Controlled helical orientation of carbazole in amino acid derived poly(N‐propargylamide)s

Novel L ‐alanine and L ‐glutamic acid derivatized, carbazole‐containing N‐propargylamides [N‐(9‐carbazolyl)ethyloxycarbonyl‐L ‐alanine N′‐propargylamide and N‐(9‐carbazolyl)ethyloxycarbonyl‐L ‐glutamic acid‐γ‐benzyl ester N′‐propargylamide] were synthesized and polymerized with (nbd)Rh⁺[η⁶‐C₆H₅B^?(C₆H₅)₃] (nbd = norbornadiene) as a catalyst to obtain the corresponding polymers with moderate molecular weights in high yields. Polarimetry, circular dichroism, and ultraviolet–visible spectroscopy studies revealed that both poly[N‐(9‐carbazolyl)ethyloxycarbonyl‐L ‐alanine N′‐propargylamide] and poly[N‐(9‐carbazolyl)ethyloxycarbonyl‐L ‐glutamic acid‐γ‐benzyl ester N′‐propargylamide] took a helical structure with a predominantly one‐handed screw sense in tetrahydrofuran, CHCl₃, and CH₂Cl₂. The helix content of poly[N‐(9‐carbazolyl)ethyloxycarbonyl‐L ‐alanine N′‐propargylamide] could be tuned by heat or the addition of a protic solvent, and the helical sense of poly[N‐(9‐carbazolyl) ethyloxycarbonyl‐L ‐glutamic acid‐γ‐benzyl ester N′‐propargylamide] was inverted by heat in CHCl₃ or in mixtures of tetrahydrofuran and CH₂Cl₂. Poly[N‐(9‐carbazolyl) ethyloxycarbonyl‐L ‐alanine N′‐propargylamide] and poly[N‐(9‐carbazolyl)ethyloxycarbonyl‐L ‐glutamic acid‐γ‐benzyl ester N′‐propargylamide] also took a helical structure in film states. They showed small fluorescence in comparison with the monomers and redox activity based on carbazole. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 253–261, 2007     

Multifunctional materials based on polyazomethines derived from 2,5‐dihydroxy‐1,4‐benzoquinone and siloxane diamines

New polyazomethines have been synthesized by the reaction between 2,5‐dihydroxy‐1,4‐benzoquinone and siloxane diamines differing by the siloxane sequence length. A dimer has also been prepared as a model compound. The products were characterized by spectral (FTIR and ¹H‐NMR) and elemental analyses, GPC, viscosity measurements, solubility tests, and transmission electron microscopy (TEM). The different properties have been investigated by adequate techniques: thermal (DSC and TGA), spectral (UV–vis and fluorescence spectroscopy), redox (Differential Pulse Voltammetry). pH‐sensitivity and metal complexing ability were also evaluated. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1862–1872, 2008     

Thermal gelation or gel melting: (ethylene glycol)113‐(l‐alanine)12 and (ethylene glycol)113‐(l‐lactic acid)12

When PEG (M.W.～5000 Daltons) is conjugated to poly(l ‐alanine), the polymer aqueous solutions (<10.0 wt.%) undergo sol‐to‐gel (thermal gelation), whereas it is conjugated to poly(l ‐lactic acid), the polymer aqueous solutions (>30.0 wt.%) undergo gel‐to‐sol (gel melting) as the temperature increases. In the search for molecular origins of such a quite different phase behavior, poly(ethylene glycol)‐poly(l ‐alanine) (PEG‐PA; EG₁₁₃‐A₁₂) and poly(ethylene glycol)‐poly(l ‐lactic acid) (PEG‐PLA; EG₁₁₃‐LA₁₂) are synthesized and their aqueous solution behavior is investigated. PEG‐PAs with an α‐helical core assemble into micelles with a broad size distribution, and the dehydration of PEG drives the aggregation of the micelles, leading to thermal gelation, whereas increased molecular motion of the PLA core overwhelms the partial dehydration of PEG, thus gel melting of the PEG‐PLA aqueous solutions occurs. The core‐rigidity of micelles must be one of the key factors in determining whether a polymer aqueous solution undergoes sol‐to‐gel or gel‐to‐sol transition, as the temperature increases. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, , 52, 2434–2441     

