Targeted Drug Delivery in Plants: Enzyme‐Responsive Lignin Nanocarriers for the Curative Treatment of the Worldwide Grapevine Trunk Disease Esca

Abstract Nanocarrier (NC)‐mediated drug delivery is widely researched in medicine but to date has not been used in agriculture. The first curative NC‐based treatment of the worldwide occurring grapevine trunk disease Esca, with more than 2 billion infected plants causing a loss yearly of $1.5 billion, is presented. To date, only repetitive spraying of fungicides is used to reduce chances of infection. This long‐term treatment against Esca uses minimal amounts of fungicide encapsulated in biobased and biodegradable lignin NCs. A single trunk injection of <10 mg fungicide results in curing of an infected plant. Only upon Esca infection, ligninolytic enzymes, secreted by the Esca‐associated fu…

Hyperbranched PEG by Random Copolymerization of Ethylene Oxide and Glycidol

The synthesis of hyperbranched poly(ethylene glycol) (hbPEG) in one step was realized by random copolymerization of ethylene oxide and glycidol, leading to a biocompatible, amorphous material with multiple hydroxyl functionalities. A series of copolymers with moderate polydispersity ($\overline {M} _{{\rm w}} /\overline {M} _{{\rm n}} $ < 1.8) was obtained with varying glycidol content (3-40 mol-%) and molecular weights up to 49 800 g mol(-1) . The randomly branched structure of the copolymers was confirmed by (1) H and (13) C NMR spectroscopy and thermal analysis (differential scanning calorimetry). MTS assay demonstrated low cell toxicity of the hyperbranched PEG, comparable to the highly…

ChemInform Abstract: Multifunctional Poly(ethylene glycol)s

In the rapidly evolving multidisciplinary field of polymer therapeutics, tailored polymer structures represent the key constituent to explore and harvest the potential of bioactive macromolecular hybrid structures. In light of the recent developments for anticancer drug conjugates, multifunctional polymers are becoming ever more relevant as drug carriers. However, the potentially best suited polymer, poly(ethylene glycol) (PEG), is unfavorable owing to its limited functionality. Therefore, multifunctional linear copolymers (mf-PEGs) based on ethylene oxide (EO) and appropriate epoxide comonomers are attracting increased attention. Precisely engineered via living anionic polymerization and d…

Covalently Binding of Bovine Serum Albumin to Unsaturated Poly(Globalide-Co-ε-Caprolactone) Nanoparticles by Thiol-Ene Reactions.

When nanoparticles (NPs) are introduced to a biological fluid, different proteins (and other biomolecules) rapidly get adsorbed onto their surface, forming a protein corona capable of giving to the NPs a new "identity" and determine their biological fate. Protein-nanoparticle conjugation can be used in order to promote specific interactions between living systems and nanocarriers. Non-covalent conjugates are less stable and more susceptible to desorption in biological media, which makes the development of engineered nanoparticle surfaces by covalent attachment an interesting topic. In this work, the surface of poly(globalide-co-e-caprolactone) (PGlCL) nanoparticles containing double bonds i…

High biocompatibility and improved osteogenic potential of amorphous calcium carbonate/vaterite.

In human bone, amorphous calcium carbonate (ACC) is formed as a precursor of the crystalline carbonated apatite/hydroxyapatite (HA). Here we describe that the metastable ACC phase can be stabilized by inorganic polyphosphate (polyP) that is also used as a phosphate source for the non-enzymatic carbonate/phosphate exchange during HA formation. This polymer was found to suppress the transformation of ACC into crystalline CaCO3 at a percentage of 5% [w/w] ("CCP5") with respect to CaCO3 and almost completely at 10% [w/w] ("CCP10"). Both preparations (CaCO3/polyP) are amorphous, but also contain small amounts of vaterite, as revealed by XRD, FTIR and SEM analyses. They did not affect the growth/…

Interleukin-2 Functionalized Nanocapsules for T Cell-Based Immunotherapy.

A major demand on immunotherapy is the direct interference with specific immune cells in vivo. In contrast to antibody-engineered nanoparticles to control dendritic cells function, targeting of T cells for biomedical applications still remains an obstacle as they disclose reduced endocytic activities. Here, by coupling the cytokine interleukin-2 (IL-2) to the surface of hydroxyethyl starch nanocapsules, we demonstrated a direct and specifc T cell targeting in vitro and in vivo by IL-2 receptor-mediated internalization. For this purpose, defined amounts of azide-functionalized IL-2 were linked to alkyne-functionalized hydroxyethyl starch nanocapsules via copper-free click reactions. In combi…

PEG-based Multifunctional Polyethers with Highly Reactive Vinyl-Ether Side Chains for Click-Type Functionalization

Introduction of highly reactive vinyl ether moieties along a poly(ethylene-glycol) (PEG) backbone has been realized by copolymerization of the novel epoxide monomer ethoxy vinyl glycidyl ether (EVGE) with ethylene oxide (EO). A series of copolymers with varying structure (block and random) as well as EVGE comonomer content (5-100%) with molecular weights in the range of 3,900-13,200 g/mol and narrow molecular weight distributions (M-w/M-n = 1.06-1.20) has been synthesized and characterized with respect to their microstructure and thermal properties. The facile transformation of the vinyl ether side chains in click type reactions was verified by two different post polymerization modification…

Water-soluble and redox-responsive hyperbranched polyether copolymers based on ferrocenyl glycidyl ether

Water-soluble copolymers of ferrocenyl glycidyl ether (fcGE) and glycidol were prepared via anionic ring-opening multibranching polymerization (ROMBP). The resulting hyperbranched materials with molecular weights (Mn) of 3500 to 12 300 g mol−1 and relatively narrow molecular weight distributions (Mw/Mn = 1.40–1.69) exhibit both temperature- as well as redox-responsive behavior, which was studied via turbidity measurements. The cloud point temperatures (Tc) were adjusted between 45 and 60 °C through variation of the fcGE comonomer content. Additionally, these Tcs can be increased by the addition of an oxidizing agent. The extent of oxidation of the materials was quantified by Mosbauer spectr…

Ferrocenyl Glycidyl Ether: A Versatile Ferrocene Monomer for Copolymerization with Ethylene Oxide to Water-Soluble, Thermoresponsive Copolymers

The first ferrocene-containing epoxide monomer, ferrocenyl glycidyl ether (fcGE), is introduced. The monomer has been copolymerized with ethylene oxide (EO). This leads to electroactive, water-soluble, and thermoresponsive poly(ethylene glycol) (PEG) derived copolyethers. Anionic homo- and copolymerization of fcGE with EO was possible. Molecular weights could be varied from 2000 to 10 000 g mol–1, resulting in polymers with narrow molecular weight distribution (Mw/Mn = 1.07–1.20). The ferrocene (fc) content was varied from 3 to 30 mol %, obtaining water-soluble materials up to 10 mol % incorporation of the apolar ferrocenyl comonomer. Despite the steric bulk of fcGE, random copolymers were …

From CO2 -Based Multifunctional Polycarbonates With a Controlled Number of Functional Groups to Graft Polymers

Acid‐Labile Amphiphilic PEO‐ b ‐PPO‐ b ‐PEO Copolymers: Degradable Poloxamer Analogs

