Synthesis of amphiphilic star-shaped and graft copolymers based on polystyrene and poly(ethylene oxide)

Amphiphilic block macromonomers possessing a central unsaturation were synthesized by condensation of polystyrene half-ester of maleic acid {α-[2-(3-carboxyacryloyloxy)ethyl]-ω-sec-butylpoly[1-phenylethylene]} with poly(ethylene glycol) monoether or polystyrene-block-poly(ethylene oxide). In the radical monomer cis-trans-isomerization homopolymerization of the diblock macromonomers, four-to eight-armed amphiphilic star-shaped copolymers were obtained. Radical copolymerization of the diblock macromonomers with styrene led to graft copolymers with low degree of grafting. The triblock macromonomers proved to be unable to polymerize.     

Synthesis of ABC-triblock copolymers for light emitting diodes

In this paper we report on the synthesis and characterization of ABC-triblock copolymers poly(N-vinylcarbazole)-block-poly(4-(1-pyrenyl)butyl vinyl ether)-block-poly(2-[4-(2-phenyl-1,3,4-oxdiazolyl)phenyloxy]ethyl vinyl ether) 15 . The ABC-triblock copolymers were synthesized by sequential living cationic polymerization of N-vinylcarbazole 11 , 4-(1-pyrenyl)butyl vinyl ether 10 and 2-chloroethyl vinyl ether 3 . In a second step, the reactive pendant chloro groups of the poly(2-chloroethyl vinyl ether) segment of the block copolymers were substituted with 2-(4-hydroxyphenyl)-5-phenyl-1,3,4-oxadiazole 6 to form fully functionalized ABC'-triblock copolymers. The molecular weight of the block copolymers varied from M _n = 4800 to 14000. The thermal behavior is discussed with respect to the block copolymer composition and compared with corresponding polymer blends. LED characteristics of a single layer device for one of the block copolymers are presented as an example.     

Synthesis of a new antithrombogenic block copolymer containing fluorinated segments: poly(nonafluorohexyl acrylate-b-styrene)

Two types of block copolymers, 3a and 3b , were synthesized from α-hydro-ω-(2-hydroxyethylthio)poly[1-(3,3,4,4,5,5,6,6,6-nonafluorohexyloxycarbonyl)ethylene] ( 1a ) or α-hydro-ω-(2-aminoethylthio)poly[1-(hexyloxycarbonyl)ethylene] ( 1b ) and α,ω-bis(4-cyanatophenylthio)-poly(1-phenylethylene) ( 2 ), respectively, and the adhesion of blood platelets to these polymer surfaces was evaluated. Adhesion and activation of platelets were found to be effectively suppressed at the lamellar-microdomain surface of block copolymer 3a , having a surface free energy gap between microdomains of about 20 dyn/cm, whereas no such a suppression was observed for the microdomain structured surface of block copolymer 3b with a small surface free energy gap between the microdomains. Further, a random copolymer from nonafluorohexyl acrylate and styrene without microdomain structure does not suppress the adhesion and activation of platelets. From these results, it was concluded that the microdomain morphology and the surface free energy gap between microdomain is important to produce antithrombogenicity.     

PLA-b-SMA as an Amphiphilic Diblock Copolymer for Encapsulation of Lipophilic Cargo

The encapsulation of active pharmaceutical ingredients (APIs) within drug delivery systems such as polymeric nanoparticles (PNPs) vastly improves the therapeutic efficiency of the incorporated APIs. PNPs synthesized using amphiphilic block copolymers are efficient drug delivery systems as the hydrophobic block facilitates the encapsulation of lipophilic components and the hydrophilic block constitutes the hairy corona of the PNP that stabilizes the nanocarriers against aggregation in solution. Poly(styrene-alt-maleic acid) (SMA) is an attractive polymer for the hydrophilic corona of PLA-based nanoparticles as it allows for post polymerization functionalization and aids in the prevention of NP aggregation. The synthesis of a novel PLA-b-SMA block copolymer, via sequential ring opening polymerization (ROP) and reversible addition–fragmentation chain transfer (RAFT) polymerization, is presented. PLA macro-CTAs, synthesized via ROP, can be chain extended via RAFT copolymerization of styrene and maleic anhydride to yield PLA-b-SMAnh and via RAFT polymerization of N-vinylpyrrolidone to yield PLA-b-PVP block copolymers. Controlled hydrolysis of the anhydride moieties converts PLA-b-SMAnh into PLA-b-SMA. Monodisperse PLA-b-SMA and PLA-b-PVP nanoparticles (NPs) ranging in diameter between 60 and 220 nm are prepared. The lipophilic fluorescent dye DiI is encapsulated within the NPs successfully and these fluorescent NPs are used in a preliminary cell uptake study.     

