RAFT synthesis of thioether-based,AB diblock copolymer nanocarriers for reactive oxygen species–triggered release

A well-defined AB diblock copolymer of 2-vinyl-4,4-dimethylazlactone (VDA) and N,N-dimethylacrylamide (DMA) was generated by reversible addition-fragmentation chain transfer (RAFT) radical polymerization. The VDA-DMA diblock copolymer was reacted with 2-(methylthio)ethylamine (MTEA) and 3-(methylthio)propylamine (MTPA) to yield two novel thioether functional diblock copolymers whose structure was confirmed using ¹H NMR and FTIR spectroscopy. Both diblock copolymers formed micelles (20–30 nm) in aqueous media as confirmed by dynamic light scattering (DLS) and transmission electron microscopy. The self-assembled micelles were loaded with Nile Red, a model hydrophobic drug to study their ROS-triggered release mechanism. On addition of hydrogen peroxide (H₂O₂), the most common ROS species, the hydrophobic thioether core of these micelles oxidized, and both diblock copolymers became more hydrophilic. This triggered their disassembly and subsequent cargo release as characterized by UV–visible spectroscopy. The Nile Red loaded micelles demonstrated similar in-vitro ROS-mediated release when exposed to endogenous oxidants in a model inflammation environment simulated by the presence of activated macrophages. The responsive nanomaterials developed in this article have promising potential as drug carriers in applications where ROS-triggered delivery of cargo is required such as in inflammatory conditions.     

PEO–PPO based star-block copolymer T904 as pH responsive nanocarriers for quercetin: Solubilization and release study

Solubilization of quercetin (QN), a hypolipidemic drug in aqueous micellar solution of a star-like octablock Tetronic® T904 covering different salt concentration, pH and temperature is investigated. The change in pH modulates the charge of the copolymer which alters the dibasic nature of the centrally located ethylenediamine moiety and makes T904 undergo deprotonation favoring self assembly. At low pH, the columbic repulsion among the positively charged amine groups of Tetronic® hinders micellization while presence of salt facilitates it. The drug solubility data for micelles in aqueous/salt solutions determined by UV–Visible spectroscopy and micellar size with loaded drug from dynamic light scattering (DLS) are reported. Hydrophobic/anionic QN, deprotonates T904 and induces the micellization in acidic pH thus assisting solubilization. The expected locus (site) of the QN in T904 micelles was successfully correlated by the significant and positive cross peaks obtained from two-dimensional nuclear Overhauser effect spectroscopy (2D-NOESY). The evaluated in vitro release profile employing different kinetic models explains the controlled release of drug from T904 micelles.     

Novel supramolecular block copolymer containing organic–inorganic pentablock copolymer by ATRP of styrene and vinyl acetate using polydimethylsiloxane/cyclodextrin inclusion complexes as macroinitiator

Organic–inorganic pentablock copolymers have been synthesized via atom transfer radical polymerization (ATRP) of styrene (St) and vinyl acetate (VAc) monomers at 60 °C using CuCl/N,N,N′,N″,N″-pentamethyldiethylenetriamine as a catalyst system initiated from boromoalkyl-terminated poly(dimethylsiloxane) (PDMS)/cyclodextrins macroinitiator (Br-PDMS/γ-CD). Br-PDMS-Br was reacted with γ-CD in different conditions with inclusion complexes being characterized through hydrogen nuclear magnetic resonance (¹H NMR) and differential scanning calorimetry (DSC). Resulting Br-PDMS-Br/γ-CD inclusion complexes were taken as macroinitiators for ATRP of St and VAc. Well-defined poly(styrene)-b-poly(vinyl acetate)-b-poly(dimethylsiloxane/γ-cyclodextrin)-b-poly(vinyl acetate)-b-poly(styrene) (PSt-b-PVAc-b-PDMS/γ-CD-b-PVAc-b-PSt) pentablock copolymer was characterized by ¹H NMR, gel permeation chromatograph (GPC) and DSC. There was a good agreement between the number-average molecular weight calculated from ¹H NMR spectra and that of theoretically calculated. Pentablock copolymers consisting of Br-PDMS-Br/γ-CD inclusion complex as central blocks (inorganic block) and PVAc and PSt as terminal blocks were synthesized by this technique. PSt-b-PVAc-b-PDMS/γ-CD-b-PVAc-b-PSt pentablock copolymer can undergo a temperature-induced reversible transition upon heating of the copolymer complex from white complex at 22 °C to green complex in 55 °C which characterized with XRD and ¹H NMR. XRD showed a change in crystallinity percent of St peak with changing the temperature which calculated by Origin75 software.     