Poly ((ethylene oxide)-b-(propylene oxide)-b-(ethylene oxide)) triblock copolymers commonly known as poloxamers or Pluronics constitute an important class of nonionic, biocompatible surfactants. Here, a method is reported to incorporate two acid-labile acetal moieties in the backbone of poloxamers to generate acid-cleavable nonionic surfactants. Poly(propylene oxide) is functionalized by means of an acetate-protected vinyl ether to introduce acetal units. Three cleavable PEO-PPO-PEO triblock copolymers (Mn,total = 6600, 8000, 9150 g·mol(-1) ; Mn,PEO = 2200, 3600, 4750 g·mol(-1) ) have been synthesized using anionic ring-opening polymerization. The amphiphilic copolymers exhibit narrow molec…

Functional Group Distribution and Gradient Structure Resulting from the Living Anionic Copolymerization of Styrene and para-But-3-enyl Styrene

The functional group distribution along the polymer backbone resulting from the living anionic copolymerization of styrene (S) and para-but-3-enyl styrene (pBuS) was investigated in cyclohexane at room temperature. A variety of copolymers with different comonomer contents x(S) = 0–0.84 have been synthesized with molecular weight dispersities Mw/Mn ≤1.12. All polymers have been characterized in detail by 1H NMR spectroscopy, size exclusion chromatography (SEC), and differential scanning calorimetry (DSC). A detailed understanding of the monomer sequence distribution during the copolymerization was achieved by real-time 1H NMR spectroscopy. This technique permits us to determine the changing …

Squaric acid mediated chemoselective PEGylation of proteins: reactivity of single-step-activated α-amino poly(ethylene glycol)s.

The covalent attachment of poly(ethylene glycol) (PEG) to therapeutically active proteins (PEGylation) has become an important method to deal with the pharmacological difficulties of these polypeptides, such as short body-residence times and immunogenicity. However, the derivatives of PEG used for PEGylation lack further functional groups that would allow the addition of targeting or labeling moieties. Squaric acid diethyl ester was used for the chemoselective single-step activation of poly(ethylene glycol)s into the respective ester amides. The resultant selective protein-reactive poly(ethylene glycol)s were investigated with respect to their selectivity towards amino acid residues in bovi…

Combining oxyanionic polymerization and click-chemistry: a general strategy for the synthesis of polyether polyol macromonomers

We describe a synthetic pathway to tailor-made amphiphilic macromonomers by a combination of anionic ring-opening polymerization and copper-catalyzed azide–alkyne cycloaddition (CuAAC). Linear polyglycerol and poly(glyceryl glycerol) were synthesized in a controlled manner by anionic ring-opening polymerization of ethoxyethyl glycidyl ether or isopropylidene glyceryl glycidyl ether, respectively, with narrow and monomodal molecular weight distributions (Mw/Mn < 1.20) and molecular weights ranging from 850 g mol−1 to 2500 g mol−1. After end-capping with propargyl bromide and removal of the protecting groups, the hydrophilic precursors were quantitatively clicked to a series of hydrophobic az…

Rapid Access to Polyfunctional Lipids with Complex Architecture via Oxyanionic Ring-Opening Polymerization

Polymer-coated liposomes, particularly poly(ethylene glycol) (PEG)-substituted liposomes, have emerged as long-circulating carrier systems for drug delivery and diagnostic purposes. A rapid synthesis of three different types of multifunctional lipids with structurally diverse hydrophilic, polyether-based architectures via one- or two-pot approaches is described. Architectural variation is achieved by the combination of different oxyanionic polymerization strategies and various glycidyl ether building units. Branched polyglycerol lipids have been prepared via cholesterol- or 1,2-bis-n-alkyl glyceryl ether-initiated, oxyanionic ring-opening polymerization (ROP) of protected glycidyl ethers an…

Nanovesicles as Drug Delivery Vehicles: Liposomes and Polymersomes

Fast Access to Amphiphilic Multiblock Architectures by the Anionic Copolymerization of Aziridines and Ethylene Oxide.

An ideal system for stimuli-responsive and amphiphilic (block) polymers would be the copolymerization of aziridines with epoxides. However, to date, no copolymerization of these two highly strained three-membered heterocycles had been achieved. Herein, we report the combination of the living oxy- and azaanionic ring-opening polymerization of ethylene oxide (EO) and sulfonamide-activated aziridines. In a single step, well-defined amphiphilic block copolymers are obtained by a one-pot copolymerization. Real-time 1H NMR spectroscopy revealed the highest difference in reactivity ratios ever reported for an anionic copolymerization (with r1 = 265 and r2 = 0.004 for 2-methyl- N-tosylaziridine/EO …

Carbohydrate-Based Nanocarriers Exhibiting Specific Cell Targeting with Minimum Influence from the Protein Corona.

Whenever nanoparticles encounter biological fluids like blood, proteins adsorb on their surface and form a so-called protein corona. Although its importance is widely accepted, information on the influence of surface functionalization of nanocarriers on the protein corona is still sparse, especially concerning how the functionalization of PEGylated nanocarriers with targeting agents will affect protein corona formation and how the protein corona may in turn influence the targeting effect. Herein, hydroxyethyl starch nanocarriers (HES-NCs) were prepared, PEGylated, and modified on the outer PEG layer with mannose to target dendritic cells (DCs). Their interaction with human plasma was then s…

Surface Modification of Porous Polyethylene Implants with an Albumin-Based Nanocarrier-Release System

Background: Porous polyethylene (PPE) implants are used for the reconstruction of tissue defects but have a risk of rejection in case of insufficient ingrowth into the host tissue. Various growth factors can promote implant ingrowth, yet a long-term gradient is a prerequisite for the mediation of these effects. As modification of the implant surface with nanocarriers may facilitate a long-term gradient by sustained factor release, implants modified with crosslinked albumin nanocarriers were evaluated in vivo. Methods: Nanocarriers from murine serum albumin (MSA) were prepared by an inverse miniemulsion technique encapsulating either a low- or high-molar mass fluorescent cargo. PPE implants …

Kontrollierte Polymermikrostruktur in anionischer Polymerisation durch Kompartimentierung

Controlling the Polymer Microstructure in Anionic Polymerization by Compartmentalization.

An ideal random anionic copolymerization is forced to produce gradient structures by physical separation of two monomers in emulsion compartments. One monomer (M) is preferably soluble in the droplets, while the other one (D) prefers the continuous phase of a DMSO-in-cyclohexane emulsion. The living anionic copolymerization of two activated aziridines is thus confined to the DMSO compartments as polymerization occurs selectively in the droplets. Dilution of the continuous phase adjusts the local concentration of monomer D in the droplets and thus the gradient of the resulting copolymer. The copolymerizations in emulsion are monitored by real-time 1 H NMR kinetics, proving a change of the re…

Biodegradable Protein Nanocontainers

The application of synthetic polymers for drug delivery often requires tremendous efforts to ensure biocompatibility and -degradation. To use the body's own substances can help to overcome these problems. Herein, we present the first synthesis of nanocontainers entirely composed of albumin proteins. These protein nanocontainers (PNCs) were loaded with hydrophilic compounds and release of the payload is triggered through natural lysis in vitro in human monocyte-derived dendritic cells (moDCs). No aggregation of PNCs in human blood plasma was observed, indicating stability for blood circulation. As the PNCs were readily taken up by moDCs, they are considered as a promising delivery platform f…