The effect of RAFT-derived cationic block copolymer structure on gene silencing efficiency

In this work a series of ABA tri-block copolymers was prepared from oligo(ethylene glycol) methyl ether methacrylate (OEGMA(475)) and N,N-dimethylaminoethyl methacrylate (DMAEMA) to investigate the effect of polymer composition on cell viability, siRNA uptake, serum stability and gene silencing. Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization was used as the method of polymer synthesis as this technique allows the preparation of well-defined block copolymers with low polydispersity. Eight block copolymers were prepared by systematically varying the central cationic block (DMAEMA) length from 38 to 192 monomer units and the outer hydrophilic block (OEGMA(475)) from 7 to 69 units. The polymers were characterized using size exclusion chromatography and (1)H NMR. Chinese Hamster Ovary-GFP and Human Embryonic Kidney 293 cells were used to assay cell viability while the efficiency of block copolymers to complex with siRNA was evaluated by agarose gel electrophoresis. The ability of the polymer-siRNA complexes to enter into cells and to silence the targeted reporter gene enhanced green fluorescent protein (EGFP) was measured by using a CHO-GFP silencing assay. The length of the central cationic block appears to be the key structural parameter that has a significant effect on cell viability and gene silencing efficiency with block lengths of 110-120 monomer units being the optimum. The ABA block copolymer architecture is also critical with the outer hydrophilic blocks contributing to serum stability and overall efficiency of the polymer as a delivery system.     

Functional polymers and sequential copolymers by phase transfer catalysis, 1. Alternating block copolymers of unsaturated polyethers and aromatic poly(ether sulfone)s

Williamson etherification in the presence of phase transfer catalysts was successfully applied to the synthesis of alternating block copolymers and regular copolymers. Unsaturated polyethers( 5a and 5b ) containing chloroallylic (electrophilic) end groups (prepared from cis-or trans-1, 4-dichloro-2-butene and Bisphenol A) and aromatic poly(ether sulfone)s ( 3a ) containing terminal phenol (nucleophilic) groups were polycondensed in the presence of tetrabutylammonium hydrogen sulfate as phase transfer catalyst to give alternating block copolymers. The same telechelic polymers were chain-extended with dinucleophilic or dielectrophilic monomers under similar reaction conditions. Both the regular copolymers and the alternating block copolymers were characterized by gel pormeation chromatography and DSC.     

Synthesis of block copolymers from 1-chloro-1-octyne and other acetylenes through their sequential living polymerization by MoOCl4?n-Bu4Sn?EtOH

Block copolymerizations of 1-chloro-1-octyne (1-ClO) with several substituted acetylenes were examined by means of living polymerization. o-(Trifluoromethyl)phenylacetylene (o-CF₃PA), o-(trimethylsilyl)phenylacetylene (o-Me₃SiPA), 1-chloro-2-phenylacetylene (1-ClPA), p-butyl-o,o,m,m-tetrafluorophenylacetylene (p-BuF₄PA), and tert-butylacetylene (t-BuA) were used as comonomers, and the MoOCl₄-n-Bu₄Sn-EtOH (mole ratio 1:1:1) catalyst, which is known to effect living polymerization of substituted acetylenes, was employed. When o-CF₃PA and 1-CIPA were the comonomers in combination with 1-CIO, block copolymers were exclusively obtained in both orders of monomer addition. In the cases of o-Me₃SiPA and p-BuF₄PA as comonomers, the copolymerizations initiated from 1-CIO produced block copolymers selectively, whereas the homopolymers of o-Me₃SiPA and p-BuF₄PA also formed if the order of monomer addition was reversed. The pair of 1-CIO and t-BuA did not selectively yield block copolymers irrespective of the order of monomer addition. Thus, block copolymerization occurred between 1-CIO and monomers that show high “livingness” and close reactivities.     

