Synthetic multifunctional pores: lessons from rigid-rod beta-barrels

In this account, studies on synthetic multifunctional pores formed by rigid-rod beta-barrels are summarized comprehensively. The first section outlines the evolution of synthetic multifunctional pores from the introduction of rigid-rod molecules in bioorganic chemistry and the discovery of synthetic beta-barrels in comparison with pertinent developments in related areas of research. Design strategies to position active sites at the inner surface of rigid-rod beta-barrel pores are described in the second section. The third section focuses on the characteristics of transmembrane barrel-stave pores, emphasizing the dynamic nature of supramolecular oligomers with the aid of notional phase and energy diagrams. Section four introduces multifunctionality with the use of synthetic pores as hosts of a rich collection of guests, reaching from inorganic cations to organic macromolecules like peptides, oligonucleotides, polysaccharides and polyacetylenes. In section five, practical applicability of molecular recognition by synthetic multifunctional pores is documented with non-invasive fluorometric enzyme sensing. The application of host-guest chemistry within synthetic pores to couple molecular recognition and translocation with molecular transformation is the topic of section six. The last section mentions some perspectives and challenges with synthetic multifunctional pores.     

Fluorescence Turn‐on Synthetic Lipid Rafts on Supramolecular Sheets and Hierarchical Concanavalin A Assembly

Here we report fluorescence turn‐on synthetic lipid rafts by self‐assembly of a cationic distyrylanthracene derivative on a negatively‐charged sheet in an aqueous solution. First, the negatively‐charged 2D membrane structure is formed by lateral associations of aromatic rods with carboxylate groups. Then, the synthetic rafts are floated on the surface of the negatively‐charged sheets through electrostatic interactions. The fluorescence of the synthetic rafts is turned on due to the aggregation of the positively‐charged AIE dye on the sheets, facilitating monitoring of the formation of rafts. Concanavalin A (Con A) protein can load hierarchically onto the synthetic rafts at neutral pH to provide discrete Con A aggregates with a uniform size of ≈12 nm. The uniform aggregates of Con A on the synthetic rafts can stimulate Jurkat cells with enhanced efficiency, as compared with random‐sized aggregates of Con A.     

钯催化合成香豆素研究进展

香豆素是一类苯并六元含氧杂环类化合物,具有抗氧化、抗菌、抗炎等多种生理活性,受到人们的广泛关注。近年来不断有香豆素的新合成方法报道,特别是高效的过渡金属钯催化合成反应。本文综述了近20年来钯络合物催化合成香豆素骨架的研究进展,主要包括羰基化反应、炔烃芳基化反应、烯烃芳基化反应和偶联反应,以期为合成新型香豆素提供参考。     

Biomolecular Densely Grafted Brush Polymers: Oligonucleotides,Oligosaccharides and Oligopeptides

In this Minireview, we describe synthetic polymers densely functionalized with sequence-defined biomolecular sidechains. We focus on synthetic brush polymers of oligonucleotides, oligosaccharides, and oligopeptides, prepared via graft-through polymerization from biomolecule functionalized monomers. The resulting structures are brush polymers wherein a biomolecular graft is positioned at each monomer backbone unit. We describe key synthetic milestones, identify synthetic opportunities, and highlight recent advances in the field, including biological applications.     

合成高分子基温敏水凝胶在眼病治疗中的研究进展

由于眼部存在角膜/结膜屏障、血-房水屏障和血-视网膜屏障等,有效的眼部给药依然面临巨大挑战.近年来,温敏水凝胶在眼部给药领域受到了广泛关注.在室温下,温敏水凝胶材料呈液态,便于以局部滴加或玻璃体内注射的方式给药;当与眼部接触升温并超过其临界成胶温度时,能以物理交联的方式快速凝胶化,从而实现原位缓释给药,提高药物生物利用度.在众多温敏水凝胶材料中,合成高分子具有材料和功能多样化等优势,其中较常见的为泊洛沙姆、聚乙二醇/聚酯和聚(N-异丙基丙烯酰胺).本综述首先介绍了以上3类合成高分子基温敏水凝胶材料的制备方法和成胶特性.然后,围绕眼部给药存在的难点,探讨这些温敏水凝胶在治疗角膜病、干眼症、青光眼和眼部炎症等各种眼病中的相关研究进展.最后,我们比较了这3种水凝胶在使用性能上的优缺点,并对未来眼科温敏水凝胶的材料设计提出了设想和展望.     