Fully degradable protein nanocarriers by orthogonal photoclick tetrazole-ene chemistry for the encapsulation and release

The encapsulation of sensitive drugs into nanocarriers retaining their bioactivity and achieving selective release is a challenging topic in current drug delivery design. Established protocols rely on metal-catalyzed or unspecific reactions to build the (mostly synthetic) vehicles which may inhibit the drug's function. Triggered by light, the mild tetrazole–ene cycloaddition enables us to prepare protein nanocarriers (PNCs) preserving at the same time the bioactivity of the sensitive antitumor and antiviral cargo Resiquimod (R848). This catalyst-free reaction was designed to take place at the interface of aqueous nanodroplets in miniemulsion to produce core–shell PNCs with over 90% encapsul…

Pencil Lead as a Matrix for MALDI-ToF Mass Spectrometry of Sensitive Functional Polymers

With the increase in complexity of functional polymers in recent years, MALDI-ToF has become an important tool for gaining precise information on polymer functionality, end groups, and, in special cases, molecular weights. Here we describe how pencil lead, deposited by simply drawing with a regular pencil onto conventional MALDI-ToF targets, can be used as a very attractive matrix for MALDI-ToF mass spectrometry of synthetic polymers. Highly sensitive polymers such as silyl hydride functional poly(styrene), poly(butadiene), and poly(isoprene) have been investigated using conventional MALDI-ToF matrices as well as pencil lead. In all cases, the use of pencil lead prevented oxidation of the h…

Aliphatic Polyethers: Classical Polymers for the 21st Century.

Polyethers-polymers with the structural element (R'-O-R)n in their backbone--are an old class of polymers which were already used at the time of the ancient Egyptians. However, still today these materials are highly important with applications in all areas of our life, reaching from the automotive and paper industry to cosmetics and biomedical applications. In this Review, different aliphatic polyethers like poly(epoxide)s, poly(oxetane)s, and poly(tetrahydrofuran) are discussed. Special emphasis is placed on the history, the polymerization techniques (industrially and in academia), the properties, the applications as well as recent developments of these materials.

Enlarging the Toolbox: Epoxide Termination of Polyferrocenylsilane (PFS) as a Key Step for the Synthesis of Amphiphilic PFS-Polyether Block Copolymers.

Epoxide termination and functionalization of living poly(ferrocenyldimethylsilane) (PFDMS) is introduced by precapping the living PFDMS with a 4/2 molar mixture of 1,1-diphenylethylene and 1,1-dimethylsilacyclobutane acting as a “carbanion pump” system. Subsequent addition of allyl glycidyl ether (AGE) leads to quantitatively functionalized PFDMS–AGE polymers with molecular weights between 1500 and 15 400 g mol–1 and polydispersity indices ≤1.10, carrying one hydroxyl group and an additional allylic double bond. PFDMS–AGE was then applied as a macroinitiator for the living anionic ring-opening polymerization of ethylene oxide (EO) to generate amphiphilic and water-soluble poly(ferrocenyldim…

Multifunctional Poly(ethylene glycol)s

In the rapidly evolving multidisciplinary field of polymer therapeutics, tailored polymer structures represent the key constituent to explore and harvest the potential of bioactive macromolecular hybrid structures. In light of the recent developments for anticancer drug conjugates, multifunctional polymers are becoming ever more relevant as drug carriers. However, the potentially best suited polymer, poly(ethylene glycol) (PEG), is unfavorable owing to its limited functionality. Therefore, multifunctional linear copolymers (mf-PEGs) based on ethylene oxide (EO) and appropriate epoxide comonomers are attracting increased attention. Precisely engineered via living anionic polymerization and d…

Tailoring the stealth properties of biocompatible polysaccharide nanocontainers.

Fundamental development of a biocompatible and degradable nanocarrier platform based on hydroxyethyl starch (HES) is reported. HES is a derivative of starch and possesses both high biocompatibility and improved stability against enzymatic degradation; it is used to prepare nanocapsules via the polyaddition reaction at the interface of water nanodroplets dispersed in an organic miniemulsion. The synthesized hollow nanocapsules can be loaded with hydrophilic guests in its aqueous core, tuned in size, chemically functionalized in various pathways, and show high shelf life stability. The surface of the HES nanocapsules is further functionalized with poly(ethylene glycol) via different chemistri…

Synthesis and Characterization of Poly(glyceryl glycerol) Block Copolymers

Polymeric hepatitis C virus non-structural protein 5A nanocapsules induce intrahepatic antigen-specific immune responses

Targeting antigen combined with adjuvants to hepatic antigen-presenting cells (APCs) is essential for the induction of intrahepatic T cellular immunity controlling and resolving viral infections of the liver. Intravenous injection of antigen-loaded nanoparticles is a promising approach for the delivery of antigens to liver APCs. Accordingly, polymeric nanocapsules (NCs) synthesized exclusively of hepatitis C virus non-structural protein 5A (NS5A) and the adjuvant monophosphoryl lipid A (MPLA) adsorbed to the nanocapsule surface were developed. Aim of the present study was the evaluation of the in vitro and in vivo behavior of MPLA-functionalized NS5A-NCs regarding the interaction with liver…

Polymere Janus-Partikel

Branched Versus Linear Polyisoprene: Flory-Huggins Interaction Parameters for their Solutions in Cyclohexane

Flory-Huggins interaction parameters were determined as a function of composition for solutions of linear and of branched polyisoprene in cyclohexane (CH) at 25, 45, and 65 °C by means of vapor pressure measurements (moderate to concentrated solutions) and by vapor pressure osmometry (dilute solutions). The results demonstrate that CH is a considerably worse solvent for branched polyisoprene than for the linear analog at all temperatures and at all compositions. This observation corroborates the expectation based on a recent phenomenological approach, which accounts explicitly for the incapability of the segments of an individual polymer molecule to spread out over the entire volume of the …

Biodegradable lignin nanocontainers

The abundant biomaterial lignin was used to prepare hollow nanocapsules by interfacial polyaddition in inverse miniemulsions. These cross-linked lignin nanocontainers can be loaded with hydrophilic substances which can be released by an enzymatic trigger from natural plant extracts revealing them as potential nanocontainers for agricultural applications.

Double-Hydrophilic Linear-Hyperbranched Block Copolymers Based on Poly(ethylene oxide) and Poly(glycerol)

A convenient 4-step (2-pot) approach for the synthesis of biocompatible, double hydrophilic linear-hyperbranched block copolymers based on poly(ethylene oxide) (PEO) and poly(glycerol) (PG) is described. The polymers consisting exclusively of an aliphatic polyether structure were prepared from linear PEO-b-(l-PG) precursor block copolymers, obtained via anionic polymerization of ethylene oxide and subsequently ethoxyethyl glycidyl ether (EEGE). In order to generate initiating functionalities for glycidol, the protected hydroxyl groups of the P(EEGE) block were recovered by hydrolysis with hydrochloric acid. Partial deprotonation of the linear poly(glycerol) block with cesium hydroxide permi…

Kohlenhydrat-basierte Nanocarrier mit spezifischem Zell-Targeting und minimalem Einfluss durch die Proteinkorona

