Chitosan‐Hydroxybenzotriazole Aqueous Solution: A Novel Water‐Based System for Chitosan Functionalization

Summary: A chitosan‐hydroxybenzotriazole (HOBt) aqueous solution prepared by simply mixing chitosan and HOBt in water provides an effective system to functionalize chitosan in an aqueous environment. This aqueous solution in combination with water‐soluble carbodiimide (WSC) allows the conjugation of functional groups onto chitosan under mild conditions without requiring any organic solvents or acid and heat. In this contribution, a series of model reactions that use a novel water‐based system of chitosan to functionalize the polymer with boc‐L ‐phenylalanine, poly(ethylene glycol) methyl ether, and dicarboxylated poly(ethylene glycol) is demonstrated.

Chitosan‐HOBt is effectively conjugated with R‐COOH via a water‐soluble carbodiimide (WSC) conjugating agent.     

Thermoresponsive Poly(2‐oxazine)s

The monomers 2‐methyl‐2‐oxazine (MeOZI), 2‐ethyl‐2‐oxazine (EtOZI), and 2‐n‐propyl‐2‐oxazine (nPropOZI) were synthesized and polymerized via the living cationic ring‐opening polymerization (CROP) under microwave‐assisted conditions. pEtOZI and pnPropOZI were found to be thermoresponsive, exhibiting LCST behavior in water and their cloud point temperatures (T_CP) are lower than for poly(2‐oxazoline)s with similar side chains. However, comparison of poly(2‐oxazine) and poly(2‐oxazoline)s isomers reveals that poly(2‐oxazine)s are more water soluble, indicating that the side chain has a stronger impact on polymer solubility than the main chain. In conclusion, variations of both the side chains and the main chains of the poly(cyclic imino ether)s resulted in a series of distinct homopolymers with tunable T_CP.     

Stimuli‐Responsive Water‐Soluble Fullerene (C60) Polymeric Systems

This review documents the advances in stimuli‐responsive water‐soluble fullerene (C₆₀) polymeric systems. Stimuli‐responsive polymers, when grafted onto C₆₀ impart “smart” and “responsive” characteristics, and these novel materials adopt various morphologies when subjected to external stimuli, such as pH, temperature, and salt. Various synthetic approaches for producing C₆₀‐polymers are outlined and discussed. The responsive behavior, water solubility, and self‐assembly characteristics of these C₆₀‐polymers make them attractive for applications such as drug delivery, temperature sensors, and personal care.     

Synthesis of thermo‐responsive poly(N‐vinylcaprolactam)‐containing block copolymers by cobalt‐mediated radical polymerization

Thermo‐responsive block copolymers based on poly(N‐vinylcaprolactam) (PNVCL) have been prepared by cobalt‐mediated radical polymerization (CMRP) for the first time. The homopolymerization of NVCL was controlled by bis(acetylacetonato)cobalt(II) and a molecular weight as high as 46,000 g/mol could be reached with a low polydispersity. The polymerization of NVCL was also initiated from a poly(vinyl acetate)‐Co(acac)₂ (PVAc‐Co(acac)₂) macroinitiator to yield well‐defined PVAc‐b‐PNVCL block copolymers with a low polydispersity (M_w/M_n = 1.1) up to high molecular weights (M_n = 87,000 g/mol), which constitutes a significant improvement over other techniques. The amphiphilic PVAc‐b‐PNVCL copolymers were hydrolyzed into unprecedented double hydrophilic poly(vinyl alcohol)‐b‐PNVCL (PVOH‐b‐PNVCL) copolymers and their temperature‐dependent solution behavior was studied by turbidimetry and dynamic light scattering. Finally, the so‐called cobalt‐mediated radical coupling (CMRC) reaction was implemented to PVAc‐b‐PNVCL‐Co(acac)₂ precursors to yield novel PVAc‐b‐PNVCL‐b‐PVAc symmetrical triblock copolymers. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Thermoresponsive Synergistic Hydrogen Bonding Switched by Several Guest Units in a Water‐Soluble Polymer

Thermoresponsive synergistic hydrogen bonding (H‐bonding) switched by several guest units in a water‐soluble polymer is reported. Adjusting the distribution of guest units can effectively change the synergistic H‐bonding inside polymer chains, thus widely switch the preorganization and thermoresponsive behavior of a water‐soluble polymer. The synergistic H‐bonding is also evidenced by converting less polar aldehyde groups into water‐soluble oxime groups, which bring about the lowering‐down of cloud point and an amplified hysteresis effect. This is a general approach toward the wide tunability of thermosensitivity of a water‐soluble polymer simply by adjusting the distribution of several guest H‐bonding units.     

