’s method, and then chemical unfolding, kinetic behavior, and thermal inactivation of mutated enzyme were compared with the wild type. Based on our results, the Q292C mutation resulted in a significant improvement in kinetic stability and resistance against chemical unfolding of the enzyme while kinetic parameters and pH profile of enzyme activity were remained unaffected. The results of the present study provided an insight towards designing phenylalanine ammonia lyases with higher stability.     

1,3‐Dipolar Cycloaddition of 4‐Chlorobenzonitrile Oxide with Some Dipolarophiles: Theoretical Analysis of Regioselectivity

Reaction of 4‐chlorobenzonitrile oxide ( 2 ) which was generated in situ with acrylo nitrile ( 3 ), vinyl acetate ( 4 ) and allyl bromide ( 5 ) as dipolarphile afforded the new cycloadducts 6a , 7a , and 8a compounds, respectively. Reactivity and regiochemistry of these reactions were investigated using activation energy calculations and density functional theory‐based reactivity indexes. The theoretical ¹³C NMR chemical shifts of the cycloadducts which were obtained by gauge‐invariant atomic orbital method were comparable with the observed values.     

One-Pot Synthesis of N-Alkyl Sulfonyl Hydrazones by Dialkyl Acetylenedicarboxylate-Mediated Reaction of Trialkylphosphites with Sulfonyl Hydrazones

Stable derivatives of N-alkyl sulfonyl hydrazone were obtained in excellent yields from the reaction between electron-deficient acetylenic ester compounds and sulfonyl hydrazones in the presence of trialkylphosphites in dichloromethan at room temperature.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Dinuclear copper complexes of pyridylphenylphosphine ligands: Characterization of a mixed-valence Cu/Cu dimer

Homo bi-copper complexes [Cu₂{PhP(2-py)₂}₂(NO₃)₃] (1) and [Cu₂{P(2-py)₃}₂Cl₂] (2), were synthesized from the reaction of Cu(NO₃)₂·3H₂O and CuCl₂·2H₂O with their corresponding 2-pyridylphosphine ligands. Compound 1 has a mixed valence Cu(I)-Cu(II) core with electron acceptor phosphine atoms and two NO₃⁻ anions coordinated in a monodentate fashion to Cu(I), giving it a distorted tetrahedral geometry. The environment of Cu(II) in 1 is composed of four nitrogen atoms from pyridyl and another NO₃⁻ anion in a square pyramidal geometry. This complex shows luminescence and a low energy absorption band at 969 nm corresponding to intermetallic electron transfer between the copper centers. Complex 2 was prepared from the treatment of copper(II) chloride with tris(2-pyridyl)phosphine, producing a binuclear copper complex which possesses a crystallographic inversion center. The copper geometry in this complex is distorted tetrahedral with coordination of one Cl⁻, two nitrogens from one bridging tris(2-pyridyl)phosphine ligand and one P atom from the other bridging tris(2-pyridyl)phosphine ligand, in a similar way observed in related complexes. The products have been characterized by spectroscopic methods and also by the single-crystal X-ray diffraction method.     

Copper(ii) ketimides in sp3 C–H amination

Commercially available benzophenone imine (HN CPh₂) reacts with β-diketiminato copper(ii) tert-butoxide complexes [Cu^II]–O^tBu to form isolable copper(ii) ketimides [Cu^II]–N CPh₂. Structural characterization of the three coordinate copper(ii) ketimide [Me₃NN]Cu–N CPh₂ reveals a short Cu-N_ketimide distance (1.700(2) Å) with a nearly linear Cu–N–C linkage (178.9(2)°). Copper(ii) ketimides [Cu^II]–N CPh₂ readily capture alkyl radicals R˙ (PhCH(˙)Me and Cy˙) to form the corresponding R–N CPh₂ products in a process that competes with N–N coupling of copper(ii) ketimides [Cu^II]–N CPh₂ to form the azine Ph₂C N–N CPh₂. Copper(ii) ketimides [Cu^II]–N CAr₂ serve as intermediates in catalytic sp³ C–H amination of substrates R–H with ketimines HN CAr₂ and ^tBuOO^tBu as oxidant to form N-alkyl ketimines R–N CAr₂. This protocol enables the use of unactivated sp³ C–H bonds to give R–N CAr₂ products easily converted to primary amines R–NH₂via simple acidic deprotection.

