Nopadiene: A Pinene-Derived Cyclic Diene as a Styrene Substitute for Fully Biobased Thermoplastic Elastomers.

The bicyclic 1,2-substituted, 1,3-diene monomer nopadiene (1R,5S)-2-ethenyl-6,6-dimethylbicyclo[3.1.1]hept-2-ene was successfully polymerized by anionic and catalytic polymerization. Nopadiene is produced either through a facile one-step synthesis from myrtenal via Wittig-olefination or via a scalable two-step reaction from nopol (10-hydroxymethylene-2-pinene). Both terpenoids originate from the renewable ß-pinene. The living anionic polymerization of nopadiene in apolar and polar solvents at 25 °C using organolithium initiators resulted in homopolymers with well-controlled molar masses in the range of 5.6-103.4 kg·mol-1 (SEC, PS calibration) and low dispersities (D) between 1.06 and 1.18. By means of catalytic polymerization with Me4CpSi(Me)2NtBuTiCl2 and (Flu)(Pyr)CH2Lu(CH2TMS)2(THF), the 1,4 and 3,4- microstructures of nopadiene are accessible in excellent selectivity. In pronounced contrast to other 1,3-dienes, the rigid polymers of the sterically demanding nopadiene showed an elevated glass temperature, Tg,∞ = 160 °C (in the limit of very high molar mass, Mn). ABA triblock copolymers with a central polymyrcene block and myrcene content of 60-75 mol %, with molar masses of 100-200 kg/mol were prepared by living anionic polymerization of the pinene-derivable monomers nopadiene and myrcene. This diene copolymerization resulted in thermoplastic elastomers displaying nanophase separation at different molar ratios (DSC, SAXS) and an upper service temperature about 30 K higher than that for traditional petroleum-derived styrenic thermoplastic elastomers due to the high glass temperature of polynopadiene. The materials showed good thermal stability at elevated temperatures under nitrogen (TGA), promising tensile strength and ultimate elongation of up to 1600%.

Bifunctional Carbanionic Synthesis of Fully Bio-Based Triblock Structures Derived from ß-Farnesene and ll-Dilactide: Thermoplastic Elastomers.

Current environmental challenges and the shrinking fossil-fuel feedstock are important criteria for the next generation of polymer materials. In this context, we present a fully bio-based material, which shows promise as a thermoplastic elastomer (TPE). Due to the use of ß-farnesene and L-lactide as monomers, bio-based feedstocks, namely sugar cane and corn, can be used. A bifunctional initiator for the carbanionic polymerization was employed, to permit an efficient synthesis of ABA-type block structures. In addition, the "green" solvent MTBE (methyl tert-butyl ether) was used for the anionic polymerisation, enabling excellent solubility of the bifunctional anionic initiator. This afforded low dispersity (D=1.07 to 1.10) and telechelic polyfarnesene macroinitiators. These were employed for lactide polymerization to obtain H-shaped triblock copolymers. TEM and SAXS revealed clearly phase-separated morphologies, and tensile tests demonstrated elastic mechanical properties. The materials featured two glass transition temperatures, at - 66 °C and 51 °C as well as gyroid or cylindrical morphologies, resulting in soft elastic materials at room temperature.

Tailoring thermoresponsiveness of biocompatible polyethers: copolymers of linear glycerol and ethyl glycidyl ether.

