ATRP synthesis and association properties of thermoresponsive anionic block copolymers

Thermosensitive anionic block copolymers of sodium 2‐acrylamido‐2‐methylpropanesulfonate (AMPS) and N‐isopropylacrylamide (NIPAAM) with different block lengths were prepared by atom transfer radical polymerization (ATRP). Controlled polymerization was achieved by using ethyl 2‐chloropropionate (ECP) as initiator and CuCl/CuCl₂/tris(2‐dimethylaminoethyl)amine (Me₆TREN) catalytic system in DMF:water 50:50 (v/v) mixtures at 20 °C. Blocks lengths ranging from 36 to 98 repeating units were obtained. The association properties in aqueous solutions at different NaCl ionic strengths were studied as a function of temperature and polymer concentration by dynamic light scattering, fluorescence spectroscopy, and energy‐filtered transmission electron microscopy. The block copolymers with a higher pNIPAAM/pAMPS ratio formed spherical core‐shell type micelles independently of the ionic strength. The block copolymers with lower pNIPAAM/pAMPS ratio formed core‐shell type micelles at high ionic strength. Larger particles were observed at low ionic strength, which could be due to the formation of vesicles or compound micelles/micellar clusters. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4830–4842, 2008     

Temperature-controlled photosensitization properties of benzophenone-conjugated thermoresponsive copolymers

We previously found that a copolymer, poly(NIPAM- co-BP), consisting of N-isopropylacrylamide (NIPAM) and benzophenone (BP) units, behaves as a photosensitizer showing temperature-controlled oxygenation activity by singlet oxygen ( (1)O 2) in water ( J. Am. Chem. Soc. 2006, 128, 8751-8753 ). This polymer shows a heat-induced oxygenation enhancement at <20 degrees C, while showing suppression at >20 degrees C. This is driven by a heat-induced phase transition of the polymer from coil to micelle and then to globule state, controlling the stability and diffusion of (1)O 2 and the location of substrate. In the present work, effects of polymer concentration and BP content of the polymer on the oxygenation activity were studied at 5-35 degrees C. Increase in the polymer concentration leads to activity decrease at >20 degrees C due to strong polymer aggregation, suppressing incident light absorption of the BP units. With a decrease in BP content of the polymer, heat-induced oxygenation enhancement at <20 degrees C is more pronounced because formation of small size micelles accelerates (1)O 2 oxygenation. The obtained findings reveal that the polymer with low BP content, when used at high concentration, shows clear-cut off- on- off activity change against the temperature window: very low activity at <5 degrees C and >25 degrees C, and very high activity at middle temperature range.     

Flocculation‐resistant multimolecular micelles with thermoresponsive corona from dendritic heteroarm star copolymers

In this article, we report the self‐assembly of flocculation‐resistant multimolecular micelles with thermoresponsive corona from novel dendritic heteroarm star copolymers. The micelles have a core‐shell‐corona structure at room temperature according to pyrene probe fluorescence spectrometry, proton nuclear magnetic resonance (¹H NMR), transmission electron microscopy, and dynamic light scattering measurements. Increasing the temperature above the lower critical solution temperature (LCST), the micelles show high flocculation‐resistant ability resulting from a structure transition from core‐shell‐corona to core‐shell confirmed by a quantitative variable temperature ¹H NMR analysis method using potassium hydrogen phthalate as an external standard. A big volume change of the micelles is observed during the LCST transition. The drug loading and temperature‐dependent release properties of the micelles are also investigated by using coumarin 102 as a model drug, which displays a rapid drug release at a temperature above the LCST. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

pH triggered self-assembly of core cross-linked star polymers possessing thermoresponsive cores

Core cross-linked star polymers possessing responsiveness to pH and temperature stimuli have been prepared, and we demonstrate how changes to pH and temperature can be used to trigger the release and uptake of a hydrophobic dye.     