Thiol‐responsive micelles based on nonionic gemini surfactants with a cystine disulfide spacer

Thiol‐responsive micelles consisting of novel nonionic gemini surfactants with a cystine disulfide spacer are reported. The gemini surfactants, (C₁₈‐Cys‐mPEG)₂ and ((C₁₈)₂‐Lys‐Cys‐mPEG)₂, were synthesized from polyethylene glycol, cysteine, and stearic acid, and their structures were confirmed by ¹H NMR and gel permeation chromatography. (C₁₈‐Cys‐mPEG)₂ and ((C₁₈)₂‐Lys‐Cys‐mPEG)₂ formed micelles with average diameters of 13 and 22 nm above the critical micelle concentration of 6.5 and 4.7 µg mL^?1, respectively. The micelles of ((C₁₈)₂‐Lys‐Cys‐mPEG)₂ containing more stearoyl groups showed encapsulated more hydrophobic indomethacin (IMC) with higher entrapment efficiencies than those of (C₁₈‐Cys‐mPEG)₂. The gemini surfactant micelles exhibited an accelerated release of encapsulated IMC with the concentration of the reducing agent, glutathione (GSH), whereas they were unaffected by the presence of reduced GSH (GSSG). The 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)?2‐(4‐sulfophenyl)?2H‐tetrazolium studies revealed the noncytotoxic nature of the gemini surfactant micelles. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 582–589     

Redox‐ and pH‐Responsive Cysteamine‐Modified Poly(aspartic acid) Showing a Reversible Sol–Gel Transition

Synthesis and characterization of a pH‐ and redox‐sensitive hydrogel of poly(aspartic acid) are reported. Reversible gelation and dissolution are achieved both in dimethylformamide and in aqueous medium via a thiol‐disulphide interconversion in the side chain of the polymers. Structural changes are confirmed by Raman microscopy and rheological measurements. Injectable aqueous solutions of thiolated poly(aspartic acid) can be converted into mechanically stable gels by oxidation, which can be useful for drug encapsulation and targeted delivery. Reduction‐facilitated release of an entrapped drug from disulphide cross‐linked hydrogels is studied.

     

N‐vinylcaprolactam‐based microgels: Synthesis and characterization

Poly(N‐vinylcaprolactam) (PVCL) is well known for its thermoresponsive behavior in aqueous solutions. PVCL combines useful and important properties; it is biocompatible polymer with the phase transition in the region of physiological temperature (32–38 °C). This combination of properties allows consideration of PVCL as a material for design biomedical devices and use in drug delivery systems. In this work, PVCL based temperature‐sensitive crosslinked particles (microgels) were synthesized in a batch reactor to analyze the effect of the crosslinker, initiator, surfactant, temperature, and VCL concentration on polymerization process and final microgels characteristics. The mean particle diameters at different temperatures and the volume phase‐transition temperature of the final product were analyzed. To obtain information about the inner structure of microgel particles, semicontinuous polymerizations were carried out and the evolution of the hydrodynamic average particle diameters at different temperatures of the microgel synthesized was investigated. In the case of microgel particles obtained in a batch reactor the size and the swelling‐de‐swelling behavior as a function of the temperature of the medium can be tuned by modulating the reaction variables. When the microgel particles were synthesized in a semibatch reactor different swelling‐de‐swelling behaviors were observed depending on particles inner structure. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2510–2524, 2008     

Temperature‐induced self‐assembly of degalactosylated xyloglucan at low concentration

