A novel simple pyrolytic approach towards anhydronucleosides

An interesting novel gas phase thermal intramolecular substitution reaction was discovered, which led to the conversion of the 2-β-d-N-glucosyl, 2-β-d-N-galactosyl and 2-β-d-N-ribosyl derivatives of 3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-ones into their corresponding 3,2′-anhydro-β-d-mannosyl, 3,2′-anhydro-β-d-talosyl and 3,2′-anhydro-β-d-arabinosyl derivatives. The structures of these new anhydroglycosyls were determined by NMR experiments and by X-ray crystallography.     

Twist-bend nematics,liquid crystal dimers,structure–property relations

ABSTRACT

One of the current challenges in liquid crystal science is to understand the molecular factors leading to the formation of the intriguing twist-bend nematic phase (N_TB) and determine its properties. During our earlier hunt for the N_TB phase created on cooling directly from the isotropic phase and not the nematic phase, we had prepared 30 symmetric liquid crystal dimers. These had odd spacers and methylene links to the two mesogenic groups; desirable but clearly not essential features for the formation of the N_TB. Here, we report the phases that the dimers exhibit and their transition temperatures as functions of both the lengths of the spacer and the terminal chains. In addition we describe the transitional entropies, their optical textures, the X-ray scattering patterns and the ²H NMR spectra employed in characterising the phases. All of which may lead to important properties of the twist-bend nematic phase.     

A Versatile Solid-Phase Approach to the Synthesis of Oligonucleotide Conjugates with Biodegradable Hydrazone Linker

One of the ways to efficiently deliver various drugs, including therapeutic nucleic acids, into the cells is conjugating them with different transport ligands via labile or stable bonds. A convenient solid-phase approach for the synthesis of 5′-conjugates of oligonucleotides with biodegradable pH-sensitive hydrazone covalent bonds is proposed in this article. The approach relies on introducing a hydrazide of the ligand under aqueous/organic media to a fully protected support-bound oligonucleotide containing aldehyde function at the 5′-end. We demonstrated the proof-of-principle of this approach by synthesizing 5′-lipophilic (e.g., cholesterol and α-tocopherol) conjugates of modified siRNA and non-coding RNAs imported into mitochondria (antireplicative RNAs and guide RNAs for Mito-CRISPR/system). The developed method has the potential to be extended for the synthesis of pH-sensitive conjugates of oligonucleotides of different types (ribo-, deoxyribo-, 2′-O-methylribo-, and others) with ligands of different nature.     

Stereoselective synthesis of dihydrothiadiazinoazines and dihydrothiadiazinoazoles and their pyrolytic desulfurization ring contraction

Intramolecular base catalyzed C-C bond formation led to exclusive stereoselective syntheses of trans-6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines, trans-7,8-dihydro-6H-[1,2,4]triazino[3,4-b][1,3,4]thiadiazin-4-ones, and trans-3,4-dihydro-2H-[1,3,4]thiadiazino[2,3-b]quinazolin-10-one. trans-6,7-Dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines isomerize slowly in CDCl₃ and more rapidly in DMSO-d₆ into the corresponding cis-stereoisomers. The other trans-6,7-dihydro-[1,3,4]thiadiazines isomerize also in DMSO-d₆ into the corresponding cis-stereoisomers. Pyrolytic conversion of these heterocyclic condensed dihydrothiadiazines into their corresponding pyrazolo[5,1-b][1,2,4]triazoles, pyrazolo[5,1-c][1,2,4]triazin-4-ones and pyrazolo[4,3-b]quinazolin-9-ones via desulfurization ring contraction is described.     

Synthesis of some novel pyrazolo[1,5-a]pyrimidine derivatives and their application as disperse dyes

A series of novel monoazo-disperse dyes containing pyrazolo[1,5-a]pyrimidine structures were synthesized starting with the coupling reaction between ethyl cyanoacetate and 4-hydroxybenzenediazonium chloride, followed by treatment of the resulting hydrazone product with hydrazine hydrate. The pyrazolohydrazone 6 is then treated with either 2,4-pentandione and enaminonitrile or aryl-substituted enaminoketones to give the target pyrazolo[1,5-a]pyrimidine dyes 7 and 15a-d. Structural assignments to the dyes were made using NMR spectroscopic methods. A new high temperature method, using microwave heating, was employed to apply these dyes to polyester fibers. Most of the dyed fabrics tested displayed moderate light fastness and excellent washing fastness properties.     

