Synthesis and characterization of dextran grafted with poly(N‐isopropylacrylamide‐co‐N,N‐dimethyl‐acrylamide)

Graft copolymers consisting of dextran as a main chain and poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide) (poly(NIPAAm‐co‐DMAAm)) as graft chains were synthesized. For the synthesis of the graft copolymers, a semitelechelic poly(NIPAAm‐co‐DMAAm) with an amino end‐group was obtained by radical copolymerization with ethanethiol as a chain transfer agent, followed by a coupling reaction of its hydroxyl end‐group with ethylenediamine. Graft copolymers with various length of the grafts were obtained from coupling reactions between carboxymethyl dextran and poly‐(NIPAAm‐co‐DMAAm) in the presence of a water‐soluble carbodiimide. The graft copolymers in phosphate buffer exhibit lower critical solution temperatures due to thermosensitivity of their grafts. There is no significant change in the hydration‐dehydration behavior of the poly(NIPAAm‐co‐DMAAm) chain after the grafting reaction. The existence of such grafts in dextran may play an important role for modulated degradation in synchronization with temperature.     

Poly(N‐isopropylacrylamide‐co‐N‐isopropylmethacrylamide) Thermo‐Responsive Microgels as Self‐Regulated Drug Delivery System

Poly(N‐isopropylacrylamide‐co‐N‐isopropylmethacrylamide) (poly(NIPAAm‐co‐NIPMAAm)) is synthesized as an attractive thermo‐responsive copolymer by an original procedure. Due to the similar structure of the two co‐monomers, the poly(NIPAAm‐co‐NIPMAAm) copolymer displays a very sharp phase transition, under physiological conditions (phosphate buffer solution at pH = 7.4). The copolymer, showing the 51/49 co‐monomer NIPAAm/NIPMAAm molar ratio, displays a lower critical solution temperature (LCST) close to that of the human body temperature (36.8 °C). The poly(NIPAAm‐co‐NIPMAAm) microgels obtained at the 51:49 co‐monomer ratio displays a volume phase transition temperature (VPTT) slightly smaller than LCST. The deswelling rate of the microgels is very high (k = 0.019 s^?1), the shrinkage occurring almost instantaneously, whereas the swelling rate is slightly lower (k = 0.0077 s^?1). The microgels are loaded with the model drug dexamethasone and the drug release is investigated at different temperatures, below and above the VPTT. Under thermal cycling operation between 32 and 38 °C, the pulsatile release of dexamethasone is observed.

     

Competition between Physical Cross‐Linking and Phase Transition Temperature in Blends Based on Poly(N‐isopropylacrylamide‐co‐N‐ethylacrylamide) Copolymers and Carboxymethyl Cellulose

The combination of thermoresponsive polymers and biopolymers is growing due to the multiple benefits, owing to their tunable properties. Numerous works focus on the preparation of materials by chemical cross‐linking, but physical cross‐linking (based on hydrogen bonding) has not been deeply studied. In this context, questions around the hydrogen bonding of physical‐crosslinking and lower critical solution temperature (LCST) need to be addressed, especially when a second comonomer is incorporated. This study is based on the preparation of blends of poly(N‐isopropylacrylamide‐co‐N‐ethylacrylamide) copolymers and carboxymethyl cellulose (CMC) by dissolution, where the LCST‐transition and physical‐crosslinking are studied. The results show a strong effect of the comonomer on the properties in comparison with the CMC, especially for solutions of methanol/water. Low contents of N‐ethylacrylamide (NEAM) can promote physical‐crosslinking and the gelation, avoiding cononsolvency observed for homopolymers. On the other hand, NEAM will disrupt the gelation when the comonomer content is high enough.     

