Reverse thermo-responsive poly(ethylene oxide) and poly(propylene oxide) multiblock copolymers

Aiming at developing new reverse thermo-responsive polymers, poly(ethylene oxide)-poly(propylene oxide) multiblock copolymers were synthesized by covalently binding the two components using carbonyl chloride and diacyl chlorides as the coupling molecules. The appropriate selection of the various components allowed the generation of systems displaying much enhanced rheological properties. For example, 15 wt% aqueous solutions of an alternating poly(ether-carbonate) comprising PEO6000 and PPO3000 segments, achieved a viscosity of 140,000 Pas, while the commercially available Pluronic F127 displayed 5,000 Pas only. Furthermore, the structure of the chain extender played a key role in determining the sol-gel transition. While poly(ether-ester)s containing therephtaloyl (para) and isophtaloyl (metha) coupling units failed to gel at any concentration, a 15 wt% aqueous solution of the polymer chain-extended with phtaloyl chloride (ortho) gelled at 43 degrees C. The water solutions were also studied by dynamic light scattering and a clear influence of the PEO/PPO ratio on the aggregate size was observed. By incorporating short aliphatic oligoesters into the backbone, prior to the chain extension stage, reverse thermal gelation-displaying biodegradable poly(ether-ester-carbonate)s, were generated.     

Biodegradable poly(ethylene oxide)/poly(epsilon-caprolactone) multiblock copolymers.

A series of poly(ethylene oxide) (PEO)/poly(epsilon-caprolactone) (PCL) containing biodegradable poly(ether ester urethane)s, covering a wide range of compositions, were synthesized and characterized. The synthesis consisted of a two-step process. During the first step, the ring-opening reaction of epsilon-caprolactone was carried out, initiated by the hydroxyl terminal groups of the PEO chain. The second step involved the chain extension of these PCL-PEO-PCL trimers with hexamethylene diisocyanate. By varying either the ethylene oxide/epsilon-caprolactone ratio or the length of both segments, we obtained a series of polymers having different morphologies and displaying a broad range of properties.     

Synthesis and characterization of poly(ethylene oxide) and poly(perfluorohexylethyl methacrylate) containing triblock copolymers

A new series of poly(perfluorohexylethyl methacrylate)‐block‐poly(ethylene oxide)‐block‐poly(perfluorohexylethyl methacrylate), PFMA‐b‐PEO‐b‐PFMA triblock copolymers has been synthesized by atom transfer radical polymerization using bifunctional PEO macroinitiators. The molecular structure of the block copolymers was confirmed by ¹H NMR spectroscopy and SEC. X‐ray scattering studies have been carried out to investigate their bulk properties. SAXS has shown cubic arrangement of spheres (bcc), hexagonally packed cylinders (hpc) and lamellar microdomain formation in the melt of triblock copolymers investigated, depending on composition. Crystallization was, however, found to destroy the ordered melt morphology and imposes a lamellar crystalline structure. WAXS, DSC and polarized light microscopy measurements confirmed the crystallization of PEO segments in block copolymers. Long PFMA blocks were found to have significant effect on PEO crystallization.

Synthesis of triblock copolymers of EO and FMA by ATRP.     

Adhesion behavior of rat lymphocytes on poly(γ-benzyl L-glutamate) derivatives having hydroxyl groups or poly(ethylene glycol) chains

Poly[γ-benzyl L -glutamate (BLG)-co-N⁵-(3-hydroxypropyl)-L -glutamine (HLG)] ( 3 ) and polyBLG/poly(ethylene glycol) (PBLG/PEG) block copolymers ( 6 ) were synthesized, and the adhesion behavior of rat lymphnode lymphocytes on these polymers was examined by the column method. An increase in the HLG content of polymer 3 caused a slight decrease in lymphocyte adhesivity. Lymphocyte subpopulation B cells were found to be more adhesive to polymers 3 than T cells, by a factor of 1,4 – 1,6. On the other hand, an increase in the PEG content of PBLG/PEG block copolymer caused a remarkable decrease inlymphocyte adhesivity and an increase in selectivity in the adhesivity between B cells and T cells up to a factor of 2,3.     