Functional poly[(ethylene oxide)-co-(β-benzyl-L-aspartate)] polymeric micelles: block copolymer synthesis and micelles formation

Well-defined α-methoxy-ω-amino and α-hydroxy-ω-amino poly(ethylene oxides) (PEOs), obtained by chemical modifications of α-hydroxy-ω-amino PEO, were studied for block copolymerization with β-benzyl-L -aspartate-N-carboxy anhydride (BLA-NCA); the block copolymers were obtained via polymerization of BLA-NCA with the primary amino end-groups of the PEOs as initiator in the mixture CHCl₃/N,N-dimethylformamide (DMF) (vol. ratio10/1). Gel-permeation chromatography (GPC) of both block copolymers showed the presence of BLA oligomers. α-Methoxy PEO/PBLA and α-hydroxy PEO/PBLA block copolymers were submitted to selective precipitation in 2-propanol; this method allowed total elimination of oligomers as shown by GPC of the purified block copolymers. Moreover, for each block copolymer, the number of BLA units determined by ¹H NMR spectroscopy (in CDCl₃) was in good agreement with the number calculated from the ratio BLA-NCA/amino end-groups of PEO. The polymeric micelles having hydroxy functions or methoxy groups on the outer-shell were prepared by dialysis against water of the corresponding solution of the pure block copolymers. These polymeric micelles were characterized by dynamic light scattering (diameter) and by fluorescence spectroscopy (critical micellar concentration, cmc) using pyrene as a fluorescence probe. Both polymeric micelles have a small diameter (<50nm) and a very low cmc (<20 mg/L in water).     

1H,1H,2H,2H‐Perfluorodecyl‐Acrylate‐Containing Block Copolymers from ARGET ATRP

Block copolymers of 1H,1H,2H,2H‐perfluorodecyl acrylate (AC8) were obtained from ARGET ATRP. To obtain block copolymers of low dispersity the PAC8 block was synthesized in anisole with a CuBr₂/PMDETA catalyst in the presence of tin(II) 2‐ethylhexanoate as a reducing agent. The PAC8 block was subsequently used as macroinitiator for copolymerization with butyl and tert‐butyl acrylate carried out in scCO₂. To achieve catalyst solubility in CO₂ two fluorinated ligands were employed. The formation of block copolymers was confirmed by size exclusion chromatography and DSC.

     

Deep in vivo two-photon imaging of blood vessels with a new dye encapsulated in pluronic nanomicelles

Our purpose is to test if Pluronic? fluorescent nanomicelles can be used for in vivo two-photon imaging of both the normal and the tumor vasculature. The nanomicelles were obtained after encapsulating a hydrophobic two-photon dye: di-stryl benzene derivative, in Pluronic block copolymers. Their performance with respect to imaging depth, blood plasma staining, and diffusion across the tumor vascular endothelium is compared to a classic blood pool dye Rhodamin B dextran (70 kDa) using two-photon microscopy. Pluronic nanomicelles show, like Rhodamin B dextran, a homogeneous blood plasma staining for at least 1 h after intravenous injection. Their two-photon imaging depth is similar in normal mouse brain, using 10 times less injected mass. In contrast with Rhodamin B dextran, no extravasation is observed in leaky tumor vessels due to their large size: 20-100 nm. In conclusion, Pluronic nanomicelles can be used as a blood pool dye, even in leaky tumor vessels. The use of Pluronic block copolymers is a valuable approach for encapsulating two-photon fluorescent dyes that are hydrophobic and not suitable for intravenous injection.     