Crosslinked polymer gels for boron extraction derived from N‐glucidol‐N‐methyl‐2‐hydroxypropyl methacrylate

Glycidyl methacrylate was reacted in 2‐methyl pyrrolidone solution with N‐methyl‐D ‐glucamine (NMG) to produce N‐D ‐glucidol, N‐methyl‐2‐hydroxy propyl methacrylate (GMHP). The reaction proceeded exclusively via ring opening of the oxirane. The resulting vinyl monomer was a waxy product and soluble in water, ethanol, methanol, DMF, and NMP. Copolymerization of GMHP with N,N′‐tetraallyl piperazinium dichloride by the inverse suspension method (water in oil), using a toluene/chloroform (3 : 1) mixture as continuous phase, led to crosslinked hydrogels in imperfect bead form. Crosslinking was also achieved without using additional crosslinker. Heating of N‐methyl‐D ‐glucamine with 10% excess of glycidyl methacrylate in NMP at 60°C for 4 h, resulting the formation of N‐methyl‐D ‐glucamine carrying two methacrylate groups. These dimethacrylate groups serve as a crosslinking agents. In situ redox polymerization of the mixture in water led to transparent hydrogels. These hydrogels in the swollen state have been demonstrated to be very efficient sorbents for the removal of boron on ppm levels. The boron loaded polymers can be regenerated by simple acid (0.1 M HCl) and base (0.1 M NaOH) treatment.     

Synthesis of Poly(N‐isopropylacrylamide)‐Block‐Poly(tert‐Butyl Methacrylate) Block Copolymer by Visible Light–Induced Metal‐Free Atom Transfer Polymerization

Atom transfer radical polymerization (ATRP) is one of the most powerful methodologies for polymerization. Well‐controlled ATRP of N‐isopropylacrylamide (NIPAAm) could be obtained in organic‐water mixture solvent with conventional metal catalyst/ligand catalyst system. However, the mixture solvent is not suitable for copolymerization of NIPAAm with hydrophobic monomers. Moreover, further purification of metal was required for biomedical polymerization. Here, poly(N‐isopropylacrylamide) (PNIPAAm) is synthesized by visible light–induced metal‐free ATRP using a photoredox catalyst. PNIPAAm is obtained with high conversion and controlled molecular weight with low dispersity. Moreover, poly(N‐isopropylacrylamide)‐block‐poly(tert‐butyl methacrylate) (PNIPAAm‐b‐PMAA) block copolymer can be synthesized by such metal‐free ATRP. PNIPAAm‐b‐PMAA can be obtained by following hydrolysis.     

Synthesis of High‐Molecular Weight Polymers Based on N,N‐Diallyl‐N‐Methylamine

High‐molecular weight polymers, namely poly(N,N‐diallyl‐N‐methylammonium trifluoroacetate) and poly(N,N‐diallyl‐N‐methylamine), were prepared by radical polymerization of N,N‐diallyl‐N‐methylamine in aqueous solution in the presence of an equimolar amount of trifluoroacetic acid and by polymerization of the newly synthesized equimolecular salt N,N‐diallyl‐N‐methylammonium trifluoroacetate in gentle conditions. We have established that chain termination is controlled by the bimolecular mechanism and that degradative chain transfer to monomer transforms into effective chain transfer (see Scheme). The possibility of controlling the polymerization rate and molecular weight of polymers is demonstrated. The mechanisms of the observed phenomena are discussed.

     

Temperature and pH Dual‐Responsive Behavior of Dendritic Poly(N‐isopropylacrylamide) with a Polyoligomeric Silsesquioxane Core and Poly(2‐hydroxyethyl methacrylate) Shell

Novel temperature and pH dual‐responsive dendritic polyoligomeric silsesquioxane (POSS)–poly(N‐isopropylacrylamide) (PNIPAm)–poly(2‐hydroxyethyl methacrylate) (PHEMA) copolymers are prepared via atom transfer radical polymerization and click reactions. The cloud points (T_c) decrease with decreasing pH from 10.0 to 5.0 due to the weakened inter‐molecular interactions and enhanced intra‐molecular hydrogen bonding, whereas the T_c exhibits a small increase from pH 5.0 to 4.0 because of the better solvation of PHEMA at highly acidic conditions. The above findings are corroborated by the different sizes of aggregates observed by dynamic light scattering. The encapsulation of a fluorescent dye and stimulated release by temperature and pH changes are also demonstrated.     