Linear polyglycerol is known as a highly hydrophilic and biocompatible polymer that is currently considered for numerous medical applications. Derived from this well-known structure, the synthesis of highly biocompatible, thermoresponsive polyether copolymers via statistical anionic ring-opening copolymerization of ethyl glycidyl ether (EGE) and ethoxy ethyl glycidyl ether (EEGE) is described. Subsequent deprotection of the acetal groups of EEGE yields copolymers of linear glycerol (linG) and EGE, P(linG-co-EGE). These copolymers showed monomodal and narrow molecular weight distributions with dispersities D ≤ 1.07. The microstructure was investigated via in situ1H NMR kinetics experiments, revealing reactivity ratios of rEEGE = 1.787 ± 0.007 and rEGE = 0.560 ± 0.002, showing a slightly favored incorporation of EEGE over EGE. Due to the deliberate incorporation of rather hydrophobic EGE units into the water soluble linPG, tunable thermoresponsive behavior is achieved with cloud point temperatures Tcp between 9.0-71.4 °C. Besides the commonly utilized method turbidimetry, temperature-dependent 1H NMR measurements were used for more accurate and reproducible results. The change of the hydrodynamic radii rH of the copolymers and their aggregates upon reaching Tcp was investigated via DOSY NMR spectroscopy. To explore possible biomedical applications, as an example, the cell viability and immunology of an exemplary P(linG-co-EGE) copolymer sample was investigated. Since both, cell viability and immunology are comparable to the gold standard PEG, the herein presented copolymers show high potential as biocompatible and thermoresponsive alternatives to PEG for biomedical applications.

Merging Styrene and Diene Structures to a Cyclic Diene: Anionic Polymerization of 1-Vinylcyclohexene (VCH).

We report the first anionic polymerization of 1-vinylcyclohexene (VCH). This structure may be considered as an intermediate between dienes and styrene. The polymerization of this cyclic 1,2-disubstituted 1,3-diene proceeded quantitatively in cyclohexane at 25 °C with sec-butyllithium as an initiator. The obtained polymers have well-controlled molecular weights in the range of 5 to 142 kg mol-1 , controlled by the molar ratio of monomer and initiator, with narrow molecular weight distributions (D<1.07-1.20). In situ 1 H NMR kinetic characterization revealed a weak gradient structure for the copolymers of styrene and VCH, (rSty =2.55, rVCH =0.39). P(VCH) obtained in cyclohexane with sec-BuLi as an initiator showed both 1,4- and 3,4-incorporation mode (ratio: 64 : 36). It was demonstrated that the microstructure of the resulting P(VCH) can be altered by the addition of a modifier (THF), resulting in increasing 3,4-microstructure (up to 78 %) and elevated glass-transition temperature up to 89 °C. Thus, the monomer VCH polymerizes carbanionically like a diene, however leading to rigid polymers with high glass transition temperature, which provides interesting options for combination with other dienes to well-defined polymer architectures and materials.

End Group Functionality of 95-99%: Epoxide Functionalization of Polystyryl-Lithium Evaluated via Solvent Gradient Interaction Chromatography.

End group functionality is a key parameter of functional polymer chains. The end-capping efficiency of living polystyryl lithium with various epoxides, namely ethylene oxide (EO), ethoxy ethyl glycidyl ether (EEGE) and isopropylidene glyceryl glycidyl ether (IGG), is investigated with solvent gradient interaction chromatography (SGIC). Generally, end-capping efficiencies >95% are observed. Hydroxy functional polystyrene (PS-OH, PS-EEGE-OH, and PS-IGG-OH) with molar masses ranging from 13.8 to 15.0 kg mol-1 are obtained, with dispersities of 1.05-1.06. Deprotection of the acetal (PS-EEGE-OH) and ketal protective group (PS-IGG-OH) is investigated. Nearly quantitative deprotection (>99%) resulting in the corresponding multihydroxy functional PS (PS-(OH)2 and PS-(OH)3 ) are observed via SGIC. Esterification of PS-OH with succinic anhydride shows a conversion of 98% to the corresponding ester. A detailed picture of side reactions during the carbanionic polymer synthesis subsequent epoxide termination is obtained, demonstrating 95-99% terminal functionality. Depending on the polarity of the end group, an elution order of PS-OH < PS-(OH)2  < PS-(OH)3  < PS-COOH is obtained in SGIC. The study demonstrates both the analytical power of SGIC and the exceptionally high terminal functionalization efficiency of anionic polymerization methods.

Polyethers Based on Short-Chain Alkyl Glycidyl Ethers: Thermoresponsive and Highly Biocompatible Materials.

