Combining cationic ring‐opening polymerization and click chemistry for the design of functionalized polyurethanes

A straightforward strategy for the synthesis and functionalization of polyurethanes (PUs) via the use of alkyne‐functionalized polytetrahydrofuran (PTHF) diols is described. The alkyne groups have been introduced into the PTHF chains by the cationic ring‐opening copolymerization of tetrahydrofuran and glycidyl propargyl ether. These PTHF prepolymers were combined with 1,4‐butanediol and hexamethylene diisocyanate for the synthesis of linear PUs with latent functionalization sites. The polyether segments of the PUs have then been coupled with several types of functionalized azides by the copper‐catalyzed azide‐alkyne “click” chemistry, for example with phosphonium containing azides for their antibacterial properties. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Combining coordination chemistry and catalysis to tie a knot by an active-metal template strategy

Collar and tie men: the smallest trefoil knot reported to date has been prepared by an active metal template synthesis. Copper(I) ions are able to constrain the well-designed structure so that it can form the loops by complexing to the bipyridine moieties in the core of the thread and the two ends of the entangled lace on opposite faces of the loop, before acting as a catalyst to close the lace.     

Polymeric phosphonium salts as a novel class of cationic biocides. IV. Synthesis and antibacterial activity of polymers with phosphonium salts in the main chain

Polymers with phosphonium salts and different alkyl spacers in the main chain were prepared, and their antibacterial activities against Staphylococcus aureus and Escherichia coli were explored by the viable cell counting method in sterile distilled water. The antibacterial activity of the polymers was found to be higher than that of the corresponding model compounds against each strain, and the effect of the molecular weight on the antibacterial activity was also observed for the compounds with the same spacer length. The antibacterial activity of the polymer samples bonded with different spacer lengths was found to increase with increasing the spacer length against both strains. © 1993 John Wiley & Sons, Inc.     

Polythioethers by Thiol‐Ene Click Polyaddition of α,ω‐Alkylene Thiols

The straightforward synthesis of a series of poly(thioether)s by photoinduced thiol‐ene click polyaddition of α,ω‐alkylene thiols is reported. It is found that linear and telechelic poly(thioether)s can be directly obtained from α,ω‐alkylene thiols with, for example, alkyl chain length of m = 1,2,3, and 9. The reaction proceeds without additives such as (radical) initiators or metal compounds and can simply be carried out by UV‐irradiation of the bulk monomer or monomer solution. Ex situ kinetic studies reveal that the reaction proceeds by a typical a step‐growth polyaddition mechanism. As the homologue series of poly(thioether)s are now synthetically accessible, new direct pathways to tailored poly(alkyl sulphoxide)s and poly(alkyl sulfone)s are now possible.

     

Ultrasound mediated green synthesis of rhodanine derivatives: Synthesis,chemical behavior,and antibacterial activity

A variety of rhodanine derivatives were synthesized via a three-component reaction of carbon disulfide, amines, and dialkyl acetylenedicarboxylate in polyethylene glycol under conventional stirring or ultrasound irradiation. The sonochemical-assisted procedure provides an improved and accelerated conversion when compared to the conventional reaction, with increased rate of reaction and quality of product obtained. The product formed, 2a, could be readily converted to bis-rhodanine under microwave conditions. Moreover, the pyranothiazoles 9a,b were prepared from the corresponding rhodanines 2a,b and malononitrile. Fifteen compounds were screened for their antibacterial activities against nine human, animal and plant pathogenic Gram-positive and Gram-negative bacteria using the agar well diffusion method. Out of these derivatives, compounds 2g and 2h were the most effective against all tested bacteria.     