Well‐defined N‐Isopropylacrylamide Dual‐Sensitive Copolymers with LCST ≈38 °C in Different Architectures: Linear,Block and Star Polymers

Reversible addition‐fragmentation chain transfer (RAFT) polymerization is used to prepare temperature‐ and pH‐sensitive statistical copolymers with lower critical solution temperature (LCST) close to 38 °C at pH 7.4 based on N‐isopropylacrylamide and methacrylic acid derivative comonomers with a pK_a close to 6. Statistical copolymers are re‐activated to prepare amphiphilic block copolymers and star polymers with cross‐linked core. The LCST is maintained by varying the architecture; however, the LCST originated behaviour changes due to self‐aggregation. Statistical copolymers and short block copolymers show complex aggregation, whereas mid‐size block copolymers and star polymers show shrinkage of aggregate dimensions. The pH of the medium has a profound impact on the self‐assembling behaviour of the different polymer architectures.     

Poly(N‐isopropylacrylamide) Networks Conjugated with Gly–Gly–His via a Merrifield Solid‐Phase Peptide Synthesis Technique for Metal‐Ion Recognition

The temperature‐dependent swelling behavior of poly(N‐isopropylacrylamide) and tripeptide Gly–Gly–His (GGH)/poly(NIPAAm) conjugate hydrogel coatings are investigated using a quartz crystal microbalance with dissipation (QCM‐D) while in contact with NaCl, ZnCl₂, NiCl₂, and CuCl₂ solutions. To fabricate the tripeptide conjugated gels, precursor gels of poly(NIPAAm‐co‐3‐aminopropylmethacrylamide[3.5 mol%]) are synthesized via free‐radical polymerization. The metal‐binding tripeptide, GGH, is subsequently synthesized in the gel via a Merrifield solid‐phase peptide synthesis (SPPS) technique, in which the amino group of the copolymer gel provides a functional site to support peptide synthesis. It is found that the logarithm of the transition temperature of the tripeptide GGH/poly(NIPAAm) conjugate hydrogel is proportional to the ionic strength, showing two distinct regions at low and high ionic strengths for the divalent ions. In the low‐ionic‐strength regime, the salting out constants are 0.08, 0.07, and 0.06 M^?1 for Cu²⁺, Ni²⁺, and Zn²⁺, respectively, which follows the known trend for binding of ions to GGH. In the high‐ionic‐strength region, when the metal‐ion binding sites in the tripeptide conjugate hydrogel are saturated, the salting out constants are similar to the salting out constants associated with pure poly(NIPAAm).

     

Multiresponsive Properties of Triple‐Shell Architectures with Poly(N,N‐diethylaminoethyl methacrylate), Poly(N‐vinylcaprolactam), and Poly(N,N‐dimethylaminoethyl methacrylate) as Building Blocks

Triple‐shell architectures, consisting of poly[(N,N‐diethylaminoethyl methacrylate)‐block‐(N‐vinylcaprolactam)‐block‐(N,N‐dimethylaminoethyl methacrylate)] triblock copolymers, are obtained by sequential reversible addition–fragmentation chain transfer polymerizations, using a terminal‐modified hyperbranched poly(β‐cyclodextrin) core as a macro chain transfer agent. UV‐vis spectroscopy results indicate that the triple‐shell architectures possess one pH response at pH 12.5 in aqueous solution at room temperature, followed by double‐temperature‐ responsiveness between 33 °C and 36 °C. The special multiresponsive properties are further confirmed by investigating the controlled release behavior of the resulting polymers using metronidazole as a model drug.     

