- Temporal and Triggered Evolution of Host-Guest Characteristics in Amphiphilic Polymer Assemblies
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An amphiphilic polymer with cleavable side chain and main chain functional groups has been designed and synthesized. Specific cleavage of either of its functional groups was found to have an effect on the morphology of the assembly. Degradation of the main chain is shown to cause morphology of the supramolecular assembly to evolve with time from a micelle-like assembly to a vesicular assembly. On the other hand, stimulus-induced cleavage of the side chains causes these nanoassemblies to disassemble. These temporal (main chain) and triggered (side chain) degradation processes have implications in the design of degradable polymers as supramolecular scaffolds for biological applications.
- Rangadurai, Poornima,Molla, Mijanur Rahaman,Prasad, Priyaa,Caissy, Matthew,Thayumanavan
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- Design and synthesis of marine sesterterpene analogues as novel estrogen receptor α degraders for breast cancer treatment
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Targeted protein degradation using small molecules is an intriguing strategy for drug development. The marine sesterterpene compound MHO7 had been reported to be a potential ERα degradation agent. In order to further improve its biological activity, two series of novel MHO7 derivatives with long side chains were designed and identified as novel selective estrogen receptor down-regulators (SERDs). The growth inhibition activity of the novel SERD compounds were significantly affected by the type and length of the side chain. Most of the derivatives were significantly more potent than MHO7 against both drug-sensitive and drug-resistant breast cancer cells. Among them, compound 16a, with IC50 values of 0.41 μM against MCF-7 cell lines and 9.6-fold stronger than MHO7, was the most potential molecule. A whole-genome transcriptomic analysis of MCF-7 cells revealed that the mechanism of 16a against MCF-7 cell was similar with that of MHO7. The estrogen signaling pathway was the most affected among the disturbed genes, but the ERα degradation activity of 16a was observed higher than that of MHO7. Other effects of 16a were confirmed similar with MHO7, which means that the basic mechanisms of the derivatives are the same with the ophiobolin backbone, i.e. the degradation of ERα is mediated via proteasome-mediated process, the induction of apoptosis and the cell cycle arrest at the G1 phase. Meanwhile, a decrease of mitochondrial membrane potential and an increase of cellular ROS were also detected. Based on these results, as a novel modified ophiobolin derived compound, 16a may warrant further exploitation as a promising SERD candidate agent for the treatment of breast cancer.
- Gong, Shuang,Hong, Kui,Liang, Jian-Jia,Liu, Ten-Yue,Qin, Kong-Ming,Xie, Bao-Hua,Yan, Jing-Jing,Yang, Liang,Yin, Yu-Ping,Yu, Wu-Lin,Zhou, Hai-Bing
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- Non-Viral CRISPR/Cas Gene Editing In Vitro and In Vivo Enabled by Synthetic Nanoparticle Co-Delivery of Cas9 mRNA and sgRNA
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CRISPR/Cas is a revolutionary gene editing technology with wide-ranging utility. The safe, non-viral delivery of CRISPR/Cas components would greatly improve future therapeutic utility. We report the synthesis and development of zwitterionic amino lipids (ZALs) that are uniquely able to (co)deliver long RNAs including Cas9 mRNA and sgRNAs. ZAL nanoparticle (ZNP) delivery of low sgRNA doses (15 nm) reduces protein expression by >90 % in cells. In contrast to transient therapies (such as RNAi), we show that ZNP delivery of sgRNA enables permanent DNA editing with an indefinitely sustained 95 % decrease in protein expression. ZNP delivery of mRNA results in high protein expression at low doses in vitro (?1). Intravenous co-delivery of Cas9 mRNA and sgLoxP induced expression of floxed tdTomato in the liver, kidneys, and lungs of engineered mice. ZNPs provide a chemical guide for rational design of long RNA carriers, and represent a promising step towards improving the safety and utility of gene editing.
- Miller, Jason B.,Zhang, Shuyuan,Kos, Petra,Xiong, Hu,Zhou, Kejin,Perelman, Sofya S.,Zhu, Hao,Siegwart, Daniel J.
