Synthesis and Properties of UCST‐Type Thermo‐ and Light‐Responsive Homopolypeptides with Azobenzene Spacers and Imidazolium Pendants

Homopolypeptide bearing azobenzene and triethylene glycol spacers, and 1‐butylimidazolium pendants, namely P(Azo‐OEG₃‐ImX) (X = Cl, I, BF₄) are prepared by 1,3‐dipolar cycloaddition and subsequent ion‐exchange reaction. Both ¹H NMR and FTIR confirm the polymer structures and reveal a high grafting efficiency (97%). P(Azo‐OEG₃‐ImI) shows reversible upper critical solution temperature (UCST)‐type thermoresponsive property in ethanol while P(Azo‐OEG₃‐ImI/BF₄) shows a UCST in ethanol/water solvent mixtures. P(Azo‐OEG₃‐ImI) shows UCST‐type phase transitions in ethanol or ethanol/water solvent mixtures. After UV irradiation, the UCST‐type cloud point temperature (T_cp) remains constant in ethanol. However, it decreases after UV irradiation and increases after visible light irradiation in ethanol/water solvent mixtures due to the trans–cis isomerization of azobenzene moieties. P(Azo‐OEG₃‐ImCl/I) shows NaI‐induced UCST in water. The T_cp of the P(Azo‐OEG₃‐ImCl/I) aqueous solution is highly related to the polymer/salt concentration and nature of counteranions. P(Azo‐OEG₃‐ImCl) also shows reversible light‐responsive properties in NaI aqueous solutions. Higher NaI concentration is needed to induce a UCST for P(Azo‐OEG₃‐ImCl) after UV irradiation. Moreover, ciprofloxacin‐loaded hydrogel containing P(Azo‐OEG₃‐ImCl) shows more efficient drug release while the UV irradiation leads to slightly low drug release.     

Loose‐Fit Polypseudorotaxanes Fabricated by γ‐CDs Threaded Onto a Single PNIPAAm‐PEG‐PNIPAAm Chain in Aqueous Solution

When γ‐CDs are added to an aqueous solution of PNIPAAm‐b‐PEG‐b‐PNIPAAm block copolymer, they are threaded onto the polymer chains to give loose‐fit polypseudorotaxanes (PPRs). The inclusion complexation shows a marked dependence on the length of the PNIPAAm blocks although the threaded γ‐CDs are preferably located on the central PEG block. The structure of the resulting PPRs is characterized by using XRD, ¹H and ¹³C CP/MAS NMR, TGA FTIR, and DSC analyses. Because of the mismatched fit between the guest polymer chain and the cavity of the host γ‐CDs, these PPRs may be promising in applications as solid stimuli‐responsive materials.     

SET‐LRP Synthesis of Well‐Defined Light‐Responsible Block Copolymer Micelles

Herein, the synthesis of well‐defined light‐sensitive amphiphilic diblock copolymers consisting of UV‐responsive poly(2‐nitrobenzyl acrylate) (PNBA) and hydrophilic poly(ethylene oxide) (PEO) blocks is reported. This is achieved by a single electron transfer living radical polymerization (SET‐LRP) of 2‐nitrobenzyl acrylate monomer initiated by PEO‐containing macroinitiator. Despite several reports on PEO‐b‐PNBA copolymers, this is the first time the PNBA block is synthesized by a controlled radical polymerization leading to the copolymers with low dispersity (Ð = 1.10). In water, the copolymers self‐assemble into well‐defined micelles with a hydrodynamic diameter of 25 nm. Upon irradiation with UV‐light, the PNBA units degrade to hydrophilic poly(acrylate) resulting in disassembly of the micelles. Considering the robustness of the reported synthetic protocol, the prepared polymers represent an interesting platform for the construction of new stimuli‐responsive drug delivery systems.     