Functionalization of magnetic nanoparticles with amphiphilic block copolymers: self-assembled thermoresponsive submicrometer particles

For the first time the four block copolymers derived from 1-alkyl[2-(acryloyloxy)ethyl]dimethylammonium bromides with hexyl (ADA) or cetyl (ADHA) groups and 2-hydroxyethylacrylate (HEA) or N-isopropylacrylamide (NIPAM) were synthesized and employed for functionalization of monodisperse iron oxide nanoparticles (NPs). The polyADA (pADA) or polyADHA (pADHA) block consists of long hydrophobic tails (C(6) or C(16)) connected to a positively charged quaternary ammonium group, making this block amphiphilic. The second block was either fully hydrophilic (pHEA) or thermoresponsive (pNIPAM). The dependence of the NP coating on the length of the hydrophobic tail in the amphiphilic block, the composition of the hydrophilic block, and the NP sizes have been studied. Unusual self-assembling of iron oxide NPs into well-defined composite submicrometer particles was observed for pADHA-b-pNIPAM in the wide range of concentrations (at the pADHA repeating unit concentrations of 0.065 × 10(-2)-2.91 × 10(-2) mmol/mL per 1 mg/mL NPs) but only two concentrations, 1.62 × 10(-2) and 1.94 × 10(-2) mmol/mL, led to regular spherical particles. The thermoresponsive behavior of these composite particles was tested using ζ-potential and dynamic light scattering measurements, while the morphology of particles was characterized by transmission electron microscopy. Coating of NPs with pADHA-b-pHEA results in the formation of individually coated NPs. The different composite particle morphologies are explained by different properties of pHEA and pNIPAM. It is demonstrated that the composite particles based on pADHA-b-pNIPAM are responsive to a magnetic field and can be recommended as magnetic stoppers in biorelated membrane separations. The incorporation of Pd species in submicrometer particles makes them promising candidates for catalytic applications as magnetically recoverable catalysts with a high magnetic response.     

Synthesis of new siloxane urethane block copolymers and their properties

Siloxane urethane block copolymers were prepared with siloxanes as the soft segment. Films were cast from a variety of solvents. Solvent has an effect on the segregation of soft and hard segments. Surface studies, including ESCA, EDS, and FT-IR, show well segregated block copolymers with enhanced siloxane on the surface. DSC studies show a low mp (-44°C) for the soft segment and a T_g for the hard segment above room temperature. These materials show higher thermal stability compared to polyether urethane block copolymers. These copolymers also show relatively good resistance to exposure to oxygen plasma and show improved flame retardancy compared to nonsiliconated, polyether polyurethane block copolymers. © 1994 John Wiley & Sons, Inc.     

Shell-crosslinked nanoparticles through self-assembly of thermoresponsive block copolymers by RAFT polymerization

A reversible addition-fragmentation chain transfer (RAFT) agent, the methyl-2-(n-butyltrithiocarbonyl)propanoate (MBTTCP) has shown to be efficient in controlling the polymerization of N,N-dimethylacrylamide (DMA), N-isopropylacrylamide (NIPAM) and N-acryloyloxysuccinimide (NAS). Two different strategies have been studied to synthesize block copolymers based on one PNIPAN block and the other a random copolymer of DMA and NAS. When a PNIPAM trithiocarbonate-terminated is used as macromolecular chain transfer agent for the polymerization of a mixture of NAS and DMA, well-defined P(NIPAM-b-(NAS-co-DMA)) block copolymers were obtained with a low polydispersity index. These thermoresponsive block copolymers dissolved in aqueous solution at 25 °C and self-assembled into micelles when the temperature was raised above the LCST of the PNIPAM block. The micelle shell containing NAS units was further crosslinked using a primary diamine in order to get shell-crosslinked nanoparticles. Upon cooling below the LCST of PNIPAM this structure may easily reorganize to form nanoparticles with a water filled hydrophilic core.     