Xyloglucan is a natural polysaccharide having a cellulose‐like backbone and hydroxyl groups‐rich side‐chains. In its native form the polymer is water‐soluble and forms gel only in presence of selected co‐solutes. When a given fraction of galactosyl residues are removed by enzymatic reaction, the polymer acquires the ability to form a gel in aqueous solution at physiological temperatures, a property of great interest for biomedical/pharmaceutical applications. This work presents data on the effect of a temperature increase on degalactosylated xyloglucan dispersed in water at concentration low enough not to run into macroscopic gelation. Results obtained over a wide interval of length scales show that, on increasing temperature, individual polymer chains and pre‐existing clusters self‐assemble into larger structures. The process implies a structural rearrangement over a few nanometers scale and an increase of dynamics homogeneity. The relation of these findings to coil‐globule transition and phase separation is discussed. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 1727–1735     

Synthesis and characterization of stimuli‐sensitive micro‐ and nanohydrogels based on photocrosslinkable poly(dimethylaminoethyl methacrylate)

The aim of this work was the development of a versatile route for the preparation of temperature‐ and pH‐responsive hydrogels with small dimensions. The copolymerization of N,N‐dimethylaminoethyl methacrylate with various amounts (5 and 10 mol %) of dimethylmaleimidoethyl methacrylate in solution with 2,2′‐azobisisobutyronitrile as an initiator is described. The structural and molecular characterization of the copolymers was performed with proton nuclear magnetic resonance, Fourier transform infrared, and ultraviolet spectroscopy, as well as size exclusion chromatography. Differential scanning calorimetry and thermogravimetry were used for the thermal characterization of the copolymers. Micro‐ and nanohydrogels of the copolymers were prepared by photocrosslinking. The gels obtained by photocrosslinking were characterized with a combination of surface plasmon resonance and optical waveguide spectroscopy, dynamic light scattering, and scanning electron microscopy. The hydrogels showed temperature‐ and pH‐responsive behavior. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 669–679, 2007     

Co‐delivery of 10‐Hydroxycamptothecin with Doxorubicin Conjugated Prodrugs for Enhanced Anticancer Efficacy

Well‐defined amphiphilic linear‐dendritic prodrugs (MPEG‐b‐PAMAM‐DOX) are synthesized by conjugating doxorubicin (DOX), to MPEG‐b‐PAMAM through the acid‐labile hydrazone bond. The amphiphilic prodrugs form self‐assembled nanoparticles in deionized water and encapsulate the hydrophobic anticancer drug 10‐hydroxycamptothecin (HCPT) with a high drug loading efficiency. Studies on drug release and cellular uptake of the co‐delivery system reveal that both drugs are released in a pH‐dependent manner and effectively taken up by MCF‐7 cells. In vitro methyl thiazolyl tetrazolium (MTT) assays and drug‐induced apoptosis tests demonstrate the HCPT‐loaded nanoparticles suppress cancer cell growth more efficiently than the MPEG‐b‐PAMAM‐DOX prodrugs, free HCPT, and physical mixtures of MPEG‐b‐PAMAM‐DOX and HCPT at equivalent DOX or HCPT doses.

     

Aqueous micro and nanoreactors based on alternating copolymers of phenylmaleimide and vinylpyrrolidone bearing pendant l‐proline stabilized with PEG grafted chains

Proline may work efficiently in water as catalyst of aldol reactions if it is hydrophobically activated. In this work, we have maximized this hydrophobic activation by the preparation of linear alternating copolymers of hydrophobic phenylmaleimide and a vinylpyrrolidone derivative bearing proline. These copolymers were water soluble above pH 5.0 and, unlike the free proline, exhibited efficient catalysis at pH 7.0. Moreover, they catalyzed and presented enantioselectivity in an aggregated form at pH 4.0 (close to the isoelectric point, IEP, of the polymer). This enantioselectivity has been related to the exclusion of water at this IEP. To control the size and stabilize the aggregates, PEG grafted copolymers were prepared by the incorporation of a PEG‐macromer (2–10 mol%), which rendered stable nano‐aggregates in water at the IEP. At this pH they catalyzed the aldol reaction in a higher rate than the non‐grafted polymer, but the enantioselectivity was decreased. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 55, 1228–1236     