Sobald Nanopartikel mit biologischen Flussigkeiten wie Blut in Kontakt kommen, adsorbieren Proteine auf ihrer Oberflache, welche die sogenannte Proteinkorona ausbilden. Die Wichtigkeit dieser Proteinhulle ist weitgehend anerkannt, jedoch untersuchen nur wenige Studien den Einfluss von Oberflachenfunktionalisierung der Nanocarrier auf die Proteinkorona. Vor allem die Variation der Proteinkorona von PEGylierten und zusatzlich mit Targeting-Molekulen versehenen Nanotragern und der Einfluss auf das Targeting sind nicht bekannt. Hydroxyethylstarke-Nanocarrier (HES-NCs) wurden synthetisiert, anschliesend PEGyliert und zusatzlich (“on top”) mit Mannose funktionalisiert, um dendritische Zellen (DCs…

Noncovalent Targeting of Nanocarriers to Immune Cells with Polyphosphoester‐Based Surfactants in Human Blood Plasma

Abstract Dendritic cells (DCs) are part of the immune system and can internalize pathogens by carbohydrate receptors. The uptake induces maturation and migration of the DCs resulting in an adaptive immune response by presenting antigens to T‐cells. Thus, targeted delivery to DCs is a powerful tool for immunotherapy. However, in blood, specific targeting is challenging as blood proteins adsorb to the nanocarriers and mask the targeting molecules. Additionally, covalent coupling of targeting groups to nanocarriers requires new chemistry for each nanocarrier, while a general strategy is missing. A general protocol by noncovalent adsorption of mannosylated polyphosphoesters (PPEs) on the nanoca…

Hyperbranched Polyglycerol-Based Lipids via Oxyanionic Polymerization: Toward Multifunctional Stealth Liposomes

We describe the synthesis of linear-hyperbranched lipids for liposome preparation based on linear poly(ethylene glycol) (PEG) and hyperbranched polyglycerol (PG). Molecular weights were adjusted to values around 3000 g/mol with varying degrees of polymerization of the linear and the branched segments in analogy to PEG-based stealth lipids; polydispersities were generally low and below 1.3. The hydrophobic anchors were introduced into the lipid structures as initiators for the anionic polymerization of ethylene oxide and are either based on cholesterol or on different aliphatic glyceryl ethers. Complete incorporation of the apolar initiators was evidenced by MALDI-ToF analysis at all stages …

Automated Large-Scale Synthesis of Supramolecular Oligo(p-benzamide) Block Copolymers

A fully automated large-scale synthesis procedure has been developed that allows the preparation of supramolecular rod−coil copolymers on a 100 g scale. The new reaction cycle allows the stepwise growth of oligo(p-benzamide)s onto the chain end of amine-terminated polymers. Amine-terminated poly(ethylene glycol) (PEG, Mn = 5000 g mol-1) and poly(styrene) (PS, Mn = 2950 g mol-1) were prepared, and an octa(p-benzamide) oligomer block was grown from the chain end in an automated computer-controlled reaction cycle. Plotting the apparent molecular weight of the PEG copolymer against the number of reaction cycles revealed a linear relationship, which emphasized the high level of control this meth…

Hydrophilicity Regulates the Stealth Properties of Polyphosphoester‐Coated Nanocarriers

Increasing the plasma half-life is an important goal in the development of drug carriers, and can be effectively achieved through the attachment of polymers, in particular poly(ethylene glycol) (PEG). While the increased plasma half-life has been suggested to be a result of decreased overall protein adsorption on the hydrophilic surface in combination with the adsorption of specific proteins, the molecular reasons for the success of PEG and other hydrophilic polymers are still widely unknown. We prepared polyphosphoester-coated nanocarriers with defined hydrophilicity to control the stealth properties of the polymer shell. We found that the log P value of the copolymer controls the composit…

Poly(phosphonate)-mediated Horner–Wadsworth–Emmons reactions

A novel, general protocol for a polymer-mediated Horner–Wadsworth–Emmons (HWE) reaction is reported. The polyvalent polymeric reagent was prepared via acyclic diene metathesis (ADMET) polymerization. Homo- and copolymers of reactive poly(phosphonate)s with molecular weights up to 40 000 g·mol−1 and molecular weight dispersities Đ < 2 were successfully synthesized. Subsequent application of these polymers in the HWE reaction to prepare a library of aromatic α,β-unsaturated ketones (chalcons) has proven to be an efficient synthetic pathway to minimize purification efforts, as the polymeric side-product can be removed by simple precipitation. In this paper we also demonstrate for the first tim…

Carbanions on Tap – Living Anionic Polymerization in a Microstructured Reactor

The paper describes the living anionic polymerization of styrenes to homo- and diblock copolymers in continuous flow, using a microstructured mixing set-up ("microreactor"). Reaction times and experimental effort are significantly reduced compared to classical batch methods that often require stringent reaction conditions and strict drying of the apparatus by "break-seal" and "high vacuum" techniques. In continuous flow, residual impurities can be removed by purging the reactor with monomer and initiator solution before polymer samples are collected at the device outlet on a scale of up to 200 g.h -1 . Facile molecular weight adjustment is achieved by variation of the flow rates of initiato…

Linear–dendritic block copolymers: The state of the art and exciting perspectives

Concurrent with the rapid development of both dendrimers and hyperbranched polymers, a novel class of block copolymer architectures has emerged from the combination of these dendritic architectures with linear chains, the “linear–dendritic block copolymers” (LDBCs). This review gives a comprehensive summary of the state of the art in this rapidly developing field from pioneering early work to promising recent approaches.The different strategies leading to these hybrid architectures with either perfect dendrimer/dendron building blocks or imperfect, yet more conveniently accessible hyperbranched segments, are reviewed and compared. The consequences of the unusual polymer topology for supramo…

Poly(methyl ethylene phosphate) hydrogels

Abstract A degradable and water-soluble polyphosphoester (PPE), namely poly(methyl ethylene phosphate)-dimethacrylate (PMEP-DMA), was synthesized and crosslinked by UV irradiation to prepare PPE-hydrogels. Hydrogels with 10 and 15 wt% of PMEP were prepared after UV-irradiation with an additional 0.2 wt% of photoinitiator. The colorless and transparent PPE hydrogels were studied for their swelling and water uptake. The rheological analysis demonstrated their viscoelastic behavior. The PPE hydrogels were compared to poly(ethylene glycol) (PEG) hydrogels prepared from PEG-macromonomers of similar degrees of polymerization. Hydrolysis experiments proved a successful disintegration of the PPE hy…

MPLA-coated hepatitis B virus surface antigen (HBsAg) nanocapsules induce vigorous T cell responses in cord blood derived human T cells.

