Contrast Inversion in TEM Studies of Poly(ferrocenylsilane)‐block‐Poly(dimethylsiloxane) Diblock Copolymers

This paper describes an unusual contrast inversion phenomenon in TEM imaging of PFS‐b‐PDMS block copolymer bulk samples. It is clearly observed especially in samples that show a lamellar morphology that the contrast inversion is accompanied by a contraction of the PDMS domains and an expansion of the Fe‐rich domains. The location of the iron‐ and silicon‐rich domains was monitored by EDX analysis. We infer that the contrast inversion was caused by electron beam radiation‐induced damage to, and possible cross‐linking of, PDMS chains. A simple way to selectively deposit metal on electron beam patterned polymer film was demonstrated.

     

Controlled Synthesis of Well Defined Poly(3‐hydroxyalkanoate)s‐based Amphiphilic Diblock Copolymers Using Click Chemistry

A modular synthesis of short chain length and medium chain length poly(3‐hydroxyalkanoate)s‐b‐poly(ethylene glycol) (PHAs‐b‐PEG) diblock copolymers is described. First, length‐controlled oligomers of hydrophobic poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBHV), poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (PHBHHx), and poly(3‐hydroxyoctanoate‐co‐hydroxyhexanoate) (PHOHHx) containing a carboxylic acid end group were obtained by thermal treatment, with molar masses ranging from 3 800 to 15 000 g · mol^?1. After quantitative functionalization with propargylamine, ligation with azide‐terminated poly(ethylene glycol) of 5 000 g · mol^?1 was accomplished using the copper (I) catalyzed azide alkyne cycloaddition (CuAAC). Well‐defined diblock copolymers were obtained up to 93% yield, with molar masses ranging from 9 900 to 23 100 g · mol^?1. All products were fully characterized using ¹H NMR, COSY, SEC, TGA, and DSC.

     

Amphiphilic Block Copolymers Containing Regioregular Poly(3‐hexylthiophene) and Poly(2‐ethyl‐2‐oxazoline)

Poly(3‐hexylthiophene)‐block‐poly(2‐ethyl‐2‐oxazoline) amphiphilic rod–coil diblock copolymers have been synthesized by a combination of Grignard metathesis (GRIM) and ring‐opening cationic polymerization. Diblock copolymers containing 5, 15, and 30 mol‐% poly(2‐ethyl‐2‐oxazoline) have been synthesized and characterized. The synthesized rod–coil block copolymers display nanofibrillar morphology where the density of the nanofibrills is dependent on the concentration of the poly(2‐ethyl‐2‐oxazoline) coil segment. The conductivity of the diblock copolymers was lowered from 200 to 35 S · cm^?1 with an increase in the content of the insulating poly(2‐ethyl‐2‐oxazoline) block. By contrast, the field‐effect mobility decreased by 2–3 orders of magnitude upon the incorporation of the poly(2‐ethyl‐2‐oxazoline) insulating segment.

     

Synthesis of Three Types of Amphiphilic Poly(ethylene glycol)‐block‐Poly(sebacic anhydride) Copolymers and Studies of their Micellar Solutions

Summary: Linear, three‐ and four‐armed block copolymers based on PEG and PSA were synthesized by melt polycondensation reactions. The CMC of the copolymer was measured using the dye solubilization method. The copolymers were found to self‐aggregate in water to form micelles above the CMC. The micellar solutions were prepared with different methods and investigated by DLS and AFM. The DLS method was used to measure the mean hydrodynamic diameters of the micelles. It was found that preparation method and condition of the micellar solution, as well as the structure and composition of the copolymer had effects on the hydrodynamic diameter of the copolymer micelles. AFM studies showed that the morphology of the micelle was spherical.

Synthesis of 3‐armed stars based on poly(ethylene glycol) and poly(sebacic anhydride).     

Micellar Structures of Hydrophilic/Lipophilic and Hydrophilic/Fluorophilic Poly(2‐oxazoline) Diblock Copolymers in Water

Amphiphilic poly(2‐alkyl‐2‐oxazoline) diblock copolymers of 2‐methyl‐2‐oxazoline (MOx) building the hydrophilic block and either 2‐nonyl‐2‐oxazoline (NOx) for the hydrophobic or 2‐(1H,1H′,2H,2H′‐perfluorohexyl)‐2‐oxazoline (FOx) for the fluorophilic block were synthesized by sequential living cationic polymerization. The polymer amphiphiles form core/shell micelles in aqueous solution as evidenced using small‐angle neutron scattering (SANS). Whereas the diblock copolymer micelles with a hydrophobic NOx_n block are spherical, the micelles with the fluorophilic FOx_n are slightly elongated, as observed by SANS and TEM. In water, the micelles with fluorophilic and lipophilic cores do not mix, but coexist.

