0000000000017912
AUTHOR
Christoph Schüll
Catechol Acetonide Glycidyl Ether (CAGE): A Functional Epoxide Monomer for Linear and Hyperbranched Multi-Catechol Functional Polyether Architectures
A protected catechol-containing epoxide monomer, catechol acetonide glycidyl ether (CAGE), is introduced. CAGE is conveniently obtained in three steps and enables the incorporation of surface-active catechol moieties into a broad variety of hydrophilic and biocompatible polyether architectures by copolymerization. Via acidic cleavage of the acetal protecting groups, the polymer-attached catechol functionalities are liberated and available for surface attachment or metal complexation. CAGE has been copolymerized with ethylene oxide and glycidol to obtain both linear poly(ethylene glycol) and hyperbranched polyglycerol copolymers, respectively, with multiple surface-adhesive catechol moieties…
A fully synthetic glycopeptide antitumor vaccine based on multiple antigen presentation on a hyperbranched polymer.
For antitumor vaccines both the selected tumor-associated antigen, as well as the mode of its presentation, affect the immune response. According to the principle of multiple antigen presentation, a tumor-associated MUC1 glycopeptide combined with the immunostimulating T-cell epitope P2 from tetanus toxoid was coupled to a multi-functionalized hyperbranched polyglycerol by "click chemistry". This globular polymeric carrier has a flexible dendrimer-like structure, which allows optimal antigen presentation to the immune system. The resulting fully synthetic vaccine induced strong immune responses in mice and IgG antibodies recognizing human breast-cancer cells.
Branched Acid-Degradable, Biocompatible Polyether Copolymers via Anionic Ring-Opening Polymerization Using an Epoxide Inimer
The introduction of acid-degradable acetal moieties into a hyperbranched polyether backbone has been achieved by the design of a novel epoxide-based degradable inimer. This new monomer, namely, 1-(glycidyloxy)ethyl ethylene glycol ether (GEGE), has been copolymerized in the anionic ring-opening polymerization (AROP) with ethylene oxide (EO) or glycidol (G), respectively, yielding branched polyethers, that is, P(EO-co-GEGE) and P(G-co-GEGE), that possess an adjustable amount of acid-cleavable acetal units. In addition, a novel class of multiarm star copolymers P(G-co-GEGE-g-EO) with acid-labile polyether core and PEG side chains was synthesized by using the P(G-co-GEGE) copolymers as multifu…
Nonlinear Macromolecules by Ring-Opening Polymerization
Ring-opening polymerization (ROP) is a well-established method for the controlled synthesis of linear polymers, which can be found in various everyday applications. However, during the past decades, there has been an increasing interest in the generation of nonlinear highly branched polymers, profiting from the fascination created by the structurally perfect dendrimers. The applicability of various heterocyclic monomers renders the ring-opening multibranching polymerization (ROMBP), a versatile tool for the generation of multifunctional hyperbranched polymers. First, the historical key steps leading to the development of ROMBP are described, which is the basis for the controlled synthesis o…
Directing the self-assembly of semiconducting copolymers: the consequences of grafting linear or hyperbranched polyether side chains.
The synthesis and self-assembly of novel semiconducting rod-coil type graft block copolymers based on poly(para-phenylene vinylene) (PPV) copolymers is presented, focusing on the ordering effect of linear versus hyperbranched side chains. Using an additional reactive ester block, highly polar, linear poly(ethylene glycol), and hyperbranched polyglycerol side chains are attached in a grafting-to approach. Remarkably, the resulting novel semiconducting graft copolymers with polyether side chains show different solubility and side-chain directed self-assembly behavior in various solvents, e.g., cylindrical or spherical superstructures in the size range of 10 to 120 nm, as shown by TEM. By adju…
One-step synthesis of multi-alkyne functional hyperbranched polyglycerols by copolymerization of glycidyl propargyl ether and glycidol
By copolymerization of glycidol with the alkyne-containing oxirane monomer glycidyl propargyl ether (GPE), hyperbranched polyglycerol (hbPG) with a defined number of alkyne functionalities (up to 38%) can be obtained in a one-step procedure. The number of alkynes can be adjusted by the glycidol/GPE ratio to provide multi-alkyne functional hbPGs, maintaining the highly branched polyether structure. Interestingly, the acidic proton of the alkyne moiety does not interfere with the proton exchange mechanism during the polymerization of glycidol. By specific modification of the synthesis procedure, crosslinking reactions can be suppressed. The polymers exhibit molecular weights ranging from 1800…
Linear-Hyperbranched Graft-Copolymers via Grafting-to Strategy Based on Hyperbranched Dendron Analogues and Reactive Ester Polymers
The synthesis of hyperbranched polyglycerol dendron analogues with precisely one focal amino functionality (H2N-hbPG) and their use for the synthesis of linear-hyperbranched graft-copolymers in a grafting-to approach is reported. By use of N,N-dibenzyl tris(hydroxylmethyl) aminomethane as a novel initiator for the ring-opening multibranching polymerization of glycidol, dendron analogues with one focal amino functionality of molecular weights ranging from 500 to 15000 g mol–1 and narrow to moderate polydispersities (Mw/Mn = 1.2–1.9) were synthesized, as confirmed by NMR and SEC. After removal of the benzyl protective groups, the accessibility and selective transformation of the focal amino g…
Hyperbranched poly(glycolide) copolymers with glycerol branching points via ring-opening copolymerization