Chronic hepatitis B virus (HBV) infection is the most prevalent serious liver infection in the world. A frequent route of infection represents mother-to-child transmission. Efficient control of HBV replication depends on antigen-specific cellular immune response mediated by dendritic cells (DCs). Aim of the present study was to evaluate optimized adjuvant combinations, efficiently maturing monocyte-derived neonatal and adult dendritic cells (moDCs). In addition, the potential of polymeric HBsAg-nanocapsules (HBsAg-NCs) was investigated regarding up-take by moDCs and the subsequent induction of specific T cell responses in a human co-culture model. Simultaneous stimulation of moDCs with MPLA…

Vinyl ferrocenyl glycidyl ether: an unprotected orthogonal ferrocene monomer for anionic and radical polymerization

The first orthogonal ferrocene monomer, vinyl ferrocenyl glycidyl ether (VfcGE), for both anionic and radical polymerization – without the need of a protection group – is presented. Anionic ring-opening copolymerization of VfcGE and ethylene oxide (EO) generates stimuli-responsive, multifunctional poly[(vinyl ferrocenyl glycidyl ether)-co-(ethylene oxide)] (P[VfcGE-co-EO]) copolymers (molecular weights of ca. 7500 g mol−1 and low molecular weight dispersities (Đ ≤ 1.14)). The amount of the equimolar ferrocenyl and vinyl groups are controlled by the comonomer ratio up to 15.4 mol% VfcGE. The pendant vinyl groups of P[VfcGE-co-EO] were post-modified with 3-mercaptopropionic acid via thiol–ene…

Chiroptical Induction and Molecular Recognition in Optically Active Hyperbranched Polyethers with Inherently Chiral Benzophenone Core

Hydrophilie als bestimmender Faktor des Stealth-Effekts von Polyphosphoester-funktionalisierten Nanoträgern

Amphiphilic Linear-Hyperbranched Block Copolymers with Linear Poly(ethylene oxide) and Hyperbranched Poly(carbosilane) Block

The synthesis of amphiphilic linear-hyperbranched block copolymers with a linear poly(ethylene oxide) (PEO) segment and a hyperbranched poly(carbosilane)s (PCS) block in a rapid three-step strategy is described, combining oxyanionic polymerization with carbosilane chemistry. A linear precursor block copolymer was synthesized via anionic polymerization of allyl glycidyl ether onto a commercial hydroxyl-terminated PEO, using its cesium alkoxide as macro-initiator. The resulting linear AB or ABA-type di- or triblock copolymers serve as polymer cores for the subsequent hydrosilylation polyaddition of an AB2-type carbosilane monomer. Di(allyl)methylsilane or methyldi(undec-10-enylsilane) were em…

Joining Two Natural Motifs: Catechol-Containing Poly(phosphoester)s.

Numerous catechol-containing polymers, including biodegradable polymers, are currently heavily discussed for modern biomaterials. However, there is no report combining poly(phosphoester)s (PPEs) with catechols. Adhesive PPEs have been prepared via acyclic diene metathesis polymerization. A novel acetal-protected catechol phosphate monomer was homo- and copolymerized with phosphoester comonomers with molecular weights up to 42000 g/mol. Quantitative release of the catechols was achieved by careful hydrolysis of the acetal groups without backbone degradation. Degradation of the PPEs under basic conditions revealed complete and statistical degradation of the phosphotri- to phosphodiesters. In …

Phosphonylation Controls the Protein Corona of Multifunctional Polyglycerol-Modified Nanocarriers.

Nanocarriers are a platform for modern drug delivery. In contact with blood, proteins adsorb to nanocarriers, altering their behavior in vivo. To reduce unspecific protein adsorption and unspecific cellular uptake, nanocarriers are modified with hydrophilic polymers like poly(ethylene glycol) (PEG). However, with PEG the attachment of further functional structures such as targeting units is limited. A method to introduce multifunctionality via polyglycerol (PG) while maintaining the hydrophilicity of PEG is introduced. Different amounts of negatively charged phosphonate groups (up to 29 mol%) are attached to the multifunctional PGs (Mn 2-4 kg mol-1 , Ð < 1.36) by post-modification. PGs are …

Carbohydrate nanocarriers in biomedical applications: functionalization and construction

The specific targeting of either tumor cells or immune cells in vivo by carefully designed and appropriately surface-functionalized nanocarriers may become an effective therapeutic treatment for a variety of diseases. Carbohydrates, which are prominent biomolecules, have shown their outstanding ability in balancing the biocompatibility, stability, biodegradability, and functionality of nanocarriers. The recent applications of sugar (mono/oligosaccharides and/or polysaccharides) for the development of nanomedicines are summarized in this review, including the application of carbohydrates for the surface-functionalization of various nanocarriers and for the construction of the nanocarrier its…

Rapid Synthesis and MALDI-ToF Characterization of Poly(ethylene oxide) Multiarm Star Polymers

Multiarm PEO star polymers with a purely aliphatic polyether structure have been synthesized using hyperbranched polyglycerol (PG) with different molecular weights as a multifunctional initiator. Different degrees of deprotonation of the initiator were studied with respect to molecular weight control. The results show that the degree of deprotonation is a crucial parameter for the synthesis of well-defined polymers with controlled molecular weights. Partial deprotonation of the PG hydroxyl groups (5-8%) was proven to represent an optimum for the synthesis of star polymers with molecular masses close to the theoretical values. Molecular weights of the stars ranged between 9 000 and 30000g · …

ChemInform Abstract: Polymeric Janus Particles

Since de Gennes' Nobel lecture in 1991, in which he coined the term "Janus grains", research into asymmetric particles has boomed. Macroscopic, microscopic and nanoscopic particles have been prepared in which certain parts of their surface differ in chemical composition, polarity, color, or any other property. Spherical, cylindrical, disc-like, snowman-, hamburger-, and raspberry-like structures have been synthesized from organic or inorganic materials or even as hybrids of both. Synthetic strategies towards such particles vary greatly from simple polymer mixtures to the bulk self-assembly of sophisticated terpolymers to immobilization methods of symmetric particles. Polymeric Janus particl…

Squaric Acid Mediated Synthesis and Biological Activity of a Library of Linear and Hyperbranched Poly(Glycerol)-Protein Conjugates

Polymer-protein conjugates generated from side chain functional synthetic polymers are attractive because they can be easily further modified with, for example, labeling groups or targeting ligands. The residue specific modification of proteins with side chain functional synthetic polymers using the traditional coupling strategies may be compromised due to the nonorthogonality of the side-chain and chain-end functional groups of the synthetic polymer, which may lead to side reactions. This study explores the feasibility of the squaric acid diethyl ester mediated coupling as an amine selective, hydroxyl tolerant, and hydrolysis insensitive route for the preparation of side-chain functional, …

Polymeric janus particles.

Since de Gennes' Nobel lecture in 1991, in which he coined the term "Janus grains", research into asymmetric particles has boomed. Macroscopic, microscopic and nanoscopic particles have been prepared in which certain parts of their surface differ in chemical composition, polarity, color, or any other property. Spherical, cylindrical, disc-like, snowman-, hamburger-, and raspberry-like structures have been synthesized from organic or inorganic materials or even as hybrids of both. Synthetic strategies towards such particles vary greatly from simple polymer mixtures to the bulk self-assembly of sophisticated terpolymers to immobilization methods of symmetric particles. Polymeric Janus particl…

α ,ω n -Heterotelechelic Hyperbranched Polyethers Solubilize Carbon Nanotubes

The synthesis of novel linear-hyperbranched (linhb) polyether block copolymers based on poly(ethylene oxide) and branched poly(glycerol), bearing a single pyrene or myristyl moiety at the α-position of the linear chain is described. The polymers exhibit low polydispersity (M w /M n < 1.3) and controlled molecular weights (M n = 5 000 g·mol -1 ). The mainly hydrophilic block copolymers with multiple hydroxyl end groups readily dissolve multiwalled carbon nanotubes (MWCNTs) in water by mixing and subsequent sonification, resulting in noncovalent attachment of the linhb hybrid structure to the carbon nanotubes (CNTs). Transmission electron microscopy (TEM) was employed to visualize the solubil…