Novel polycationic biocides: Synthesis and antibacterial activity of polymeric phosphonium salts

Various polymeric phosphonium salts and the corresponding low-molecular-weight model compounds were prepared and their antibacterial activities against Staphylococcus aureus and Escherichia coli were explored by the viable cell counting method in sterile distilled water. Antibacterial activity of the polymers was found to be higher than that of the corresponding model compounds, particularly against S. aureus. Furthermore, the polymeric phosphonium salt exhibited a higher activity by 2 orders of magnitude than the polymeric quaternary ammonium salt with the same structure except the cationic part. Compounds with the longest alkyl chain (octyl) studied were found to exhibit particularly high activity, and this finding may be ascribed to the contribution of the increased hydrophobicity of the compounds to the cidal activity. © 1993 John Wiley & Sons, Inc.     

三芥子酸甘油酯类似物的合成及抑菌活性

以N-(2-溴乙基)邻苯二甲酰亚胺或N-(4-溴丁基)邻苯二甲酰亚胺和硫氢化钠为起始原料,通过取代、肼解、亲核加成等反应合成了10个三芥子酸甘油酯(erucin)类似物,通过核磁共振氢谱、碳谱及质谱对其结构进行了确认。采用比浊法初步测试了其对大肠杆菌、金黄色葡萄球菌、白色葡萄球菌、藤黄八叠球菌、枯草芽孢杆菌、蜡状芽孢杆菌和四联球菌等7种菌的生长抑制活性,测试结果显示,化合物对测试菌种都表现出较好的生长抑制活性,其中苄硫乙基-1-硫代异硫氰酸酯(5e)和苄硫基丁基-1-硫代异硫氰酸酯(5j)活性最高,对大肠杆菌的最低生长抑制浓度仅为7.8μg/m L,对金黄色葡萄球菌的最低生长抑制浓度也仅为15.6μg/m L和31.2μg/m L。     

1,2,4-噁二唑类化合物的合成及抗菌活性研究

以对溴苯腈为原料,通过多步反应合成了一系列3-(吗啉苯基)-5-取代-1,2,4-异噁唑类化合物和3-(吗啉苯基)-5-取代-4,5-二氢-1,2,4-噁二唑类化合物,并用1HNMR、13C NMR和MS进行了结构确证。这些化合物对测试的部分革兰氏阳性菌,如金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌显示出一定的抗菌活性,但与噁唑烷酮类上市药物利奈唑胺相比,抗菌活性有明显下降。这一结果表明对于化合物的抗菌活性,1,2,4-噁二唑杂环不如噁唑烷酮结构有效。     

Synthesis and anti-inflammatory activity of triazole-based macrocyclic amides through click chemistry

Triazole-based macrocyclic amides 1–12 with amide group as the intrannular functionality has been synthesized through click chemistry. Triazole-based macrocyclic amides 1–12 show good anti-inflammatory activity even at low concentration (50?µg/mL) when compared to that of the reference drug prednisolone. BINOL-based chiral macrocyclic amides and pyridine-based macrocyclic amides show better anti-inflammatory activity than the other synthesized macrocyclic amides.     

"Click" immobilization on alkylated silicon substrates: model for the study of surface bound antimicrobial peptides

We describe an effective approach for the covalent immobilization of antimicrobial peptides (AMPs) to bioinert substrates via Cu(I) -catalyzed azide-alkyne cycloaddition (CuAAC). The bioinert substrates were prepared by surface hydrosilylation of oligo(ethylene glycol) (OEG) terminated alkenes on hydrogen-terminated silicon surfaces. To render the OEG monolayers "clickable", mixed monolayers were prepared using OEG-alkenes with and without a terminal alkyne protected by a trimethylgermanyl (TMG) group. The mixed monolayers were characterized by X-ray photoelectron spectroscopy (XPS), elliposometry and contact angle measurement. The TMG protecting group can be readily removed to yield a free terminal alkyne by catalytic amounts of Cu(I) in an aqueous media. This step can then be combined with the subsequent CuAAC reaction. Thus, the immobilization of an azide modified AMP (N3-IG-25) was achieved in a one-pot deprotection/coupling reaction. Varying the ratio of the two alkenes in the deposition mixture allowed for control over the density of the alkynyl groups in the mixed monolayer, and subsequently the coverage of the AMPs on the monolayer. These samples allowed for study of the dependence of antimicrobial activities on the AMP density. The results show that a relative low coverage of AMPs (～1.6×10(13) molecule per cm(2)) is sufficient to significantly suppress the viability of Pseudomonas aeruginosa, while the surface presenting the highest density of AMPs (～2.8×10(13) molecule per cm(2)) is still cyto-compatible. The remarkable antibacterial activity is attributed to the long and flexible linker and the site-specific "click" immobilization, which may facilitate the covalently attached peptides to interact with and disrupt the bacterial membranes.     