Influence of poly(ethylene oxide)‐poly(propylene oxide)‐poly(ethylene oxide) triblock copolymers on stereoselective catalysis in water

The first application of (EO)_n‐(PO)_m‐(EO)_n triblock copolymers as surfactants in asymmetric hydrogenation is described. We observed a dependence of the activity and enantioselectivity on the asymmetric hydrogenation of methyl (Z)‐α‐acetamidocinnamate on the length of the (PO)_m domain of the copolymer. The activity and enantioselectivity were observed to be independent of the hydrophilic‐lipophilic‐balance (HLB) or the critical micelle concentration (cmc) of the copolymer. The size of the (EO)_n unit does not play an important role, however the addition of a small amount of SDS enhances the enantioselectivities significantly. The triblock copolymers were also successfully used as phase transfer reagent in two‐phase Suzuki carbon‐carbon coupling reactions. The use of polymeric reagents in micellar and phase‐transfer systems has the advantage that these reagents can be easily separated from the reaction mixture by means of a membrane.     

Synthesis and structural study of an ABA block copolymer consisting of poly(γ-benzyl L-glutamate) as the a block and poly(ethylene oxide) as the B block

ABA-type block copolymers composed of poly(γ-benzyl L -glutamate) (PBLG) as the A component and poly(ethylene oxide) (PEO) as the B component were synthesized by polymerization of γ-benzyl L -glutamate N-carboxyanhydride initiated by primary amines located at both ends of the PEO chain. The morphology examined by transmission electron microscopy using ruthenium tetroxide staining revealed a lamellar type of microphase separation of the copolymers. From circular dichroism measurements in ethylene dichloride solution, as well as from infrared spectra measurements in the solid state, it was found that the polypeptide block exists in the α-helical conformation, as in PBLG homopolymer. Wide-angle X-ray diffraction patterns for the block copolymers depend on the casting solvent and show basically similar reflections as the PBLG homopolymer.     

Synthesis and characterization of new ABA triblock copolymers with poly[3(S)-isobutylmorpholine-2,5-dione] and poly(ethylene oxide) blocks

ABA type block copolymers with poly[3(S)-isobutylmorpholine-2,5-dione] (PIBMD, A) and poly(ethylene oxide) (M_n = 6 000, PEO, B) blocks, PIBMD-b-PEO-b-PIBMD, were synthesized via ring-opening polymerization of 3(S)-isobutylmorpholine-2,5-dione in the presence of hydroxytelechelic poly-(ethylene oxide) with stannous octoate as a catalyst. M_n of the resulting copolymers increases with increasing 3(S)-isobutylmorpholine-2,5-dione content in the feed at constant mole ratio of monomer (M) to catalyst (C) (M/C = 125). No racemization of the leucine residue takes place during both homopolymerization of IBMD and polymerization of IBMD in the presence of PEO and Sn(Oct)₂. The melting temperature of the PIBMD segments in the block copolymers depends on the length of the PIBMD blocks. The melting temperature of the PEO blocks is lower than that of the homopolymer, and the crystallinity of the PEO block decreases with increasing length of the PIBMD blocks. The PIBMD block crystallizes first upon cooling from the melt. This leads to only imperfect crystallization or no crystallization of the PEO blocks.     

Biodegradable random copolypeptides of β-benzyl L-aspartate and γ-methyl L-glutamate for the controlled release of testosterone

The random copolypeptides of β-benzyl L -aspartate (β-Bz L -Asp) and γ-methyl L -glutamate (γ-Me L -Glu) were synthesized and implanted subcutaneously in rats. It was found that the resulting copolypeptides are degraded and also have good biocompatibility in vivo. On the basis of these results, poly(β-Bz L -Asp-co-γ-Me L -Glu) was tried to be used as a material for a drug delivery system. Copolypeptide-testosterone composites were prepared at a pressure of 200 kg/cm² in the presence of a slight amount of dichloroethane. The in vivo release rate of testosterone from copolypeptide-drug composites was about 5,5 times higher than that in vitro. The in vivo release rate remained relatively constant over a period of 90 days at 0,22 mg/day. The serum testosterone concentration in castrated rats was 0,40 ng/ml and the value went up to 6,8 ng/ml after the biodegradable copolypeptide-testosterone composite was implanted and was kept constant for the duration of test.     