Temperature and pH dependent solubility of novel poly(N‐isopropylacrylamide)‐copolymers

Temperature and pH sensitive polymers were prepared by the copolymerization of N‐isopropylacrylamide (NIPAAm) with varying amounts of acrylamide derivatives bearing carboxylic groups attached to spacers with different chain length (C_nAAm). Aqueous solutions of the copolymers show lower critical solution temperature behaviour (LCST). The LCSTs of the aqueous solutions of these copolymers decrease with increasing comonomer content and spacer chain length. Through the use of suitable amounts of the monomers it was possible to accurately predict the phase transition temperature and values were obtained between 10 and 32°C. The LCSTs also strongly depend on the pH‐value of the solution. An increase of the pH‐value leads to a significant increase in LCST due to the formation of a more hydrophilic copolymer. Through altering the pH it is possible to obtain phase transition temperatures between 10 to 50°C. The LCST behaviour was investigated by means of DSC as a standard method which allows the measurement of the phase transition over a wide range of temperatures and pH‐values. Comparison of these results with those from other methods (mainly turbidimetric and viscosimetric measurements) shows a two step mechanism for the phase separation.     

Facile Surface Modification and Application of Temperature Responsive Poly(N‐isopropylacrylamide‐co‐dopamine methacrylamide)

The temperature‐responsive poly(N‐isopropylacrylamide) [PNIPAAm] has been exploited for various biomedical applications. In this work, poly(N‐isopropylacrylamide‐co‐dopamine methacrylamide) [P(NIPAAm‐co‐DMAAm)] was synthesized for facile surface modification and application to cell sheets. ¹H NMR, FT‐IR, and GPC confirmed the successful synthesis of P(NIPAAm‐co‐DMAAm). The lower critical solution temperature was measured to be ca. 29.2 °C by UV–Vis spectroscopy. AFM imaging clearly visualized the transient phase transition of the temperature‐responsive polymer bound on silicon substrate by coordination bond formation. Furthermore, the adhesive and temperature responsive P(NIPAAm‐co‐DMAAm) could be successfully applied to the facile preparation of NIH‐3T3 fibroblast cell sheets.     

Biodegradable Multiblock Polymers Based on N‐(2‐Hydroxypropyl)methacrylamide Designed as Drug Carriers for Tumor‐Targeted Delivery

Biodegradable multiblock (co)polymers based on N‐(2‐hydroxypropyl)methacrylamide (HPMA) for drug delivery applications are prepared by azide–alkyne polycycloaddition of end‐functionalized precursors synthesized by reversible addition–fragmentation chain transfer polymerization. Copper‐catalyzed polyaddition of the heterotelechelic polymer precursors containing azide and alkyne groups provides (A)_x‐type multiblock (co)polymers. For the first time, thermally degradable multiblock polymers of (AB)_x‐type are prepared via polyaddition of homotelechelic polymer diazides with azo‐compounds containing two alkyne groups. A novel type of HPMA‐based multiblock (co)polymers undergoing the pH‐dependent hydrolysis is reported. The (co)polymers containing the Asp‐Pro‐Lys sequence are relatively stable in an aqueous buffer at physiological pH 7.4; however, they undergo rapid hydrolysis at pH 5.0 corresponding to the pH in lysosomes. The multiblock polymer containing the Gly‐Phe‐Leu‐Lys linkage is degraded in the presence of the lysosomal protease cathepsin B. Thermal degradation of the (AB)_x‐type multiblock polymers proceeds even at 37 °C, yielding a mixture of polymer degradation products with molecular weights below the renal threshold.

     

Self‐Healing Metallo‐Supramolecular Amphiphilic Polymer Conetworks

The current challenge in self‐healing materials resides in the design of materials which exhibit improved mechanical properties and self‐healing ability. The design of phase‐separated nanostructures combining hard and soft phases represents an attractive approach to overcome this limitation. Amphiphilic polymer conetworks are nanostructured materials with robust mechanical properties, which can be tailored by tuning the polymer composition and chemical functionality. This article highlights the design of phase‐separated nanostructured polymers from metallo‐supramolecular amphiphilic polymer conetworks, and their application for self‐healing surfaces. The synthesis of poly(N‐(pyridin‐4‐yl)acrylamide)‐l‐polydimethylsiloxane polymer conetworks from the poly(pentafluorophenyl acrylate)‐l‐polydimethylsiloxane activated ester is presented. Loading of ZnCl₂ salt into the phase‐separated polymer conetwork strengthens the network by cross‐linking the poly(N‐(pyridin‐4‐yl)acrylamide) phases, while offering reversible interactions needed for self‐healing ability.     