ALTMET Polymerization of Amino Acid-Based Monomers Targeting Controlled Drug Release

Giving the imminent necessity of a new generation of biodegradable and biocompatible polymers prepared from feedstock, the synthesis of a potentially biodegradable amino acid-based copolymer by the alternating diene metathesis (ALTMET) strategy is herein presented. The reaction was tailored to minimize isomerization and deactivation of ruthenium catalysts by intramolecular coordination with the amide carbonyl group of the amino-acid-based monomer. Alternated l-lysine–phosphoester copolymers with molar masses higher than 18 000 g/mol were obtained using Hoveyda–Grubbs second-generation and Umicore M2 catalysts. The copolymer was further used to prepare nanoparticles loaded with rifampicin (u…

Sulfur’s role in the flame retardancy of thio-ether–linked hyperbranched polyphosphoesters in epoxy resins

Abstract Hyperbranched polyphosphoesters are promising multifunctional flame retardants for epoxy resins. These polymers were prepared via thiol-ene polyaddition reactions. While key chemical transformations and modes of actions were elucidated, the role of sulfur in the chemical composition remains an open question. In this study, the FR-performance of a series of phosphorus-based flame retardant additives with and without sulfur (thio-ethers or sulfones) in their structure are compared. The successful synthesis of thio-ether or sulfone-containing variants is described and verified by 1H and 31P NMR, also FTIR and MALDI-TOF. A decomposition process is proposed from pyrolytic evolved gas an…

Poly(phosphonate)s via Olefin Metathesis: Adjusting Hydrophobicity and Morphology

Olefin metathesis step-growth (acyclic diene metathesis (ADMET)) and chain-growth (ring-opening metathesis) polymerization was used to prepare linear poly(phosphonate)s with variable hydrophilicity. The first phosphonate monomer, i.e., di(undec-10-en-1-yl) methylphosphonate, for ADMET polymerization was developed, and potentially degradable and biocompatible, unsaturated poly(phosphonate)s were prepared with molecular weights up to 23 000 g mol–1 with molecular weight dispersities Đ < 2. These polymers were studied with respect to their interaction with a calcium phosphate bone substitute material from an aqueous nanoparticle dispersion that was prepared by a solvent evaporation miniemulsio…

ChemInform Abstract: Carbohydrate Nanocarriers in Biomedical Applications: Functionalization and Construction

The specific targeting of either tumor cells or immune cells in vivo by carefully designed and appropriately surface-functionalized nanocarriers may become an effective therapeutic treatment for a variety of diseases. Carbohydrates, which are prominent biomolecules, have shown their outstanding ability in balancing the biocompatibility, stability, biodegradability, and functionality of nanocarriers. The recent applications of sugar (mono/oligosaccharides and/or polysaccharides) for the development of nanomedicines are summarized in this review, including the application of carbohydrates for the surface-functionalization of various nanocarriers and for the construction of the nanocarrier its…

Drug Delivery in Plants: Targeted Drug Delivery in Plants: Enzyme-Responsive Lignin Nanocarriers for the Curative Treatment of the Worldwide Grapevine Trunk Disease Esca (Adv. Sci. 15/2019)

In article number 1802315, Jochen Fischer, Frederik R. Wurm, and co‐workers report the first nanocarrier‐mediated drug delivery in plants. Enzyme‐degradable lignin nanocarriers are injected into the trunks of grapevine plants. They release a fungicide selectively inside of the plants and are able to cure the worldwide fungal plant disease Esca for the first time. This strategy will reduce the extensive spraying of pesticides in agriculture. Image credit: Katharina Maisenbacher.

Macromol. Rapid Commun. 3/2010

Microstructure analysis of biocompatible phosphoester copolymers

Copolymers with varying compositions of 2-ethoxy-2-oxo-1,3,2-dioxaphospholane (EEP) and 2-ethoxy-4-methyl-2-oxo-1,3,2-dioxaphospholane (EMEP) have been synthesized via 1,5,7-triazabicyclo[4.4.0]dec-5-ene-catalyzed anionic ring-opening polymerization. The molecular weights and comonomer ratios were well controlled and polymers with reasonable molecular weight distributions (<1.5) were obtained in all cases. The copolymers were investigated by 1H and 31P NMR spectroscopies to determine the underlying microstructure via detailed dyad analysis. The copolymers were found to be nontoxic to HeLa cells. Furthermore, the obtained copolymers of EEP and EMEP show thermoresponsive properties, i.e., exh…

Ferrocenyl-functionalized long chain branched polydienes

A convenient two-step approach for the synthesis of ferrocenyl-functionalized long chain branched polydienes, based on both butadiene and isoprene, respectively, is presented. Classical living anionic polymerization was used to synthesize different AB n type poly(diene) macromonomers with moderate molecular weights between 1700 and 3200 g/mol and narrow polydispersity. Quantitative end-capping with chlorodimethylsilane resulted in the desired AB n macromonomer structures. In the ensuing Pt-catalyzed hydrosilylation polyaddition, branched, functionalized polydienes were obtained by a concurrent AB n + AR type of copolymerization with mono-and difunctional ferrocenyl silanes (fcSiMe 2 H or fc…

Branched and Functionalized Polybutadienes by a Facile Two-Step Synthesis

Anionic polymerization was used to prepare silane-endfunctionalized polybutadiene macromonomers with different molecular weights ranging from 9 000 to 34000 g .mol- 1 . These were polymerized by a hydrosilylation reaction in bulk to obtain branched polymers, using Karstedt's catalyst. Surprisingly, the addition of monofunctional silanes during the polymerization showed only a minimal effect concerning the degree of polymerization. Furthermore, it was possible to introduce a variety of functional silanes without increasing the overall number of reaction steps by a convenient AB 2 + A type "pseudocopolymerization" method. All branched polymers were analyzed by SEC, SEC-MALLS, SEC-viscosimetry…

From an epoxide monomer toolkit to functional PEG copolymers with adjustable LCST behavior.

The lower critical solution temperature (LCST) behavior of novel poly(ethylene glycol) (PEG)-based copolymers bearing multiple functional groups, obtained by anionic ring-opening (co)polymerization (AROP), has been investigated. Variable comonomer ratios of ethylene oxide (EO) and the corresponding oxiranes isopropylidene glyceryl glycidyl ether (IGG), ethoxyl vinyl glycidyl ether (EVGE), allyl glycidyl ether (AGE), or N,N-dibenzyl amino glycidyl (DBAG), particularly designed to implement functional groups at the PEG backbone, were found to influence the LCST behavior. Sharp transitions from translucent to opaque solutions, comparable to other well-established stimuli-responsive polymers, w…

Asymmetric Micellization of Oragnometallic Polyether Block Copolymers

A Facile Two-Step Route to Branched Polyisoprenes via ABn-Macromonomers

A facile two-step synthesis for branched poly(isoprene)s (PI) based on polyaddition of AB n -type macromonomers is described. The synthesis of the macromonomers was achieved by anionic polymerization of isoprene and subsequent end-capping of the polymers by addition of chlorodimethylsilane to the living carbanions. This led to PI-based macromonomers with narrow polydispersity (M w /M n < 1.15) and molecular weights in the range of 1700 -22100 g mol -1 . Synthesis of the branched polymers was carried out by a hydrosilylation-based polymerization of the macromonomers. Characterization via SEC, SEC-MALLS, coupled SEC-viscosimetry and 1 H-NMR-spectroscopy supported the formation of branched str…