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supporting information
p. 1059 - 1063
(2017/01/18)
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- Synthesis and Surface Properties of a Novel Sodium 3-(3-Alkyloxy-3-oxopropoxy)-3-oxopropane-1-sulfonate at the Air-Water Interface
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The present paper describes the synthesis and evaluation of surface properties of a novel series of anionic surfactant, namely sodium 3-(3-alkyloxy-3-oxopropoxy)-3-oxopropane-1-sulfonate with varying alkyl chain length (C8-C16). Synthesis involves initial formation of the 3-alkyloxy-3-oxopropyl acrylate along with fatty acrylate during the direct esterification of fatty alcohol with acrylic acid in the presence of 0.5 % NaHSO4 at 110 C followed by sulfonation of the terminal double bond of the 3-alkyloxy-3-oxopropyl acrylate. Synthesized compounds were evaluated for surface and thermodynamic properties such as critical micelle concentration (CMC), surface tension at CMC (γcmc), efficiency of surface adsorption (pC20), surface excess (Γmax), minimum area per molecule at the air-water interface (A min), free energy of adsorption (?G ads), free energy of micellization (?G mic), wetting time, emulsifying properties, foaming power and calcium tolerance. Effect of chain length on CMC follows the classic trend, i.e. decrease in CMC with the increase in alkyl chain length. High pC20 (>3) value indicates higher hydrophobic character of the surfactant. These surfactants showed very poor wetting time and calcium tolerance, but exhibited good emulsion stability and excellent foamability. Foaming power and foam stability of C14-sulfonate were found to be the best among the studied compounds. Foam stability of C14-sulfonate was also studied at different concentrations over time and excellent foam stability was obtained at a concentration of 0.075 %. Thus this novel class of surfactant may find applications as foam boosters in combination with other suitable surfactants.
- Kumar, Pandari Phani,Nayak, Rati Ranjan,Kanjilal, Sanjit
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p. 689 - 695
(2015/06/23)
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- A lewis acid-promoted pinner reaction
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Carbonitriles and alcohols react in a Lewis acid-promoted Pinner reaction to carboxylic esters. Best results are obtained with two equivalents of trimethylsilyl triflate as Lewis acid. Good yields are achieved with primary alcohols and aliphatic or benzylic carbonitriles, but the straightforward synthesis of acrylates and benzoates starting with acrylonitrile and benzonitrile, respectively, is similarly possible. Phenols are not acylated under these reaction conditions. The method has been used for the first total synthesis of the natural product monaspilosin. In the reaction of benzyl alcohols variable amounts of amides are formed in a Ritter-type side reaction.
- Pfaff, Dominik,Nemecek, Gregor,Podlech, Joachim
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supporting information
p. 1572 - 1577
(2013/10/22)
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- A hydrogen chloride-free pinner reaction promoted by lewis acids
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A hydrogen chloride-free variation of the Pinner reaction was developed, in which alcohols react with carbonitriles to furnish carboxylates. Best results were achieved with aliphatic alcohols, and aliphatic or benzylic nitriles in the presence of 2 equiv. of trimethylsilyl triflate (Me3SiOTf). With these substrates, yields exceeding 80% were achieved. A strictly neutral variation of this protocol is possible, when 1 equiv. of Et3N is added to the reaction mixture. Copyright
- Pfaff, Dominik,Nemecek, Gregor,Podlech, Joachim
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p. 1851 - 1856,6
(2012/12/12)
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- Facile acetylation of alcohols, ethers and ketals with catalytic FeCl3 in AcOH
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A simple and efficient protocol for the conversion of alcohols, ethers and ketals to acetates using catalytic FeCl3(5mol%) in AcOH, or AcOH (3eq) in CH2Cl2 in very high yield is reported. A variety of other acids such as CF3CO2H, HCO2H, CH2=CHCO2H, CH3CH2CO2H, CH3(CH2)2CO2H have also been utilised for the acylation of alcohols successfully.