Influence of the Addition of Polystyrene‐block‐poly(methyl methacrylate) Copolymer (PS‐b‐PMMA) on the Morphologies Generated by Reaction‐Induced Phase Separation in PS/PMMA/Epoxy Blends

Homogeneous solutions of polystyrene (PS) and poly(methyl methacrylate) (PMMA) in diglycidylether of bisphenol A, containing about 8 wt.‐% total thermoplastic, and with or without 0.5 wt.‐% of a PS‐b‐PMMA block copolymer, were polymerized in two ways (i) in the presence of a tertiary amine (benzyldimethylamine, BDMA), or (ii) using a stoichiometric amount of a diamine (4,4′‐diaminodiphenyl sulfone, DDS). A double phase‐separation was recorded by light transmission during polymerization. A PS‐rich phase was separated at low conversions and a PMMA‐rich phase was segregated at more advanced conversions. The addition of the block copolymer produced significant changes in the morphologies generated. For the BDMA‐initiated polymerization, the presence of the block copolymer made the small PMMA‐rich domains clearly discernible in transmission electron microscopy (TEM) micrographs. For the DDS‐cured system, the addition of the block copolymer led to a dispersion of small PS‐rich particles encapsulated by PMMA shells. The possibility of generating a stable dispersion of biphasic particles by polymerization‐induced phase separation opens a new way to modify thermosetting polymers for toughening purposes.     

Complexation of Amino‐Acid‐Based Block Copolymers With Dual Thermoresponsive Properties and Water‐Soluble Silsesquioxane Nanoparticles

Smart organic–inorganic hybrids are prepared using non‐covalent interactions between water‐soluble silsesquioxane nanoparticles and two amino acid‐based block copolymers prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization. A block copolymer displaying lower critical solution temperature (LCST) and upper critical solution temperature (UCST) is employed, in which only poly(N‐acryloyl‐4‐trans‐hydroxy‐L ‐proline) segment could interact with the nanoparticles, whereas another poly(N‐acryloyl‐L ‐proline methyl ester) segment shows a thermoresponsive property without any interaction. The complexation of another type of dual thermosensitive block copolymer with two different LCSTs and the silsesquioxane nanoparticles is also investigated.     

Nanoporous Gold Film Prepared by the Epoxidation of Poly(styrene‐b‐butadiene) Diblock Copolymer Templated Micelles

A new approach is developed for the preparation of nanoporous gold (Au) films using diblock copolymer micelles as templates. Stable Au nanoparticles (NPs) with a narrow distribution are prepared by modifying NPs functionalized with 4‐(dimethylamino)pyridine ligands (DMAP Au NPs) and a spherical micelle formed through the epoxidation of poly(styrene‐b‐butadiene) diblock copolymer to produce poly(styrene‐b‐vinyl oxirane) (PS‐b‐PBO) in tetrahydrofuran–acetonitrile solution. The exchange reaction of 4‐aminothiophenol of PS‐b‐PBO diblock copolymer micelles with DMAP Au NPs can produce block copolymer–Au NPs composite films. After the pyrolysis of the diblock copolymer templates at a specific temperature to avoid the collapse of the Au NPs, a nanoporous Au film is prepared.     

Ultrasound‐Induced Disruption of Amphiphilic Block Copolymer Micelles

Ultrasound‐induced disruption of PEO‐b‐PTHPMA, PEO‐b‐PIBMA, PEO‐b‐PTHFEMA, and PEO‐b‐PMMA block copolymer micelles in aqueous solution was investigated. Fluorescence change of loaded NR, DLS, IR, AFM, and SEM show that those micelles could be disrupted differently by 1.1 MHz high‐intensity focused ultrasound beams. The micelles of PEO‐b‐PIBMA and PEO‐b‐PTHPMA appear to be more sensitive to ultrasound irradiation, resulting in a more severe micellar disruption, and IR spectra show evidence of ultrasound‐induced chemical reactions, most likely hydrolysis. PEO‐b‐PMMA appear to resist HIFU irradiation better, and IR analysis found no evidence of chemical reactions. This study provides new evidence for the prospect of ultrasound‐responsive BCP micelles for controlled delivery applications.