The polymerization of short-chain alkyl glycidyl ethers (SCAGEs) enables the synthesis of biocompatible polyethers with finely tunable hydrophilicity. Aliphatic polyethers, most prominently poly(ethylene glycol) (PEG), are utilized in manifold biomedical applications due to their excellent biocompatibility and aqueous solubility. By incorporation of short hydrophobic side-chains at linear polyglycerol, control of aqueous solubility and the respective lower critical solution temperature (LCST) in aqueous solution is feasible. Concurrently, the chemically inert character in analogy to PEG is maintained, as no further functional groups are introduced at the polyether structure. Adjustment of the hydrophilicity and the thermoresponsive behavior of the resulting poly(glycidyl ether)s in a broad temperature range is achieved either by the combination of the different SCAGEs or with PEG as a hydrophilic block. Homopolymers of methyl and ethyl glycidyl ether (PGME, PEGE) are soluble in aqueous solution at room temperature. In contrast, n-propyl glycidyl ether and iso-propyl glycidyl ether lead to hydrophobic polyethers. The use of a variety of ring-opening polymerization techniques allows for controlled polymerization, while simultaneously determining the resulting microstructures. Atactic as well as isotactic polymers are accessible by utilization of the respective racemic or enantiomerically pure monomers. Polymer architectures varying from statistical copolymers, di- and triblock structures to star-shaped architectures, in combination with PEG, have been applied in various thermoresponsive hydrogel formulations or polymeric surface coatings for cell sheet engineering. Materials responding to stimuli are of increasing importance for "smart" biomedical systems, making thermoresponsive polyethers with short-alkyl ether side chains promising candidates for future biomaterials.

Ordering kinetics of a tapered copolymer based on isoprene and styrene.

High molar mass copolymers with a tapered interface are mechanically tough materials with an accessible order-to-disorder transition temperature and hence processability. We report the first ordering kinetics for a tapered tetrablock copolymer in comparison to a conventional diblock copolymer made sequentially. We show that tapered copolymers belong to the Brazovskii "universality class," where fluctuations play a dominant role. Consequently, the order-to-disorder transition has a very weak, fluctuation-induced first-order character. The ordering kinetics of the lamellar phase from the supercooled disordered melt revealed several distinct differences associated with the range of metastability (increased), the timescales (bimodal), and the exact mechanism of ordering. The results are discussed in terms of the reduced interaction parameter and the introduction of structural defects within the lamellar grains.

Temperature Variation Enables the Design of Biobased Block Copolymers via One-Step Anionic Copolymerization.

A one-pot approach for the preparation of diblock copolymers consisting of polystyrene and polymyrcene blocks is described via a temperature-induced block copolymer (BCP) formation strategy. A monomer mixture of styrene and myrcene is employed. The unreactive nature of myrcene in a polar solvent (tetrahydrofuran) at -78 °C enables the sole formation of active polystyrene macroinitiators, while an increase of the temperature (-38 °C to room temperature) leads to poly(styrene-block-myrcene) formation due to polymerization of myrcene. Well-defined BCPs featuring molar masses in the range of 44-117.2 kg mol-1 with dispersities, Ð, of 1.09-1.21, and polymyrcene volume fractions of 30-64% are accessible. Matrix assisted laser desorption ionization-time of flight mass spectrometry measurements reveal the temperature-controlled polymyrcene block formation, while both transmission electron microscopy and small-angle X-ray scattering measurements prove the presence of clearly microphase-separated, long range-ordered domains in the block copolymers. The temperature-controlled one-pot anionic block copolymerization approach may be general for other terpene-diene monomers.

The Unique Versatility of the Double Metal Cyanide (DMC) Catalyst: Introducing Siloxane Segments to Polypropylene Oxide by Ring-Opening Copolymerization.