Novel C60‐Anchored Two‐Armed Poly(tert‐butyl acrylate): Synthesis and Characterization

Summary: A multistep synthetic procedure for preparing novel C₆₀‐anchored two‐armed poly(tert‐butyl acrylate) was developed. First, two‐armed poly(tert‐butyl acrylate) bearing a malonate ester core with well‐controlled molecular weight was synthesized through atom transfer radical polymerization. The effective Bingel reaction between C₆₀ and the well‐defined polymer was then carried out to yield C₆₀‐anchored polymer. GPC, ¹H NMR, and UV‐vis spectroscopy indicated that the C₆₀‐anchored polymer was a monosubstituted and ‘closed’ 6,6‐ring‐bridged methanofullerene derivative.

Schematic of a novel C₆₀‐anchored two‐armed polymer.     

A doubly responsive AB diblock copolymer: RAFT synthesis and aqueous solution properties of poly (N‐isopropylacrylamide‐block‐4‐vinylbenzoic acid)

We describe herein the synthesis and self‐assembly characteristics of a doubly responsive AB diblock copolymer comprised of N‐isopropylacrylamide (NIPAM) and 4‐vinylbenzoic acid (VBZ). The AB diblock copolymer was prepared via reversible addition‐fragmentation chain transfer (RAFT) radical polymerization in DMF employing a trithiocarbonate‐based RAFT agent. PolyNIPAM was employed as the macroRAFT agent. The NIPAM homopolymerization was shown to possess all the characteristics of a controlled process, and the blocking with VBZ was judged, by size exclusion chromatography, to be essentially quantitative. The NIPAM‐VBZ block copolymer was subsequently demonstrated to be able to form normal and inverse micelles in the same aqueous solution by taking advantage of the stimuli responsive characteristics of both building blocks. Specifically, and as judged by NMR spectroscopy and dynamic light scattering, raising the temperature to 40 °C (above the lower critical solution temperature of the NIPAM block), while at pH 12 results in supramolecular self‐assembly to yield nanosized species that are composed of a hydrophobic NIPAM core stabilized by a hydrophilic VBZ corona. Conversely, lowering the solution pH to 2.0 at ambient temperature results in the formation of aggregates in which the VBZ block is now hydrophobic and in the core, stabilized by the hydrophilic NIPAM block. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5864–5871, 2007     

Novel temperature‐ and pH‐responsive graft copolymers composed of poly(L‐glutamic acid) and poly(N‐isopropylacrylamide)

A series of novel temperature‐ and pH‐responsive graft copolymers, poly(L ‐glutamic acid)‐g‐poly(N‐isopropylacrylamide), were synthesized by coupling amino‐semitelechelic poly(N‐isopropylacrylamide) with N‐hydroxysuccinimide‐activated poly(L ‐glutamic acid). The graft copolymers and their precursors were characterized, by ESI‐FTICR Mass Spectrum, intrinsic viscosity measurements and proton nuclear magnetic resonance (¹H NMR). The phase‐transition and aggregation behaviors of the graft copolymers in aqueous solutions were investigated by the turbidity measurements and dynamic laser scattering. The solution behavior of the copolymers showed dependence on both temperature and pH. The cloud point (CP) of the copolymer solution at pH 5.0–7.4 was slightly higher than that of the solution of the PNIPAM homopolymer because of the hydrophilic nature of the poly(glutamic acid) (PGA) backbone. The CP markedly decreased when the pH was lowered from 5 to 4.2, caused by the decrease in hydrophilicity of the PGA backbone. At a temperature above the lower critical solution temperature of the PNIPAM chain, the copolymers formed amphiphilic core‐shell aggregates at pH 4.5–7.4 and the particle size was reduced with decreasing pH. In contrast, larger hydrophobic aggregates were formed at pH 4.2. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4140–4150, 2008     

