Solubility of budesonide in {ethanol + water} mixtures from T = (293.2 to 313.2) K: Experimental measurement and mathematical modelling

The solubility of budesonide (BDS) in binary mixtures of ethanol and water at T = (293.2–313.2) K is determined and mathematically represented using two cosolvency models, i.e. Jouyban–Acree model and Jouyban–Acree–van’t Hoff model. The mean relative deviations for fitting the solubility data of BDS in binary mixtures of ethanol + water are 6.6% and 6.5%, respectively. Furthermore, the apparent thermodynamic properties, dissolution enthalpy, dissolution entropy, and Gibbs free energy change of dissolution process of BDS in all the mixed solvents were calculated according to van’t Hoff and Gibbs equations. Dissolution of BDS in these mixed solvents is an endothermic process.     

Novel axially chiral bis-arylthiourea-based organocatalysts for asymmetric Friedel-Crafts type reactions

It has been shown that catalytic amounts (10-20 mol %) of novel axially chiral bis-arylthioureas promote the asymmetric organocatalytic Friedel-Crafts type addition of indole and N-methylindole to nitroolefins. The optimum catalyst is capable of promoting the reaction between challenging substrates such as N-methylindole and nitroolefins bearing aliphatic β-substituents with enantioselectivity unprecedented for an organocatalytic system.     

The extraordinary reactions of phenyldimethylsilyllithium with N,N-disubstituted amides

Phenyldimethylsilyllithium reacts with N,N-dimethylamides in a variety of ways, depending upon the stoichiometry, the temperature and, most subtly, on the structure of the amide, with quite small-seeming changes in structure leading to profound changes in the nature of the products. When equimolar amounts of the silyllithium reagent and N,N-dimethylamides 6 are combined in THF at -78 degrees C, and the mixture quenched at -78 degrees C, the product is the corresponding acylsilane . If the same mixture is warmed to -20 degrees C before quenching, the product is a cis enediamine 11. The enediamines are easily isomerised from cis to trans, easily oxidised to dienediamines , and, with more difficulty, hydrolysed to alpha-aminoketones 13. If two equivalents of the silyllithium reagent are used, the product is an alpha-silylamine 20. The mechanism of formation of the enediamines appears to be by way of a Brook rearrangement of the tetrahedral intermediate 17 followed by loss of a silanoxide ion to give a carbene or carbene-like species. The 'carbene' combines with the Brook-rearranging nucleophile to give an intermediate 28, which loses another silanoxide ion to give the enediamine. The same carbene can be attacked by a second equivalent of the silyllithium reagent to give the alpha-silylamine 20. Other nucleophiles, like alkyllithiums, phenyllithium, and tributylstannyllithium also trap the carbene to give products 48-52. The intermediate anions in these reactions, when benzylic, can be further trapped with alkylating agents to give the products 33, 34 and 53-55. In special cases, the anion formed by attack on the carbene can be trapped by intramolecular reactions displacing internal leaving groups, as in the formation of the enamine 37 and the cyclopentane 41, or attacking a carbonyl group, as in the formation of the indanone 61, or attacking a double or triple bond, as in the formation of the cyclopentanes 71 and 75. In another special case, the carbene reacts with vinyllithium to give an allyllithium intermediate 56, which selectively attacks another molecule of carbene to give eventually the gamma-aminoketone 58. Small changes in the structure of the amide lead to a variety of other pathways each of which is discussed in the text. Notably, each member of the homologous series of amides Ph(CH2)nCONMe2 gives rise to a substantially different product: when n= 0, the reaction is normal, and the yield of the alph]-silylamine 20e is high; when n=1, proton transfer in the intermediate anion 64 and displacement of the phenyl group leads to the silaindane 66; when n=2, fragmentation of the intermediate anion 80, and capture of the carbene by benzyllithium leads to the 1,4-diphenylbut-2-ylamine 83; and when n=3, proton transfer in the intermediate anion 67 and displacement of the phenyl group leads to the silacyclopentane 69.     