Vitamin C Loaded Polyethylene: Synthesis and Properties of Precise Polyethylene with Vitamin C Defects via Acyclic Diene Metathesis Polycondensation

A polyethylene-like polymer with an in-chain vitamin C group was synthesized by olefin metathesis polymerization. Here, we describe both the synthesis and a comprehensive physical characterization. Because of the olefin metathesis synthesis, the vitamin C groups are equidistantly arranged in the polyethylene (PE) main chain. Their separation was adjusted to 20 CH2 units. After hydrogenation, a semicrystalline polymer is obtained that is soluble in polar solvents. Because of its size and steric effect, the vitamin C acts as a chain defect, which is expelled from the crystal lattice, yielding a lamellar crystal with a homogeneous thickness corresponding to the interdefect distance. The physic…

“Functional Poly(ethylene glycol)”: PEG-Based Random Copolymers with 1,2-Diol Side Chains and Terminal Amino Functionality

A series of poly(ethylene glycol-co-isopropylidene glyceryl glycidyl ether) (P(EO-co-IGG)) random copolymers with different fractions of 1,2-isopropylidene glyceryl glycidyl ether (IGG) units was synthesized. After acidic hydrolysis a new type of "functional PEGs", namely poly(ethylene glycol-co-glyceryl glycerol) (P(EO-co-GG)) was obtained. Using an initiator that releases a terminal amino moiety after deprotection, functional end groups with orthogonal reactivity to the in-chain groups were obtained. All polymers showed narrow molecular weight distributions (1.07-1.19), and control of the molecular weights was achieved in the range 5000-30 000 g/mol. Random incorporation of both comonomer…

Hyperbranched-linear-hyperbranched ABA-type block copolymers based on poly(ethylene oxide) and polyglycerol

BACKGROUND: Until recently, hyperbranched polymers were thought to be ill-defined materials that were not useful as building blocks for well-defined complex polymer architectures. It is a current challenge to develop strategies that offer rapid access to well-defined hyperbranched block copolymers. RESULTS: A convenient three-step protocol for the synthesis of double-hydrophilic hyperbranched–linear–hyperbranched ABA-type triblock copolymers based on poly(ethylene oxide) (PEO) and hyperbranched polyglycerol (hbPG) is presented. The Bola-type polymers exhibiting an aliphatic polyether structure were prepared from a linear (lin) linPG-b-PEO-b-linPG precursor triblock. The materials exhibit lo…

Multihydroxyl-Functional Polystyrenes in Continuous Flow

We describe the synthesis of end-functionalized polystyrenes by living anionic polymerization in a microstructured reactor via termination by acetal-protected functional epoxides. Initiation of styrene polymerization by alkyllithium takes place in a micromixing device with efficient heat and mass transfer properties. A newly developed continuous polymerization−termination sequence enabled quantitative functionalization of the living carbanions by nucleophilic displacement with different, specifically designed glycidyl ethers (ethoxy ethyl glycidyl ether (EEGE), 1,2-isopropylidene glyceryl glycidyl ether (IGG), and trans-2-phenyl-1,3-dioxane glycidyl ether (PDGE)). Upon acidic hydrolysis the…

Ferrocene-Containing Multifunctional Polyethers: Monomer Sequence Monitoring via Quantitative 13C NMR Spectroscopy in Bulk

Ferrocenyl glycidyl ether (fcGE) and allyl glycidyl ether (AGE) are copolymerized via living anionic ring-opening polymerization to generate polyfunctional copolymers with molecular weights up to 40 300 g/mol and low molecular weight dispersities (Mw/Mn < 1.18). Copolymerizations were carried out in bulk at 100 °C and unexpectedly found to proceed without any isomerization of the allyl double bonds. The copolymerization behavior of fcGE and AGE was monitored by in situ quantitative 13C NMR kinetic measurements in bulk, evidencing the formation of random copolymers under these conditions, showing no gradient of comonomer incorporation. The redox-active behavior of the copolymers and homopoly…

Processing and adjusting the hydrophilicity of poly(oxymethylene) (co)polymers: nanoparticle preparation and film formation

Handling the insoluble POM: the preparation of nanoparticles based on hyperbranched-linear-hyperbranched ABA triblock copolymers with variable hydrophilicity and composed of short hyperbranched polyglycerol (hbPG) as the A-blocks and linear poly(oxymethylene) (POM) as a B-block is described. The POM-hbPG-nanoparticles with diameters in the range of 190 to 250 nm were generated in a convenient process, combining the solvent evaporation process with the miniemulsion technique, a water borne handling for POM-copolymers. Furthermore, the film formation properties of the nanoparticles were investigated by deposition on silicon and subsequent sintering, which leads to films with a thickness in th…

Amino Functional Poly(ethylene glycol) Copolymers via Protected Amino Glycidol

The synthesis of poly(ethylene glycol) (PEG) copolymers with multiple amino functionalities within the chain is described, relying on an epoxide comonomer bearing a protected amino group. N,N-dibenzyl amino glycidol (DBAG) and ethylene oxide (EO) were copolymerized via anionic polymerization, leading to well-defined polymers with varied comonomer content and low polydispersities (Mw/Mn in the range of 1.1 to 1.2). Subsequent hydrogenolysis with Pearlman’s catalyst afforded poly(ethylene glycol-co-amino glycerol)s (PEG-co-PAG) with a precisely adjusted number of randomly incorporated amino groups in the range of 2−15%. For the first time, the kinetics of an EO copolymerizations have has been…

Hyperbranched Polymers

Life is branched! Statistically branched (=hyperbranched) polymers have become an important class of materials in modern chemistry. Not only due to straightforward synthetic approaches which were developed in the last decade but also due to the vast amount of available monomers, hyperbranched polymers have replaced perfect dendrimers in many areas and they will have an even higher impact in future. This chapter highlights classic and modern syntheses of hyperbranched polymers and their unique properties and presents their versatility in the macromolecular toolbox for the design of complex nonlinear architectures.

Artificial cartilage bio-matrix formed of hyaluronic acid and Mg2+-polyphosphate.

Here we show that inorganic polyphosphate (polyP), a polyanionic metabolic regulator consisting of multiple phosphate residues linked by energy-rich phosphoanhydride bonds, is present in the synovial fluid. In a biomimetic approach, to enhance cartilage synthesis and regeneration, we prepared amorphous polyP microparticles with Mg2+ as counterions. The particles were characterised by X-ray diffraction (XRD), energy-dispersive X-ray (EDX) and Fourier transformed infrared spectroscopic (FTIR) analyses. Similar particles were obtained after addition of Mg2+ ions to a solution containing hyaluronic acid, as a major component of the synovial fluid, and soluble Na-polyP. The viscous paste-like ma…

Ligand-Binding Cooperativity Effects in Polymer-Protein Conjugation.

