Differential operators on homogeneous spaces. I

Summary In this paper, we extend recent work of one of us [Br] to investigate an old problem of the other one [B2]. Given a connected semisimple complex Lie-groupG with Lie-algebrag, we study the representation of the enveloping algebra of by global differential operators on a complete homogeneous spaceX=G/P. It turns out that the kernelI _x of _X is the annihilator of a generalizedVerma-module. On the other hand, we study the associated graded ideal grI _x , and relate it to the geometry of a generalizedSpringer-resolution, that is a map of the cotangent-bundle ofX onto a nilpotent variety in , as studied e.g. in [BM1]. We prove, for instance, that grI _x is prime if and only if _X is birational with normal image. In general, we show that is prime. Equivalently, the associated variety ofI _x in is irreducible: In fact, it is the closure of theRichardson-orbit determined byP. For the homogeneous spaceY=G/(P, P), we prove that the analogous idealI _y has for associated variety the closure of theDixmier-sheet determined byP. From this main result, we derive as a corollary, that for any module induced from a finitedimensional LieP-module the associated variety of the annihilator is irreducible, proving an old conjecture [B2], 2.5. Finally, we give some applications to the study of associated varieties of primitive ideals.     

New stereoselective preparation of (Z)-3-perfluoroalkyl-3-magnesiated enoates by an iodine-magnesium exchange reaction

(Z)-Ethyl-3-perfluoroalkyl-3-magnesiated crotonates were prepared from (Z)-ethyl-3-perfluoroalkyl-3-iodo enoates by iodine-magnesium exchange reaction with isopropylmagnesium bromide in THF at -78 degrees C. These new reagents reacted with a range of electrophiles, leading to polyfunctional products bearing a perfluoroalkyl group.     

Photochemistry of 3-Substituted 1-Iminopyridinium Ylides. Regiospecific versus non-regiospecific photoisomerization patterns [1]

3-Substituted 1-iminopyridinium ylides 1 undergo photo-induced ring enlargement to 1H-1,2-diazepines. With strongly electron-withdrawing substituents the ring expansion process is regiospecific and leads exclusively to 4-substituted 1 H-1, 2-diazepines. Weak electron-donating substituents, like a methyl group and halogen atoms, do not have any directing effect since both 4- and 6-substituted 1 H -1,2-diazepines are obtained. With strong electron-donating substituents no diazepines are formed; instead one observes photo-induced isomerization to the 2-aminopyridine derivatives, the process being non-regiospecific. Regiospecific photo-induced ring expansion processes are explained in terms of a simple HMO model.     

Influence of plasticizers and crosslinking on the properties of biodegradable films made from sodium caseinate

Plasticized protein films were prepared by the casting method from water solution of sodium caseinate and plasticizers with the aim to obtain environmentally friendly materials for packaging applications. Mechanical properties (tensile strength, elongation and Young’s modulus) of caseinate based films were determined versus ratio of protein to plasticizer, plasticizer type and relative humidity conditions. Among the different polyol-type plasticizers tested, glycerol (Gly) and triethanolamine (TEA) were the most efficient for the improvement of mechanical properties (high strains for low stresses). Further, chemical crosslinking between formaldehyde (HCHO) and free amino groups (ε-NH₂) of sodium caseinate was performed to increase water resistance of TEA plasticized films. Optimal mechanical properties, i.e. elastic modulus of 105 MPa, tensile strength of 8-9 MPa for elongation at break about 110-125% were obtained for HCHO/ε-NH₂ ratios higher than 1.35. Protein specific water solubility was determined from a 280 nm absorbance. For convenient crosslinker (HCHO) content sodium caseinate solubility can be lowered to less than 5 wt% after 24 h immersion in water.     

2-Trimethylsilylethyl sulfides in the von Braun cyanogen bromide reaction: selective preparation of thiocyanates and application to nucleoside chemistry

Mixed 2-(trimethylsilyl)ethyl sulfides were synthesized and used in the von Braun cyanogen bromide reaction for preparing selectively thiocyanates in high yield. We show here that this cleavage reaction is highly selective in methanol in comparison with the reaction of the corresponding non-silyl sulfide analogues. This reaction was applied to the synthesis of nucleosidic thiocyanates such as the new nucleosides 14 and 18 in the search for mechanism-based inhibitors of ribonucleoside diphosphate reductase and bioactive molecules. The selective cleavage is possible for sulfides bearing hydroxyl functions and aromatic rings. The reactions of cyanogen bromide as cyanating and brominating agent were observed for the first time under the same conditions with the naphthoxyhexyl 2-trimethylsilylethyl sulfide 7, which, treated with cyanogen bromide in dichloromethane, led selectively to the p-bromonaphthoxyhexyl thiocyanate 10 in 89% yield. Another reaction induced by cyanogen bromide was observed in dichloromethane with the 2-(trimethylsilylethyl)thio nucleoside 13, which gives the corresponding symmetrical disulfide 21 in good yield.     