Synthesis and Gas Permeability of Chemically Cross‐Linked Polynorbornene Dicarboximides Bearing Fluorinated Moieties

This work reports on the synthesis of a novel bifunctional norbornene dicarboximide monomer (HFDA) based on 4,4′‐(hexafluoroisopropylidene)bis(p‐phenyleneoxy)dianiline and its application as a cross‐linking agent in the ring‐opening metathesis polymerization (ROMP) with N‐3‐trifluoromethylphenyl‐exo,endo‐norbornene‐5,6‐dicarboximide (mCF₃) employing the Grubbs 2nd generation catalyst (I) and cis‐1,4‐diacetoxy‐2‐butene as a chain transfer agent (CTA) to yield a series of soluble nonlinear highly branched chains polymers with increasing degree of cross‐linking. A comparative study of gas transport in membranes based on these cross‐linked polynorbornene dicarboximides is performed and the gases studied are hydrogen, oxygen, nitrogen, carbon dioxide, methane, ethylene, and propylene. It is found that cross‐linking increases the gas permeability, leads to the highest separation factor reported to date for the H₂/C₃H₆ mixture in this kind of polymers, and also enhances the CO₂ plasticization resistance up to 14 atm upstream pressure. The chemical cross‐linking approach employed in this research is an effective tool to enhance gas transport properties for dense polynorbornene dicarboximide membranes.     

High pressure synthesis of new N,N‐diphenyl‐pendent aromatic ionene polymers from N,N,N ′,N ′‐tetraphenyl‐m‐xylylenediamine and aliphatic dihalides

New aromatic‐containing ionene polymers having N,N‐diphenyl pendent groups were synthesized for the first time by solution polycondensation of N,N,N ′,N ′‐tetraphenyl‐m‐xylylenediamine with aliphatic dihalides like p‐xylylene dibromide in acetonitrile at 200°C under a high pressure of 500 MPa. The inherent viscosity values of the polymers were rather low. These N,N‐diphenyl‐pendent aromatic ionene polymers were soluble in polar solvents such as DMF and m‐cresol but not in water, and showed normal polyelectrolyte behavior in ethanol solutions.     

Functionalized Polymers from α‐Hydroxyalkylated N‐Vinylcaprolactam

Hydroxyalkylation of N‐vinylcaprolactam (NVCL) in α‐position via ring‐opening reaction of propylene oxide and ε‐caprolactone, respectively, yields in precursors for multifunctional NVCL derivatives. Homo‐ and copolymers of hydroxyfunctionalized NVCL derivatives, synthesized by free radical mechanism, are further investigated regarding their thermoresponsive behavior. Esterification of hydroxypropylated NVCL derivative with methacrylic anhydride is carried out yielding a versatile bifunctional cross‐linker. Networks are obtained either via free radical polymerization of the cross‐linker or anionic polymerization of only the methacrylic function and subsequent polymer analogous cross‐linking of the vinylic side groups. The rheological behavior during and after curing is investigated by oscillatory rheology. Furthermore, N‐vinylcaprolactam anion is used as an initiator for the anionic ring‐opening polymerization of ε‐caprolactone. Copolymerization of poly(ε‐caprolactone) macromonomer with NVCL yields graft copolymers. A polymerizable thermotropic liquid crystalline (LC) derivative is prepared by coupling cholesteryl chloroformate to NVCL. The thermal behavior of LC derivative is investigated by differential scanning calorimetry and polarized light microscopy.

     

Novel Soluble N‐Phenyl‐Carbazole‐Containing PPVs for Light‐Emitting Devices: Synthesis,Electrochemical, Optical,and Electroluminescent Properties

