Synthesis, characterization and primary evaluation of the synthetic efficiency of supported vinyltins and allyltins

Supported vinyltins and allyltins grafted to an insoluble cross-linked polystyrene matrix were prepared using methods usually employed in solution, like hydrostannylation of alkynes, transmetallation of a tin halide with organomagnesium or organozinc reagents, and substitution of an allyl halide by a supported stannylanion or S_N2′ substitution of a supported β-stannylacrolein acetal by cyanocopper reagents in the presence of boron trifluoride etherate. The insoluble grafted organotin reagents were analysed by HRMAS NMR, allowing an unambiguous assignment of their isomeric distribution or the identification of side products. When involved in Stille cross-coupling reactions (vinyltins) or in addition on aldehydes (allyltins), these supported reagents exhibit similar reactivity and similar stereoselectivity when compared to the tributyltin analogues, with the advantage to prevent problems due to the contamination by tin residues.     

Structures of micelles formed by synthetic alkyl glycosides with unsaturated alkyl chains

Three new alkyl glycosides with similar molecular structures (oleyl and oleoyl alkyl chains and various head groups: disaccharide, trisaccharide and disaccharide with an additional amidoethoxy spacer) were synthesized and their supramolecular structure in aqueous solution was investigated. Small angle neutron scattering, surface tension measurement and the contact preparation method were applied to get molecular structure-property relationships. Although the chemical structures differ only in small details, their CMC values, lyotropic phase behaviour, surface area per surfactant molecule in the micelle and at the liquid-air interface, and the size and shape of the micelles are very different. We have found three different types of aggregates: spherical, cylindrical and polymer-like micelles in dilute solutions.     

Copolymers for hepatocyte-specific targeting carrying galactose and hydrophobic alkyl groups

Core-forming hydrophobic alkyl groups were incorporated into amphiphilic PVLA to enhance the stability and inclusion ability of the homopolymeric micelles in water. The CAC and hepatocyte targeting in the synthesized P(VLA-co-VBH) were investigated in vitro. The CAC of the copolymers decreased and the stability of the copolymeric micelles increased with the incorporation of hydrophobic groups into the homopolymer. The galactose moieties in the copolymer could be recognized by the ASGP-R of the hepatocytes through a receptor-mediated mechanism. The copolymers efficiently delivered a water-insoluble drug to the hepatocytes. Hence, they be used to deliver hydrophobic drugs to cure various liver diseases.     

Direct formation of giant vesicles from synthetic polypeptides

This report describes direct formation of giant vesicles from a series of poly(L-lysine)-block-poly(L-phenylalanine) (PLL-b-PPA) block copolymers from their water solution. These polymers are prepared by successive ring-opening polymerization (ROP) of the two alpha-amino acid N-carboxyanhydrides and then removing the side chain protecting groups by acidolysis. The structures of the copolymers are confirmed by nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), and size exclusion chromatography (SEC). The vesicles are studied by atomic force microscopy (AFM), field emission scanning electron microscopy (ESEM), and confocal laser scanning microscopy (CLSM). Rhodamine B is used as a fluorescent probe to confirm the existence of the vesicle with an aqueous interior. The vesicle size is in the range 0.55-6 microm, depending on the absolute and relative lengths of the two blocks, on initial polymer concentration, and on solution pH. The vesicles are still stable in water for 2 months after preparation. Addition of the copolymer to DNA solution results in complex formation with it. The complex assumes the morphology of irregular particles of less than 2 microm. It is expected to be used in drug and gene delivery.     

烷基和酰基钴化合物合成方法研究进展

总结了烷基和酰基钴化合物及其膦配体衍生物的合成方法,综述了其合成方法研究进展.指出烷基和酰基钴化合物是多种重要催化反应如氢甲酰化反应、甲醇同系化反应、酰胺羰基化反应的循环中间体;近年来,烷基和酰基钴化合物因可以催化羰基化聚合反应而引起了广泛的关注.     

Mechanistic and synthetic aspects of the reaction of alkyl esters of phosphorus with trimethylstannyl halides

The reaction of trimethylstannyl halides with trialkyl phosphates has been studied. The results are interpreted in terms of a mechanism involving a trimethylstannyloxyphosphonium salt intermediate. The much lower reactivity of the stannyl halides compared with their silicon analogs is explained by the lower ionization of the stannyl halide phosphate complexes and the unfavourable direction of the decomposition of the phosphonium salt intermediate. The reaction may be useful in synthesis of phosphates containing only one O-stannyl group, which can be used in generation of the acid function or replaced in reactions with compounds containing active halogen.     

Subnanometer size uncapped quantum dots via electroporation of synthetic vesicles

The very rapid, usually diffusion-controlled, self-aggregation of nascent molecules of semiconductors (MX) or metals (M) in solution represents an experimental challenge for arresting the growth of the particles at a desired size. Unfortunately, the typical remedy used, namely capping of the clusters with a protective coating, alters their intrinsic electronic and optical properties. An additional defect of capping's virtue is that it prevents the observation of further cluster growth—which is especially important in the subnanometer (molecular) size regime, where particle growth is associated with dramatic changes in structure, surface states, and transition energy.

We have developed a novel method for the preparation of subnanometer size uncapped quantum dots, which also allows the monitoring of their growth up to several hundreds of nanometer in diameter. The essence of the method is the initial encapsulation of the metal ion (M⁺) in synthetic vesicles (liposomes) and the placement of the anion (X⁻) in the bulk solution. Exposure of the suspension to a rectangular pulse of a high-voltage homogenous electric field E of suitable intensity and duration causes the formation of transient pores in the vesicle's bilayer (electroporation). A fraction of the metal ions that are ejected through the pores react with the anions in the bulk, and the freshly created monomers (MX) adsorb on the exterior surface of the vesicle. On the vesicle surface, the self-aggregation is slowed down to the hour and day timescales which allows for convenient spectral monitoring of the growth of the clusters.

