Search Results (8)

A novel and general approach to the practical ROMP polymerization of cinchona alkaloid derivatives providing novel hybrid materials having quinine attached on a poly(norbornene-5,6-dicarboxyimide) matrix is presented. The concept involves an easy modification of quinine (in general, any cinchona alkaloid) toward clickable 9-azide that reacts with N-propargyl-cis-5-norbornene-exo-2,3-dicarboxylic imide in Cu(I)-catalyzed Huisgen cycloaddition (click chemistry). The resulting monomers undergo a controllable ROMP reaction that leads to novel polymers of a desired length and solubility. This sequence allows for the facile preparation of a regularly decorated polymeric material having one quinine moiety per single mer of the polymer chain inaccessible using typical immobilization methods. A poly(norbornene-5,6-dicarboxyimide) type of polymeric matrix was selected due to the high reactivity of the exo-norbornene motif in Ru(II)-catalyzed ROMP and its chemical and thermal stability as well as convenient, scalable access from inexpensive cis-5-norbornene-exo-2,3-dicarboxylic anhydride (‘one-pot’ Diels–Alder reaction of dicyclopentadiene and maleic anhydride). An appropriate combination of a Grubbs catalyst, Ru(II) (G1, G2), and ROMP conditions allowed for the efficient synthesis of well-defined soluble polymers with mass parameters in the range Mn = 2.24 × 10⁴ – 2.26 × 10⁴ g/mol and Mw = 2.90 × 10⁴–3.05 × 10⁴ g/mol with good polydispersity, Đ_M = 1.32–1.35, and excellent thermal stability (up to 309°C T_d10). Spectroscopic studies (NMR and electronic circular dichroism (ECD)) of these products revealed a linear structure with the slight advantage of a trans-configuration of an olefinic double bond. The resulting short-chain polymer discriminates mandelic acid enantiomers with a preference for the (R)-stereoisomer in spectrofluorimetric assays. This concept seems to be rather general with respect to other molecules dedicated to incorporation into the poly(norbornene-5,6-dicarboxyimide) chain. Full article

Stimulus-responsive hydrogels have been widely used in the field of drug delivery because of their three-dimensional pore size and the ability to change the drug release rate with the change in external environment. In this paper, the temperature-sensitive monomer 2-methyl-2-acrylate-2-(2-methoxyethoxy-ethyl) ethyl ester (MEO₂MA) and oligoethylene glycol methyl ether methacrylate (OEGMA) as well as the pH-sensitive monomer N,N-Diethylaminoethyl methacrylate (DEAEMA) were used to make the gel with temperature and pH response. Four kinds of physicochemical double-crosslinked amphiphilic co-network gels with different polymerization degrees were prepared by the one-pot method using the stereocomplex between polylactic acid as physical crosslinking and click chemistry as chemical crosslinking. By testing morphology, swelling, thermal stability and mechanical properties, the properties of the four hydrogels were compared. Finally, the drug release rate of the four gels was tested by UV–Vis spectrophotometer. It was found that the synthetic hydrogels had a good drug release rate and targeting, and had great application prospect in drug delivery. Full article

In this work, we designed a series of new carbohydrate-based coumarin carbonic anhydrase IX inhibitors by using 1,2,3-triazoles as linker. Next, these designed compounds were synthesized by the optimized one-pot click chemistry reaction condition. Subsequently, these target compounds were assayed for the inhibition of three carbonic anhydrase isoforms (CA I, CA II and CA IX). Intriguingly, all the compounds showed better CA IX inhibitory activity than initial coumarin fragments. Among them, compound 10a (IC₅₀: 11 nM) possessed the most potent CA IX inhibitory activity, which was more potent than the reference drug acetazolamide (IC₅₀: 30 nM). Notably, compound 10a showed 3018-fold, 1955-fold selectivity relative to CA I and CA II, respectively. Meanwhile, representative compounds could reduce tumor cell viability and the extracellular acidification in HT-29 and MDA-MB-231 cancer cell lines. Even more interestingly, our target compounds had no apparent cytotoxicity toward MCF-10A cell line. In addition, the in vitro stability assays also indicated our developed compounds possessed good liver microsomal metabolic stabilities and plasma stability. Furthermore, representative compounds revealed relatively low hERG cardiac toxicity and acute toxicity. Furthermore, docking studies were carried out to understand the interactions of our target compounds with the protein target CA IX. Collectively, our results suggest that compound 10a, as a selective CA IX inhibitor, could be an important lead compound for further optimization and development as an anticancer agent. Full article