     

A Convenient Method for the Synthesis of the Amphiphilic Triblock Copolymer Poly(L‐lactic acid)‐block‐Poly(L‐lysine)‐block‐Poly(ethylene glycol) Monomethyl Ether

The amphiphilic triblock copolymer PLA‐b‐PLL‐b‐MPEG is prepared in three steps through acylation coupling between the terminal amino groups of PLA‐b‐PZLL‐NH₂ and carboxyl‐terminal MPEG, followed by the deprotection of amines. The block copolymers are characterized via FT‐IR, ¹H NMR, DSC, GPC, and TEM. TEM analysis shows that the triblock polymers can form polymeric micelles in aqueous solution with a homogeneous spherical morphology. The cytotoxicity assay indicates that the final triblock polymer micelles after deprotection show low cytotoxicity against Bel7402 human hepatoma cells. MPEG and PLL were introduced into the main chain of PLA affording a kind of ideal bioabsorbable polymer materials, which is expected to be useful in drug and gene delivery.

     

Synthesis and Characterization of Comb‐Like Copolymers Based on Poly(ε‐caprolactone) and Poly(α‐olefin)

Comb‐like copolymers based on a polyolefin backbone of poly(10‐undecene‐1‐ol) (PUol) with poly(ε‐caprolactone) (PCL) side chains are synthesized in two steps. After synthesis of PUol by metallocene‐catalyzed polymerization, the side‐chain hydroxyl functionalities of this polar polyolefin are used as an initiator for the ring‐opening polymerization (ROP) of ε‐caprolactone (CL). In this context, copolymers with different lengths of PCL grafts are prepared. The chemical structure and the composition of the synthesized copolymers are characterized by ¹H and ¹³C NMR spectroscopy. It is shown that the hydroxyl end groups of PUol act effectively as initiating sites for the CL ROP. Size‐exclusion chromatography (SEC) measurements confirm the absence of non‐attached PCL and the expected increase in molar mass after grafting. The thermal and decomposition behaviors are investigated by DSC and thermogravimetric analysis (TGA). The effect of the length of the PCL grafts on the crystallization behavior of the comb‐like copolymers is investigated by DSC and wide‐angle X‐ray scattering (WAXS).

     

Synthesis and Self‐Assembly of Amphiphilic Block Copolymers from Biobased Hydroxypropyl Methyl Cellulose and Poly(l‐lactide)

A series of well‐defined hydroxypropyl methyl cellulose‐block‐poly(l ‐lactide) (HPMC‐b‐PLLA) diblock copolymers are synthesized via UV‐initiated thiol‐ene click reaction of thiol‐terminated HPMC with different block lengths and allyl‐terminated PLLA, using 2,2‐dimethoxy‐2‐phenylacetophenone as photocatalyst. The former is obtained by coupling the reducing aldehyde endgroup of short chain HPMC with the amine group of cysteamine, and the latter by ring‐opening polymerization of l ‐lactide in the presence of allyl alcohol. Fourier transform infrared (FT‐IR), nuclear magnetic resonance (¹H NMR), and diffusion ordered spectroscopy NMR confirm the successful coupling of both blocks. The molar mass of the resulting copolymers ranges from 7000 to 12 800 g mol⁻¹ as determined by size exclusion chromatography. The copolymers are able to self‐assemble in aqueous medium, yielding micelles of 50–100 nm with core–shell structure as evidenced by dynamic light scattering, transmission electron microscopy, and ¹H NMR. The critical micelle concentration of copolymers ranges from 0.12 to 0.15 mg mL⁻¹. Last but not the least, the copolymers exhibit thermoresponsive behavior with a lower critical solution temperature around 80 °C.

     

Synthesis of PLLA‐MPEG Diblock Copolymers by Microwave‐Assisted Copolymerization of L‐Lactide and Methoxy Poly(ethylene glycol)

PLLA‐MPEG diblock copolymers with a controlled number‐average molar mass ranging from 7 330 to 117 610 g · mol^?1 and an L ‐lactide conversion ranging from 65.1 to 97.3% were synthesized effectively in 20 min at 100 °C by MPEG‐initiated ROP of L ‐lactide under microwave irradiation. Prolonged microwave irradiation time led to the degradation of the copolymers because the ROP reaction and the thermal degradation reaction occurred simultaneously at the later stage of the reaction process. The differential scanning calorimetric and thermogravimetric study indicated that higher melting temperatures and thermal stability were obtained for PLLA‐MPEG diblock copolymers with longer PLLA segments.