LC/ESI-MS/MS method for quantification of 28 synthetic cannabinoids in neat oral fluid and its application to preliminary studies on their detection windows

Serum and urine samples are commonly used for the analysis of synthetic cannabinoids in biofluids; however, their utilization as analytical matrices for drug abstinence control features some substantial drawbacks. While for blood collection invasive sampling is inevitable, the urinary analysis of synthetic cannabinoids is limited by the lack of available reference standards of the respective major metabolites. Moreover, the long detectability of synthetic cannabinoids in both matrices hampers the identification of a recent synthetic cannabinoid use. This article describes the development, validation and application of an LC/ESI-MS/MS method for the quantification of 28 synthetic cannabinoids in neat oral fluid (OF) samples. OF samples were prepared by protein precipitation using ice-cold acetonitrile. Chromatographic separation was achieved by gradient elution on a Luna Phenyl Hexyl column (50?×?2 mm, 5 μm), while detection was carried out on a QTrap 4000 instrument in positive ionization mode. The limits of detection ranged from 0.02 to 0.40 ng/mL, whereas the lower limits of quantification ranged from 0.2 to 4.0 ng/mL. The method was applied to authentic samples collected during two preliminary studies in order to obtain insights into the general detectability and detection windows of synthetic cannabinoids in this matrix. The results indicate that synthetic cannabinoids are transferred from the blood stream into OF and vice versa only at a very low rate. Therefore, positive OF samples are due to contamination of the oral cavity during smoking. As these drug-contaminations could be detected up to approximately 2 days, neat oral fluid appears to be well suited for detection of a recent synthetic cannabinoid use.

Design of synthetic peptidic constructs for the vaccine development against viral infections

The practical development of modern vaccines has been greatly advanced by the availability of synthetic antigens. The use of such synthetic antigens might be more acceptable for human therapy since synthetic peptides do not have any of the potential dangers associated with the induction of an infection by recombinant viruses. However, synthetic peptides alone are often not immunogenic enough, and a strong immunoadjuvant is usually employed for their elaboration. Unfortunately, only a few adjuvants used in experimental models are allowed for use in human beings. In this regard, different presentations of synthetic peptides such as incorporation into liposomes, modification of the lipophilic properties by means of a covalently coupled fatty acid moiety and the synthesis of larger constructs such as multiple antigenic peptides (MAP) have been demonstrated to yield efficient immunological reagents for the amplification in the analysis and induction of immune responses to a variety of infectious agents. This review outlines recent research on synthetic peptide immunology. The development of a MAP with a built-in adjuvant is highlighted as a robust method for vaccine design.     

Establishing the synthetic origin of amphetamines by 2H NMR spectroscopy

Nine samples of N-acetyl-3,4-methylenedioxyamphetamine (N-acetyl-MDA), prepared according to the most common synthetic procedures, are submitted to (2)H NMR spectroscopy. The relative deuterium content at the various sites of the molecule is shown to depend on its synthetic history. The technique provides a chemical fingerprint of N-acetyl-MDAs and it can be used to trace back the precursor materials and the synthetic pathways employed in the preparation of the samples.     

Sample size and retention values in gradient liquid chromatography of synthetic polymers

Summary Retention times in gradient liquid chromatography of synthetic polymers are often dependent on sample size. They increase with column load if the separation mechanism is governed by a solution process but decrease with increasing load if the mechanism is governed by adsorption. Since retention times independent of sample size are a prerequisite for peak identification as well as for the correct measurement of elution bands of samples with a broad distribution, measures to counteract sample-size effects deserve attention. Usually both solubility and adsorption are effective in gradient liquid chromatography of synthetic polymers. An appropriate balance of both effects is suitable for diminishing the influence of sample size on retention time of synthetic polymers. Ternary gradients allowing independent control of solubility and adsorption are promising.     

Deciding whether to go with the flow: evaluating the merits of flow reactors for synthesis

The fine chemicals and pharmaceutical industries are transforming how their products are manufactured, where economically favorable, from traditional batchwise processes to continuous flow. This evolution is impacting synthetic chemistry on all scales-from the laboratory to full production. This Review discusses the relative merits of batch and micro flow reactors for performing synthetic chemistry in the laboratory.     

Design of synthetic peptides for diagnostics

Due to the advantageous properties of synthetic molecules compared to biological ones biological molecules in diagnostic tests are replaced increasingly by synthetic ones, usually synthetic peptides or related molecules. The replacement of biological antigens by synthetic peptides is most advanced at present, as well as the use of site-specific antibodies induced with synthetic peptides. Moreover recent results indicate that synthetic molecules may also replace antibodies. Ultimately this will lead to diagnostic assays built of synthetic molecules only.     

New Advances in the Synthesis of Emerging Cyclic Amidrazones to Foster Bioisosterism of Azaheterocycles

The pace and the scope of new molecules design is often constrained by limitations in synthetic chemistry. The azaheterocyclic amidrazones are of particular interest for bioisosteric considerations in drug discovery. However, the lack of efficient synthetic access has undoubtedly hampered their occurrence in the drug chemical space. Our current results describe a robust synthetic access relying on cyclization of aminohydrazine in presence of various orthoesters by either metal free- or metal-catalyzed condensations. This optimized synthetic access to cyclic amidrazones as original scaffold should inspire the chemist community and further drive innovation in the design of molecular structure for many applications (for example, drugs, materials, dyes).     

