A Novel C1q Domain-Containing Protein Isolated from the Mollusk Modiolus kurilensis Recognizing Glycans Enriched with Acidic Galactans and Mannans

C1q domain-containing (C1qDC) proteins are a group of biopolymers involved in immune response as pattern recognition receptors (PRRs) in a lectin-like manner. A new protein MkC1qDC from the hemolymph plasma of Modiolus kurilensis bivalve mollusk widespread in the Northwest Pacific was purified. The isolation procedure included ammonium sulfate precipitation followed by affinity chromatography on pectin-Sepharose. The full-length MkC1qDC sequence was assembled using de novo mass-spectrometry peptide sequencing complemented with N-terminal Edman’s degradation, and included 176 amino acid residues with molecular mass of 19 kDa displaying high homology to bivalve C1qDC proteins. MkC1qDC demonstrated antibacterial properties against Gram-negative and Gram-positive strains. MkC1qDC binds to a number of saccharides in Ca2+-dependent manner which characterized by structural meta-similarity in acidic group enrichment of galactose and mannose derivatives incorporated in diversified molecular species of glycans. Alginate, κ-carrageenan, fucoidan, and pectin were found to be highly effective inhibitors of MkC1qDC activity. Yeast mannan, lipopolysaccharide (LPS), peptidoglycan (PGN) and mucin showed an inhibitory effect at concentrations three orders of magnitude greater than for the most effective saccharides. MkC1qDC localized to the mussel hemal system and interstitial compartment. Intriguingly, MkC1qDC was found to suppress proliferation of human adenocarcinoma HeLa cells in a dose-dependent manner, indicating to the biomedical potential of MkC1qDC protein.

Solubility Property of Baganuur Coal: Performance Assessment by FTIR Spectroscopic Analysis

In the present work, the extraction of Mongolian Baganuur coal in solvents as pyridine and ionic liquid with 1-butyl-3-methyl-imidazolium chloride ([Bmim]Cl) anion was first applied. The as recieved coal, its extracts and insoluble residues were then characterized using the Fourier transform infrared (FTIR) spectroscopy. The obtained FTIR spectra have revealed many new features in the field of coal study. An appearance or sharpening of the particular bands after the chemical treatment allow a determination of inactive or weak fundamental vibrations precisely. Some emphasis are as follows, substantial quantitative change, the integrated area decrease of water molecule band at 3260 cm−1 comparing to as received sample and ionic liquid treated extract, can be seen for the extract spectrum in the pyridine treatment. Pyridine react to coal structure particularly in long-wave frequency zone means very susceptible to the oxygen containing functional group. Upon interaction between acidic group of the coal and the basic solvent as pyridine, the inter-fragment hydrogen and ester bonding in the coal structure is breaking, thus increasing the solubility of the individual fragments via producing new components. Towards forming H bond in the short wave zone Cl− anion shows a strong effect on the coal molec-ular structure. A stabilization of hydrogen bonds show well fluidization and a strong intermolecular interaction of the process via its powerful spectral intensity that is followed many new bands and con-siderable strengthening of band spectral integral area in this frequency region. In long-wave vibrational region there are appearances of many new bands, shift in frequency and depletion of the as recieved coal bands. [Bmim]Cl treatment exhibits the highest effect of the disruption on the carboxylic acids dimer.

2,5-disubstituted-4-thiazolidinones: Synthesis, anti-inflammatory, free radical scavenging potentials and structural insights through molecular docking

: The present work reports synthesis and screening of fifteen 2,5-disubstituted-4-thiazolidinones with different substitutions of varied arylidene groups at imino. The structures of the compounds were confirmed by spectral characterization. The compounds were subjected to in vivo anti-inflammatory and in vitro antioxidant activities. The derivatives possessed remarkable activities quite close to standard drugs used. Unlike conventional non-selective NSAIDs, the synthesized compounds did not contain any acidic group, thereby ensuring a complete cure from ulcers. To further substantiate the claim for safer derivatives, the active compounds were docked against the cyclooxygenase (COX)-2 enzyme. It was found that 4-fluorophenylimino substituent at 2- position and 3-nitro moiety on a 5-benzylidene nucleus of the 4-thiazolidinone derivative fitted in the COX-2 binding pocket. The compounds exhibited remarkable activity in scavenging free radicals, as depicted by the DPPH assay method. The structure-activity relationship was also established in the present work with respect to the nature and position of the substituents. The active compounds were evaluated for drug-like nature under Lipinski’s rule of five, and the toxicity behaviour of active compounds was predicted using ADMETlab software. The compounds have the potential to target degenerative disorders associated with inflammation and the generation of free radicals.

Impact Modifiers and Compatibilizers for Versatile Epoxy-Based Adhesive Films with Curing and Deoxidizing Capabilities

Epoxy resins with acidic compounds feature adhesion, robustness, and deoxidizing ability. In this study, hybrid adhesive films with deoxidizing and curing capabilities for semiconductor packaging were fabricated. The compatibilizing effects and mechanical properties were chiefly investigated by using various additive binders (thermoplastic amorphous polymers) and compatibilizing agents. The curing, deoxidizing, thermal, and rheological properties were systematically investigated. For uniform film formation and maximizing deoxidizing curable abilities, a thermoplastic--thermoset mixture containing a phenyl and carboxylic acid-based additive (benzoic acid), and a polycarbonate was chosen as the model adhesive film. Without either a phenyl or an acidic group in the compatibilizing agent, deoxidizing and compatibilizing effects were not achieved. The manufactured hybrid adhesive film can be effectively used, especially for electronic devices that require deoxidization and adhesion.