     

Poly(N,N‐dimethylacrylamide)‐block‐Poly(L‐lysine) Hybrid Block Copolymers: Synthesis and Aqueous Solution Characterization

Four poly(N,N‐dimethylacrylamide)‐block‐poly(L ‐lysine) (PDMAM‐block‐PLL) hybrid diblock copolymers and two PLL homo‐polypeptides are prepared via ROP of ε‐trifluoroacetyl‐L ‐lysine N‐carboxyanhydride initiated by primary amino‐terminated PDMAM and n‐hexylamine respectively. The PLL blocks render the copolymers a multi‐responsive behavior in aqueous solution due to their conformational transitions from random coil to α‐helix with increasing pH, and from α‐helix to β‐sheet upon heating. The random coil‐to‐α‐helix transition is found to depend on the PLL length: the longer the peptide segment, the more readily the transition occurred. The same trend was observed for the α‐helix‐to‐β‐sheet transition, which was found to be inhibited for short polypeptides unless conjugated with the PDMAM block.

     

Synthesis and Characterization of Block Copolymers of ε‐Caprolactone and DL‐Lactide Initiated by Ethylene Glycol or Poly(ethylene glycol)

Biodegradable copolymers were prepared by ring‐opening polymerization of sequentially added ε‐caprolactone and DL ‐lactide in the presence of ethylene glycol or poly(ethylene glycol), using zinc metal as catalyst. Polymerization was performed in bulk and yielded block copolymers with predetermined PEG/PCL/PLA segments. The obtained polymers were characterized by ¹H NMR, SEC, IR, DSC, TGA, and X‐ray diffraction. Data showed that the copolymers preserved the excellent thermal behavior inherent to PCL. The crystallinity of PLA‐containing copolymers was reduced with respect to PCL homopolymer. The presence of both hydrophilic PEG and fast degrading PLA blocks should improve the biocompatibility and biodegradability of the materials, which are of interest for applications as substrate in drug delivery or as scaffolding in tissue engineering.

Block copolymerization of ε‐caprolactone and DL ‐lactide initiated by dihydroxyl PEG.     

Dual‐Functional PEI–Poly(γ‐Cholesterol‐l‐Glutamate) Copolymer for Drug/Gene Co‐delivery

Novel dual‐functional PEI‐poly(γ‐cholesterol‐l ‐glutamate) (PEI‐PCHLG) copolymers are developed for the first time. A series of PEI‐PCHLG (PEI‐1, PEI‐2, PEI‐3, and PEI‐4) with various PEI percentages and molecular weights are successfully synthesized, among which the poor organic solvent solubility of PEI‐1 precludes its further application. The other three copolymers can spontaneously self‐assemble into micelles; the critical micelle concentration (CMC) values are 0.66, 1.3, and 0.95 μmol L^?1, respectively. PEI‐2 and PEI‐4, with lower CMC, are worth being further developed as promising drug carriers because of their resistance to dilution in circulation after systemic administration. However, PEI‐4 can form smaller‐sized micelles than PEI‐2 and has similar in vitro cytotoxicity to PEI. Thus, PEI‐4 is further investigated. PEI‐4 micelles can not only incorporate docetaxel (DTX) with high encapsulation efficiency (91.0%) and drug loading (4.3%), but also load pDNA efficiently at a ratio of 8:1 (w/w). DTX‐loaded PEI‐4 micelles (DTX‐PEI‐4) can also carry genes with the same gene‐binding capacity as PEI‐4 micelles. The above three micelles (DTX‐PEI‐4, pDNA‐PEI‐4, and pDNA/DTX‐PEI‐4) are sub‐micrometer‐sized and spherical. The results indicate that PEI‐4 containing 28.9% PEI, one of the PEI‐PCHLG copoly­mers, is a potential carrier for gene delivery, drug delivery, or even drug/gene co‐delivery.

