Papers by Frederik R Wurm
ACS Macro Letters, 2021
Reversible addition−fragmentation chain transfer (RAFT) polymerization has become a straightforwa... more Reversible addition−fragmentation chain transfer (RAFT) polymerization has become a straightforward approach to block copolymers using a wide variety of functional vinyl monomers. Polyphosphoester (PPE) macroinitiators from ringopening polymerization (ROP) of their corresponding cyclic phosphoesters have been previously prepared for atom transfer radical polymerization; however, to date, these biodegradable macroinitiators for RAFT polymerization have not been reported. Herein, a macromolecular RAFT-chain transfer agent (CTA) based on poly(ethyl ethylene phosphonate) was prepared by the organocatalytic ROP of 2-ethyl-2-oxo-1,3,2-dioxaphospholane using 2-cyano-5-hydroxypentan-2-yl dodecyl trithiocarbonate as the initiator and 1,8-diazabycyclo[5.4.0]undec-7-ene as the catalyst. Precise macro-CTAs of degrees of polymerization (DP n) from 34 to 70 with Đ ≤ 1.10 were prepared and used in the dioxane solution RAFT polymerization of acrylamide, acrylates, methacrylates, and 2-vinylpyridine to yield a library of well-defined block copolymers. Additionally, the PPE-based macro RAFT-CTA was used as a nonionic surfactant in a typical aqueous emulsion polymerization of styrene to produce well-defined nanoparticles with the hydrophilic PPEs on their surface as the stabilizing agent. This general protocol allowed the combination of polyphosphoesters with RAFT polymerization.
ACS Macro Letters, 2019
Linear polyethylenimine (L-PEI), a standard for nonviral gene delivery, is usually prepared by hy... more Linear polyethylenimine (L-PEI), a standard for nonviral gene delivery, is usually prepared by hydrolysis from poly(2-oxazoline)s. Lately, anionic polymerization of sulfonamide-activated aziridines had been reported as an alternative pathway toward well-defined L-PEI and linear polyamines. However, desulfonylation of the poly(sulfonyl aziridine)s typically relied on harsh conditions (acid, microwave) or used a toxic solvent (e.g., hexamethylphosphoramide). In addition, the drastic change of polarity requires solvents, which keep poly(sulfonyl aziridine)s as well as L-PEI in solution, and only a limited number of strategies were reported. Herein, we prepared 1-(4-cyanobenzenesulfonyl) 2-methyl-aziridine (1) as a monomer for the anionic ring-opening polymerization. It was polymerized to well-defined and linear poly(sulfonyl aziridine)s. The 4cyanobenzenesulfonyl-activating groups were removed under mild conditions to linear polypropylenimine (L-PPI). Using dodecanethiol and diazabicyclo-undecene (DBU) allowed ≥98% desulfonylation and a reliable purification toward polyamines with high purity and avoiding main-chain scission. This method represents a fast approach in comparison to previous methods used for postpolymerization desulfonylation and produces linear well-defined polyamines. The high control over molecular weight and dispersities achieved by living anionic polymerization are the key advantages of our strategy, especially if used for biomedical applications, in which molecular weight might correlate with toxicity. The synthesized polypropylenimine was further tested as a cell-transfection agent and proved, with 16.1% transfection efficiency of the cationic nanoparticles, to be an alternative to L-PEI obtained from the 2-oxazoline route. This general strategy will allow the preparation of complex macromolecular architectures containing polyamine segments, which were not accessible before.
European Polymer Journal, 2020
Polyphosphoesters (PPEs) are a class of (bio)degradable polymers with high chemical versatility a... more Polyphosphoesters (PPEs) are a class of (bio)degradable polymers with high chemical versatility and functionality. In particular, water-soluble PPEs with the phosphoester group in the polymer backbone are currently discussed as a potential alternative to poly(ethylene glycol) (PEG). Ring-opening polymerization of typically 5membered cyclic phosphoesters gives straightforward access to various well-defined PPEs. Several PPE candidates have proven their biocompatibility in vitro in terms of cytocompatibility, antifouling properties, "stealth effect", degradability (hydrolytic and enzymatic), and some promising in vivo results in drug delivery vehicles. The possibility to control the properties with the appropriate tuning of the lateral chain makes PPEs especially appealing. This review summarizes recent developments of such PPEs for biomedical applications, e.g. in protein-polymer conjugates, hydrogels for tissue engineering, or nanocarriers for drug and gene delivery. We summarize the progress made over the years, highlighting the strengths and the shortcomings of PPEs for these applications to date. We critically evaluate the current state of the art, try to assess their potential and to predict future perspectives, shedding light on the pathway that needs to be followed to translate into clinics.