Synthesis and aqueous solution properties of functionalized and thermoresponsive poly(D,L-lactide)/polyether block copolymers

Tri- and pentablock amphiphilic copolymers containing hydrophobic poly(D,L-lactide) block(s) and hydrophilic polyethers were synthesized in order to obtain new precursor architectures suitable for drug delivery systems. Polyglycidol-6-poly(ethylene oxide)-b-poly(D,L-lactide) possess high hydroxyl functionality provided by the linear polyglycidol block. Thus very stable hydroxyl functionalized micelles in aqueous media were obtained. On the other hand poly(D,L-lactide)-b-poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide)-b-poly(D,L-lactide) form temperature sensitive aggregates. The copolymers obtained were analyzed by SEC and NMR, and their aqueous solution properties were followed by cloud point measurements and determination of critical micellization temperature. TEM was used for particles visualization.     

Synthesis of novel multi-arm star azobenzene side-chain liquid crystalline copolymers with a hyperbranched core

A series of novel multi-arm star side-chain liquid crystalline (LC) copolymers with hyperbranched core moieties were synthesized by atom transfer radical polymerization (ATRP) using a multi-functional hyperbranched polyether as the initiator and chlorobenzene as the solvent. The multi-functional hyperbranched polyether initiator was prepared from poly(3-ethyl-3-(hydroxymethyl)oxetane) (PEHO) and 2-bromo-2-methylpropionyl bromide. The azobenzene side-chain liquid crystalline arms were designed to have an LC conformation of poly[6-(4-methoxy-4^′-oxy-azobenzene)hexyl methacrylate] with different molecular weights. Their characterization was performed with ¹H NMR, size exclusion chromatograph (SEC), differential scanning calorimetry (DSC) and thermal polarized optical microscopy (POM). The multi-arm star side-chain liquid crystalline copolymers exhibited a smectic and a nematic phase, and the phase transition temperatures from the smectic to the nematic phase and from the nematic to isotropic phase increased with increasing the molecular weight of the multi-arm star side-chain liquid crystalline copolymers from 1.78 × 10⁴ to 9.07 × 10⁴.     

Synthesis of three‐arm star block copolymers

We describe the synthesis and characterization of three‐arm star block copolymers based on polystyrene, poly(ethylene oxide), poly(ϵ‐caprolactone), poly(methyl methacrylate), poly(tert‐butyl methacrylate) and poly(L‐lactide) blocks. The copolymers were obtained by a route consisting of two successive initiation steps on functional macroinitiator. Some results on micellization and crystallization are given. They indicate an increase in the miscibility of different incompatible blocks.     

End group polarity and block symmetry effects on cloud point and hydrodynamic diameter of thermoresponsive block copolymers

Thermoresponsive block copolymers are of interest for delivery vehicles in the body. Often an interior domain is designed for the active agent and the exterior domain provides stability in the bloodstream, and may carry a targeting ligand. There is still much to learn about how block sequence and chain end identity affect micelle structure, size, and cloud points. Here, hydrophilic oligo(ethylene glycol) methyl ether acrylate and more hydrophobic di(ethylene glycol) methyl ether methacrylate monomers were polymerized to give amphiphilic block copolymers with amphiphilic chain ends. The block sequence and chain end identity were both controlled by appropriate choice of RAFT chain transfer agents to study the effect of ‘matched’ and ‘mismatched’ chain end polarity with amphiphilic block sequence. The affect of matching or mismatching chain end polarity and block sequence was studied on the hydrodynamic diameter, cloud point, and temperature range of the chain collapse on linear di‐ and triblock copolymers and star diblock polymers. The affects of matching or mismatching chain end polarity were significant with linear diblock copolymers but more complex with triblock and star copolymers. Explanations of these results may help guide others in designing thermoresponsive block copolymers. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2838–2848     