Summary: Novel PPV derivatives (PCA8‐PV and PCA8‐MEHPV) containing N‐phenyl‐carbazole units on the backbone were successfully synthesized by the Wittig polycondensation of 3,6‐bisformyl‐N‐(4‐octyloxy‐phenyl)carbazole with the corresponding tributyl phosphonium salts in good yields. The newly formed and dominant trans vinylene double bonds were confirmed by FT‐IR and NMR spectroscopy. The polymers (with of 6 289 for PCA8‐PV and 7 387 for PCA8‐MEHPV) were soluble in common organic solvents and displayed high thermal stability (T_gs are 110.7 °C for PCA8‐PV and 92.2 °C for PCA8‐MEHPV, respectively) because of the incorporation of the N‐phenyl‐carbazole units. Cyclic voltammetry investigations (onsets: 0.8 V for PCA8‐PV and 0.7 V for PCA8‐MEHPV) suggested that the polymers possess enhanced hole injection/transport properties, which can be also attributed to the N‐phenyl‐carbazole units on the backbone. Both the single‐layer and the double‐layer light‐emitting diodes (LEDs) that used the polymers as the active layer emitted a greenish‐blue or bluish‐green light (the maximum emissions located 494 nm for PCA8‐PV and 507 nm for PCA8‐MEHPV, respectively). Compared with those of the single‐layer devices, the emission efficiencies of the double‐layer devices, in which an electron‐transporting layer (Alq₃) was added, were enhanced by a factor of 10, implying that the better hole‐electron balance is achieved because of the incorporation of the electron‐transporting layer.

The N‐phenyl‐carbazole‐containing polymers synthesized.     

Controlled Anionic Block Copolymerization with N,N‐Dialkylacrylamide as a Second Block

Summary: Novel well‐defined block copolymers composed of polystyrene, poly(2‐vinylpyridine), poly(ethylene oxide), or poly(tert‐butyl methacrylate) as the first block and poly(N,N‐dialkylacrylamide) (PDAlAAm) as the second block were synthesized by ligated anionic polymerization. The latter was carried out in tetrahydrofuran (THF) initiated by 1,1‐diphenyloligostyryllithium in the presence of ZnEt₂ and LiCl. At first the role of the additives LiCl and ZnEt₂ on the mode of the anionic homopolymerization of N,N‐dialkylacrylamide was investigated. Polymerization in the presence of ZnEt₂ resulted in syndiotactic polymers with narrow molecular weight distribution only. In the presence of both additives, the reaction mixture became heterogeneous with a high degree of isotacticity of the polymers. Despite the fact that the polymerizations were performed in heterogeneous phase, the DAlAAm monomers were polymerized in a quantitative yield. The efficiency of the first block of active sites was always higher than 0.71. Preliminary studies using dynamic light scattering of aqueous hydrochloric acid solutions of poly[(2‐vinylpyridine)‐block‐(N,N‐diethylacrylamide)] block copolymers at different temperatures and at pH 2 showed that above 45 °C, micelle‐like aggregates were formed. The heating and cooling cycles were reversible but showed hysteresis, which was obviously due to the isotactic structure of the poly(N,N‐diethylacrylamide) block.

Temperature dependence of the scattering intensity of various poly[(2‐vinylpyridine)‐block‐(N,N‐diethylacrylamide)] block copolymers.     

Functionalized Biocompatible Poly(N‐vinyl‐2‐caprolactam) With pH‐Dependent Lower Critical Solution Temperature Behaviors

Functionalized temperature‐ and pH‐sensitive poly(N‐vinyl‐2‐caprolactam) (PVCL) polymers are prepared by copolymerizing monomers of N‐vinyl‐2‐caprolactam (VCL) and a VCL derivative, 3‐(tert‐butoxycarbonyl)‐N‐vinyl‐2‐caprolactam (TBVCL). Different molar compositions are studied, with the functional monomer at 9 and 14 mol%, respectively, (COOH‐PVCL9 and COOH‐PVCL14). Sharp, complete, and reversible phase transitions of the copolymers with little hysteresis are shown to be pH‐dependent, with cloud points ranging from 35 to 44 °C for COOH‐PVCL9, and 29 to 64 °C for COOH‐PVCL14, upon pH change from 2.0 to 7.4. Cytotoxicity assay demonstrates that the functionalized PVCL copolymers are biocompatible with NIH/3T3 up to 2 mg mL^?1. Such new PVCL‐based water soluble copolymers with tunable properties could be useful in a variety of biomedical applications.