The combination of hydrophobic polydimethylsiloxane (PDMS) blocks with hydrophilic polyether segments plays a key role for silicone surfactants. Capitalizing on the double metal cyanide (DMC) catalyst, the direct (i.e., statistical) copolymerization of cyclic siloxanes and epoxides is shown to be feasible. The solvent-free one-pot copolymerization of hexamethylcyclotrisiloxane and propylene oxide results in the formation of gradient propylene oxide (PPO)-PDMS copolymers. Copolymers with up to 46% siloxane content with low dispersities (Р< 1.2) are obtained in the molecular weight range of 2100-2900 g mol-1 . The polymerization kinetics are investigated by pressure monitoring and in situ 1 H and in situ 29 Si NMR spectroscopy. Contact angle measurements reveal the impact of siloxane incorporation manifest in strongly increased hydrophobicity of PPO-PDMS copolymers and a glass transition of -95 °C for 46% SiO content. This unusual copolymerization offers promise for the synthesis of silicone/polyether polyols.

Stability of Alkyl Chain-Mediated Lipid Anchoring in Liposomal Membranes.

Lipid exchange among biological membranes, lipoprotein particles, micelles, and liposomes is an important yet underrated phenomenon with repercussions throughout the life sciences. The premature loss of lipid molecules from liposomal formulations severely impacts therapeutic applications of the latter and thus limits the type of lipids and lipid conjugates available for fine-tuning liposomal properties. While cholesterol derivatives, with their irregular lipophilic surface shape, are known to readily undergo lipid exchange and interconvert, e.g., with serum, the situation is unclear for lipids with regular, linear-shaped alkyl chains. This study compares the propensity of fluorescence-labeled lipid conjugates of systematically varied lengths to migrate from liposomal particles consisting mainly of egg phosphatidyl choline 3 (EPC3) and cholesterol into biomembranes. We show that dialkyl glyceryl lipids with chains of 18-20 methylene units are inherently stable in liposomal membranes. In contrast, C16 lipids show some lipid exchange, albeit significantly less than comparable cholesterol conjugates. Remarkably, the C18 chain length, which confers noticeable anchor stability, corresponds to the typical chain length in biological membranes.

"Dumb" pH-Independent and Biocompatible Hydrogels Formed by Copolymers of Long-Chain Alkyl Glycidyl Ethers and Ethylene Oxide.

The formation and rheological properties of hydrogels based on amphiphilic ABA triblock polyether copolymers are described, relying solely on the hydrophobic interaction of long-chain alkyl glycidyl ether (AlkGE)- based A-blocks that are combined with a hydrophilic poly(ethylene glycol) (PEG) midblock. Via anionic ring-opening copolymerization (AROP), ethylene oxide (EO) and long-chain alkyl glycidyl ethers (AlkGEs) were copolymerized, using deprotonated poly(ethylene glycol) (PEG) macroinitiators (Mn of 10, 20 kg mol-1). The polymerization afforded amphiphilic ABA triblock copolymers with molar masses in the range of 21-32 kg mol-1 and dispersities (D) of D = 1.07-1.17. Kinetic studies revealed random copolymerization of EO and AlkGE, indicating random spacing of the hydrophobic AlkGE units by polar EO units. Following this approach, the hydrophobicity of the apolar blocks of amphiphilic ABA triblock polyethers can be tailored. Detailed rheological measurements confirmed the successful formation of hydrogels at different pH values as a consequence of nonpolar interactions and alkyl chain crystallization. Hydrogel formation was also observed at different ionic strengths (i.e., varied salt concentration), based on the hydrophobic aggregates. This behavior is in contrast to other often-used supramolecular cross-linking strategies, such as Coulomb interactions, complexation, or hydrogen bonding. Micro-differential scanning calorimetry (µ-DSC) measurements of the hydrogels revealed crystalline hydrophobic domains with melting temperatures in the physiological temperature range. In 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays, diblock copolymers possessing structural analogy to the triblock copolymers were studied to assess the general cytotoxicity of amphiphilic polyethers bearing long alkyl chains at the polyether backbone, using splenic immune cells. At intermediate polymer concentrations, no cytotoxic effects were observed. This indicates that long-chain alkyl glycidyl ethers are promising for the introduction of highly hydrophobic as well as crystalline motifs at the polyether backbone in hydrogels for biomedical purposes.