- Sharma,Mahalingam,Nagarajan,Ilangovan,Radhakrishna, Palakodety
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p. 1200 - 1202
(2007/10/03)
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- Hypervalent (tert-butylperoxy)iodanes generate iodine-centered radicals at room temperature in solution: Oxidation and deprotection of benzyl and allyl ethers, and evidence for generation of α-oxy carbon radicals
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1-(tert-Butylperoxy)-1,2-benziodoxol-3(1H)-one (1a) oxidizes benzyl and allyl ethers to the esters at room temperature in benzene or cyclohexane in the presence of alkali metal carbonates. Since this reaction is compatible with other protecting groups such as MOM, THP, and TBDMS ethers, and acetoxy groups, and because esters are readily hydrolyzed under basic conditions, this new method provides a convenient and effective alternative to the usual reductive deprotection. Oxidation with 1a occurs readily with C-H bonds activated by both enthalpic effects (benzylic, allylic, and propargylic C-H bonds) and/or polar effects (α-oxy C-H bonds), generating α-oxy carbon-centered radicals, which can be detected by nitroxyl radical trapping. Measurement of the relative rates of oxidation for a series of ring-substituted benzyl n-butyl ethers 2d and 2p-s indicated that electron-releasing groups such as p-MeO and p-Me groups increase the rate of oxidation, and Hammett correlation of the relative rate factors with the σ+ constants of substituents afforded the reaction constant ρ+ = -0.30. The large value of the isotope effect obtained for the oxidation of benzyl n-butyl ether 2d (k(H)/k(D) = 12-14) indicates that the rate-determining step of the reactions probably involves a high degree of benzylic C-H bond breaking. The effects of molecular dioxygen were examined, and the mechanism involving the intermediacy of the tert-butylperoxy acetal 5 and/or the hydroperoxy acetal 32 is proposed. Particularly noteworthy is the finding that (tert-butylperoxy)iodane 1a can generate the tert-butylperoxy radical and the iodine-centered radical 33a, even at room temperature in solution, via homolytic bond cleavage of the hypervalent iodine(III)-peroxy bond.
- Ochiai, Masahito,Ito, Takao,Takahashi, Hideo,Nakanishi, Akinobu,Toyonari, Mika,Sueda, Takuya,Goto, Satoru,Shiro, Motoo
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p. 7716 - 7730
(2007/10/03)
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- A New Synthetic Method of Macrocyclic Lactones from ω-Iodoalkylacrylates
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When the photostimulated cyclization reaction of ω-iodoalkylacrylates was performed in the presence of metal hydride complexes such as sodium cyanoborohydride (NaBH3CN), sodium borohydride (NaBH4) and potassium borohydride (KBH4), the corresponding macrocyclic lactones were produced.The use of NaBH3CN led to the highest yield of lactones.
- Abe, Motoji,Hayashikoshi, Takaoki,Kurata, Takeo
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p. 1789 - 1792
(2007/10/02)
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- The 'Baylis - Hillman reaction' mechanism and applications revisited
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It is shown that reaction of aryl, benzyl, alkyl and functionalised alkyl acrylic esters with benzaldehyde, in the presence of 1,4-diazabicyclo[2.2.2] octane, strongly depends upon the electronic and steric effects of the ester part. This influence is also observed in condensation of furfuraldehyde. Moreover, for the first time, it is shown that the overall condensation is equilibrated.
- Fort, Yves,Berthe, Marie Christine,Caubere, Paul
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p. 6371 - 6384
(2007/10/02)
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- Cosmetic emulsions containing acrylamide copolymer
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Water-in-oil emulsions wherein the emulsifier is a copolymer of 1 mol of acrylamide with 2 to 20 mols of at least one ethylenically unsaturated ester copolymerizable therewith selected from the group consisting of vinyl alkylcarboxylates, alkyl and cycloalkyl acrylates, and alkly and cycloalkyl methacrylates, wherein the alkyl and cycloalkyl groups contain 6 to 24 carbon atoms, and the continuous phase is a cosmetically acceptable oil, which can be prepared easily, safely and inexpensively. The emulsions are substantially odorless and are cosmetically acceptable for the care of the skin.
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- Process for the preparation of Diels-Alder adducts of halogenated cyclopentadienes
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An improved process for the preparation of solid Diels-Alder adducts of halogenated cyclopentadienes and mono- or diolefins is disclosed wherein the reactants are combined in an aqueous emulsion. The adducts are obtained in excellent yield and in an extremely fine particulate form. The new process avoids the use of organic solvents which are relatively costly, hazardous to use, and from which the adducts are usually obtained as relatively large crystals which require pulverization prior to use.
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