     

Photocrosslinkable Poly(ε‐caprolactone)‐b‐Hyperbranched Polyglycerol (PCL‐b‐hbPG) with Improved Biocompatibility and Stability for Drug Delivery

The major limitations of nanocarriers for drug delivery are the poor biocompatibility and low stability that may induce the unintended burst release of loaded drugs during blood circulation. To overcome these limitations, a photocrosslinkable amphiphilic block copolymer consisting of hydrophobic poly(ε‐caprolactone) (PCL) block and a hydrophilic hyperbranched polyglycerol (hbPG) block with improved biocompatibility and stability for drug delivery is developed. They are readily prepared via UV‐triggered chemical crosslinking with 4‐hydroxycinnamic acid (CA) modification in the hbPG block. The photocrosslinked hbPG‐b‐PCL‐CA nanoparticles are spherical and the size of nanoparticles is increased to 60 ± 30 nm. Photocrosslinked hbPG‐b‐PCL‐CA nanoparticles exhibit significantly high stability in a physiological buffer and the loaded drug in sustained manner. In addition, photocrosslinked hbPG‐b‐PCL‐CA nanoparticles show good biocompatibility in vitro and in vivo. These data imply the promising potential of photocrosslinked hbPG‐b‐PCL‐CA nanoparticles as nanocarriers for drug delivery.

     

Dual UV‐ and pH‐Responsive Supramolecular Vesicles Mediated by Host–Guest Interactions for Drug Controlled Release

To control the release of the drugs at specific time and location, dual UV‐ and pH‐responsive supramolecular vesicles are described mediated by host–guest interactions. The hydrophobic segment β‐CD‐Azo‐Ace (where β‐CD, Azo, and Ace refer to β‐cyclodextrin, azobenzene, and acetal, respectively) forms the inclusion with α‐CD and the inclusion further self‐assembles to form supramolecular vesicles in aqueous medium. The nanospherical supramolecular vesicles are ≈50 nm and high‐efficiently load the drugs. Furthermore, supramolecular vesicles are dual UV‐ and pH‐responsive, thus release the drugs at specific time (stimulated by UV) and location (stimulated by pH), which will have significant advantages for cancer treatment.

     

Stereoblock Copolymerization of Propylene and Methyl Methacrylate with Single‐Site Metallocene Catalysts

Sequential stereoblock copolymerization of propylene (P) and methyl methacrylate (MMA) using Group IV single‐site metallocene catalysts efficiently produces PP‐b‐PMMA stereodiblock copolymers. When activated with B(C₆F₅)₃, C₂‐symmetric rac‐Et(Ind)₂ZrMe₂ yields isotactic‐PP‐b‐isotactic‐PMMA diblock copolymer, whereas C_s‐symmetric Me₂Si(C₅Me₄)(tBuN)TiMe₂ affords atactic‐PP‐b‐syndiotactic‐PMMA diblock copolymer. In the copolymerization catalyzed by the C₂‐symmetric catalyst, a very small amount of PMMA homopolymer formed can be removed from the copolymer by extracting the bulk polymer product with boiling methylene chloride. However, separation of isotactic PP formed if any from the copolymer product approves very difficult, due to very similar solubility between the diblock copolymer and isotactic PP homopolymer in various high‐boiling chlorinated solvents. On the other hand, in the copolymerization catalyzed by the C_s‐symmetric catalyst, both PMMA and atactic PP homopolymers formed in small weight fractions during the copolymerization can be successfully removed from the predominant copolymer product by solvent extraction using boiling heptane. After successful removal of both homopolymers, for example, an atactic‐PP‐b‐syndiotactic‐PMMA diblock copolymer has high molecular weight (M _n = 21 100), narrow molecular weight distribution (PDI = 1.08), high PMMA incorporation (33.8 mol‐% of PMMA), and moderate syndiotacticity for the PMMA block ([rr] ≈ 80%). Furthermore, the comonomer composition in the copolymer can be controlled by the time for propylene polymerization and the conversion of MMA. A pronounced activator effect is observed; when the same C_s‐symmetric catalyst is activated with Ph₃CB(C₆F₅)₄, formation of homopolymers is predominated.