Synthesis,Self‐Assembly,and Multi‐Stimuli Responses of a Supramolecular Block Copolymer

A supramolecular block copolymer is prepared by the molecular recognition of nucleobases between poly(2‐(2‐methoxyethoxy)ethyl methacrylate‐co‐oligo(ethylene glycol) methacrylate)‐SS‐poly(ε‐caprolactone)‐adenine (P(MEO₂MA‐co‐OEGMA)‐SS‐PCL‐A) and uracil‐terminated poly(ethylene glycol) (PEG‐U). Because the block copolymer is linked by the combination of covalent (disulfide bond) and noncovalent (A U) bonds, it not only has similar properties to conventional covalently linked block copolymers but also possesses a dynamic and tunable nature. The copolymer can self‐assemble into micelles with a PCL core and P(MEO₂MA‐co‐OEGMA)/PEG shell. The size and morphologies of the micelles/aggregates can be adjusted by altering the temperature, pH, salt concentration, or adding dithiothreitol (DTT) to the solution. The controlled release of Nile red is achieved at different environmental conditions.

     

Visible Light and pH Responsive Polymer‐Coated Mesoporous Silica Nanohybrids for Controlled Release

A visible light and pH responsive anticancer drug delivery system based on polymer‐coated mesoporous silica nanoparticles (MSNs) has been developed. Perylene‐functionalized poly(dimethylaminoethyl methacrylates) sensitive to visible light and pH are electrostatically attached on the surface of MSNs to seal the nanopores. Stimulation of visible light and acid can unseal the nanopores to induce controlled drug release from the MSNs. More interestingly, the release can be enhanced under the combined stimulation of the dual‐stimuli. The synergistic effect of visible light and acid stimulation on the efficient release of anticancer drugs from the nanohybrids endows the system with great potential for cancer therapy.

     

Synthesis of pH‐ and thermoresponsive poly(2‐n‐propyl‐2‐oxazoline) based copolymers

Polymers that possess lower critical solution temperature behavior such as poly(2‐alkyl‐2‐oxazoline)s (PAOx) are interesting for their application as stimulus‐responsive materials, for example in the biomedical field. In this work, we discuss the scalable and controlled synthesis of a library of pH‐ and temperature‐sensitive 2‐n‐propyl‐2‐oxazoline P(nPropOx) based copolymers containing amine and carboxylic acid functionalized side chains by cationic ring opening polymerization and postpolymerization functionalization strategies. Using turbidimetry, we found that the cloud point temperature (CP) is strongly dependent on both the polymer concentration and the polymer charge (as a function of pH). Furthermore, we observed that the CP decreased with increasing salt concentration, whereas the CP increased linearly with increasing amount of carboxylic acid groups. Finally, turbidimetry studies in PBS‐buffer indicate that CPs of these polymers are close to body temperature at biologically relevant polymer concentrations, which demonstrates the potential of P(nPropOx) as stimulus‐responsive polymeric systems in, for example, drug delivery applications. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1573–1582     

Catalysts and temperature driven melt polycondensation reaction for helical poly(ester‐urethane)s based on natural L‐amino acids