We present an electron paramagnetic resonance (EPR) spectroscopic characterization of structural and dynamic effects that stem from post-translational modifications of bovine serum albumin (BSA), an established model system for polymer-protein conjugation. Beyond the typical drug delivery and biocompatibility aspect of such systems, we illustrate the causes that alter internal dynamics and therefore functionality in terms of ligand-binding to the BSA protein core. Uptake of the paramagnetic fatty acid derivative 16-doxyl stearic acid by several BSA-based squaric acid macroinitiators and polymer-protein conjugates was studied by EPR spectroscopy, aided by dynamic light scattering (DLS) and z…

Janus Micelles Induced by Olefin Metathesis

A facile one-step procedure for hydrophobic modification and simultaneous TEM contrast enhancement via a regioselective olefin metathesis reaction using Grubbs' catalyst is presented. Polyether diblock copolymers were investigated, and both the chain ends of the hydrophilic and the hydrophobic block were hydrophobically modified. Modification of the hydrophilic block results in nonsymmetric supramolecular structures (Janus micelles) which self-assemble into larger hierarchically organized super-micelles.

Multifunktionelle Poly(ethylenglycole)

Acid-Labile Surfactants Based on Poly(ethylene glycol), Carbon Dioxide and Propylene Oxide: Miniemulsion Polymerization and Degradation Studies

Partially degradable, nonionic AB and ABA type di- and triblock copolymers based on poly(propylene carbonate) and poly(ethylene glycol) blocks were synthesized via immortal copolymerization of carbon dioxide and propylene oxide, using mPEG or PEG as a macroinitiator, and (R,R)-(salcy)-CoOBzF5 as a catalyst in a solvent-free one-pot procedure. The amphiphilic surfactants were prepared with molecular weights (Mn) between 2800 and 10,000 g·mol−1 with narrow molecular weight distributions (1.03–1.09). The copolymers were characterized using 1H-, 13C- and DOSY-NMR spectroscopy and size exclusion chromatography (SEC). Surface-active properties were determined by surface tension measurements (crit…

Protein Corona Mediated Stealth Properties of Biocompatible Carbohydrate‐based Nanocarriers

Long-chain branched ROMP polymers

This article describes the construction of branched ROMP-polymer architectures via polycondensation of ABn-type macromonomers. For this convergent strategy, a polymer was synthesized that carries several hydroxyl-groups along the polymer chain and one carboxylic acid group at the chain end. An esterification reaction between these functional groups yielded long-chain branched polymers. The polymers were analyzed by NMR and SEC to monitor the condensation reaction. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2009

Electroactive linear-hyperbranched block copolymers based on linear poly(ferrocenylsilane)s and hyperbranched poly(carbosilane)s.

A convenient two-step protocol is presented for synthesis of linear-hyperbranched diblock copolymers consisting of a linear, organometallic poly(ferrocenylsilane) (PFS) block and hyperbranched poly(carbosilane) (hbPCS) segments. Linear PFS diblock copolymers were synthesized through photolytic ring-opening polymerization of dimethyl[1]silaferrocenophane as the first block and methylvinyl[1]sila-ferrocenophane as the second. These block copolymers served as polyfunctional cores in a subsequent hydrosilylation polyaddition of different silane-based AB 2 monomers. Three AB 2 monomers (methyldiallylsilane; methyldiundecenylsilane, and ferrocenyldiallylsilane) were investigated; they introduced …

Hyperbranched Polyglycerols with Elevated Molecular Weights: A Facile Two-Step Synthesis Protocol Based on Polyglycerol Macroinitiators

Hyperbranched polyglycerol (PG) is established as one of the few hyperbranched polymers that offer the possibility to control molecular weight up to Mn = 6000 g/mol. This work introduces a facile 2-step strategy that relies on the use of a low molecular weight PG (Mn = 500 and 1000 g/mol) as a macroinitiator for the slow addition of glycidol, permitting to overcome previous limitations concerning molecular weights and molecular weight control. A systematic investigation of the effect of the degree of deprotonation on the control of the polymerization reaction has been carried out. A series of hyperbranched PGs with molecular weights up to Mn = 24000 g/mol has been obtained under fully contr…

Hetero-Multifunctional Poly(ethylene glycol) Copolymers with Multiple Hydroxyl Groups and a Single Terminal Functionality

Hetero-multifunctional poly(ethylene glycol-co-glycerol) random copolymers with multiple hydroxyl functionalities and a single terminal functionality have been prepared by copolymerization of ethylene oxide (EO) and ethoxy ethyl glycidyl ether (EEGE) with the use of a suitable initiator, introducing a protected amino group or a double bond, respectively. Acidic deprotection was used for removal of the acetal protecting groups in the chain, and the terminal amino group was regenerated by catalytic hydrogenation. A series of copolymers with narrow polydispersity was obtained, varying comonomer fractions from 3 to 67% and molecular weights in the range of 5 000-32 000 g · mol(-1) (1.05 < $\ove…

Macromol. Rapid Commun. 6/2007

Polymerization of Ethylene Oxide, Propylene Oxide, and Other Alkylene Oxides: Synthesis, Novel Polymer Architectures, and Bioconjugation.

The review summarizes current trends and developments in the polymerization of alkylene oxides in the last two decades since 1995, with a particular focus on the most important epoxide monomers ethylene oxide (EO), propylene oxide (PO), and butylene oxide (BO). Classical synthetic pathways, i.e., anionic polymerization, coordination polymerization, and cationic polymerization of epoxides (oxiranes), are briefly reviewed. The main focus of the review lies on more recent and in some cases metal-free methods for epoxide polymerization, i.e., the activated monomer strategy, the use of organocatalysts, such as N-heterocyclic carbenes (NHCs) and N-heterocyclic olefins (NHOs) as well as phosphazen…

Functional PEG-based polymers with reactive groups via anionic ROP of tailor-made epoxides

In this review article functional epoxide monomers that are suitable for controlled ring-opening polymerization (ROP) are discussed. Functional epoxides possess reactive groups, which either are directly accessible or carry suitable protective groups that can be removed in a facile one-step reaction after polymerization. The methods used to obtain linear, functional aliphatic polyethers rely on living polymerization techniques for the synthesis of well-defined structures. Materials properties, such as thermo-responsive behavior in combination with different functional groups that can be addressed selectively, render these novel materials interesting for a variety of applications.

Synthesis and noncovalent protein conjugation of linear-hyperbranched PEG-poly(glycerol) alpha,omega(n)-telechelics.

Linear-hyperbranched, heterobifunctional alpha,omega(n) telechelic block copolymers consisting of a linear poly(ethylene glycol) (PEG) chain and a hyperbranched polyglycerol (PG) block have been prepared in five steps, using a protected amino-functional initiator. The polyfunctionality omega(n) (OH groups) can be adjusted by the degree of polymerization (DP(n)) of the polyglycerol block. Subsequent introduction of a single biotin unit by amidation in alpha-position permitted noncovalent bioconjugation with avidin.

Polyphosphoester surfactants as general stealth coatings for polymeric nanocarriers

Opsonization of nanocarriers is one of the most important biological barriers for controlled drug delivery. The typical way to prevent such unspecific protein adsorption and thus fast clearance by the immune system is the covalent modification of drug delivery vehicles with poly(ethylene glycol) (PEG), so-called PEGylation. Recently, polyphosphoesters (PPEs) were identified as adequate PEG substitutes, however with the benefits of controllable hydrophilicity, additional chemical functionality, or biodegradability. Here, we present a general strategy by non-covalent adsorption of different nonionic PPE-surfactants to nanocarriers with stealth properties. Polyphosphoester surfactants with dif…