Insight into the effect of methylated urea on the phase transition of aqueous solutions of poly(N‐isopropylacrylamide) by microcalorimetry: Hydrogen bonding and van der Waals interactions

The effect of different functional groups of methylated urea on the phase transition of poly(N‐isopropylacrylamide) (PNIPAM) aqueous solutions has been studied by a high‐sensitivity differential scanning calorimetry. The results reveal that with the addition of osmolytes with N? H groups, the enthalpy change increases with the number of DSC cycles, presumably due to the gradual formation of hydrogen bonds with dehydrated C?O groups of PNIPAM at high temperature. Moreover, with the addition of tetramethylurea (TMU) without hydrogen bond donor groups, the enthalpy change of PNIPAM solution remains unchanged with the number of DSC cycles and decreases with the TMU concentration, suggesting that the van der Waals interactions between TMU and isopropyl groups of PNIPAM and the weakening of hydrophobic interactions between isopropyl groups play a dominant role in the effect of TMU on the phase transition of PNIPAM. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 1145–1151     

Poly(azomethine) Rotaxanes: Novel Water Soluble Supramolecular Polymers with High Molar Mass

A novel type of supramolecular poly(azomethine) was synthesized by the polycondensation of an inclusion complex of β‐cyclodextrin/poly(oxypropylene)diamine with one of β‐cyclodextrin/terephthaldehyde and a subsequent reaction with [60]fullerene as the end capping agent. Molar mass determination by gel permeation chromatography showed that the polymers had a high molar mass (about 150 kg · mol⁻¹) with a very narrow polydispersity. Isothermal titration calorimetric studies confirmed that each poly‐(oxypropylene)diamine unit could host seven cyclodextrin molecules, which was further supported by ¹H NMR spectroscopy and molecular modeling studies. Additional characterization by ¹³C NMR and FT‐IR spectroscopy, as well as by thermogravimetric analysis, confirmed the structure of the cyclodextrin‐based polyrotaxane.

     

Synthesis,Characterization, and thermoresponsive properties of Helical Polypeptides Derivatized from Poly(γ−4‐(3‐chloropropoxycarbonyl)benzyl‐L‐glutamate)

A series of side‐chain‐functionalized α‐helical polypeptides, i.e., poly(γ‐4‐(3‐chloropropoxycarbonyl)benzyl‐_L‐glutamate) (6) have been prepared from n‐butylamine initiated ring‐opening polymerization (ROP) of γ‐4‐(3‐chloropropoxycarbonyl)benzyl‐_L‐glutamic acid‐based N‐carboxyanhydride. Polypeptides bearing oligo‐ethylene‐glycol (OEG) groups or 1‐butylimidazolium salts were prepared from 6 via copper‐mediated [2+3] alkyne‐azide 1,3‐dipolar cycloaddition or nuleophilic substitution, respectively. CD and FTIR analysis revealed that the polymers adopt α‐helical conformations both in solution and the solid state. Polymers bearing OEG (m = 3) side‐chains showed reversible LCST‐type phase transition behaviors in water while polymers bearing 1‐butylimidazolium and I^? counter‐anions exhibited reversible UCST‐type transitions in water. Variable‐temperature UV‐vis analysis revealed that the phase transition temperatures (T_pts) were dependent on the main‐chain length and polymeric concentration. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2469–2480     

Poly(p‐phenylene ethynylene) Incorporating Sterically Enshrouding m‐Terphenyl Oxacyclophane Canopies

A sterically encumbered m‐terphenyl oxacyclophane substituted with two aryl iodide substituents has been prepared as a versatile monomer for the preparation of π‐conjugated polymers. The monomer has been used to prepare a poly(p‐phenylene ethynylene) derivative (P1) incorporating oxacyclophane units as canopies that shield one side of the π‐system from inter‐chain interactions. The photophysical properties of P1 in dilute solution compare well to those of a poly(p‐phenylene ethynylene) derivative (P2) that lacks the canopy. The presence of the steric canopy leads to a diminished inter‐chain interaction in the solid state and enhances the kinetic response of P1 to vapors of nitro‐organics such as TNT, presumably by increasing the permeability of P1 to these analytes over that of P2.