Synthesis of A2B star block copolymers from a heterotrifunctional initiator

We described the obtention of A₂B star block copolymers through the use of a new heterotrifunctional initiator. That way, well‐defined (PCL)₂‐arm‐PtBuMA and (PCL)₂‐arm‐PS star block copolymers have been synthesized from a heterotrifunctional initiator bearing two hydroxyl groups able to initiate ROP of CL (with AlEt₃ or Sn(Oct)₂ as coinitiator) and a bromide function able to initiate ATRP of tBuMA or styrene. Firstly, we have proceeded using a sequential process (two‐steps), leading to an intermediate macroinitiator. Secondly, attempt to polymerize these two monomers in a simultaneous process (one‐step), that is directly from the mixture of monomers, initiator, coinitiators, and solvent, has been realized and has shown that some interferences between the two polymerizations occurred, leading to an inhibition of ATRP when Sn(Oct)₂ was used and an unexpected increase in control when AlEt₃ was used as catalyst for the ROP (obtention of well‐defined (PCL)₂‐arm‐PtBuMA with pdi of 1.18). © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1796–1806, 2006     

Poly(ether amide) triblock and star block copolymers

Triblock and three arm, poly(ether amide) star block copolymers have been synthesized and characterized. Di- and tri-functional amine terminated polyethers were reacted with caprolactam at elevated temperatures to produce the block copolymers. The polyether amines were incorporated at levels ranging from 5%-40%. Differential scanning calorimetry(DSC) evaluation reveals no reduction in the crystalline melting point of the polycaprolactam end blocks up to 40% polyether incorporation. Dynamic mechanical spectroscopy and FTIR were used to confirm the incorporation of the polyether. A comparison is made between triblock and star block copolymers, and between poly(propylene glycol) and poly(ethylene glycol) polyether midblocks. These block copolymers have improved impact performance as well as a flexural modulus that first increases and then decreases as the amount of polyether is increased in the block copolymer.     

Multiarm star block and multiarm star mixed‐block copolymers via azide‐alkyne click reaction

The synthesis of multiarm star block (and mixed‐block) copolymers are efficiently prepared by using Cu(I) catalyzed azide‐alkyne click reaction and the arm‐first approach. α‐Silyl protected alkyne polystyrene (α‐silyl‐alkyne‐PS) was prepared by ATRP of styrene (St) and used as macroinitiator in a crosslinking reaction with divinyl benzene to successfully give multiarm star homopolymer with alkyne periphery. Linear azide end‐functionalized poly(ethylene glycol) (PEG‐N₃) and poly (tert‐butyl acrylate) (PtBA‐N₃) were simply clicked with the multiarm star polymer described earlier to form star block or mixed‐block copolymers in N,N‐dimethyl formamide at room temperature for 24 h. Obtained multiarm star block and mixed‐block copolymers were identified by using ¹H NMR, GPC, triple detection‐GPC, atomic force microscopy, and dynamic light scattering measurements. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 99–108, 2010     

Synthesis of block and star copolymers by photoinduced radical coupling process

The general design for the synthesis of AB diblock, and A₂B and AB₂ star copolymers based on the statistical coupling of poly(styrene) (PSt) and poly (methyl methacrylate) (PMMA) macromolecules containing photoreactive benzophenone is presented. For this purpose, mono- and bifunctional initiators for Atom Transfer Radical Polymerization (ATRP) bearing benzophenone group were synthesized and characterized. End- and mid-chain benzophenone functional PSt and PMMA with low molecular weights were obtained by ATRP using these initiators in the presence of CuBr/N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA) catalytic complex. Poly(styrene-block-methyl methacrylate) (PSt-b-PMMA) copolymers were prepared by photolysis of the solutions containing end functional PSt and PMMA in THF at λ = 350 nm for 60 min in the presence of a hydrogen donor such as N-methyldiethanolamine (NMDEA). The proposed mechanism assumes hydrogen abstraction of photoexcited benzophenone moiety by NMDEA. Ketyl radicals resulting from abstraction reaction undergo radical-radical coupling to form benzpinacol structure at the core. Formation of A₂B and AB₂ type star copolymers upon irradiation of solutions containing appropriate combinations of end- and mid-chain functional polymers was also demonstrated. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2938–2947, 2009     

Synthesis of well-defined star block copolymers using 1,1-diphenylethylene chemistry

We described the use of 1,1 diphenylethylene derivatives in the synthesis of well-defined star block copolymers. Classical end-capping of polystyryl carbanion with −CH₂CH₂OTBDMSi derivative gives a heterobifunctional macroinitiator leading to ABC star block copolymers through successive anionic and ring opening polymerizations (ROP) or anionic and atom transfer radical (ATRP) polymerizations. An unexpected reaction between polystyryl carbanion and −CH₂OTBDMSi derivative, strongly depending on the medium polarity, opens an easy way to either A₂B or A₃B star block copolymers.     

