New types of hyperbranched 1,2,3-triazole-alkoxysiloxane functional polymers for metal embedded nanocomposite surface coatings.

In this study, using the "click-chemistry" azide-alkyne cycloaddition reaction, two new types of polymers, namely, water-soluble amine-functional and water-insoluble pyridine-functional hyperbranched 1,2,3-triazoleorganoethoxysiloxane polymers, capable of stabilizing ultra-small silver nanoparticles and efficient for chemical surface modification were synthesized and characterized by 1H-NMR, 13C-NMR, 29Si-NMR and FT-IR spectroscopy, MALDI and GPC. Coordinatively active hetero-organic polymers with a flexible branched polyethoxysiloxane backbone bearing chelating 1,2,3-triazolyl-dimethylamine and -pyridine conjugated functional groups were exploited towards coordination with Ag+ metal ions, and formation and stabilization of narrowly dispersed silver nanoparticles (Ag-NPs) obtained in the process of radiation induced metal ion reduction. The influence of the chemically assisted radiation process on the Ag-NP size and size distribution was investigated. Hyperbranched polyorganoethoxysiloxanes loaded with Ag-NPs were covalently cross-linked on a Stöber silica surface, demonstrating the efficiency of the developed hetero-organic functional polymers in the preparation of functional nanocomposite coatings for various applications (heterogeneous catalytic systems, antibacterial materials, nanoparticle-based optical sensing devices, etc.). The nanocomposites were investigated and characterized by TEM-EDS, DLS, UV-Vis spectroscopy and 29Si MAS NMR spectroscopy.

Photoinduced assembly of the 3,4,4a,7a-tetrahydro-1H-cyclopenta[b]pyridine-2,7-dione core on the basis of allomaltol derivatives.

A novel photochemical method for the construction of previously unknown substituted 4a,7a-dihydroxy-5-methyl-3,4,4a,7a-tetrahydro-1H-cyclopenta[b]pyridine-2,7-diones based on readily available allomaltol derivatives containing an amide group was established. The proposed approach includes the photoinduced contraction of an allomaltol ring and the subsequent intramolecular cyclization of an unstable α-hydroxy-1,2-diketone intermediate. For the first time we have shown the use of a side chain amide function as a trapping element for the final cyclization of photogenerated α-hydroxy-1,2-diketones. The structures of two synthesized photoproducts were determined by X-ray diffraction.

A new derivative of acetylsalicylic acid and carnosine: synthesis, physical and chemical properties, biological activity.

PURPOSE: The aim of this study was to create and assess biological activity of a new compound based on carnosine and acetylsalicylic acid (ASA) that will comprise antioxidant effect with antiplatelet activity, while simultaneously preventing side effects on the gastrointestinal tract. METHODS: Salicyl-carnosine (SC) was synthesized by condensation of ASA and carnosine. Antioxidant activity was determined by spectrophotometric and chemiluminescence methods. Antiplatelet activity was carried out by the light transmission-aggregometry method using the inductor ADP. Chronic gastric ulcer in rats was modeled using glacial acetic acid. RESULTS: Using SOD-like activity, iron-induced chemiluminescence, BaSO4-activated respiratory burst, and evaluation of red blood cell structure stabilization during oxidative damage induced by sodium hypochlorite, it was shown that SC possesses antioxidant activity analogous, or better, than that of carnosine. Antiplatelet activity of SC was evaluated in the blood of healthy individuals, and was also shown to be comparable to, or exceeding that of ASA. Also SC demonstrates high resistance to hydrolysis by tissue and serum carnosinases. Most importantly, it was shown that SC has protected the gastric mucosa against the formation of stomach ulcerative lesions and promoted their epithelization, therefore overcoming the undesirable inherent side effects of ASA. CONCLUSIONS: SC preserves pharmacologically significant properties of ASA and carnosine while retaining an anti-ulcer activity and resistance to the carnosinase hydrolysis at the same time. These properties are particularly promising for the potential development of new anti-inflammatory and antithrombotic drugs. Graphical abstract .

One-pot synthesis of substituted pyrrolo[3,4-b]pyridine-4,5-diones based on the reaction of N-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-arylethyl)acetamide with amines.

The condensation of primary amines with N-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-arylethyl)acetamides was explored. Thus, a previously unknown recyclization of the starting material was observed in acidic ethanol in the presence of an amine, which provided the corresponding dihydropyrrolone derivative as the major reaction product. Based on this transformation, a practical and convenient one-pot synthetic method for substituted pyrrolo[3,4-b]pyridin-5-ones could be devised.

Synthesis and characterization of nonsymmetric cyclopentene-based dithienylethenes.

Nonsymmetric cyclopentene-based dithienylethenes, containing both thienyl and benzothienyl units, have been synthesized for the first time, employing intramolecular McMurry reaction as a key transformation to target compounds 10 and 16. Photochromic properties of these compounds were examined in toluene and acetonitrile solutions, PMMA layers, solid films, and crystal phase. To explain an unprecedented single-crystalline photochromism phenomena of 10, X-ray crystallographic analysis was performed, revealing a significant influence of strong S···S interatomic interactions on the intramolecular distance between two photochemical reaction centers in the molecule. Compound 16 could be further synthetically modified in a step-by-step manner, thus serving as potential key intermediate to various complex bifunctional photochromic molecules.

Potent, orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors.

Two structurally distinct series of SCD (Delta9 desaturase) inhibitors (1 and 2) have been previously reported by our group. In the present work, we merged the structural features of the two series. This led to the discovery of compound 5b (CVT-12,012) which is highly potent in a human cell-based (HEPG2) SCD assay (IC(50)=6nM). This compound has 78% oral bioavailability in rats and is preferentially distributed into liver (76 times vs plasma) with relatively low brain penetration. In a five-day study (sucrose fed rats) compound 5b significantly reduced SCD activity in a dose-dependent manner as determined by GC analysis of fatty acid composition in plasma and liver, and significantly reduced liver triglycerides versus the control group ( approximately 50%).

Synthesis and Properties of Multiarmed Geminis.

Three families of multiarmed and multicationic gemini surfactants, having pentaerythritol, dipentaerythritol, or adamantane cores, were synthesized and examined for their colloidal properties in water. Geminis with four or six six-carbon chains are highly water-soluble and do not self-assemble. But surface tension and conductivity measurements show that the geminis with four or six eight-carbon chains form micelles in the 3-6 mM range (compared to 0.5 M for a corresponding surfactant with a single chain). According to dynamic light scattering, these micelles are small (<30 Å diameter); no evidence of dendritic growth below 25 mM is evident. Geminis with four or six 12-carbon chains are too water-insoluble to examine for micelle formation. It is concluded the outward projection of the hydrocarbon chains in water greatly enhances the propensity of the surfactants to self-assemble. Micellar growth is seemingly restricted by chain pairing, chain looping, and associative ring formation. Since the aggregates have, despite these effects, greater residual water-hydrocarbon contact than found in typical micelles, water solubility of surfactants having longer chains is impaired.