Diblock Copolymers with Azobenzene Side‐Groups and Polystyrene Matrix: Synthesis,Characterization and Photoaddressing

Summary: Diblock copolymers with a photoaddressable dispersed phase containing p‐methoxy substituted azobenzene side groups and a polystyrene matrix were synthesized and characterized. The block copolymers were prepared by a sequential living anionic polymerization of butadiene and styrene. The poly(1,2‐butadiene) segment was hydroborated and the hydroxy‐functions converted by a polymeranalogous reaction with the azo chromophore as side groups. The block copolymers were synthesized with different compositions by varying the length of the polystyrene segment and the length of the functionalized segment in order to obtain different morphologies. In this paper, for the first time a comparison of the cis‐trans photo‐isomerization behavior and photoaddressing with respect to different morphologies of the block copolymers is presented. To complete the comparison, the corresponding homopolymer and a statistical copolymer were also synthesized and investigated. A different photoaddressing behavior between homopolymer, statistical copolymer and the block copolymers was observed. One principal difference and advantage for photo addressable block copolymers is the lack of a formation of surface gratings which occurs in homopolymers and statistical copolymers.

TEM of a poly(1,2‐butadiene)‐block‐polystyrene copolymer containing azobenzene side‐groups.     

Thermoresponsive Glycopolymers via Controlled Radical Polymerization

New glycomonomers 3′‐(1′,2′:5′,6′‐di‐O‐isopropylidene‐α‐D ‐glucofuranosyl)‐6‐methacrylamido hexanoate (MAIpGlcC₅) and 3′‐(1′,2′:5′,6′‐di‐O‐isopropylidene‐α‐D ‐glucofuranosyl)‐6‐methacrylamido undecanoate (MAIpGlcC₁₀) with hydrophobic spacer units were synthesized and their homopolymers, as well as random copolymers with N‐isopropylacrylamide (NiPAAm) were prepared in varying compositions. The acidolysis of the isopropylidene protection groups of the polymers gave well‐defined sugar‐containing water‐soluble homopolymers (PMAGlcC_n, n = 5, 10) and copolymers. By using the reversible addition–fragmentation chain transfer (RAFT) process, it was possible to afford these copolymers with a polydispersity index (PDI) of 1.1–1.5. Furthermore, NiPAAm homopolymers with an active chain transfer unit at the chain end could be prepared by RAFT, which were used as macro‐chain transfer agents (macro‐CTAs) to prepare a variety of sugar containing responsive block copolymers from new glycomonomers by the monomer addition concept. The cloud points of the aqueous solutions of the copolymers were strongly affected by the comonomer content, spacer chain length of the glycomonomer, and the chain architecture of the copolymers. Especially by the block copolymer concept, glycopolymers with lower critical solution temperatures (LCSTs) in the physiologically interesting range could be realized.

     

Preparation of ABCBA-type block copolymers by use of macro-initiators containing peroxy and azo groups

Some new macroinitiators ( 5 ) containing azo and peroxy groups were synthesized by transformation of esters of poly(ethylene glycol) ( 1 ) (PEG) of different molecular weight with hydroxyl end groups and an azo group in the middle into the corresponding polymers with tert-butylperoxycarbonyl end groups by reaction with terephthaloyl chloride and subsequently with tert-butyl hydroporoxide. Decomposition in the presence of styrene at 60°C or with 3,6,9-triazaun-decane-1,11-diamine in presence of methyl methacrylate gave the corresponding ABA block copolymer 6 and the ABBA block copolymer 7 , respectively. Both block copolymers were used as polymeric initiators. The ABCBA block copolymer 8 was synthesized from 6 and methyl methacrylate or from 7 and styrene by thermally induced polymerization at 80°C. The resulting block copolymers were separated from the homopolymers by selective solvent extraction and characterized by spectroscopic and fractional precipitation methods.     