Comparative study of recent wide-pore materials of different stationary phase morphology, applied for the reversed-phase analysis of recombinant monoclonal antibodies

Various recent wide-pore reversed-phase stationary phases were studied for the analysis of intact monoclonal antibodies (mAbs) of 150 kDa and their fragments possessing sizes between 25 and 50 kDa. Different types of column technology were evaluated, namely, a prototype silica-based inorganic monolith containing mesopores of ～250 Å and macropores of ～?1.1 μm, a column packed with 3.6 μm wide-pore core-shell particles possessing a wide pore size distribution with an average around 200 Å and a column packed with fully porous 1.7 μm particles having pore size of ～300 Å. The performance of these wide-pore materials was compared with that of a poly(styrene–divinyl benzene) organic monolithic column, with a macropore size of approximately 1 μm but without mesopores (stagnant pores). A systematic investigation was carried out using model IgG1 and IgG2 mAbs, namely rituximab, panitumumab, and bevacizumab. Firstly, the recoveries of intact and reduced mAbs were compared on the two monolithic phases, and it appeared that adsorption was less pronounced on the organic monolith, probably due to the difference in chemistry (C18 versus phenyl) and the absence of mesopores (stagnant zones). Secondly, the kinetic performance was investigated in gradient elution mode for all columns. For this purpose, peak capacities per meter as well as peak capacities per time unit and per pressure unit (PPT) were calculated at various flow rates, to compare performance of columns with different dimensions. In terms of peak capacity per meter, the core-shell 3.6 μm and fully porous 1.7 μm columns outperformed the two monolithic phases, at a temperature of 60 °C. However, when considering the PPT values, the core-shell 3.6 μm column remained the best phase while the prototype silica-based monoliths became very interesting, mostly due to a very high permeability compared with the organic monolith. Therefore, these core-shell and silica-based monolith provided the fastest achievable separation. Finally, at the maximal working temperature of each column, the core-shell 3.6 μm column was far better than the other one, because it is the only one stable up to 90 °C. Lastly, the loading capacity was also measured on these four different phases. It appeared that the organic monolith was the less interesting and rapidly overloaded, due to the absence of mesopores. On the other hand, the loading capacity of prototype silica-based monolith was indeed reasonable.     

Synthesis of unnatural 3′-phospha-2′-deoxyfuranose nucleoside analogues

This Letter describes the synthesis of racemic analogues of unnatural 2′-deoxy nucleoside with a phosphorus atom replacing the carbon atom in the 3′-position. A seven-step sequence was developed in racemic series to afford unnatural 3′-phospha-2′-deoxyfuranose nucleosides. The phospha nucleoside analogues were tested against HCV, but did not show any antiviral activity at a 10 μM maximum concentration used for the inhibition assays of analogues 2-T, 2-C and 4-Tα.     

Characterization of glycosyl inositol phosphoryl ceramides from plants and fungi by mass spectrometry

Although glycosyl inositol phosphoryl ceramides (GIPCs) represent the most abundant class of sphingolipids in plants, they still remain poorly characterized in terms of structure and biodiversity. More than 50 years after their discovery, little is known about their subcellular distribution and their exact roles in membrane structure and biological functions. This review is focused on extraction and characterization methods of GIPCs occurring in plants and fungi. Global methods for characterizing ceramide moieties of GIPCs revealed the structures of long-chain bases (LCBs) and fatty acids (FAs): LCBs are dominated by tri-hydroxylated molecules such as monounsaturated and saturated phytosphingosine (t18:1 and t18:0, respectively) in plants and mainly phytosphingosine (t18:0 and t20:0) in fungi; FA are generally 14–26 carbon atoms long in plants and 16–26 carbon atoms long in fungi, these chains being often hydroxylated in position 2. Mass spectrometry plays a pivotal role in the assessment of GIPC diversity and the characterization of their structures. Indeed, it allowed to determine that the core structure of GIPC polar heads in plants is Hex(R1)-HexA-IPC, with R1 being a hydroxyl, an amine, or a N-acetylamine group, whereas the core structure in fungi is Man-IPC. Notably, information gained from tandem mass spectrometry spectra was most useful to describe the huge variety of structures encountered in plants and fungi and reveal GIPCs with yet uncharacterized polar head structures, such as hexose–inositol phosphoceramide in Chondracanthus acicularis and (hexuronic acid)₄–inositol phosphoceramide and hexose–(hexuronic acid)₃–inositol phosphoceramide in Ulva lactuca.

A two-point calibration method for quantifying organic binary mixtures using secondary ion mass spectrometry in the presence of matrix effects

Quantification of the composition of binary mixtures in secondary ion mass spectrometry (SIMS) is required in the analyses of technological materials from organic electronics to drug delivery systems. In some instances, it is found that there is a linear dependence between the composition, expressed as a ratio of component volumes, and the secondary ion intensities, expressed as a ratio of intensities of ions from each component. However, this ideal relationship fails in the presence of matrix effects and linearity is observed only over small compositional ranges, particularly in the dilute limits. In this paper, we assess an empirical method, which introduces a power law dependence between the intensity ratio and the volume fraction ratio. A previously published physical model of the organic matrix effect is employed to test the limits of the method and a mixed system of 3,3′-bis(9-carbazolyl) biphenyl and tris(2-phenylpyridinato)iridium (III) is used to demonstrate the method. This paper introduces a two-point calibration, which determines both the exponent in the power law and the sensitivity factor for the conversion of ion intensity ratio into volume fraction ratio. We demonstrate that this provides significantly improved accuracy, compared with a one-point calibration, over a wide compositional range in SIMS quantification and with a weak dependence on matrix effects. Because the method enables the use of clearly identifiable secondary ions for quantitative purposes and mitigates commonly observed matrix effects in organic materials, the two-point calibration method could be of significant benefit to SIMS analysts.