Efficiency Boosting of Surfactants with Poly(ethylene oxide)-Poly(alkyl glycidyl ether)s: A New Class of Amphiphilic Polymers.

Twenty years ago, it was found that adding small amounts of amphiphilic block copolymers like poly(ethylene propylene)-co-poly(ethylene oxide) (PEP-b-PEO) to microemulsion systems strongly increases the efficiency of medium-chain surfactants to solubilize water and oil. Although being predestined to serve as a milestone in microemulsion research, the effect has only scarcely found its way into applications. In this work, we propose new types of efficiency boosters, namely, poly(ethylene oxide)-poly(alkyl glycidyl ether carbonate)s (PEO-b-PAlkGE) and their "carbonated" poly(ethylene oxide)-poly(carbonate alkyl glycidyl ether) analogs. Their synthesis via anionic ring-opening polymerization (AROP) from commercially available long-chain alkyl glycidyl ethers (AlkGE) and monomethoxypoly(ethylene glycol)s as macroinitiators can be performed at low cost and on a large scale. We demonstrate that these new PEO-b-PAlkGE copolymers with dodecyl and hexadecyl side chains in the nonpolar block strongly increase the efficiency of both pure and technical-grade n-alkyl polyglycol ether surfactants to form microemulsions containing pure n-alkanes or even technical-grade waxes, a result that could be of interest for industrial applications where reduced surfactant needs would have significant economic and ecological implications. For n-decane microemulsions, the boosting effect of PEO-b-PAlkGE and PEP-b-PEO polymers can be scaled on top of each other, when plotting the efficiency semilogarithmically versus the polymeric coverage of the amphiphilic film. Interestingly, a somewhat different scaling behavior was observed for n-octacosane microemulsions at elevated temperatures, suggesting that the polymers show less self-avoidance and rather behave as almost ideal chains. A similar trend was found for the increase of the bending rigidity κ upon polymeric coverage of the amphiphilic film, which was obtained from the analysis of small-angle neutron scattering (SANS) measurements.

Long-Chain Alkyl Epoxides and Glycidyl Ethers: An Underrated Class of Monomers.

Long-chain epoxides and specifically alkyl glycidyl ethers represent a class of highly hydrophobic monomers for anionic ring-opening polymerization (AROP), resulting in apolar aliphatic polyethers. In contrast, poly(ethylene glycol) is known for its high solubility in water. The combination of hydrophobic and hydrophilic monomers in block and statistical copolymerization reactions enables the synthesis of amphiphilic polyethers for a wide range of purposes, utilizing micellar interactions in aqueous solutions, e.g., viscosity enhancement of aqueous solutions, formation of supramolecular hydrogels, or for polymeric surfactants. Controlled polymerization of these highly hydrophobic long-chain epoxide monomers via different synthesis strategies, AROP, monomer-activated anionic ring-opening polymerization, catalytic polymerization, or via postmodification, enables precise control of the hydrophilic/lipophilic balance. This renders amphiphilic polymers highly interesting candidates for specialized applications, e.g., as co-surfactants in microemulsion systems. Amphiphilic polyethers based on propylene oxide and ethylene oxide, such as poloxamers are already utilized in many established applications due to the high biocompatibility of the polyether backbone. Long alkyl chain epoxides add an interesting perspective to this area and permit structural tailoring. This review gives an overview of the recent developments regarding the synthesis of amphiphilic polyethers bearing long alkyl chains and their applications.

Hydroxamic Acid: An Underrated Moiety? Marrying Bioinorganic Chemistry and Polymer Science.