Assessment of the bioactive compounds,antioxidant and antibacterial activities of Isodon rubescens as affected by drying methods

The influence of natural drying (ND), hot-air drying (HD), vacuum drying (VD), infrared drying (ID) and freeze drying (FD) on bioactive compounds and bioactivities of Isodon rubescens (Hemsl.) was investigated in this study. The results showed that different drying methods resulted in the differences in bioactive compositions’ content, antioxidant and antibacterial activities of extracts from I. rubescens. FD sample possessed the highest content of total phenolics, total flavonoids and several main phenolic compounds, as well as the stronger antioxidant and antibacterial activities, followed by ND, HD and VD, the lowest for ID samples. For this reason, freeze drying would seem to be more advisable for the drying I. rubescens, and future studies could focus on the quality evaluation and optimising various drying parameters.     

Synthesis of nitrogen-containing monoterpenoids with antibacterial activity

Abstract

Incorporation of the Beckmann rearrangement into the presented research resulted in the formation of nitrogen-containing terpenoid derivatives originating from naturally occurring compounds. Both starting monoterpenes and obtained derivatives were subjected to estimation of their antibacterial potential. In the presented study, Staphylococcus aureus was the most sensitive to examined compounds. The Minimal Inhibitory Concentration (MIC) experiments performed on S. aureus demonstrated that the (?)-menthone oxime (?)-8 and (+)-pulegone oxime (+)-13 had the best antibacterial activity among the tested derivatives and starting compounds. Their MIC₉₀ value was 100?µg/mL. The obtained derivatives were also evaluated for their inhibitory activity against bacterial urease. Among the tested compounds, three active inhibitors were found – oxime 14 and lactams (?)-15 and 16 limited the activity of Sporosarcina pasteurii urease with K_i values of 174.3?µM, 43.0?µM and 4.6?µM, respectively. To our knowledge, derivative 16 is the most active antiureolytic lactam described to date.     

三氯新的结构改造及抑菌活性初探

本论文对三氯新的结构进行了改造,合成了四个未见文献报道的三氯羟基二苯醚衍生物,它们的结构均经红外、核磁、高分辨质谱证实.对新化合物进行了抗金黄色葡萄球菌和大肠杆菌活性的测试,其中有一个新化合物在20ug/mL浓度下对两种菌都有活性.     

Living cationic polymerization of an azide‐containing vinyl ether toward addressable functionalization of polymers

We first achieved the living cationic polymerization of azide‐containing monomer, 2‐azidoethyl vinyl ether (AzVE), with SnCl₄ as a catalyst (activator) in conjunction with the HCl adduct of a vinyl ether [H‐CH₂CH(OR)‐Cl; R ? CH₂CH₂Cl, CH₂CH(CH₃)₂]. Despite the potentially poisoning azide group, the produced polymers possessed controlled molecular weights and fairly narrow distributions (M_w/M_n ～ 1.2) and gave block polymers with 2‐chloroethyl vinyl ether. The pendent azide groups are easily converted into various functional groups via mild and selective reactions, such as the Staudinger reduction and copper‐catalyzed azide‐alkyne 1,3‐cycloaddition (CuAAC; a “click” reaction). These reactions led to quantitative pendent functionalization into primary amine (? NH₂), hydroxy (? OH), and carboxyl (? COOH) groups, at room temperature and without any acidic or basic treatment. Thus, poly(AzVE) is a versatile precursor for a wide variety of functional vinyl ether polymers with well‐defined structures and molecular weights. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1449–1455, 2010     