     

One‐Pot Synthesis of PTFEMA‐b‐PMMA‐b‐PTFEMA by Controlled Radical Polymerization with a Difunctional Initiator in Conjugation with Photoredox Catalyst of Ir(ppy)3 Under Visible Light

Visible‐light‐induced free radical polymerization of methyl methacrylate (MMA) and 1,1,1‐trifluoroethyl methacrylate (TFEMA) with a difunctional initiator, dimethyl 2,6‐dibromoheptanedioate (DMDBHD), conjugated with a photoredox catalyst, tris(2‐phenylpyridinato)iridium(III) (fac‐[Ir(ppy)₃]), is investigated. Kinetic studies demonstrate that homopolymerizations of both MMA and TFEMA are controlled radical polymerizations. The linear increase of molecular weights with monomer conversion and the narrow PDIs (1.2–1.4) reveal a good living character. In addition, PTFEMA‐b‐PMMA‐b‐PTFEMA triblock copolymer is prepared by a one‐pot process with sequential monomer addition. The of the triblock copolymers increases linearly with monomer conversion and the PDI of block copolymers is still maintained around 1.2–1.4. Experimental data confirm that the products are pure block polymers. Furthermore, the molar fraction of the TFEMA monomeric unit in the block copolymer is about 21.96%, close to the theoretical value 21.00% calculated from the monomer conversion.

     

Controlled synthesis of anthracene‐labeled ω‐amine polystyrene to be used as a probe for interfacial reaction with mutually reactive PMMA

Anthracene‐labeled polystyrene (PS) end‐capped by a primary amine has been synthesized by atom transfer radical copolymerization of styrene with 3‐isopropenyl‐α,α‐dimethylbenzyl isocyanate (m‐TMI). The m‐TMI co‐monomer (5.7 mol‐%) does not perturb the control of the radical polymerization of styrene. The pendant isocyanate groups of the copolymer chains of low polydispersity (M _w/M _n = 1.25) and controlled molecular weight (up to 35 000) have been derivatized into anthracene by a reaction with 9‐methyl(aminomethyl)anthracene. The anthracene‐labeled PS (ca. 2 mol‐% label) has been conveniently analyzed by size‐exclusion chromatography with a UV detector (SEC‐UV). Moreover, the ω‐bromide end‐group of the copolymer chains has been derivatized into a primary amine, making the labeled PS chains reactive towards non‐miscible poly(methyl methacrylate) (PMMA) chains end‐capped by an anhydride. The interfacial coupling of the mutually reactive PS and PMMA chains has been studied under static conditions (i.e., at the interface between thin PS and PMMA films) and successfully analyzed by SEC‐UV.

SEC‐UV traces for anth‐PS‐NH₂ (80 μg · ml⁻¹; sample A5; Table 1 ), and PMMA‐anh (80 μg · ml⁻¹; sample B1; Table 1 ).     

Temperature and pH dependence of the catalytic activity of colloidal platinum nanoparticles stabilized by poly[(vinylamine)‐co‐(N‐vinylisobutyramide)

Colloidal platinum nanoparticles in the size range of 5–35 Å have been successfully prepared in water at room temperature by NaBH₄ reduction of ionic platinum in the presence of poly[(vinylamine)‐co‐(N‐vinylisobutyramide)] (PVAm‐co‐PNVIBA). To our knowledge, the temperature‐ and pH‐responsive copolymer was used for the first time as the stabilizer of colloidal metal particles. Three PVAm‐co‐PNVIBA copolymers with PVAm contents of 4.1, 8.3, and 19.8 mol‐% were examined. The particle size and morphology of the platinum colloids varied with the copolymer composition, as confirmed by TEM measurements. The polymer‐stabilized Pt nanoparticles precipitated on heating above their critical flocculation temperatures (CFTs), which were strongly dependent on the solution pH and the copolymer composition. The CFTs were 0.2–1.6°C lower than the lower critical solution temperatures (LCSTs) of the copolymers free in water and the differences increased with increasing PVAm content. The catalytic activity of the Pt nanoparticles was investigated in the aqueous hydrogenation of allyl alcohol. It was found that the activity was regulated through temperature‐ and pH‐induced phase separation. The PVAm content also strongly effected the catalytic activity and the morphology of phase separated catalysts. With a PVAm content of 4.1 mol‐%, the colloidal platinum sol reversibly changed its catalytic activity with changes in temperature.     