Bismuth trichloride–mediated cleavage of phenolic methoxymethyl ethers

A simple and efficient method for removal of phenolic methoxymethyl ethers in the presence of 30 mol% of bismuth trichloride in acetonitrile/water is described. Notable features of the cleavage protocol entail use of an ecofriendly bismuth reagent, ease of handling, low cost, operational simplicity, and good functional group compatibility. A number of structurally varied phenolic methoxymethyl ethers were cleaved in good to excellent yields.     

Gas-phase pyrolysis of benzimidazole derivatives: novel route to condensed heterocycles

Gas-phase pyrolysis of N-(1H-benzimidazol-2-yl)-N′-arylidenehydrazines 1a-e gave the corresponding arylnitriles 2a-e, 2-aminobenzimidazole 3, 2,4,5-triphenylimidazole 4, 1,3-diphenyl-8H-2,3a,8-triazacyclopenta[a]indene 5, and 5,11-diphenyl-6H,12H-dibenzimidazo[1,2-a];1’,2’-d]pyrazine 6. The kinetics and analysis of the products of reaction are reported and used to elucidate the mechanism of the elimination process.     

Assessment of the PW86+PBE+XDM density functional on van der Waals complexes at non-equilibrium geometries

The deficiency of conventional density-functional theory (DFT) in properly describing van der Waals (vdW) (especially dispersion-bound) complexes has been extensively addressed in the past decade. There are now several new methods published in the literature that are capable of accurately capturing weak dispersion interactions in complexes at equilibrium geometries. However, the performance of these new methods at non-equilibrium geometries remains to be assessed. We have previously published [F. O. Kannemann and A. D. Becke, J. Chem. Theory Comput. 6, 1081 (2010); A. D. Becke, A. A. Arabi, and F. O. Kannemann, Can. J. Chem. 88, 1057 (2010)] that the functional PW86+PBE+XDM for exchange + correlation + dispersion, respectively, is a highly accurate functional for general thermochemistry and vdW complexes at equilibrium geometries. Here, we show that this nonempirical, except for two parameters in the dispersion damping part, functional also performs well for vdW complexes at compressed and stretched intermonomer separations. The mean absolute relative error (MARE) is 9.4% overall for vdW complexes in the "S22×5" database incorporating compressed and stretched geometries [J. Rezac, K. E. Riley, and P. Hobza, J. Chem. Theory Comput. 7, 2427 (2011)]. Our largest MARE on the S22×5 database is 13.3% on the compressed geometry set.     

An Oxidant- and Solvent-Stable Protease Produced by <Emphasis Type="Italic">Bacillus cereus</Emphasis> SV1: Application in the Deproteinization of Shrimp Wastes and as a Laundry Detergent Additive

The current increase in amount of shrimp wastes produced by the shrimp industry has led to the need in finding new methods for shrimp wastes disposal. In this study, an extracellular organic solvent- and oxidant-stable metalloprotease was produced by Bacillus cereus SV1. Maximum protease activity (5,900 U/mL) was obtained when the strain was grown in medium containing 40 g/L shrimp wastes powder as a sole carbon source. The optimum pH, optimum temperature, pH stability, and thermal stability of the crude enzyme preparation were pH 8.0, 60 °C, pH 6–9.5, and <55 °C, respectively. The crude protease was extremely stable toward several organic solvents. No loss of activity was observed even after 60 days of incubation at 30 °C in the presence of 50% (v/v) dimethyl sulfoxide and ethyl ether; the enzyme retained more than 70% of its original activity in the presence of ethanol and N,N-dimethylformamide. The protease showed high stability toward anionic (SDS) and non-ionic (Tween 80, Tween 20, and Triton X-100) surfactants. Interestingly, the activity of the enzyme was significantly enhanced by oxidizing agents. In addition, the enzyme showed excellent compatibility with some commercial liquid detergents. The protease of B. cereus SV1, produced under the optimal culture conditions, was tested for shrimp waste deproteinization in the preparation of chitin. The protein removal with a ratio E/S of 20 was about 88%. The novelties of the SV1 protease include its high stability to organic solvents and surfactants. These unique properties make it an ideal choice for application in detergent formulations and enzymatic peptide synthesis. In addition, the enzyme may find potential applications in the deproteinization of shrimp wastes to produce chitin.