In vitro and ex vivo platelet interactions with hydrophilic-hydrophobic poly(ethylene oxide)-polystyrene multiblock copolymers

Hydrophilic-hydrophobic multiblock copolymers synthesized from telechelic oligomers of poly(ethylene oxide) (PEO) and polystyrene (PS) have been used to study the influence of hydrophilic and hydrophobic balance on interfacial interactions of these surfaces with blood components. In vitro coagulation assays show no inherent ability of these amphiphilic surfaces to affect contact activation or coagulation factors. In vitro platelet adhesion and release reactions from rabbit platelet-rich plasma were shown to be greatest on Biomer and PS homopolymer surfaces and least on cross-linked PEO surfaces, with the PEO-PS block copolymers demonstrating intermediate responses. These same substrates were tested in a new low-flow, low-shear arterio-artery shunt system in rabbits. Whole blood occlusion times were not a direct function of hydrophilic content as both PEO and PS homopolymers and Biomer showed short occlusion times, while PEO-PS block copolymers prolonged occlusion times considerably, depending on composition. Overall, results suggest that PEO-PS block copolymers promote unique whole blood responses in contrast to homopolymer and Biomer controls which are more complex than direct correlations to bulk hydrophilic and hydrophobic contents.     

Synthesis of chromophore-labelled polystyrene/poly(ethylene oxide) diblock copolymers

Polystyrene/poly(ethylene oxide) diblock copolymers bearing anthracene or phenanthrene groups at the block junctions were synthesized by sequential anionic polymerization using cumylpotassium as initiator. Labelled copolymers were characterized by means of ultraviolet (UV) spectroscopy, gel-permeation chromatography (GPC) and ¹H NMR spectroscopy. The solutions of the prepared copolymers in water and 1,2-dichloroethane/methanol mixtures were studied by fluorescence spectroscopy. The intermolecular energy transfer process confirms the presence of organized structures (micelles) in solutions.     

Synthesis and properties of well-defined multiblock copolymers: poly(4,4′-isopropylidenediphenyl carbonate)-block-polystyrene

Well-defined poly(4,4′-isopropylidenediphenyl carbonate)-block-polystyrene multiblock copolymers, PC-b-PS, were prepared by condensation of PC prepolymers having chloroformyl end-groups with PS prepolymers having hydroxyl end-groups. Both prepolymers had narrow molecular weight distribution (PC prepolymer: M?_w/M?_n ≤ 1,31, PS prepolymer: M?_w/M?_n ≤ 1,03). The course of the polycondensation reaction depends on the molecular weight of the prepolymers used as substrates. After fractionation, the obtained multiblock copolymers are homogeneous in chemical composition and have a narrow molecular weight distribution. The mechanical properties of the copolymers depend on the weight fraction of the PS blocks. All copolymers exhibit two glass transition temperatures, close to those of the parent homopolymers.     

Control of vitamin B12 release from poly(ethylene glycol)/poly(butylene terephthalate) multiblock copolymers

The release of vitamin B12 (1355 Da) from matrices based on multiblock copolymers was studied. The copolymers were composed of hydrophilic poly(ethylene glycol)-terephthalate (PEGT) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Vitamin B12 loaded films were prepared by using a water-in-oil emulsion method. The copolymer properties, like permeability, could be varied by increasing the PEG-segment length from 300 up to 4,000 g/mol and by changing the wt% of PEGT. From permeation and release experiments. the diffusion coefficient of vitamin B12 through PEGT/PBT films of different compositions was determined. The diffusion coefficient of Vitamin B12 was strongly dependent on the composition of the copolymers. Although an increased wt% of PEGT (at a constant PEG-segment length) resulted in a higher diffusion coefficient, a major effect was observed at increasing PEG-segment length. By varying the copolymer composition, a complete release of vitamin B12 in 1 day up to a constant release for over 12 weeks was obtained. The release rate could be effectively tailored by blending copolymers with different PEG-segment lengths. The swelling and the crystallinity of the matrix could explain the effect of the matrix composition on the release behavior.     