Even 150 years after their discovery, hydroxamic acids are mainly known as the starting material for the Lossen rearrangement in textbooks. However, hydroxamic acids feature a plethora of existing and potential applications ranging from medical purposes to materials science, based on their excellent complexation properties. This underrated functional moiety can undergo a broad variety of organic transformations and possesses unique coordination properties for a large variety of metal ions, for example, Fe(III), Zn(II), Mn(II), and Cr(III). This renders it ideal for biomedical applications in the field of metal-associated diseases or the inhibition of metalloenzymes, as well as for the separation of metals. Considering their chemical stability and reactivity, their biological origin and both medical and industrial applications, this Perspective aims at highlighting hydroxamic acids as highly promising chelators in the fields of both medical and materials science. Furthermore, the state of the art in combining hydroxamic acids with a variety of polymer structures is discussed and a perspective regarding their vast potential at the interface of bioinorganic and polymer chemistry is given.

Multifunctional Fe(III)-Binding Polyethers from Hydroxamic Acid-Based Epoxide Monomers.

Multiple hydroxamic acids are introduced at poly(ethylene glycol) (PEG) via copolymerization of ethylene oxide with a novel epoxide monomer containing a 1,4,2-dioxazole-protected hydroxamic acid (HAAGE). AB- and ABA-type di- and triblock copolymers as well as statistical copolymers of HAAGE and ethylene oxide are prepared in a molecular weight range between 2600 and 12 000 g mol-1 with low dispersities (Ð < 1.2). Cleavage of the acetal protecting group after the polymerization is achieved by mild acidic treatment, releasing multiple free hydroxamic acids tethered to the polyether backbone. The chelation properties of different polymer architectures (statistical versus diblock and ABA triblock) are investigated and compared with regard to the number and position of hydroxamic acids. Separation of the hydroxamic acid units by at least 5 ethylene glycol monomer units is found to be essential for high Fe(III) binding efficiency, while block copolymers are observed to be the best-suited architecture for polymer network and hydrogel formation via Fe(III) chelation.

Acid-Cleavable Poly(ethylene glycol) Hydrogels Displaying Protein Release at pH†5.

PEG is the gold standard polymer for pharmaceutical applications, however it lacks degradability. Degradation under physiologically relevant pH as present in endolysosomes, cancerous and inflammatory tissues is crucial for many areas. The authors present anionic ring-opening copolymerization of ethylene oxide with 3,4-epoxy-1-butene (EPB) and subsequent modification to introduce acid-degradable vinyl ether groups as well as methacrylate (MA) units, enabling radical cross-linking. Copolymers with different molar ratios of EPB, molecular weights (Mn ) up to 10 000 g mol-1 and narrow dispersities (D<1.05) were prepared. Both the P(EG-co-isoEPB)MA copolymer and the hydrogels showed pH-dependent, rapid hydrolysis at pH 5-6 and long-term storage stability at neutral pH (pH 7.4). By designing the degree of polymerization and content of degradable vinyl ether groups, the release time of an entrapped protein OVA-Alexa488 can be tailored from a few hours to several days (hydrolysis half-life time t1/2 at pH 5: 13 h to 51 h).

A general concept for the introduction of hydroxamic acids into polymers.

Hydroxamic acids (HA) form stable complexes with a large variety of metal-ions, affording hydroxamates with high complexation constants. Hydroxamic acid moieties play a crucial role in the natural iron metabolism. In this work, 1,4,2-dioxazoles linked to a hydroxyl group are introduced as key compounds for the installation of hydroxamic acids at synthetic polymers in well-defined positions. A general synthetic scheme is developed that gives access to a series of novel functional key building blocks that can be universally used to obtain hydroxamic acid-based monomers and polymers, for instance as protected HA-functional initiators or for the synthesis of a variety of novel HA-based monomers, such as epoxides or methacrylates. To demonstrate the excellent stability of the dioxazole-protected hydroxamic acids, direct incorporation of the dioxazole-protected hydroxamic acids into polyethers is demonstrated via oxyanionic polymerization. Convenient subsequent deprotection is feasible under mild acidic conditions. α-Functional HA-polyethers, i.e. poly ethylene glycol, polypropylene glycol and polyglycerol based on ethylene oxide, propylene oxide and ethoxy ethyl glycidyl ether, respectively are prepared with low dispersities (<1.2) in the molecular weight range of 1000 to 8500 g mol-1. Water-soluble hydroxamic acid functional poly(ethylene glycol) (HA-PEG) is explored for a variety of biomedical applications and surface coating. Complexation of Fe(iii) ions, coating of various metal surfaces, enabling e.g., solubilization of FeO x nanoparticles by HA-PEGs, are presented. No impact of the polyether chain on the chelation properties was observed, while significantly lower anti-proliferative effects were observed than for deferoxamine. HA-PEGs show the same complexation behavior as their low molecular weight counterparts. Hydroxamic acid functional polymers are proposed as an oxidatively stable alternative to the highly established catechol-based systems.