Liquid-Crystalline side-chain AB block copolymers by direct anionic polymerization of a mesogenic methacrylate

AB block copolymers with a liquid-crystalline and an amorphous block are synthesized by anionic copolymerization of 4-[4-(4-methoxyphenylazo)phenoxy]butyl methacrylate ( 1 ) with either styrene or methyl methacrylate (MMA). The polymerization of 1 proceeds from polystyrenelithium capped with 1,1-diphenylethylene to produce polystyrene-block-poly( 1 ), while poly( 1 )-block-PMMA is prepared by addition of MMA to the “living” poly( 1 ) anion. A large variety of block copolymers is obtained with narrow molecular weight distribution and definite composition. The mesophase behaviour of these samples is analyzed with respect to the chain length of the liquid-crystalline block. Electron microscopy of a high-molecular-weight polystyrene-block-poly( 1 ) provides direct evidence for a microphase-separated structure composed of spherical polystyrene domains embedded in a liquid-crystalline matrix. For the corresponding poly( 1 )-block-PMMA, however, electron microscopy indicates no structure, although dynamic mechanical analysis proves microphase separation.     

Block Copolymers from Organomodified Siloxane‐Containing Macroinitiators by Atom Transfer Radical Polymerization

Alternating copolymers of 1,3‐diisopropenylbenzene and 1,1,3,3‐tetramethyldisiloxane were synthesized by hydrosilylation–polyaddition. These linear copolymers were functionalized at both ends with 2‐bromoisobutyryl or benzyl chloride moieties. Subsequently, the obtained organomodified siloxane‐containing macroinitiators were successfully used for the preparation of ABA‐type block copolymers by atom transfer radical polymerization (ATRP) of styrene and tert‐butyl acrylate. The high chain‐end functionality of the macroinitiators was confirmed by ¹H NMR analysis of the macroinitiators and GPC measurements of the obtained ABA‐type block copolymers. The macroinitiator peaks disappeared in GPC traces after ATRP, and the obtained block copolymers showed a significantly narrower molecular‐weight distribution than the macroinitiators.

Synthesis of ABA‐type block copolymers by means of ATRP using organomodified siloxane‐containing, benzyl chloride functionalized macroinitiators.     

Reduction of nitrogen coordinated to polymer bound chlorobis(η-cyclopentadienyl)titanium

Dinitrogen complexes of poly{1-[4-(chlorodicyclopentadienyltitanio)phenyl]ethylene-co-1-(4-bromophenyl)ethylene-co-1-phenylethylene} ( 2a – e ) were synthesized. It was found that there is an equilibrium between the mononuclear and binuclear complex. Ammonia was formed after hydrolysis of the reaction mixtures resulting from 2a – e and lithium naphthalide in a nitrogen atmosphere. The yield of ammonia increased extremely with decreasing content of titanocene in the polymer. In the system with 2a 41,7 mol ammonia were formed per 1 mol of titanium.     

Atom Transfer Radical Polymerization of Solketal Acrylate Using Cyclohexanone as the Solvent

Summary: Solketal acrylate (SA) was homopolymerized by atom transfer radical polymerization (ATRP) using CuBr/N,N,N′,N″,N″‐pentamethyldiethylenetriamine as the catalyst and cyclohexanone as the solvent with controlled molecular weights and low polydispersities. The prepared bromine‐terminated homopolymers, PSA, were used as macroinitiators to initiate polymerization of tert‐butyl acrylate (tBA) under similar ATRP conditions to produce diblock copolymers, PSA‐b‐PtBA, with controlled molecular weights and low polydispersities. ATRP of SA using bromine‐terminated PtBA as the macroinitiator was also carried out and diblock copolymers, PtBA‐b‐PSA, were obtained. The PSA block was selectively hydrolyzed by stirring for 3 h in 6 N HCl/THF (1/9, v/v) at room temperature to form a poly(glycerol monoacrylate) block. Both blocks of PSA and PtBA were hydrolyzed by stirring in anhydrous trifluoroacetic acid (TFA)/dichloromethane for 4 h, then adding water to the system and stirring for another 3 h to form corresponding diblock copolymers of glycerol monoacrylate and acrylic acid.

Kinetic plot for the atom transfer radical polymerization of solketal acrylate at 90 °C.     