Controlled synthesis of α,β-difunctional poly(hexafluoropropylene oxide)

An improved method is described for the preparation of difunctional poly(hexafluoropropylene oxide) of moderate molecular weight (M _n ≈ 6000) in good yield (>80 wt.-%). With the dependence of chain transfer constant on initiator concentration known, at least under controlled conditions, good molecular-weight control can be achieved.     

Synthesis and characterization of multiblock copolymers poly[poly(L-lactide)-block-polydimethylsiloxane]

The preparation of multiblock copolymers poly[poly(L -lactide)-block-polydimethylsiloxane] by polycondensation of bifunctional oligomers via hydrosilylation is described. The procedure consists first to synthesize the two bifunctional oligomers α,ω-disilyl-polydimethylsiloxane and α,ω-diallyl-poly(L -lactide). The former is prepared in one step by cationic polymerization of octamethylcyclotetrasiloxane in the presence of 1,1,3,3-tetramethyldisiloxane as end-blocker. Two steps are necessary to prepare α,ω-diallyl-poly(L -lactide). The first one is the polymerization of L-lactide initiated by the system ethylene glycol/tin 2-ethylhexanoate. In a second step, the hydroxyl end-groups of the resulting α,ω-dihydroxy-poly(L -lactide) are transformed, by reaction with allyl isocyanate, into terminal allylic functions. Different multiblock copolymers were prepared by hydrosilylation (catalyzed by hexachloroplatinic acid) using the same α,ω-diallyl-poly(L -lactide) (M?_n = 2000 g · mol ^?1) and various α,ω-disilyl-polydimethylsiloxanes (M?_n from 1 750 to 9 000 g · mol ^?1). The influence of parameters such as temperature, stoichiometry of reactive end-groups and catalyst concentration on the molecular weight of the copolymers was studied. High molecular weight copolymers were obtained (DP_n > 12 by SEC). In addition to the biodegradability of the lactic acid units, the immiscibility of the polydimethylsiloxane and poly(L -lactide) blocks imparts thermoplastic elastomer properties to these copolymers. The crystallinity of the poly(L -lactide) phase is dependent on the molecular weight of the polydimethylsiloxane blocks.     

Gas permeability of the racemic form of poly(γ-benzyl glutamate)

Sorption of carbon dioxide gas by a film of the racemic form of poly(γ-benzyl glutamate) was observed over the temperature range from 10 to 40°C and the permeability coefficient of carbon dioxide gas through the film was measured over the temperature range from 30 to 120°C. Different sorption isotherms were obtained in the ranges above and below the glass-like transition temperature, respectively. The result indicates that the sorption behavior is influenced by the side chain mobility. The amount of sorption by the racemic form of poly(γ-benzyl glutamate) does not vary with the intermolecular benzene ring stacking, but is similar to that of the form C of poly(γ-benzyl-L -glutamate) which contains no stacking. The breakdown of the intermolecular benzene ring stacking, which was confirmed by X-ray diffraction analysis and differential scanning calorimetry, results in an abrupt increase of the permeability and the diffusion coefficients, and conversely the formation of the stacking leads to an abrupt decrease in the permeability and the diffusion coefficients. Below the transition temperature, the permeability coefficient of the racemic form of poly(γ-benzyl glutamate) is smaller than that of the forms A, B, and C of poly(γ-benzyl-L -glutamate), related to the benzene ring stacking. The diffusion coefficient was estimated from the free volume theory, and the calculated value was compared with the value obtained from the permeability and the solubility coefficients. The fractional free volume was estimated to be about 0,068, when the best fit between the experimental and the calculated diffusion coefficients was obtained by a trial and error method.     