Determination of volatile hydride-forming metals in steel by atomic absorption spectrometry

A scheme of analysis is presented for the determination of arsenic, antimony, bismuth, lead, selenium, tellurium and tin in steel by evolution of their volatile hydrides and subsequent atomic absorption spectrometry in an argon—hydrogen-entrained air flame. The method is rapid and applicable to a wide range of steels. Detection limits in steel of 1 p.p.m. for arsenic, antimony, bismuth, selenium and tellurium, 2 p.p.m. for tin and 7 p.p.m. for lead are reported. There is some interference in the determination of lead from copper and nickel, but the method could become a viable alternative to existing procedures in the determination of lead in steels of low alloy content, and in irons. Accuracy and precision data are presented.     

Nitrile anions: solvent-dependent cyclizations

Extensive cyclizations in hydrocarbon and polar solvents demonstrate a profound solvent sensitivity for intramolecular nitrile anion alkylations. S(N)i cyclizations enforce very precise steric constraints in the transition state, allowing correlation of the cyclization stereochemistry with the orbital orientation of the nitrile anion. Collectively the cyclizations suggest a continuum of nitrile anion transition states, varying from planar to fully pyramidal, that selectively cyclize to cis- and trans-decalins, respectively.     

The epitaxial growth of cholesterol crystals from bile solutions on calcite substrates

Epitaxial relationships between the surfaces of inorganic and bioorganic crystals can be an important factor in crystal nucleation and growth processes in a variety of biological environments. Crystalline cholesterol monohydrate (ChM), a constituent of both gallstone and atherosclerotic plaques, is often found in association with assorted mineral phases. Using in situ atomic force microscopy (AFM) and well-characterized model bile solutions, the nucleation and epitaxial growth of ChM on calcite (104) surfaces in real-time is demonstrated. The growth rates of individual cholesterol islands formed on calcite substrates were determined at physiological temperatures. Evidence of Ostwald's ripening was also observed under these experimental conditions. The energetics of various (104) calcite/(001) ChM interfaces were calculated to determine the most stable interfacial structure. These simulations suggest that the interface is fully hydrated and that cholesterol hydroxyl groups are preferentially positioned above carbonate ions in the calcite surface. This combination of experimental and theoretical work provides a clearer picture of how preexisting mineral seeds might provide a viable growth template that can reduce the energetic barrier to cholesterol nucleation under some physiological conditions.     

A HIGH RESOLUTION FLUORESCENCE DECAY AND DEPOLARIZATION STUDY OF HUMAN PLASMA APOLIPOPROTEINS

Abstract— Human plasma apolipoprotein A-I (apoA-I) and apolipoprotein C-I (apoC-I) were investigated by time-resolved fluorescence decay and depolarization. The tryptophyl fluorescence of apoA-I undergoes a double-exponential decay with lifetimes of 1.07 and 3.43 ns which remain unchanged over the range of apoA-I concentration studied.
The time-resolved fluorescence of both native and denatured forms of apoC-I exhibits an unusual tryptophyl fluorescence decay that was best fit to a triexponential function with lifetimes at 3.7 ± 0.2, 1.1 ± 0.1 and 0.1 ns at 2°C. The native and denatured forms of apoC-I had rotational correlation times of 1.42 and 1.19 ns at 20°C respectively. A shorter rotational correlation time associated with the internal tryptophan motions was not observed or resolved.
The decay of tryptophyl fluorescence in apoC-I/DPPC/cholesterol complex at 20°C is also triexponential with lifetimes at 4.94, 1.28 and 0.21 ns, which are longer than those of the uncomplexed forms. Two rotational correlation times of 28.32 and 0.59 ns at 20°C were resolved by fluorescence depolarization measurements. The long rotational time remained constant with temperatures above 30°C. Also, the temperature dependence of the order parameter, S², resembled a lipid phase transition curve with a transition midpoint at 38°C. The tryptophan and thus apoC-I are found to be affected by the bulk changes in the lipid.