Remarkably efficient synthesis of 2H-indazole 1-oxides and 2H-indazoles via tandem carbon-carbon followed by nitrogen-nitrogen bond formation

Base-catalyzed tandem carbon-carbon followed by nitrogen-nitrogen bond formations quantitatively converted N-alkyl-2-nitro-N-(2-oxo-2-aryl-ethyl)-benzenesulfonamides to 2H-indazoles 1-oxides under mild conditions. Triphenylphosphine or mesyl chloride/triethylamine-mediated deoxygenation afforded 2H-indazoles.     

A single parameter determines mesophase transitions in Swollen Liquid Crystals

We report how the control of a single parameter, the co-surfactant, determines the phase transitions of oil-in-water swollen liquid crystals (SLCs) prepared with cetyltrimethylammonium bromide (CTAB), from cubic to hexagonal, lamellar, and finally sponge-like structures. SLCs are complex mixtures (surfactant + co-surfactant + water + salt + oil) usually prepared to form hexagonal mesophases, with cell parameters tunable between 3 and 30 nm. These hexagonal mesophases were successfully used as nanoreactors to prepare a broad range of nanostructured materials. Because the potential of these mesophases as adaptive nanoreactors has not been extended to other liquid crystal geometries than the hexagonal, we studied in a first step the structure evolution of SLCs made with CTAB, cyclohexane, pentanol-1, water and different stabilising salts. We used small-angle X-ray scattering (SAXS), polarised light microscopy and Freeze-Fracture TEM to provide a partial phase diagram and list the different mesophases obtained as a function of composition. We report that the adjustment of a single parameter, the co-surfactant (pentanol-1), determines the phase transition between cubic, hexagonal, lamellar, and sponge-like structures, all other parameters such as the nature and concentration of salt, or amount of oil being constant.     

Trans or (Unusual) Cis Geometry in d(2) Octahedral Dioxo Complexes. A DFT Study

Geometry optimization of the cis and the trans isomers of several octahedral dioxo complexes of d(2) electronic configuration are performed using the gradient-corrected density functional theory (B3LYP and, for some key structures, BP86). With only monodentate sigma donor ligands (ReO(2)(NH(3))(4)(+), 7), the usual energy order is found (i.e., the trans isomer is the most stable). Complexes with a chelating bidentate ligand, OsO(2)(OCH(2)CH(2)O)(NH(3))(2) (10) and ReO(2)(HN=CHCH=NH)(NH(3))(2)(+) (11), are used as models for the experimental complexes 5 and 2 in which the arrangement of the O=M=O unit is trans and cis, respectively. Our calculations actually show an inversion of the relative energy of the two isomers in going from 10 to 11: while the trans isomer is found to be the most stable in 10, the unusual cis diamagnetic isomer is favored by about 29 kcal mol(-)(1) in 11. This result is traced to the geometric and electronic properties of the bidentate ligand, in particular an acute bite angle and good pi acceptor character. In complex 14 with a bipyridine chelating ligand (weaker pi acceptor than diaza-1,4-butadiene in 11), this energy difference is, however, reduced to 7.5 kcal mol(-)(1) (partial geometry optimization).     

Synthesis of 2′-Deoxy-5-(isothiazol-5-yl)uridine and Its Interaction with the HSV-1 Thymidine Kinase

2′-Deoxy-5-(isothiazol-5-yl)uridine ( 12 ) was synthesized starting from 2′-deoxy-5-iodouridine using a Pd-catalysed cross-coupling reaction with propiolaldehyde diethyl acetal followed by deprotection and ring closure using thiosulfate. 2′-Deoxyuridine 12 has a particular place among the 5-heteroaryl-substituted 2′-deoxyuridines in that it has a high affinity for herpes simplex virus type 1 (HSV-1)-encoded thymidine kinase (TK) without antiviral activity. Biochemical studies revealed that 12 is a substrate for viral TK. We further investigated the interaction of 12 with the HSV-1 thymidine kinase. The conformation of 12 in solution was established by NMR spectroscopy. The most stable conformer 12A has the S-atom of the isothiazole ring placed in the neighbourhood of the C(4)?O group of the pyrimidine moiety. The compound was docked in its most stable conformation in the active site of HSV-1 TK and subjected to energy minimization. This demonstrated that the isothiazole moiety binds in a cavity lined by the side chains of Tyr-132, Arg-163, Ala-167, and Ala-168 and that the C(3) atom of the isothiazole moiety is located in close proximity of the phenolic O-atom of Tyr-132 and the aliphatic part of the Arg-163 side chain.     