Poly(L‐lactide) Nanoparticles via Ring‐Opening Polymerization in Non‐aqueous Emulsion

The preparation of poly(L ‐lactide) nanoparticles via ring‐opening polymerization (ROP) of L ‐lactide is conducted in non‐aqueous emulsion. In this process, acetonitrile is dispersed in either cyclohexane or n‐hexane as the continuous phase and stabilized by a PI‐b‐PEO, respectively, a PI‐b‐PS copolymer as emulsifier. The air and moisture sensitive N‐heterocyclic carbene 1,3‐bis(2,4,6‐trimethylphenyl)‐2‐ididazolidinylidene (SIMes) catalyzes the polymerization of L ‐lactide at ambient temperatures. Spherical poly(L ‐lactide) nanoparticles with an average diameter of 70 nm and a tunable molecular weight are generated. Hence, the non‐aqueous emulsion technique demonstrates its good applicability toward the generation of well‐defined poly(L ‐lactide) nanoparticles under very mild conditions.     

One‐Step Method for Synthesis of PDMS‐Based Macroazoinitiators and Block Copolymers from the Initiators

Summary: This paper presents a facile one‐step method for the synthesis of macroazoinitiator (MAI) by direct polycondensation of hydroxyalkyl‐terminated polydimethylsiloxane (PDMS) with 4,4′‐azobis‐4‐cyanopentanoic acid (ACPA) under mild conditions. The PDMS‐based MAI was characterized by FTIR, ¹H NMR, GPC, and UV spectroscopy, and further used as an initiator for polymerization of methyl methacrylate (MMA) to obtain PMMA‐co‐PDMS block copolymer. TEM observation and DSC analysis demonstrated that the PMMA‐co‐PDMS block copolymer had a microphase‐separated structure.

Schematic representation for syntheses of macroazoinitiators (MAI) by the direct polycondensation and corresponding block copolymers.     

Synthesis and Micellization Properties of Novel Symmetrical Poly(ε‐caprolactone‐b‐[R,S] β‐malic acid‐b‐ε‐caprolactone) Triblock Copolymers

Summary: A four‐step strategy to synthesize well‐defined amphiphilic poly(ε‐caprolactone‐b‐[R,S] β‐malic acid‐b‐ε‐caprolactone) triblock copolymers [P(CL‐b‐MLA‐b‐CL)], which combines the anionic polymerization of [R,S] benzyl β‐malolactonate (MLABz), and the coordination‐insertion ring‐opening polymerization (ROP) of ε‐caprolactone (CL), followed by the selective removal of benzyloxy protective groups of the central poly(malolactonate) block is described. The first step involves MLABz initiated by potassium 11‐hydroxydodecanoate in the presence of 18‐crown‐6 ether. This step was carried out at 0 °C with an initial monomer concentration of 0.2 mol · L^?1 in order to limit the occurrence of undesirable transfer and termination reactions by proton abstraction. After selective reduction of the carboxylic acid end‐group of the resulting α‐hydroxy, ω‐carboxylic poly([R,S] benzyl β‐malolactonate) leading to an α,ω‐dihydroxy PMLABz, the polymerization of CL was initiated by each hydroxyl end‐groups previously activated by AlEt₃. Finally, after catalytic hydrogenation of the benzyl ester functions, the P(CL‐b‐MLA‐b‐CL) triblock copolymer was recovered and the amphiphilic character evidenced by UV spectroscopy. As demonstrated, the CMC of these new P(CL‐b‐MLA‐b‐CL) triblock copolymer is higher by one order of magnitude than that of a P(MLA‐b‐CL) diblock copolymer of similar composition.

Concentration dependence of pyrene I₃₃₈/I₃₃₅ intensitiy ratio for P(MLA‐b‐CL) diblock and P(CL‐b‐MLA‐b‐CL) triblock copolymers in water.     

Multi‐Responsive Supramolecular Double Hydrophilic Diblock Copolymer Driven by Host‐Guest Inclusion Complexation between β‐Cyclodextrin and Adamantyl Moieties

Well‐defined β‐CD‐terminated poly(N‐isopropylacrylamide) (β‐CD‐PNIPAM) was synthesized via a combination of atom transfer radical polymerization (ATRP) and click chemistry. Moreover, adamantyl‐terminated poly(2‐(diethylamino)ethyl methacrylate) (Ad‐PDEA) was synthesized by ATRP using an adamantane‐containing initiator. Host‐guest inclusion complexation between β‐CD and adamantyl moieties drives the formation of supramolecular double hydrophilic block copolymers (DHBC) from β‐CD‐PNIPAM and Ad‐PDEA. The obtained supramolecular PNIPAM‐b‐PDEA diblock copolymer exhibits intriguing multi‐responsive and reversible micelle‐to‐vesicle transition behavior in aqueous solution by dually playing with solution pH and temperatures.