Synthesis and characteristic of double hydrophilic block copolymer with amine pendant chains

Novel double hydrophilic block copolymers with amine pendant chains were synthesized by polymerization of 4-vinyl benzylamine hydrochloric salt using 4,4′-azo-bis[4-cyanopentanoate poly（ethylene glycol） ester] as macroazoinitiator. The structures of the copolymers were characterized by ^1H NMR, FTIR spectra and acid-base titration, GPC-MALS techniques.     

Dispersion of carbon nanotubes by the branched block copolymer Tetronic 1107 in an alcohol–water solution

The dispersion of carbon nanotubes (CNTs) by the branched block copolymer Tetronic 1107 was investigated in mixed solvents consisting of water and one of the following alcohols: ethanol, n-propanol, ethylene glycol (EG), or glycerol (GLY). The maximum concentration of dispersed CNTs (C _limit) and the optimum T1107 concentration (C _opt) to disperse the maximum amount of CNTs in different solvents were obtained from UV–vis–NIR absorbance spectra. The addition of ethanol or n-propanol to water dramatically increases the C _limit. The value of C _opt follows the order: n-propanol–water?>?ethanol–water?>?EG–water?≈?GLY–water mixtures. I _D/I _G was used to characterize the defect density of CNTs dispersed in the mixed solvents, which was investigated by Raman spectroscopy. The I _D/I _G values in n-propanol–water and ethanol–water mixtures are higher than those in EG–water and GLY–water mixtures. High-resolution transmission electron microscopy is used to confirm a favorable dispersion in the presence of different alcohols.     

Structural diversity of metal–organic frameworks via employment of azamacrocycles as a building block

Research on incorporating macrocycles into metal–organic frameworks (MOFs) has been performed intensively due to the opportunities afforded by merging a merit of macrocycles with MOF chemistry, which lead to novel hybrid materials for potential application. Among the numerous kinds of macrocycles, azamacrocycles are used as traditional and popular chelating agents in supramolecular coordination chemistry, because they are very easily functionalized by joining pendant arms and possess a strong propensity to complex metal cations, accounting for the amine functionalities. With this as background, many types of azamacrocyclic MOFs have been synthesized, granting compositionally and topologically new MOFs. The macrocyclic rings can serve as additional adsorption sites or catalytic sites, and the pendant arms on the macrocycles can also play versatile roles such as structure-directing agents, pore-decorating moieties, or rotatable molecular gates for opening/closing pores. In this review, we comprehensively discuss the syntheses, structures, and features of azamacrocyclic MOFs reported to date. Based on representative studies, advantages of these compounds are described, such as how the azamacrocycles increase the structural diversity and complexity of the MOFs and induce novel structural properties within the architectures.     

A new method for loading mesoporous silica nanoparticles with drugs: Sol–gel synthesis using drug micelles as a template

It has been shown that mesoporous nanocontainers from SiO₂ may be obtained by the sol–gel synthesis using drug (Miramistin) micelles as a template. The nanocontainers resulting from the combination of the stages of their synthesis and loading are characterized by a very high content of the drug (no less than 0.9 g per 1 g of SiO₂). The kinetics of Miramistin desorption from the mesoporous particles into an aqueous medium has been studied under static and quasi-dynamic conditions. The desorption has been shown to rather strongly depend on pH. Possible mechanisms of the desorption process have been discussed.     