Effect of water addition on the coupling of homopolymers by click chemistry

Homopolymers bearing terminal azide and alkyne groups can be coupled via click chemistry to yield diblock copolymers. When performed in solvents that dissolved both homopolymers, the click reaction was found in this study to be inefficient, probably due to the embedding of the reactive end groups inside the random coils of the polymers. The efficiency was only slightly affected by the addition of a small amount of water into the reaction mixture. However, the reaction efficiency increased dramatically near the water volume fraction where one or both of the reacting polymers began to precipitate. Further increases in water content caused the polymer(s) to undergo macroscopic phase separation and the click reaction efficiency decreased once again. A possible explanation for the observed effect of water on the polymer coupling reaction is proposed. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Heptyl α‐D‐Mannosides Grafted on a β‐Cyclodextrin Core To Interfere with Escherichia coli Adhesion: An In Vivo Multivalent Effect

n‐Heptyl α‐D ‐mannoside (HM) has previously been identified as a nanomolar FimH antagonist able to prevent Escherichia coli adhesion. We have designed mono‐ and heptavalent glycoconjugates in which HM is tethered to β‐cyclodextrin (β‐CD) through short and long spacers. One‐pot click or co‐clicking procedures were developed to directly obtain the glycoconjugates from unprotected HM and β‐CD precursors. These FimH antagonists were examined biophysically and in vivo. Reverse titrations by isothermal calorimetry led to trapping of the short‐tethered heptavalent β‐CD in a complex with three FimH lectins. Combined dynamic light scattering and small‐angle X‐ray solution scattering data allowed the construction of a model of the FimH trimer. The heptavalent β‐CDs were shown to capture and aggregate living bacteria in solution and are therefore also able to aggregate FimH when attached to different bacteria pili. The first in vivo evaluation of multivalent FimH inhibitors has been performed. The heptavalent β‐CDs proved to be much more effective anti‐adhesive agents than monovalent references with doses of around 2 μg instilled in the mouse bladder leading to a significantly decreased E. coli load. Intravenously injected radiolabeled glycoconjugates can rapidly reach the mouse bladder and >2 μg concentrations can easily be retained over 24 h to prevent fluxing bacteria from rebinding.     

二氢吲哚-2,3-二酮衍生物抑菌活性研究进展

二氢吲哚-2,3-二酮是一种结构简单且应用广泛的药物小分子,其衍生物的合成、结构和药理活性等备受关注。已有报道表明二氢吲哚-2,3-二酮具有抗菌、抗衰老、降血脂、抗癫痫、抗病毒等多种生物活性。本文主要围绕抑菌生物活性,对国内外关于二氢吲哚-2,3-二酮类化合物的构效关系进行分析总结,为后期该类新型抗菌化合物的设计合成提供参考。     

Polymeric phosphonium salts as a novel class of cationic biocides. V. Synthesis and antibacterial activity of polyesters releasing phosphonium biocides

Polyesters were prepared which retained phosphonium biocides as counter ions of sodium sulfonate moieties incorporated into the polymers, and surface antibacterial activity of the polyester films against Staphylococcus aureus and Escherichia coli was explored. These films exhibited a high surface antibacterial activity against S. aureus and E. coli, particularly against S. aureus, and the activity was affected by the structure and the compositional ratio of the phosphonium salts. Amount of the released phosphonium salts was very small, so that liberation of the phosphonium biocides can be expected to occur over a long period. Morphological changes of the cells of S. aureus and E. coli in contact with the polyester films were evaluated by scanning electron microscopy. It was found that the surface antibacterial activity of the polyester films was rather bacteriostatic than bactericidal as evidenced by no morphological changes of the bacterial cells in contact with the phosphonium biocides © 1993 John Wiley & Sons, Inc.