The discussion will focus on the behavior of vesicles in an electric field, the mechanism of electroporation, and our experimental and density functional theoretical findings of previously unobserved, unusual spectroscopic properties of subnanometer size AgBr, CdS, PbS, ZnS and gold quantum dots.     

A remarkable enhancement of the rate of ester thiolysis by synthetic amphiphile vesicles

Cationic surfactant vesicles accelerate the rate of thiolysis of p-nitrophenyl octanoate by n- heptylmercaptan by several million fold in the pH range from 4 to 6, providing an efficient system for ester thiolysis in aqueous solution that is functional even at pH4, i.e. more than 6 pH units below the pKa of the SH group. Analysis of the data in terms of an ion exchange formalism implies that this rate acceleration is due primarily to concentration of the reagents in the dimensionally-restrited environment provided by the vesicle, coupled with small contributions from enhanced dissociation and reactivity of the nucleophile at the vesicle surface(s).     

Maximizing synthetic efficiency: multi-component transformations lead the way

With the emergence of high-throughput screening in the pharmaceutical industry in the early 1990's, organic chemists were faced with a new challenge: how to prepare large collections of molecules (the libraries) to "feed" the high-throughput screen? The unique exploratory power of some reactions (such as the 40 year-old Ugi four-component condensation) was soon recognized to be extremely valuable to produce libraries in a time- and cost-effective manner. Over the last five years, industrial and academic researchers have made these powerful transformations into one of the most efficient and cost-effective tools for combinatorial and parallel synthesis.     

A mild, palladium-catalyzed method for the dehydrohalogenation of alkyl bromides: synthetic and mechanistic studies

We have exploited a typically undesired elementary step in cross-coupling reactions, β-hydride elimination, to accomplish palladium-catalyzed dehydrohalogenations of alkyl bromides to form terminal olefins. We have applied this method, which proceeds in excellent yield at room temperature in the presence of a variety of functional groups, to a formal total synthesis of (R)-mevalonolactone. Our mechanistic studies have established that the rate-determining step can vary with the structure of the alkyl bromide and, most significantly, that L(2)PdHBr (L = phosphine), an intermediate that is often invoked in palladium-catalyzed processes such as the Heck reaction, is not an intermediate in the active catalytic cycle.     

Exploitation of synthetic surfactant vesicles for enhanced fluorescence of metal chelates

The use of synthetic surfactant vesicles as a means for enhancing the photoluminescence of metal chelates is illustrated and a sensitive fluorimetric determination of aluminium with quinolin-8-ol-5-sulphonic acid in vesicles of didodecyldimethylammonium bromide is given. The influence of different variables on the organized aluminium-quinolin-8-ol-5-sulphonic acid reaction is investigated and possible mechanisms of the observed enhancing effects are discussed. The limit of detection is 1 μg l^?1 of aluminium. The optimized fluorimetric method has been successfully applied to the determination of aluminium in tap waters and dialysis fluids.     

Theoretical analysis of the potential distribution and transportation behavior of the ordered alkyl monolayer-silicon junction

A theoretical approach to the determination of the potential distribution within an organic monolayer sandwiched metal-insulator-semiconductor junction has been proposed with two simplified models, e.g. static (capacitance) model and dynamic (resistance) model. Compared with the resistance model, the capacitance model has been confirmed to be more valid for determining the potential distribution of the system. Further, the transportation behavior of the system has been simulated with a modified electron-tunneling model.     

Preparation and evaluation of unimolecular pentavalent and hexavalent antigenic constructs targeting prostate and breast cancer: a synthetic route to anticancer vaccine candidates

Several novel, fully synthetic, carbohydrate-based antitumor vaccines have been assembled. Each construct consists of multiple cancer-related antigens displayed on a single polypeptide backbone. Recent advances in synthetic methodology have allowed for the incorporation of a complex oligosaccharide terminating in a sialic acid residue (i.e., GM2) as one of the carbohydrate antigens. Details of the vaccine synthesis as well as the results of preliminary immunological investigations are described herein.     

Liquid chromatography/tandem mass spectrometry method for quantification of trans-stilbene glycoside in rat plasma and its pharmacokinetic application

A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC‐MS/MS) method was developed and validated for the quantification of trans‐stilbene glycoside (SG) in rat plasma. As trans‐SG can be rapidly isomerized under light exposure, trans‐SG plasma samples were prepared in the dark and assayed immediately. Trans‐SG and internal standard were extracted by protein precipitation. Chromatographic separation was achieved on a C₁₈ column with a gradient elution program. The detection of analytes was performed by negative ion via multiple reaction monitoring mode. The precursor‐to‐product ions of m/z 405.1 → 242.9 for trans‐SG and m/z 389.1 → 226.9 for polydatin (internal standard) were monitored. No interference of endogenous components was observed for any plasma samples that we studied.The method was linear over the concentration range of 1.0–1000.0 ng/mL with a good correlation coefficient. The lower limit of quantification was 1.0 ng/mL for trans‐SG. The intra and inter‐batch accuracy for trans‐SG in stable rat plasma samples ranged from 93.3 to 102.7% and the variation was less than 8.1%. The extraction recoveries of trans‐SG in rat plasma were from 102.8 to 112.4% and the matrix effects were also acceptable. This method was successfully applied to pharmacokinetic study of trans‐SG in rats after intravenous administration. Copyright © 2012 John Wiley & Sons, Ltd.