Synthesis and Self Assembly of Hydrogen-Bonded Supramolecular Polymers

New synthetic methodologies towards hydrogen bonded supramolecular polymers are described. Focus is directed on synthetic work towards telechelics with hydrogen bonds either as side chain moieties or as endgroups. Physical ordering effects related to polymers and particles are discussed citing own and related work in ∼60 references.     

Membrane structure and its correlation with membrane permeability

Methods for the investigation of pore and molecular structure of synthetic membranes are reviewed. Membranes are classified as coarse-porous, fine-porous, and solution-diffusion membranes, on one hand; and homogeneous, asymmetric, and composite on the other, Pore structure of synthetic membranes can be elucidated in detail only by electron and raster electron microscopic investigations. Inspection of molecular structure requires diversely specific test probes such as low-energy neutron scattering and/or diffraction, and gas sorption and permeability measurements, as well as thermodynamic and thermomechanical analysis. Other methods used to elucidate pore and molecular structure of synthetic membranes are discussed and, concurrently, membrane structure is correlated with membrane permeability.     

The shortest synthetic route to puromycin analogues using a modified Robins approach

We are reporting on the utility of commercial vinyl isocyanate for a practical synthetic route from adenosine to N(6)-bis-demethylpuromycin in seven steps and 65% overall yield. A clean one-pot conversion of 3'-bromo-2'-carbamoyl derivative 8 to 3'-amino-3'-deoxyadenosine derivative 10 is the main feature of this synthetic pathway. This synthesis is the shortest synthetic route toward 3'-(aminoacylamido)deoxyadenosines to date.     

The biodeterioration of synthetic resins used in conservation

Synthetic resins have been extensively employed by artists in their works of art, e.g. as paint binders, or by conservators for conservation treatments, e.g. as stone consolidants and protectives. It is generally thought that synthetic resins are less prone to chemical, physical and biological deterioration than other organic products but there are many articles in the scientific literature and some reports in the conservation of cultural heritage literature claiming that microorganisms are capable of degrading synthetic resins. This paper reviews the researches on the biodeterioration of synthetic resins used in the conservation of cultural heritage, including stone, painting and textile materials, carried out in the last fifty years.     

Dendralenes branch out: cross-conjugated oligoenes allow the rapid generation of molecular complexity

Twenty-seven years ago, H. Hopf published the only previous comprehensive review on branched oligoenes that had the title "Dendralenes: A Neglected Family of Hydrocarbons". The dendralenes are no longer neglected. Research into the synthesis, properties, and applications of dendralenes is rapidly gaining momentum and this Review summarizes important recent findings. From significant fundamental properties (the first demonstration of alternating behavior since the annulenes) through to unparalleled complexity-generating synthetic transformations, this fundamental oligoene family is coming of age. Effective synthetic approaches to cyclic and acyclic dendralene systems are analyzed and classified. The most powerful synthetic transformations of the dendralenes, diene-transmissive Diels-Alder reactions, are surveyed in detail.     

A process in need is a process indeed: scalable enantioselective synthesis of chiral compounds for the pharmaceutical industry

This report deals with enantioselective synthesis of viracept 1 (nelfinavir mesylate, AG 1343), a potent HIV protease inhibitor, and 3-hydroxytetradecanoic acid 3, a component of lipid A comprising lipopolysaccharide embedded in the cell surface of Gram-negative bacteria, from both strategic and practical perspectives. As regards the synthesis of 1, the synthetic approaches to its central intermediate 2 possessing the common structural motif of 1,4-differentially substituted-2-amino-3-hydroxylbutane are mainly discussed with emphasis on the molecular symmetry that has helped streamline the synthetic strategy. In the discussion of the synthetic strategies to access a single enantiomer of 3, the chiral methodologies that have been applied so far are assessed for industrial viability; the synthetic alternatives explored include resolution via diastereomeric salt formation, lipase-catalyzed kinetic resolution, asymmetric synthesis, and chiral pool approaches.     

Synthesis of protein-polymer conjugates

Protein-polymer conjugates are widely employed for applications in medicine, biotechnology and nanotechnology. Covalent attachment of synthetic polymers to proteins improves protein stability, solubility, and biocompatibility. Furthermore, synthetic polymers impart new properties such as self assembly and phase behavior. Polymer attachment at amino acid side-chains and at ligand binding sites is typically exploited. This Emerging Area focuses on synthetic methods to prepare protein-reactive polymers and also employing the protein itself as an initiator for polymerization.