Chlorosulfonyl styrene–divinylbenzene copolymer characteristics as a function of chlorosulfonation and chlorination reaction parameters

Chlorosulfonyl substituted styrene–divinylbenzene copolymer is a highly reactive intermediate used in organic synthesis. It is obtained in three steps: (1) the polymeric support in the form of spherical beads is prepared by free radical polymerization of styrene; (2) the divinylbenzene mixture and the aromatic styrene groups of the obtained copolymer are sulfonated with chlorosulfonic acid in dichloroethane and (3) this is followed by chlorination of the sulfonyl groups with PCl₅/POCl₃ mixture. Chemical analysis shows that chlorosulfonation leads to both sulfonyl and chlorosulfonyl products in which content and ratio vary as a function of reaction parameters: maximum total group content of 5.1 meq/g is reached after 3 hr reaction, at 40°C with styrene to a chlorosulfonic acid molar ratio of 12.4:1. In the chlorination reaction, sulfonyl to chlorosulfonyl conversion is also observed to vary as a function of time and chlorinating mixture composition: 99.6 mol% conversion degree is attained after 2 hr reaction with styrene/PCl₅/POCl₃ in a molar ratio of 1:4:23. © 1997 John Wiley & Sons, Ltd.     

Photoinduced optical anisotropy in azobenzene containing block copolymer–homopolymer blends. Influence of microstructure and molecular weight

Microstructure in two diblock methacrylic azo polymers and in some of their blends with PMMA of different molecular weights as well as their photoinduced anisotropy have been investigated. The block copolymers have similar structure but different azo content and degree of polymerization. A synthetic strategy based on a controlled radical polymerization (ATRP) of polymeric blocks and their coupling by click chemistry has been applied to obtain an azo block copolymer of high molecular weight. Microphase segregation has been observed in the block copolymers and in most of the blends. In blends of the block copolymer with lower degree of polymerization (Block 1) azo microdomains change from lamellar to spherical morphology when the azo content decreases from 24 to 3 wt.%. In the block copolymer with higher degree of polymerization (Block 2) and its blends, down to 3 wt.% azo content, spherical azo microdomains have been found. A decrease of the order parameter (η) and the photoinduced birefringence normalized to the azo content (|Δn|_norm) has been found in blends of Block 1 when the azo content decreases. However, |Δn|_norm and η values similar to those in the azo homopolymer have been observed in Block 2 and its blends. These blends can be used to lower the azo content while keeping a photoinduced response similar to that in the azo homopolymer.     

Ceramide formation on the γ-irradiation of galactocerebroside as a constituent of micelles

The radiation-initiated transformations of galactocerebroside (GalCer) as a constituent of micelles were studied. The radiation-chemical yields of decomposition of the starting substrate and formation of degradation products suggested that the formation of ceramide is the main process in the γ-radiolysis of GalCer. The irradiation of GalCer in the presence of dimethyl sulfoxide, which is an active scavenger of OH radicals, decreased the yield of ceramide. Ceramide was formed as a result of GalCer degradation with O-glycoside bond cleavage in the polar moiety of the lipid.     

How does cross-linking affect the stability of block copolymer vesicles in the presence of surfactant?

Block copolymer vesicles are conveniently prepared directly in water at relatively high solids by polymerization-induced self-assembly using an aqueous dispersion polymerization formulation based on 2-hydroxypropyl methacrylate. However, dynamic light scattering studies clearly demonstrate that addition of small molecule surfactants to such linear copolymer vesicles disrupts the vesicular membrane. This causes rapid vesicle dissolution in the case of ionic surfactants, with nonionic surfactants proving somewhat less destructive. To address this problem, glycidyl methacrylate can be copolymerized with 2-hydroxypropyl methacrylate and the resulting epoxy-functional block copolymer vesicles are readily cross-linked in aqueous solution using cheap commercially available polymeric diamines. Such epoxy-amine chemistry confers exceptional surfactant tolerance on the cross-linked vesicles and also leads to a distinctive change in their morphology, as judged by transmission electron microscopy. Moreover, pendent unreacted amine groups confer cationic character on these cross-linked vesicles and offer further opportunities for functionalization.     

Polymerization of lactide and synthesis of block copolymer catalyzed by copper(Ⅱ) Schiff base complex

In the present investigation, the novel copper Schiff base complex was synthesized and its catalytic activity was evaluated for the ring-opening polymerization (ROP) of lactide and block polymerization of poly(lactide) with poly(ethylene glycol)methyl ether.     