Solution-processed transparent ferroelectric nylon thin films.

Ferroelectricity, a bistable ordering of electrical dipoles in a material, is widely used in sensors, actuators, nonlinear optics, and data storage. Traditional ferroelectrics are ceramic based. Ferroelectric polymers are inexpensive lead-free materials that offer unique features such as the freedom of design enabled by chemistry, the facile solution-based low-temperature processing, and mechanical flexibility. Among engineering polymers, odd nylons are ferroelectric. Since the discovery of ferroelectricity in polymers, nearly half a century ago, a solution-processed ferroelectric nylon thin film has not been demonstrated because of the strong tendency of nylon chains to form hydrogen bonds. We show the solution processing of transparent ferroelectric thin film capacitors of odd nylons. The demonstration of ferroelectricity, as well as the way to obtain thin films, makes odd nylons attractive for applications in flexible devices, soft robotics, biomedical devices, and electronic textiles.

Functionalization of Liposomes with Hydrophilic Polymers Results in Macrophage Uptake Independent of the Protein Corona.

Liposomes are established drug carriers that are employed to transport and deliver hydrophilic drugs in the body. To minimize unspecific cellular uptake, nanocarriers are commonly modified with poly(ethylene glycol) (PEG), which is known to minimize unspecific protein adsorption. However, to date, it has not been studied whether this is an intrinsic and specific property of PEG or if it can be transferred to hyperbranched polyglycerol (hbPG) as well. Additionally, it remains unclear if the reduction of unspecific cell uptake is independent of the "basic" carrier at which a surface functionalization with polymers is usually applied. Therefore, we studied the protein corona of differently functionalized liposomes (unfunctionalized vs PEG or hbPG-functionalized) using PEGylated and PGylated lipids. Their cellular uptake in macrophages was compared. For all three liposomal samples, rather similar protein corona compositions were found, and also-more importantly-the total amount of proteins adsorbed was very low compared to other nanoparticles. Interestingly, the cellular uptake was then significantly changed by the surface functionalization itself, despite the adsorption of a small amount of proteins: although the PEGylation of liposomes resulted in the abovementioned decreased cell uptake, functionalization with hbPG lead to enhanced macrophage interaction-both in the media with and without proteins. In comparison to other nanocarrier systems, this seems to be a liposome-specific effect related to the low amount of adsorbed proteins.

Glycidyl Tosylate: Polymerization of a "Non-Polymerizable" Monomer permits Universal Post-Functionalization of Polyethers.

Glycidyl tosylate appears to be a non-polymerizable epoxide when nucleophilic initiators are used because of the excellent leaving group properties of the tosylate. However, using the monomer-activated mechanism, this unusual monomer can be copolymerized with ethylene oxide (EO) and propylene oxide (PO), respectively, yielding copolymers with 7-25 % incorporated tosylate-moieties. The microstructure of the copolymers was investigated via in situ 1 H NMR spectroscopy, and the reactivity ratios of the copolymerizations have been determined. Quantitative nucleophilic substitution of the tosylate-moiety is demonstrated for several examples. This new structure provides access to a library of functionalized polyethers that cannot be synthesized by conventional oxyanionic polymerization.