Commercially available benzophenone imine (HN CPh₂) reacts with β-diketiminato copper(ii) tert-butoxide complexes [Cu^II]–O^tBu to form isolable copper(ii) ketimides [Cu^II]–N CPh₂ that serve as intermediates in catalytic sp³ C−H amination via radical relay.     

Antiviral Therapeutic Potential of Curcumin: An Update

The treatment of viral disease has become a medical challenge because of the increasing incidence and prevalence of human viral pathogens, as well as the lack of viable treatment alternatives, including plant-derived strategies. This review attempts to investigate the trends of research on in vitro antiviral effects of curcumin against different classes of human viral pathogens worldwide. Various electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar were searched for published English articles evaluating the anti-viral activity of curcumin. Data were then extracted and analyzed. The forty-three studies (published from 1993 to 2020) that were identified contain data for 24 different viruses. The 50% cytotoxic concentration (CC50), 50% effective/inhibitory concentration (EC50/IC50), and stimulation index (SI) parameters showed that curcumin had antiviral activity against viruses causing diseases in humans. Data presented in this review highlight the potential antiviral applications of curcumin and open new avenues for further experiments on the clinical applications of curcumin and its derivatives.     

HPLC/DAD,Antibacterial and Antioxidant Activities of Plectranthus Species (Lamiaceae) Combined with the Chemometric Calculations

The increase in antibiotic resistance and the emergence of new bacterial infections have intensified the research for natural products from plants with associated therapy. This study aimed to verify the antibacterial and antioxidant activity of crude extracts of the genus Plectranthus species, being the first report on the modulation of aminoglycosides antibiotic activity by Plectranthus amboinicus extracts. The chemical composition was obtained by chemical prospecting and High-Performance Liquid Chromatography with diode arrangement detector (HPLC/DAD). The antibacterial activities of the extracts alone or in association with aminoglycosides were analyzed using the microdilution test. The antioxidant activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. The phytochemical prospection allowed the flavonoids, saponins, tannins and triterpenoids to be identified. Quercetin, rutin, gallic acid, chlorogenic acid, caffeic acid, catechin, kaempferol, glycosylated kaempferol, quercitrin, and isoquercitrin were identified and quantified. The principal component analysis (PCA) observed the influence of flavonoids and phenolic acids from Plectranthus species on studied activities. Phytochemical tests with the extracts indicated, especially, the presence of flavonoids, confirmed by quantitative analysis by HPLC. The results revealed antibacterial activities, and synergistic effects combined with aminoglycosides, as well as antioxidant potential, especially for P. ornatus species, with IC₅₀ of 32.21 µg/mL. Multivariate analyzes show that the inclusion of data from the antioxidant and antibacterial activity suggests that the antioxidant effect of these species presents a significant contribution to the synergistic effect of phytoconstituents, especially based on the flavonoid contents. The results of this study suggest the antibacterial activity of Plectranthus extracts, as well as their potential in modifying the resistance of the analyzed aminoglycosides.     

Dispersive solid-phase extraction of risperidone from plasma samples using graphene oxide aerogels and determination with liquid chromatography

A graphene oxide-based aerogel was synthesized and applied to the extraction and the determinations with the high-performance liquid chromatography-ultraviolet detector. After the characterization of the produced graphene-aerogel, it was utilized as a dispersive solid-phase extraction sorbent for risperidone extraction from plasma samples. Aerogels are materials with a large surface area-to-mass ratio and plenty of core with functional groups which can easily attach to the analytes to extract them to the second phase. The suggested method determined risperidone in plasma samples in the wide dynamic range from 20 ng/ml to 3 μg/ml. The limits of detection and quantification of the developed method were calculated as 2.4 and 8.2 ng/ml, respectively. As a novel feature, the developed method has no need to precipitate plasma proteins, improving the analytical performance of the analysis. Also, for the first time, the produced materials were utilized for the extraction of risperidone from the plasma samples. The obtained results revealed that the developed approach could be employed as an accurate method for the quantification of risperidone in real plasma samples.