Ionic effects on the behavior of thermoresponsive PEO–PNIPAAm block copolymers

The temperature‐dependent aggregation and recovery of the copolymer poly(ethylene oxide)₂₂‐b‐poly(N‐isopropylacrylamide)₂₉ with a C₁₂ end‐cap in aqueous solutions of salts and acids are investigated. Salt solutions affected the critical aggregation temperature of the copolymer in a manner predictable according to the Hofmeister series, with the kosmotropic adipic ion lowering the critical aggregation temperature and the chaotropic iodide raising it. Also, both salts and acids increased the size of copolymer aggregates formed with heating, due to the electrostatic shielding of aggregated structures provided by the electrolytes. Additionally, the presence of ionic additives caused a thermohysteretic increase in the size of copolymer aggregates with temperature cycling. The transitions of polymer structure with increasing temperature were surprisingly sharp with the C₁₂ end‐cap present, and particularly broad in samples in which the end cap had been cleaved. This observation suggested that the hydrophobic end group was responsible for imparting some degree of order to the polymer at low temperatures, which allowed for rapid reconfiguration with increasing temperature. Finally, in addition to the transitions expected from the least critical solution temperature behavior of the polymer blocks, we have observed an unexpected additional transition which we attribute to the contraction of the poly(ethylene oxide) chains of the copolymer aggregates at higher temperatures. This work illustrates the importance of considering the environment and composition of thermoresponsive block copolymers in certain applications, particularly in solutions with even modest electrolyte concentrations (1–10 mM), as it can have a profound effect on transition temperatures and morphology. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 507–516     

Amphiphilic star copolymers containing cyclodextrin core and their application as nanocarrier

Amphiphilic copolymers containing β-cyclodextrin (β-CD) core were synthesized successfully. Synthesis was initiated from tosylated cyclodextrin ((Tosyl)₇-β-CD) which is containing two types of functional groups. Hydroxyl functional groups of (Tosyl)₇-β-CD were used as initiator for ring opening polymerization of lactide. This step led to star polymers containing tosylated cyclodextrin core and polylactide arms (PLA-(Tosyl)₇-β-CD). In the next step, tosyl groups of PLA-(Tosyl)₇-β-CD were used as initiator for ring opening polymerization of 2-ethyl-2-oxazoline and amphiphilic copolymers containing cyclodextrin core, PLA and poly(2-ethyl-2-oxazoline) arms (PLA-β-CD-POX) were obtained. Loading of Congo red as guest molecule by amphiphilic copolymers was investigated. The release of guest molecule from chloroform solution of copolymers to water phase was also investigated.     

Interpolyelectrolyte complexes of soybean peroxidase with thermoresponsive copolymers

Interpolyelectrolyte complexes of soybean peroxidase with thermoresponsive N-isopropylacrylamide-sodium styrenesulfonate copolymers of various compositions are studied by the methods of high-sensitivity differential scanning calorimetry, velocity sedimentation, and nephelometry. It is shown that the enzyme preserves its tertiary structure in complexes, although the conformational stability of bound protein is lower than that of free protein. Complexes of any compositions, including stoichiometric complexes, are soluble at room temperature but precipitate during heating in the region of the conformational transition of the copolymer accompanied by formation of the complex gel. Isotherms of enzyme binding by complex gels are constructed, and their analysis makes it possible to reveal two types of binding in the system: a relatively strong stoichiometric binding of the enzyme with the copolymers and a weaker binding of the protein in the coacervate phase of the complex gel. A high yield of the protein in the complex gel, reversibility of binding, and preservation of the tertiary structure of the enzyme in complexes with the copolymers make protein-thermoresponsive polyelectrolyte systems promising for bioseparation.