Catalyst and temperature driven melt polycondensation reaction was developed for natural L‐amino acid monomers to produce new classes of poly(ester‐urethane)s. Wide ranges of catalysts from alkali, alkali earth metal, transition metal and lanthanides were developed for the condensation of amino acid monomers with diols to yield poly(ester‐urethane)s. A‐B Diblock and A‐B‐A triblock species were obtained by carefully choosing mono‐ or diols in model reactions. More than two dozens of transition metal and lanthanide catalysts were identified for the polycondensation to yield high molecular weight poly(ester‐urethane)s. Theoretical studies revealed that the carbonyl carbon in ester possessed low electron density compared to the carbonyl carbon in urethane which driven the thermo‐selective polymerization process. Optical purity of the L‐amino acid residues in the melt polycondensation process was investigated using D‐ and L‐isomers and the resultant products were analyzed by chiral‐HPLC and CD spectroscopy. CD analysis revealed that the amino acid based polymers were self‐assembled as β‐sheet and polyproline type II secondary structures. Electron and atomic force microscopic analysis confirmed the formation of helical nano‐fibrous morphology in poly(ester‐urethane)s. The newly developed melt polycondensation process is very efficient and optimized for wide range of catalysts to produce diverse polymer structures from natural L‐amino acids. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1065–1077     

Self‐Assembly and Dispersion of Chromogenic Molecules: A Versatile and General Approach for Self‐Assessing Polymers

Summary: Self‐assessing polymer blends based on poly(ethylene terephthalate glycol) or linear low‐density polyethylene and small amounts (0.5–2% w/w) of chromogenic sensor dyes are prepared and investigated. The cyano‐substituted oligo(p‐phenylene vinylene) dyes employed in the study exhibit pronounced optical absorption changes upon self‐assembly, because of charge‐transfer interactions or conformation changes. The extent of dye aggregation (and therewith the optical absorption characteristics) in these blends is significantly influenced by exposure to external stimuli. Subjecting appropriately processed samples to either temperatures above their glass transition or mechanical deformation can significantly change the extent of aggregation, which in turn leads to a color change.

Mechano‐optical response of a 1.0% w/w LLDPE/C18‐RG blend film. Pristine films are orange due to aggregated dye molecules. Deformation leads to dispersion of the dye and irreversibly changes the color to yellow.     

Synthesis and Hierarchical Self‐Assembly of Diphenylalanine‐Based Homopolymer and Copolymers By RAFT Polymerization

Dipeptide diphenylalanine has attracted significant research interests because of its ability to self‐assemble into various nanostructures such as nanotubes, nanowires, and nanoribbons. In this article, we present the synthesis and self‐assembly of a novel diphenylalanine‐based homopolymer and block/random copolymers by the reversible addition–fragmentation chain transfer (RAFT) polymerization of an acrylamide having a dipeptide moiety. The RAFT polymerization of N‐acryloyl‐l ,l ‐diphenylalanine (A‐Phe‐Phe‐OH) afforded novel amino acid‐based polymers with predetermined molecular weights and relatively narrow‐molecular weight distributions. The hierarchical self‐assembled structures of poly(A‐Phe‐Phe‐OH), which involve nanorods, larger nanofiber‐like microcrystals, and fiber bundles, were characterized by atomic force microscopy (AFM), transmission electron microscopy, scanning electron microscopy, and dynamic light scattering measurements. The circular dichroic measurements of poly(A‐Phe‐Phe‐OH) revealed its characteristic chiroptical property, which is affected by the nature of the solvents and the addition of urea and salts via hydrophobic, hydrogen bonding, and electrostatic interactions. Thermo‐ and pH‐responsive block and random copolymers composed of A‐Phe‐Phe‐OH and N‐isopropylacrylamide were synthesized by RAFT polymerization, and the thermoresponsive properties and assembled structures of the resulting copolymers were investigated by AFM and turbidity measurements. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 2562–2574     

Reduction and pH dual‐responsive block copolymers containing pendent p‐nitrobenzyl carbamate functionalities: Synthesis and self‐assembly behavior