     

A new water‐soluble branched poly(ethylene imine) derivative having hydrolyzable imidazolidine moieties and its application to long‐lasting release of aldehyde

A new water‐soluble poly(ethylene imine)‐derivative having imidazolidine moieties was developed. With using branched poly(ethylene imine) (BPEI) as a precursor, it was modified by Michael addition reaction of its primary amino group to an acrylate having poly(ethylene glycol) (PEG) chain. The modified BPEI was reacted with octanal to give the corresponding BPEI derivative having octanal‐derived imidazolidine moieties. The obtained polymer inherited the high hydrophilicity of the attached PEG chains to allow hydrolysis of the imidazolidine moieties under homogeneous conditions in aqueous media, leading to long‐lasting release of octanal. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Synthesis and characterization of electrically conducting poly(o‐/m‐toluidine‐co‐o‐/m‐aminoacetophenone) copolymers

A series of poly(o‐/m‐toluidine‐co‐o‐/m‐aminoacetophenone) copolymers combining the features of high conductivity and processibility are synthesized and characterized by a number of techniques including ¹H NMR; thermogravimetry; IR, Raman, and UV–visible spectroscopy; scanning electron microscopy; and X‐ray diffraction. The copolymers are synthesized by the emulsion and inverse emulsion methods using conventional ammonium persulfate and a new oxidant, benzoyl peroxide, respectively. The influence of the polymerization conditions such as the monomer feed ratios, solvent, and the nonsolvent is investigated. The composition of the resulting copolymers is determined by ¹H NMR analysis. The conductivity of the copolymers varies with the aminoacetophenone content in the feed and the polymerization conditions. It is interesting that the conductivity of the copolymers is higher than that of the corresponding homopolymers. The results are rationalized on the basis of the effect of the ? COCH₃ substituent on the polymer structure. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4300–4310, 2004     

Synthesis of di‐ and tri‐tertiary amine containing methacrylic monomers and their (co)polymerization via RAFT

The synthesis, reversible addition‐fragmentation chain transfer (RAFT) (co)polymerization, and aqueous phase behavior of three methacrylic monomers containing two or three pendent tertiary amine functional groups are described. Homopolymerizations were conducted with 1‐methyl‐1‐cyanoethyl dithiobenzoate (CPDB) under bulk conditions following standard RAFT procedures. All three monomers, 1,3‐bis(dimethylamino)propan‐2‐yl methacrylate ( M1 ), 1‐(bis(3‐(dimethylamino)propyl) amino)propan‐2‐yl methacrylate ( M2 ), and 2‐((2‐(2‐(dimethylamino)ethoxy)ethyl) methylamino)ethyl acrylate ( M3 ), polymerized in a controlled manner as evidenced by the kinetic and molecular weight profiles. Homopolymerizations conducted at a lower ratio of CPDB:AIBN proceeded faster than those at a higher ratio. Subsequently, the facile copolymerization behavior of M1 and M3 was demonstrated via the synthesis of a range of statistical copolymers with hexyl and lauryl methacrylate comonomers containing 10–90 mol % hydrophobic comonomer. Finally, the aqueous‐solution characteristics of the M1 – M3 homopolymers were briefly examined. All three homopolymers were shown to undergo phase transitions in aqueous media in response to changes in both temperature and pH. Specifically, 1 wt % solutions of poly M1 were shown to possess an LCST of ～22 °C, that of poly M2 at ～33 °C, and for poly M3 the observed cloud point was ～63 °C. Additionally, all homopolymers became hydrophobic and phase separated at high solution pH. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1877–1890, 2009     

Poly(amidoamine) Conjugates Containing Doxorubicin Bound via an Acid‐Sensitive Linker