Nucleation and crystallization of blends of poly(propylene) and ethylene/α‐olefin copolymers

In this work, the nucleation and crystallization of immiscible blends of poly(propylene) (PP) with ethylene/α‐olefin copolymers of different branching contents (Linear Low Density Poly(ethylene), LLDPE, Very Low Density Poly(ethylene), VLDPE, and Ultra Low Density Poly(ethylene), ULDPE) were studied. Melt‐mixed blends of LLDPE/PP, VLDPE/PP and ULDPE/PP were prepared covering a wide composition range by means of twin screw extrusion. Additionally, blends containing 0.1% of the nucleating agent Sorbitol were prepared. The thermal behaviour of the blends was studied by means of Differential Scanning Calorimetry (DSC) whereas the morphology was investigated by means of Scanning Electron Microsopy. When PP droplets constituted the dispersed phase of the blends, fractionated crystallization of the PP component lead to coincident crystallization with the ethylene/α‐olefin matrix, regardless of the branch content of the copolymer. This complex crystallization process occurred when a small fraction of PP droplets initiated the crystallization upon cooling, causing nucleation of the ethylene/α‐olefin copolymer matrix and subsequently simultaneous crystallization of the rest of the PP droplets and the matrix. The fractionated crystallization process disappears if nuclei capable of being active at low supercooling are injected in any of the blends. The injection of nuclei was achieved by the use of sorbitol (a powerful nucleating agent for α‐PP) or by self‐nucleation of the PP component. When PP constituted the matrix in the blends, a nucleation process of the ethylene/α‐olefin copolymers was observed. The nucleation of the ethylene/α‐olefin copolymers by PP, sorbitol or PP/sorbitol mixture was found to be particularly effective for the most linear chains within the wide chain branching distribution present in these copolymers. A peculiar synergistic nucleation effect on LLDPE was produced by the addition of a mixture of PP and sorbitol. Even the addition of 1% PP and 0.1% sorbitol was enough to produce a very strong nucleation effect on the LLDPE, only comparable to that caused by self‐nucleation.     

Controlled synthesis and solution behavior of macrocyclic poly[(styrene)‐b‐(ethylene oxide)] copolymers

A series of cyclic poly[(styrene)‐b‐(ethylene oxide)] diblock copolymers 4 (1.5 kg/mol < M_n < 1.1 kg/mol) with narrow molecular weight distributions (I ≤ 1.12) have been synthesized. They were obtained by intramolecular cyclization of linear α‐diethyl acetal‐ω‐styrenyl poly(styrene ethylene oxide) 3 , under high dilution conditions. The use of well‐defined linear precursors in association with a cyclization process based on an unimolecular end‐to‐end coupling reaction allows the formation of macrocyclic diblocks in high yield (more than 90%). The structural characterization and the solution behavior of both the linear and cyclic amphipathic diblock copolymers have been investigated by means of NMR, size exclusion chromatography, and viscosimetry.     

Effect of ethanol on the asymmetric synthesis catalyzed by poly(5-benzyl L-glutamate) and poly(4-benzyl L-aspartate)

In the asymmetric addition of dodecanethiol ( 1 ) to isopropenyl methyl ketone ( 3 ) catalyzed by the terminal amino group of poly(5-benzyl L -glutamate) (PBLG) ( 7b ) and poly(4-benzyl L -aspartate) (PBLA) ( 7a ), the effect of addition of ethanol was studied. In the reaction catalyzed by PBLG, the magnitude of the optical rotation of the addition product increased without changing the sign with the addition of ethanol. In the reaction catalyzed by PBLA, on the other hand, the sign of the optical rotation of the product was inverted with the addition of ethanol. The effect of ethanol was discussed in relation to the mechanism of the reaction as well as the conformation of the polymeric catalyst.     

Functionalized poly(ε-caprolactone) and copolymers with ethylene oxide through heterogeneous anionic coordinated polymerization. NMR characterization and crystallinity

Functionalized poly(ε-caprolactone)s have been easily prepared by using a new heterogeneous catalytic system consisting of aluminium alcoholate supported on porous silica and the corresponding alcohol in excess. The polymers have been fully characterized by ¹H and ¹³C NMR spectroscopy. Oligo(caprolactone-co-ethylene oxide)s have been synthesized by the same catalytic system. The diad comonomer distribution as obtained by ¹H NMR suggests a blocky structure. In addition, low degrees of crystallization have been determined by means of DSC.