The Aggregation Behavior of Poly(ethylene oxide)‐Poly(methyl methacrylate) Diblock Copolymers in Organic Solvents

Poly(ethylene oxide)‐poly(methyl methacrylate) and poly(ethylene oxide)‐poly(deuteromethyl methacrylate) block copolymers have been prepared by group transfer polymerization of methyl methacrylate (MMA) and deuteromethyl methacrylate (MMA‐d₈), respectively, using macroinitiators containing poly(ethylene oxide) (PEO). Static and dynamic light scattering and surface tension measurements were used to study the aggregation behavior of PEO‐PMMA diblock copolymers in the solvents tetrahydrofuran (THF), acetone, chloroform, N,N‐dimethylformamide (DMF), 1,4‐dioxane and 2,2,2‐trifluoroethanol. The polymer chains are monomolecularly dissolved in 1,4‐dioxane, but in the other solvents, they form large aggregates. Solutions of partially deuterated and undeuterated PEO‐PMMA block copolymers in THF have been studied by small‐angle neutron scattering (SANS). Generally, large structures were found, which cannot be considered as micelles, but rather fluctuating structures. However, ¹H NMR measurements have shown that the block copolymers form polymolecular micelles in THF solution, but only when large amounts of water are present. The micelles consist of a PMMA core and a PEO shell.     

Block Copolymers of Methyl Vinyl Ether and Isobutyl Vinyl Ether With Thermo‐Adjustable Amphiphilic Properties

The thermo‐adjustable hydrophilic/hydrophobic properties of AB, ABA and BAB block copolymers in which A is poly(methyl vinyl ether) (PMVE) and B is poly(isobutyl vinyl ether) (PIBVE) have been investigated. The block copolymers were prepared by “living” cationic polymerization using sequential addition of monomers. The polymerizations were carried out with the system acetal/trimethylsilyl iodide as initiator and ZnI₂ as activator. The initiating system based on diethoxyethane leads to AB block copolymers whereas the initiating system based on tetramethoxypropane leads to ABA or BAB triblock copolymers. Well‐defined block copolymers of different composition with controlled molecular weights up to approx. 10 000 have been prepared. When IBVE is added to living PMVE, PIBVE‐blocks form only in the presence of an additional amount of ZnI₂, which is attributed to the fact that part of the ZnI₂ is inactive because of complex formation with PMVE. At room temperature, the combination of hydrophilic (PMVE) and hydrophobic (PIBVE) segments provides the copolymers with surfactant properties. Above the lower critical solution temperature (LCST) of PMVE, situated around 36 °C, the PMVE‐blocks become hydrophobic and the amphiphilic nature of the block copolymers is lost. The corresponding changes in hydrophilic/hydrophobic balance have been evaluated by investigation of the emulsifying properties of the block copolymers for water/decane mixtures as a function of the temperature. Below the LCST, the block copolymers have emulsifying properties similar to or better than those of the commercial PEO‐PPO block copolymers (Pluronic®). Either oil‐in‐water or water‐in‐oil emulsions can be obtained, depending on the polymer architecture and the water/decane volume ratio. The emulsifying properties are strongly reduced or completely lost above 40 °C. Emulsions obtained with a PMVE₃₆‐b‐PIBVE₅₄ block copolymer for a water/decane (v/v) ratio of 85/15 remained stable for more than six months.

50/50 and a 85/15 water/decane w/o emulsion (15 g/l) with the PMVE₃₆‐b‐PIBVE₅₄ block copolymer at 20 °C.     

Structure of polystyrene-block-poly(ethylene oxide) diblock copolymer micelles in water

Micellization in water of two homologous series of AB-type diblock copolymers, composed of polystyrene (PS) as the A block and poly(ethylene oxide) (PEO) as the B block, were investigated by small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS). The copolymers have molecular weights M _n in the range 2 000—34 800, and have in a given series, the same number of repeating units of the PS block, (N_PS = 10 and 38), and a variable number of repeating units of the PEO block (N_PEO values in the range 23–704). In order to avoid secondary association of micelles, a dialysis technique was used to prepare the micellar systems, in the case of copolymers having high M _n values of the PS block. The experimental micelle properties such as the core radius R_c and the aggregation number N of non-equilibrium structures, so called “frozen micelles”, obtained by dialysis, were found to be independent of the copolymer characteristics. However, for equilibrium structures, obtained by direct solubilization of the copolymers (N_PS = 10) in water, R_c and N were found to decrease with increasing N_PEO for the homologous series.