We report on the preparation of reduction‐responsive amphiphilic block copolymers containing pendent p‐nitrobenzyl carbamate (pNBC)‐caged primary amine moieties by reversible addition–fragmentation chain transfer (RAFT) radical polymerization using a poly(ethylene glycol)‐based macro‐RAFT agent. The block copolymers self‐assembled to form micelles or vesicles in water, depending on the length of hydrophobic block. Triggered by a chemical reductant, sodium dithionite, the pNBC moieties decomposed through a cascade 1,6‐elimination and decarboxylation reactions to liberate primary amine groups of the linkages, resulting in the disruption of the assemblies. The reduction sensitivity of assemblies was affected by the length of hydrophobic block and the structure of amino acid‐derived linkers. Using hydrophobic dye Nile red (NR) as a model drug, the polymeric assemblies were used as nanocarriers to evaluate the potential for drug delivery. The NR‐loaded nanoparticles demonstrated a reduction‐triggered release profile. Moreover, the liberation of amine groups converted the reduction‐responsive polymer into a pH‐sensitive polymer with which an accelerated release of NR was observed by simultaneous application of reduction and pH triggers. It is expected that these reduction‐responsive block copolymers can offer a new platform for intracellular drug delivery. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1333–1343     

Polymer Nanoparticles Based on Pyrene‐Functionalized Poly(acrylic acid) for Controlled Release under Photo and pH Stimulation

A novel photo and pH‐responsive amphiphilic pyrene‐functionalized polymer is synthesized by the esterification reaction between poly(acryloyl chloride) and pyrenemethanol and subsequent hydrolysis of the unreacted acylchloride groups. This random copolymer consists of hydrophobic pyrene‐containing acrylate units and hydrophilic acrylic acid units, which can self‐assemble into nanoparticles in water. Under UV irradiation, the nanoparticles can be disrupted with decreasing particle number resulted from the photolysis of pyrenylmethyl esters, where the hydrophobic segments are converted to hydrophilic acrylic acids; at low pH, the acrylic acid segments are protonated and collapsed, thus the nanoparticles will be shrunk and aggregated; at high pH, the nanoparticles change to fractal structures owing to the aggregation of partially dissociated nanoparticles and the subsequent structural reorganization of the clusters. The controlled release of Nile Red from the nanoparticles stimulated by photo and pH separately and synergistically is demonstrated. The nanoparticles self‐assembled from the dual‐stimuli‐sensitive polymer can be used as a new nanocarrier and find their applications in delivery system.

     

Stimulus‐responsive polymers based on 2‐hydroxypropyl acrylate prepared by RAFT polymerization

Homopolymerization and diblock copolymerization of 2‐hydroxypropyl acrylate (HPA) has been conducted using reversible addition fragmentation chain transfer (RAFT) chemistry in tert‐butanol at 80 °C. PHPA homopolymers were obtained with high conversions and narrow molecular weight distributions over a wide range of target degrees of polymerization. Like its poly(2‐hydroxyethyl methacrylate) isomer, PHPA homopolymer exhibits inverse temperature solubility in dilute aqueous solution, with cloud points increasing systematically on lowering the mean chain length. The nature of the end groups is shown to significantly affect the cloud point, whereas no effect of concentration was observed over the PHPA concentration range investigated. Various thermoresponsive PHPA‐based diblock copolymers were prepared via one‐pot syntheses in which the second block was either permanently hydrophilic or pH‐responsive. Preliminary studies confirmed that poly(ethylene oxide)‐poly(2‐hydroxypropyl acrylate) (PEO₄₅‐PHPA₄₈) and poly(2‐hydroxypropyl acrylate)‐ poly(2‐hydroxyethyl acrylate) (PHPA₄₉‐PHEA₆₈)diblock copolymers formed well‐defined PHPA‐core micelles in 10 mM sodium nitrate solution at 40 °C and 70 °C with mean hydrodynamic diameters of 20 nm and 35 nm, respectively. In contrast, most other PHPA‐based diblock copolymers investigated formed larger colloidal aggregates in 10 mM NaNO₃ solution at elevated temperatures. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2032–2043, 2010