     

Controlled ROMP Synthesis of Ferrocene‐Containing Amphiphilic Dendronized Diblock Copolymers as Redox‐Controlled Polymer Carriers

Novel well‐defined redox‐responsive Ferrocene (Fc)‐containing amphiphilic dendronized diblock copolymers are synthesized by the ring‐opening metathesis polymerization technique using Grubbs’ third‐generation olefin metathesis catalyst as the initiator. These dendronized block copolymers can self‐assemble into spherical micelles in aqueous solution. The size of self‐assembled micelles can be modulated by the composition (namely, the ratio of hydrophobic and hydrophilic segments) and concentration of the dendronized copolymers. The obtained micelles show reversible redox‐controlled self‐assembly behaviors using FeCl₃ as oxidant and glutathione as reductant. Furthermore, the model molecule Rhodamine B is successfully loaded in these micelles, and the oxidation‐triggered controllable release is achieved by changing the type of oxidants (FeCl₃ and H₂O₂) and their concentrations. This is the first example of redox‐responsive micelles self‐assembled by novel amphiphilic dendronized Fc‐containing block copolymers, and the present micelles are visualized to be potential candidates in many fields, especially in stimuli‐responsive drug delivery systems.     

Synthesis of Di‐block Copolymers Containing Regioregular Poly(3‐hexylthiophene) and Poly(tetrahydrofuran) by a Combination of Grignard Metathesis and Cationic Polymerizations

Poly(3‐hexylthiophene)‐block‐poly(tetrahydrofuran) was synthesized by cationic ring‐opening polymerization of tetrahydrofuran (THF) using a poly(3‐hexylthiophene) macroinitiator. Poly(3‐hexylthiophene) macroinitiator used for the ring‐opening polymerization of THF was synthesized by reacting the hydroxypropyl end‐group with trifluoromethanesulfonic anhydride in the presence of 2,6‐di‐tert‐butylpyridine. ¹H NMR spectroscopy and SEC data confirmed the formation of the di‐block copolymers. Field‐effect mobility of poly(3‐hexylthiophene)‐block‐poly(tetrahydrofuran) was measured in a thin‐film transistor configuration and was found to be 0.009 cm² · V^?1 · s^?1.

     

Metallocenic Isotactic Poly(propylene) and its Copolymers with 1‐Hexene and Ethylene

A comprehensive study of the structure and properties has been performed for copolymers of propylene‐1‐hexene, CiPH, and propylene‐ethylene, CiPE, synthesized by an isotactic metallocene catalyst system. The comonomer content constitutes the most important factor affecting the structure and properties of these CiPH and CiPE copolymers, although the length of the comonomer is also very important. Thus, a considerable decrease in crystallinity is observed in the two kinds of copolymers as the comonomer content increases. The structure in the CiPH copolymers evolves, however, from the typical, monoclinic crystal lattice to mesomorphic‐like, ordered entities for the highest 1‐hexene molar fraction, whereas in the CiPE copolymers the structural evolution with molar fraction goes from a monoclinic lattice to an almost amorphous material. All of these variations in crystal structure significantly influence the viscoelastic and mechanical behavior of these CiPH and CiPE copolymers. Consequently, the location and intensity of the different relaxation mechanisms, as well as the rigidity parameters (storage and Young's moduli and microhardness) and deformation mechanism are strongly dependent upon composition.

     

Rod‐Length Dependent Aggregation in a Series of Oligo(p‐benzamide)‐Block‐Poly(ethylene glycol) Rod‐Coil Copolymers

Summary: The synthesis of a series of rod‐coil diblock copolymers with flexible poly(ethylene oxide) chains ( = 5 000 g · mol⁻¹) and rod blocks consisting of monodisperse oligo(p‐benzamide)s is described. The formation of defined supramolecular aggregates in solution as well as the solid state has been analyzed. The length of the oligo(p‐benzamide)s has been systematically varied from n = 1 to 7 units. The influence of n on aggregation in chloroform and aqueous solution was investigated by GPC as well as UV‐vis spectroscopy. A critical aggregation length was found for chloroform (n = 5) and water (n = 4), below which no aggregation is observed under otherwise identical experimental conditions. Aggregation of the polymers in chloroform solution can be chemically reversed by the addition of PCl₅, resulting in conversion of the aromatic amides into imidoyl chlorides. Such amide‐protected block copolymers show no aggregation in NMR and GPC experiments. Imidoyl chloride formation was shown to be reversible, i.e., addition of water regenerated the oligo(p‐benzamide) blocks.

Conversion of aramide block copolymer into molecularly dissolved form using PCl₅.     