Synthetic glycosidases for the precise hydrolysis of oligosaccharides and polysaccharides

Synthetic glycosidases with a sugar-binding active site and a precisely positioned acidic group hydrolyze oligo- and polysaccharides selectively in hot water to afford desired sugar products in a single step.

Crystal structure of a 1:1 co-crystal of the anticancer drug gefitinib with azelaic acid

In the title co-crystal, C22H24ClFN4O3·C9H16O4, gefitinib (GTB; systematic name: quinazolin-4-amine) co-crystallizes with azelaic acid (AA; systematic name: nonanedioic acid). The co-crystal has the monoclinic P21/n centrosymmetric space group, containing one molecule each of GTB and AA in the asymmetric unit. A structure overlay of the GTB molecule in the co-crystal with that of its most stable polymorph revealed a significant difference in the conformation of the morpholine moiety. The significant deviation in the conformation of one of the acidic groups of azelaic acid from its usual linear chain structure could be due to the encapsulation of one acidic group in the pocket formed between the two pincers of GTB namely, the morpholine and phenyl moieties. Both GTB and AA molecules form N—H...O, O—H...N, C—H...O hydrogen bonds with C—H...F close contacts along with off-stacked aromatic π–π interactions between the GTB molecules.

EFFECT OF IONISED (ELECTROLYSED) WATER ON THE RAT EMBRYO DEVELOPMENT

The aim of this study was to investigate the effects ionised water has on embryonic development using Wistar rat animal model. For that purpose, alkaline and acidic water was prepared with a domestic water ioniser. It was found that the concentrations of Cl–, SO42– ions increased in acidic water, while in alkaline water, Ca2+ concentration decreased and halogenated hydrocarbon concentrations exceeded permitted levels. The animals were given test alkaline and acidic water, as well as tap water as control. After three months, female rats were mated. On the 21st day of gestation, they were euthanized and subjected to Caesarean sections; the number of live and dead fetuses was recorded. The fetuses were examined for external or visceral malformations and skeletal abnormalities. The data showed that embryo death was higher in acidic and alkaline experimental groups in comparison to the control group. The fetuses in both test groups were significantly shorter than in the control group. Long bones of fetal hind and front limbs were shorter in the acidic group in comparison to the control group. Retardation of limb osteogenesis was expressed in the acidic group fetuses. Therefore, in our model, ionised water had a negative effect on the embryonic development.

NOVEL PHARMACEUTICAL COCRYSTAL OF TELMISARTAN AND HYDROCHLOROTHIAZIDE

Objective: Telmisartan (TEL), commonly used antihypertensive, is poorly soluble in water and has limited and variable bioavailability. Commercially, TEL is available as a single drug and in combination with hydrochlorothiazide (HYZ). Researchers have developed cocrystals of TEL with coformers, namely, oxalic acid, glutaric acid, and saccharin. An attempt was made to prepare the cocrystals of TEL with HYZ, an active pharmaceutical ingredient (API) itself so that both the APIs are available in a single tablet. The present study was aimed at enhancement in solubility of TEL by formation of its cocrystals. Methods: The cocrystals of TEL with HYZ, in different stoichiometric ratios (1:0.5, 1:1, and 1:2), were prepared by solvent coevaporation and liquid-assisted grinding methods. The cocrystals, consisting of TEL:HYZ (in 1:0.5 ratio and 1:1 ratio), depicted maximum yield, drug content, saturation solubility, and flow properties. These cocrystals were characterized by X-ray analysis, infrared spectroscopy, and thermal analysis. Results: The crystal structure of TEL-HYX revealed that it was a cocrystal, since no proton was transferred between the TEL and HYZ molecules. It was predicted that two molecules are associated through a hydrogen bond between an acidic group of TEL and sulfonamido group of HYZ. The cocrystallization improved the solubility of TEL 7 times. In vitro release rate of tablets of cocrystals was higher than that of marketed TEL tablets. HYZ has a potential to form the cocrystals of TEL. Conclusion: The objective of improvement in the solubility of TEL was successfully achieved by the formation of cocrystals of TEL: HYZ.

DFT-Assisted Design and Evaluation of Bifunctional Amine/Pyridine-Oxazoline Metal Catalysts for Additions of Ketones to Unactivated Alkenes and Alkynes

Bifunctional catalyst systems for the direct addition of ­ketones to unactivated alkenes/alkynes were designed and modeled by density functional theory (DFT). The designed catalysts possess bidentate ligands suitable for binding of pi-acidic group 10 metals capable of activating alkenes/alkynes, and a tethered organocatalyst amine to ­activate the ketone via formation of a nucleophilic enamine intermediate. The structures of the designed catalysts before and after C–C bond formation were optimized using DFT, and reaction steps involving group 10 metals were predicted to be significantly exergonic. A novel oxazoline precatalyst with a tethered amine separated by a meta-substituted benzene spacer was synthesized via a 10-step sequence that ­includes a key regioselective epoxide ring-opening step. It was combined with group 10 metal salts, including cationic Pd(II) and Pt(II), and screened for the direct addition of ketones to several alkenes and an ­internal alkyne. 1H NMR studies suggest that catalyst-catalyst inter­actions with this system via amine–metal coordination may preclude the desired addition reactions. The catalyst design approach disclosed here, and the promising calculations obtained with square planar group 10 metals, light a path for the discovery of novel bifunctional catalysts for C–C bond formation.