     

Synthesis and Polymerization of Fused‐Ring Thienodipyrrole Monomers

The synthesis and polymerization of fused‐ring 1,7‐didodecyl‐1,7‐dihydrothieno[3,2‐b:4,5‐b′]dipyrrole monomer are reported. The FeCl₃‐mediated oxidative polymerization and Stille coupling polymerization of the thienodipyrrole monomer were employed to generate homopolymers and an alternating copolymer with thiophene. The synthesized polymers have molecular weights ranging from 1600 to 6500 g mol^?1 and display the absorption maxima at ≈355 nm.     

A Remarkably Large Phase‐Transition Effect in a Random Copolymer of Oligo(ethylene glycol) Methyl Ether Methacrylate (OEGMA)500 Induced by the Photochemistry of the 2‐(Hydroxyimino)aldehyde Group

The effect of UV irradiation on the cloud points (CP) of aqueous solutions of a random 1:1 copolymer of oligo(ethylene glycol) methyl ether methacrylate (OEGMA₅₀₀) and a 2‐(hydroxyimino)aldehyde (HIA) functionalized methacrylate is presented. CPs are determined by visible spectroscopy and dynamic light scattering (DLS). ¹H and ¹³C NMR experiments are carried out in D₂O and DMSO‐d₆ on the polymer and on an HIA‐functionalized model of the photoresponsive repeat unit. UV‐irradiated solutions exhibit an unprecedented increase of the phase‐separation temperature for an OEGMA photoresponsive copolymer (10–22 °C, depending on concentration and irradiation conditions). Phase separation is reversible with little hysteresis. With both pristine and irradiated polymer solutions, aggregate dimensions are <10 nm (DLS) at room temperature. Aggregates of >100 nm form at the CP and gradually grow as temperature increases, whereas the light‐induced processes of the repeat unit model in DMSO‐d₆ are well identified (e.g., oxime E/Z isomerization and Norrish‐Yang cyclization of the aldehyde moiety), it is not straightforward to extrapolate such behavior to the polymeric solution in water. The remarkably large phototriggered thermal effect in the present work motivates further investigations on the solvent‐dependent photochemistry of HIA as a promising functional group for the synthesis of multi‐stimuli responsive materials.     

Visible Light–Induced RAFT Polymerization of Methacrylate with 4‐(N,N‐diphenylamino)benzaldehyde as Organophotoredox Catalyst and the Effect of Temperature on the Polymerization

With UV–vis absorption in the range of 270–435 nm, 4‐(N,N‐diphenylamino)benzaldehyde (DPAB) takes efficient photoreduction quench with 4‐cynao‐4‐(phenylcarbonothioylthio)pentanoic acid (CTP). The polymerization rates of methyl methacrylate (MMA) are 0.019, 0.056, and 0.102 h^?1 at 33, 40, and 50 °C, respectively, in the presence of DPAB and CTP under visible‐light irradiation. Dark reaction produces no PMMA at 50 °C for 120 h. The living feature is demonstrated by linearly increasing M_n with the monomer conversions and narrow polydispersity index (PDI), chain extension, and block polymerizations with benzyl methacrylate (BnMA) and poly(ethylene glycol) monomethyl ether methacrylate (PEGMA). With PMMA‐CTP (M_n = 6800, PDI = 1.17), chain extension gives PMMA with M_n = 15 900 and PDI = 1.15. With PMMA‐CTP (M_n = 6000, PDI = 1.21) as macro‐RAFT, PMMA‐b‐PBnMA of M_n = 12 600 (PDI = 1.44) and M_n = 18 500 (PDI = 1.31) are prepared. These results support that there is a positive synergistic effect between polymerization temperature and visible‐light irradiation on the photo‐RAFT without losing the living features.