Aggregation Behavior of Polystyrene/Poly(acrylic acid) Heteroarm Star Copolymers in 1,4‐Dioxane and Aqueous Media

Ionic heteroarm star copolymers bearing polystyrene (PS) and poly(acrylic acid) (PAA) arms (PS_nPAA_n) were prepared by quantitative hydrolysis of the poly(tert‐butyl acrylate) (PtBA) arms of the corresponding PS_nPtBA_n star copolymer. The aggregation properties of these copolymers were studied in various solvents. In 1,4‐dioxane PS₁₂PAA₁₂ (with nearly symmetrical PS and PAA arms) forms reverse micelles of low aggregation number (N_agg) and spherical morphology. In an 80 : 20 (v/v) 1,4‐dioxane/water mixture these micelles are transformed to regular micelles with an unexpectedly high N_agg and an elongated rod‐like structure. An abnormal behavior was observed in aqueous solutions of charged PS₂₄PANa₂₄ (with asymmetrical PS and PAA arms, W_PS = 19 wt.‐%) at low concentrations. A non‐equilibrium physical gel is formed, characterized by a very high viscosity and an elastic response upon oscillatory shearing.     

Synthesis of Hydroxyl‐Terminated Poly(vinylcarbazole‐ran‐styrene) Copolymers by Nitroxide‐Mediated Polymerization

A series of poly(vinylcarbazole‐ran‐styrene) copolymers with terminal hydroxyl groups were synthesized using nitroxide mediated polymerization (NMP) with the hydroxyl‐functional initiator VA‐086 and TEMPO as the mediator at 130 °C. Polymerizations were studied as a function of vinylcarbazole feed content, target molecular weight, and VA‐086/TEMPO ratio. The characterization of the copolymers was done by GPC and NMR. For feed concentrations of 40 mol‐% vinylcarbazole, copolymers with vinylcarbazole concentration up to 33 mol‐% could be obtained with narrow molecular weight distributions (PDI = 1.35) and exhibit pseudo‐“living” character up to conversions of about 20% if the target molecular weight was >100 kg · mol^?1. ¹H NMR indicated that the hydroxyl group was retained sufficiently with a functionality typically of about 0.7 hydroxyl groups per chain. Copolymers synthesized with higher vinylcarbazole feed content exhibited slower kinetics and were less controlled, resulting in much broader molecular weight distributions. The absence of control could be attributed to the absence of thermal initiation by vinylcarbazole which is advantageous toward controlling the radical concentration during the polymerization.

     

Micellization of Poly(2‐oxazoline)‐Based Quasi‐Diblock Copolymers on Surfaces

The micellization on surfaces of two series of quasi‐diblock copoly(2‐oxazoline)s consisting of 2‐phenyl‐2‐oxazoline (PhOx) segments linked to either 2‐methyl‐2‐oxazoline (MeOx) or 2‐ethyl‐2‐oxazoline (EtOx) segments is investigated in detail. Those micelles are not pre‐existing in the initial ethanol solution but are formed during the spin‐coating process by the evaporation of the solvent inducing the precipitation of the less soluble PhOx segments. The morphology and size of the surface micelles vary according to the fraction of PhOx in the copolymers. Moreover, it is demonstrated that the chemical nature of the more soluble MeOx or EtOx segments also has an influence on the morphology of the resulting surface micelles.

     

Synthesis and Characterization of Amphiphilic Poly(ethylene oxide)‐block‐poly(hexyl methacrylate) Copolymers

We describe the preparation of amphiphilic diblock copolymers made of poly(ethylene oxide) (PEO) and poly(hexyl methacrylate) (PHMA) synthesized by anionic polymerization of ethylene oxide and subsequent atom transfer radical polymerization (ATRP) of hexyl methacrylate (HMA). The first block, PEO, is prepared by anionic polymerization of ethylene oxide in tetrahydrofuran. End capping is achieved by treatment of living PEO chain ends with 2‐bromoisobutyryl bromide to yield a macroinitiator for ATRP. The second block is added by polymerization of HMA, using the PEO macroinitiator in the presence of dibromobis(triphenylphosphine) nickel(II), NiBr₂(PPh₃)₂, as the catalyst. Kinetics studies reveal absence of termination consistent with controlled polymerization of HMA. GPC data show low polydispersities of the corresponding diblock copolymers. The microdomain structure of selected PEO‐block‐PHMA block copolymers is investigated by small angle X‐ray scattering experiments, revealing behavior expected from known diblock copolymer phase diagrams.

SAXS diffractograms of PEO‐block‐PHMA diblock copolymers with 16, 44, 68 wt.‐% PEO showing spherical (A), cylindrical (B), and lamellae (C) morphologies, respectively.