Cytotoxic effect and electrophysiological activity of S-irniine, a synthesised isomer of the natural R-irniine, on human MRC-5 fibroblasts

Numerous original alkaloids are present in tubers of Arisarum vulgare Targ. a species belonging to the Araceae family known in Morocco for its toxicity. Some previous works deal with the activity of these natural compounds as R-irniine. As the enantioselective total synthesis of irniine has been realised, the R- and S-forms were obtained and this last one could be tested. Thus, a study of the cytotoxicity and the electrophysiological activity of S-irniine was carried out on human MRC-5 fibroblasts. A cytotoxic effect of S-irniine at 40 microg/mL was detected on MRC-5 fibroblasts. An electrophysiological study was also carried out on the MRC-5 cells by using the patch-clamp technique and no effect of this compound at this concentration on the outward potassium current of MRC-5 fibroblasts was observed. Thus, this study showed, as it was for R-irniine, that the cytotoxicity of S-irniine was not explained by an effect on the potassium currents.     

Characterization of a sucrose/starch matrix through positron annihilation lifetime spectroscopy: unravelling the decomposition and glass transition processes

The triplet state of positronium, o-Ps, is used as a probe to characterize a starch-20% w/w sucrose matrix as a function of temperature (T). A two-step decomposition (of sucrose, and then starch) starts at 440 K as shown by a decrease in the o-Ps intensity (I(3)) and lifetime (τ(3)), the latter also disclosing the occurrence of a glass transition. Upon sucrose decomposition, the matrix acquires properties (reduced size and density of nanoholes) that are different from those of pure starch. A model is successfully established, describing the variations of both I(3) and τ(3) with T and yields a glass transition temperature, T(g) = (446 ± 2) K, in spite of the concomitant sucrose decomposition. Unexpectedly, the starch volume fraction (as probed through thermal gravimetry) decreases with T at a higher rate than the free volume fraction (as probed through PALS).     

Propensities and conditional probabilities

The present paper deals with the objection that Paul Humphreys raised against the propensity interpretation of probability - “Humphreys’ paradox”. An update on existing solutions is offered, and it is concluded that none of them is completely satisfactory in view of Humphreys’ 2004 rejoinder. Positively, an original solution is formulated and discussed.     

Reversible Live-Cell Labeling with Retro-engineered HaloTags Enables Long-Term High- and Super-Resolution Imaging

Self-labeling enzymes (SLE) such as the HaloTag have emerged as powerful tools in high and super-resolution fluorescence microscopy. Newly developed fluorogenic SLE substrates enable imaging in the presence of excess dye. To exploit this feature for reversible labeling, we engineered two variants of HaloTag7 with restored dehalogenase activity. Kinetic studies in vitro showed different turnover kinetics for reHaloTagS (≈0.006 s⁻¹) and reHaloTagF (≈0.055 s⁻¹). Imaging by confocal and stimulated emission depletion microscopy yielded 3-5-time enhanced photostability of reHaloTag labeling. Prominently, single molecule imaging with reHaloTags enabled controlled and stable labeling density over extended time periods. By combination with structured illumination, simultaneous visualization of single molecule diffusion and organellar dynamics was achieved. These applications highlight the potential of reHaloTag labeling for pushing the limits of advanced fluorescence microscopy techniques.     

Anionic surfactants and surfactant ionic liquids with quaternary ammonium counterions

Small-angle neutron scattering and surface tension have been used to characterize a class of surfactants (SURFs), including surfactant ionic liquids (SAILs). These SURFs and SAILs are based on organic surfactant anions (single-tail dodecyl sulfate, DS, double-chain aerosol-OT, AOT, and the trichain, TC) with substituted quaternary ammonium cations. This class of surfactants can be obtained by straightforward chemistry, being cheaper and more environmentally benign than standard cationic SAILs. A surprising aspect of the results is that, broadly speaking, the physicochemical properties of these SURFs and SAILs are dominated by the nature of the surfactant anion and that the chemical structure of the added cation plays only a secondary role.