Determination of adrenolytic drugs by SPME–LC–MS

Five adrenolytic drugs have been analyzed by liquid chromatography–mass spectrometry (LC–MS). Samples were prepared by solid-phase microextraction (SPME) using polypyrrole fibers coated on stainless steel support as an adsorbent for the drugs. Adsorption efficiencies were 95% and were close for all the drugs investigated. Relative standard deviations (RSD), calculated for samples prepared in standard solutions, were in the range 2.5–13%, however RSD values for the drugs in human plasma were 2.5–4.5%. Using LC–MS the limit of detection (LOD) and the limit of quantification (LOQ) were in the ranges 0.11–0.18 and 0.39–0.54 ng mL⁻¹, respectively, for the five drugs.     

Crystallization kinetics of polypropylene/ethylene–octene copolymer blends

Blends of polypropylene and ethylene–octene copolymers (EOC) were investigated by transmission electron microscopy, optical microscopy and differential scanning calorimetry (DSC). The main focus was on phase morphology and crystallization for blends containing EOC with different octene content (28, 37 and 52 wt.%). Also, for a given octene content (37 wt.%), the effect of molecular weight (115, 180, 229k) of EOC on morphology was observed. The largest particles were found in the blend with EOC-28 and the smallest with EOC-52. This blend with the smallest particles exhibits the fastest crystallization kinetics by two independent methods, optical microscopy and DSC. This behavior was explained by a model. Crystallizing polypropylene lamellae have to travel a longer distance going around large particles, which slows down overall crystallization growth rate. In the case of smaller particles, the obstacles are smaller and the crystallization is faster.     

The gas–liquid tunable self-assembly properties of rod–coil diblock copolymer: donor–acceptor alternating structure served as rod segment

The rod–coil diblock copolymers in which the donor–acceptor alternating structures served as the rod segment were synthesized. The supramolecular self-assembly property of the copolymers was investigated in the methanol atmosphere. By changing the assembly condition, well-defined vesicles and porous films were produced, respectively. Pores with different size dispersions were obtained by tuning the methanol atmosphere. Moreover, porous films were also decorated on diverse substrates with nonplanar structures. The investigation on self-assembly properties of this rod–coil copolymer is the complementarity to the self-assembly of rod–coil copolymers. This is a very useful self-assembly method that can be used to prepare the self-assembly nanostructures with donor–acceptor alternating copolymers.     

Modular synthesis of a block copolymer with a cleavable linkage via “click” chemistry

A diblock copolymer poly(ethylene glycol)-block-polystyrene or PEG-b-PS with an olefinic double bond at the PEG and PS junction has been prepared by modular synthesis via “click” chemistry. This involved the synthesis of PS by atom transfer radical polymerization and the nucleophilic substitution of the terminal bromide group with azide to yield azide-terminated PS. PEG with an alkynyl terminal group was prepared from reacting carboxyl-end-functionalized PEG with 4-hydroxybut-2-enyl prop-2′-ynyl succinate, which contained an alkynyl group as well as an olefin group. The PS and PEG polymers were linked via the 1,3-dipolar cycloaddition of the end azide and alkyne groups. The obtained copolymer was characterized by ¹H NMR spectroscopy and size exclusion chromatography (SEC). SEC analysis indicated that the diblock copolymer produced could be readily cleaved by ozonolysis to regenerate the constituent homopolymers.     

New block copolymers—III. Synthesis,characterization and crosslinking studies of an (A-B)n type block copolymer

A new block copolymer was prepared by low temperature polycondensation between (acid chloride)-terminated poly(trimethylene terephthalate), as the hard block, and amine-terminated butadiene/acrylonitrile rubber, as the soft block. The polymer was characterized by elemental (nitrogen) analysis, i.r. and NMR spectroscopy. The analysis of the content of the block in the copolymer was carried out by the NMR peak area integration method. The polymer is soluble in polar aprotic solvents. X-ray study reveals that the crystallinity in the polymer is due to the presence of the hard block. The polymer behaves like a thermoplastic elastomer between ambient temperature and 125°. Above 150°, particularly around 200°, the residual unsaturation of the soft block results in crosslinking. Crosslinking and thermal behaviour of the polymer are also reported.