Poly(amidoamine)s with amino pendant groups were prepared by hydrogen‐transfer polyaddition of primary and secondary amines to bis‐acrylamines. Dansyl cadaverine (DC) doxorubicin (Dox) were bound to the polymers via a cis‐aconityl spacer to give conjugates containing 3 µg of DC per mg of polymer and 28 to 35 µg of Dox per mg of polymer. Release of DC and Dox at physiological and acidic pH varied from 0 to 35% over 48 h and was pH dependent. Although the ISA1Dox conjugate (IC₅₀ = 6 µg Dox · mL^?1) presented similar toxicity as the parent polymer without Dox, ISA23Dox showed increased toxicity (IC₅₀ = 10 µg Dox · mL^?1). These results suggest that ISA23Dox is able to release biologically active Dox in vitro and that this conjugate might be suitable for further development.

     

Poly(ether tert‐amine): A novel family of multiresponsive polymer

A novel multiresponsive poly(ether tert‐amine) (PEA) was synthesized by nucleophilic addition/ring‐opening reaction of commercial poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO), and di‐epoxy and di‐amine monomer. The process of synthesis was very simple and green in ethanol as reactive media. These PEAs exhibit sharp response to temperature, pH, and ionic strength, with adjustable and sharp phase transitions in the range of 27–100 °C. The lower critical solution temperature (LCST) of PEA's aqueous solution presents a linear relationship to the PEO content (y = 35.7 + x), indicating well‐tunable LCST. The concentration of PEA has no obvious effect on LCST. Therefore, PEA will be potential in applications of drug delivery, separation, and biotechnology. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1292–1297, 2009     

Synthesis of poly[N‐isopropylacrylamide‐g‐poly(ethylene glycol)] with a reactive group at the poly(ethylene glycol) end and its thermosensitive self‐assembling character

Poly[N‐isopropylacrylamide‐g‐poly(ethylene glycol)]s with a reactive group at the poly(ethylene glycol) (PEG) end were synthesized by the radical copolymerization of N‐isopropylacrylamide with a PEG macromonomer having an acetal group at one end and a methacryloyl group at the other chain end. The temperature dependence of the aqueous solutions of the obtained graft copolymers was estimated by light scattering measurements. The intensity of the light scattering from aqueous polymer solutions increased with increasing temperature. In particular, at temperatures above 40°C, the intensity abruptly increased, indicating a phase separation of the graft copolymer due to the lower critical solution temperature (LCST) of the poly(N‐isopropylacrylamide) segment. No turbidity was observed even above the LCST, and this suggested a nanoscale self‐assembling structure of the graft copolymer. The dynamic light scattering measurements confirmed that the size of the aggregate was in the range of several tens of nanometers. The acetal group at the end of the PEG graft chain was easily converted to the aldehyde group by an acid treatment, which was analyzed by ¹H NMR. Such a temperature‐induced nanosphere possessing reactive PEG tethered chains on the surface is promising for new nanobased biomedical materials. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1457–1469, 2006     

Donor–acceptor‐based poly(toluidine‐co‐chloroaniline)s: Synthesis and characterization

A series of poly(o‐/m‐toluidine‐co‐o‐/m‐chloroaniline) copolymers of different compositions were synthesized by an emulsion method with ammonium persulfate as the oxidant. The conductivity of the copolymers was two to five orders of magnitude higher than that of the homopolymers poly(o‐toluidine) and poly(m‐chloroaniline). Among the copolymers, the copolymer of o‐toluidine and m‐chloroaniline exhibited a maximum conductivity of 0.14 S cm^?1. The conductivity of these copolymers was also higher than that of poly(aniline‐co‐chloroaniline). The properties of the copolymers were greatly influenced by the positions of the substituents and the concentrations of the individual monomers in the feed. All the copolymers were completely soluble in polar solvents such as dimethyl sulfoxide and showed higher heat stability as the chloroaniline concentration increased. These effects could be interpreted in terms of extensive hydrogen bonding and interchain linking and, therefore, higher electron delocalization in these copolymers due to the presence of electron‐rich toluidine rings adjacent to electron‐deficient chloroaniline. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1579–1587, 2005