A supported gold nanoparticle-catalyzed strategy has been utilized to promote a click chemistry reaction for the synthesis of 1,2,3-triazoles via the azide-alkyne cycloaddition (AAC) reaction. While the advent of effective non-copper catalysts (i.e., Ru, Ag, Ir) has demonstrated the catalysis of the AAC reaction, additional robust catalytic systems complementary to the copper catalyzed AAC remain in high demand. Herein, Au nanoparticles supported on Al₂O₃, Fe₂O₃, TiO₂ and ZnO, along with gold reference catalysts (gold on carbon and gold on titania supplied by the World Gold Council) were used as catalysts for the AAC reaction. The supported Au nanoparticles with metal loadings of 0.7–1.6% (w/w relative to support) were able to selectively obtain 1,4-disubstituted-1,2,3-triazoles in moderate yields up to 79% after 15 min, under microwave irradiation at 150 °C using a 0.5–1.0 mol% catalyst loading through a one-pot three-component (terminal alkyne, organohalide and sodium azide) procedure according to the “click” rules. Among the supported Au catalysts, Au/TiO₂ gave the best results. Full article

The use of thermo-reversible Lewis Pair (LP) interactions in the formation of transient polymer networks is still greatly underexplored. In this work, we describe the synthesis and characterization of polydimethylsiloxane/polystyrene (PDMS/PS) blends that form dynamic Lewis acid-Lewis base adducts resulting in reversible crosslinks. Linear PS containing 10 mol % of di-2-thienylboryl pendant groups randomly distributed was obtained in a two-step one-pot functionalization reaction from silyl-functionalized PS, while ditelechelic PDMS with pyridyl groups at the chain-termini was directly obtained via thiol-ene “click” chemistry from commercially available vinyl-terminated PDMS. The resulting soft gels, formed after mixing solutions containing the PDMS and PS polymers, behave at room temperature as elastomeric solid-like materials with very high viscosity (47,300 Pa·s). We applied rheological measurements to study the thermal and time dependence of the viscoelastic moduli, and also assessed the reprocessability and self-healing behavior of the dry gel. Full article

Here, we report the synthesis of new thermoresponsive hyperbranched polymers (HBPs) via one-pot reversible addition-fragmentation chain transfer (RAFT) copolymerisation of poly(ethylene glycol)methyl ether methacrylate (PEGMEMA, M_n = 475 g/mol), poly(propylene glycol)methacrylate (PPGMA, M_n = 375 g/mol), and disulfide diacrylate (DSDA) using 2-cyanoprop-2-yl dithiobenzoate as a RAFT agent. DSDA was used as the branching agent and to afford the HBPs with reducible disulfide groups. The resulting HBPs were characterised by Nuclear Magnetic Resonance Spectroscopy (NMR) and Gel Permeation Chromatography (GPC). Differential Scanning Calorimetry (DSC) was used to determine lower critical solution temperatures (LCSTs) of these copolymers, which are in the range of 17–57 °C. Moreover, the studies on the reducibility of HBPs and swelling behaviours of hydrogels synthesized from these HBPs were conducted. The results demonstrated that we have successfully synthesized hyperbranched polymers with desired dual responsive (thermal and reducible) and crosslinkable (via thiol-ene click chemistry) properties. In addition, these new HBPs carry the multiplicity of reactive functionalities, such as RAFT agent moieties and multivinyl functional groups, which can afford them with the capacity for further bioconjugation and structure modifications. Full article

The preparation of PEGylated fluorescent nanoparticles (NPs) based on atom transfer radical polymerization (ATRP) and “click chemistry” in one-pot synthesis is presented. First, poly(p-chloromethyl styrene-alt-N-propargylmaleimide) (P(CMS-alt-NPM)) copolymer was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization. Subsequently, the azido-containing fluorene-based polymer, poly[(9,9-dihexylfluorene)-alt-(9,9-bis-(6-azidohexyl)fluorene)] (PFC6N3), was synthesized via Suzuki coupling polymerization, followed by azidation. Finally, the PEGylated fluorescent NPs were prepared via simultaneous intermolecular “click” cross-linking between P(CMS-alt-NPM) and PFC6N3 and the ATRP of poly(ethylene glycol) methyl ether methacrylate (PEGMMA) using P(CMS-alt-NPM) as the macroinitiator. The low cytotoxicity of the PEGylated fluorescent NPs was revealed by incubation with KB cells, a cell line derived from carcinoma of the nasopharynx, in an in vitro experiment. The biocompatible PEGylated fluorescent NPs were further used as a labeling agent for KB cells. Full article

“Click” chemistry has become an efficient avenue to unimolecular polymeric nanoparticles through the self-crosslinking of individual polymer chains containing appropriate functional groups. Herein we report the synthesis of ultra-small (7 nm in size) polymethyl methacrylate (PMMA) nanoparticles (NPs) by the “metal-free” cross-linking of PMMA-precursor chains prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization containing b-ketoester functional groups. Intramolecular collapse was performed by the one-pot reaction of b-ketoester moieties with alkyl diamines in tetrahydrofurane at r.t. (i.e., by enamine formation). The collapsing process was followed by size exclusion chromatography and by nuclear magnetic resonance spectroscopy. The size of the resulting PMMA-NPs was determined by dynamic light scattering. Enamine “click” chemistry increases the synthetic toolbox for the efficient synthesis of metal-free, ultra-small polymeric NPs. Full article