Abstract Sn(Oct) 2 -catalyzed synthesis of hyperbranched poly(glycolide) copolymers with glycerol branching points in the backbone is possible via ring-opening multi-branching copolymerization (ROMBP) of glycolide and 5HDON (5-hydroxymethyl-1,4-dioxan-2-one). Using this strategy, well-defined and soluble branched polyesters with apparent molecular weights (M n ) in the range of 1300–2000 g mol −1 and varying comonomer content (5HDON/glycolide = 30:70–70:30) were obtained. 2D NMR spectroscopy, thermal analysis and MALDI-TOF mass spectrometry confirmed the successful incorporation of both monomers and the resulting branched structure. Multiple end group functionality offers the possibility fo…
Controlled Synthesis of Linear Polymers with Highly Branched Side Chains by “Hypergrafting”: Poly(4-hydroxy styrene)-graft-hyperbranched Polyglycerol
Linear polymers with hyperbranched side chains are unusual macromolecular structures due to their high number of functional groups in the side chains as well as their potential cylindrical conformation in bulk or solution. In a three-step synthesis combining anionic and oxy-anionic polymerization, hyperbranched polyglycerol was “hypergrafted” from linear poly(4-hydroxy styrene) macroinitiators to yield poly(4-hydroxy styrene)-graft-hyperbranched polyglycerol. Successful grafting with control over molecular weight (10–31 kg·mol–1) and low PDIs (<1.4) was shown by various characterization techniques. All polymers have a high side chain density, due to rapid transfer of the initiating function…
Grafting of hyperbranched polymers: From unusual complex polymer topologies to multivalent surface functionalization
Abstract In this feature article, the grafting of hyperbranched polymers to different substrates is reviewed. Both grafting onto macromolecules with different topologies (homogeneous grafting) and the resulting complex polymer architectures containing highly branched segments as well as their applications are discussed. In the second part grafting of hyperbranched polymers on surfaces, i.e., planar surfaces and spherical particles (heterogeneous grafting), with respect to specific applications, such as bio-repellent surfaces or soluble carbon nanotubes is described. In all cases, the one-step synthesis and the resulting highly branched topology of the hyperbranched building blocks is benefi…
ABA Triblock Copolymers Based on Linear Poly(oxymethylene) and Hyperbranched Poly(glycerol): Combining Polyacetals and Polyethers
The synthesis of hyperbranched-linear-hyperbranched ABA triblock copolymers based on a linear poly(oxymethylene) (POM) block and hyperbranched poly(glycerol) (hbPG) blocks is described. The polymers containing a polyacetal polyether structure were prepared from linear bishydroxy-functional POM macroinitiators, obtained by cationic ring-opening polymerization of trioxane and 1,3-dioxolane as a comonomer with formic acid as a transfer agent and subsequent hydrolysis of the formate group. Partial deprotonation of the resulting hydroxyl groups permitted “hypergrafting” of glycidol by anionic ring-opening multibranching polymerization (ROMBP). With respect to the hyperbranched blocks, the obtain…
Combining Ring-Opening Multibranching and RAFT Polymerization: Multifunctional Linear–Hyperbranched Block Copolymers via Hyperbranched Macro-Chain-Transfer Agents
The synthesis of a hyperbranched macro-chain-transfer agent for RAFT polymerization of functional methacrylate or methacrylamide monomers was achieved by selectively attaching one single CTA onto hyperbranched polyglycerol dendron analogues. The combination of ring-opening multibranching polymerization of glycidol and subsequent RAFT polymerization of the hyperbranched macro-chain-transfer agents created a new route to a variety of multifunctional linear–hyperbranched block topologies. All linear–hyperbranched block copolymers could be synthesized with controlled molecular weight (Mn = 3.2–43.7 kg/mol) and low polydispersity (PDI = 1.15–1.34). As first examples for this universal approach, …
Enhanced immunogenicity of multivalent MUC1 glycopeptide antitumour vaccines based on hyperbranched polymers.
Enhancing the immunogenicity of an antitumour vaccine still poses a major challenge. It depends upon the selected antigen and the mode of its presentation. We here describe a fully synthetic antitumour vaccine, which addresses both aspects. For the antigen, a tumour-associated MUC1 glycopeptide as B-cell epitope was synthesised and linked to the immunostimulating T-cell epitope P2 derived from tetanus toxoid. The MUC1-P2 conjugate is presented multivalently on a hyperbranched polyglycerol to the immune system. In comparison to a related vaccine of lower multivalency, this vaccine exposing more antigen structures on the hyperbranched polymer induced significantly stronger immune responses in…
Hyperbranched aliphatic polyether polyols
Hyperbranched polymers, dendritic macromolecules with branch-on-branch structures, have become an important polymer class since the early 1990s. They combine several advantages of the perfectly branched dendrimers with easy accessibility, typically in a one-step synthesis. Hyperbranched polyethers are a particularly interesting class of chemically stable and often biocompatible materials. Multifunctional hyperbranched polyethers with controllable molar mass and comparably low polydispersities can been prepared using hydroxyl-functional epoxides or oxetanes for polymerization via anionic and cationic polymerization mechanisms. Here, we review the progress in the preparation, characterization…
Polydispersity and Molecular Weight Distribution of Hyperbranched Graft Copolymers via “Hypergrafting” of ABm Monomers from Polydisperse Macroinitiator Cores: Theory Meets Synthesis
The hypergrafting strategy designates the synthesis of hyperbranched graft copolymers (HGCs) in a grafting-from approach, using ABm monomers, from multifunctional, polydisperse macroinitiator cores by slow monomer addition. Hypergrafting leads to complex polymer topologies with defined molecular weight, degree of branching (DB), and polydispersity (PD). By a generating function formalism, a generally applicable equation for the PD of HGCs (PD = PDf + (m – 1)/f) is derived, where PDf is the polydispersity of the core and f its average functionality. In addition, the complete molecular weight distribution function has been calculated for varied m and f as well as for a given distribution of i…