Polymers, 2020
Poly(ethylene) (PE) is a commonly used semi-crystalline polymer which, due to the lack of polar g... more Poly(ethylene) (PE) is a commonly used semi-crystalline polymer which, due to the lack of polar groups in the repeating unit, is not able to form Langmuir or Langmuir–Blodgett (LB) films. This problem can be solved using PEs with hydrophilic groups arranged at regular distances within the polymer backbone. With acyclic diene metathesis (ADMET) polymerization, a tool for precise addition of polar groups after a certain interval of methylene sequence is available. In this study, we demonstrate the formation of Langmuir/LB films from two different PEs with regular phosphoester groups, acting as crystallization defects in the main chain. After spreading the polymers from chloroform solution on the water surface of a Langmuir trough and solvent evaporation, the surface pressure is recorded during compression under isothermal condition. These π-A isotherms, surface pressure π vs. mean area per repeat unit A, show a plateau zone at surface pressures of ~ (6 to 8) mN/m, attributed to the fo...
Molecules, 2019
The current trend for future flame retardants (FRs) goes to novel efficient halogen-free material... more The current trend for future flame retardants (FRs) goes to novel efficient halogen-free materials, due to the ban of several halogenated FRs. Among the most promising alternatives are phosphorus-based FRs, and of those, polymeric materials with complex shape have been recently reported. Herein, we present novel halogen-free aromatic and aliphatic hyperbranched polyphosphoesters (hbPPEs), which were synthesized by olefin metathesis polymerization and investigated them as a FR in epoxy resins. We compare their efficiency (aliphatic vs. aromatic) and further assess the differences between the monomeric compounds and the hbPPEs. The decomposition and vaporizing behavior of a compound is an important factor in its flame-retardant behavior, but also the interaction with the pyrolyzing matrix has a significant influence on the performance. Therefore, the challenge in designing a FR is to optimize the chemical structure and its decomposition pathway to the matrix, with regards to time and ...
Polymer Chemistry, 2019
Hyperbranched polyphosphoesters (hbPPEs) are promising flame retardants. Herein we synthesized th... more Hyperbranched polyphosphoesters (hbPPEs) are promising flame retardants. Herein we synthesized the first phosphorus-based AB2 monomer for the synthesis of hbPPEs and assess its flame-retardant performance in an epoxy resin.
Polymer Chemistry, 2019
Novel phosphorus-based hyperbranched polymers provide multifunctional flame retardancy to epoxy r... more Novel phosphorus-based hyperbranched polymers provide multifunctional flame retardancy to epoxy resins.
Macromolecules, 2018
Living anionic polymerization gives access to well-defined polymers, but it demands strict purifi... more Living anionic polymerization gives access to well-defined polymers, but it demands strict purification of reagents and solvents. This work presents the azaanionic polymerization (AAROP) of aziridines as a robust living polymerization technique, with the ease of controlled radical polymerizations. AAROP does not require inert atmosphere and remains living in the presence of large amounts of water or alcohols. Mesyl-, tosyl-, or brosyl-activated aziridines were polymerized with up to 100-fold excess of a protic impurity with respect to the initiator and still being active for chain extension. This allowed the preparation of polyols by anionic polymerization without protective groups, as only minor initiation occurred from the alcohols. The tolerance toward protic additives lies in the electron-withdrawing effect of the activating groups, decreasing the basicity of the propagating species, while maintaining a strong nucleophilic character. In this way, competing alcohols and water are only slightly involved in the polymerization, making living anionic polymerization an easy-to-conduct technique to well-defined polyamides and-amines.
Polymer Chemistry, 2019
The synthesis of aziridine and azetidine monomers and their ring-opening polymerization via diffe... more The synthesis of aziridine and azetidine monomers and their ring-opening polymerization via different mechanisms is reviewed.
Macromolecules, 2019
Biodegradable polyethylene mimics have been synthesized by the introduction of pyrophosphate grou... more Biodegradable polyethylene mimics have been synthesized by the introduction of pyrophosphate groups into the polymer backbone, allowing not only hydrolysis of the backbone but also further degradation by microorganisms. Because of cost, low weight, and good mechanical properties, the use of polyolefins has increased significantly in the past decades and has created many challenges in terms of disposal and their environmental impact. The durability and resistance to degradation make polyethylene difficult or impossible for nature to assimilate, thus making the degradability of polyolefins an essential topic of research. The biodegradable polypyrophosphate was prepared via acyclic diene metathesis polymerization of a diene monomer. The monomer is accessible via a three-step synthesis, in which the pyrophosphate was formed in the last step by DCC coupling of two phosphoric acid derivatives. This is the first report of a pyrophosphate group localized in an organic polymer backbone. The polypyrophosphate was characterized in detail by NMR spectroscopy, size exclusion chromatography, FTIR spectroscopy, differential scanning calorimetry, and thermogravimetry. X-ray diffraction was used to compare the crystallization structure in comparison to analogous polyphosphates showing poly(ethylene)-like structures. In spite of their hydrophobicity and water insolubility, the pyrophosphate groups exhibited fast hydrolysis, resulting in polymer degradation when films were immersed in water. Additionally, the hydrolyzed fragments were further biodegraded by microorganisms, rendering these PE mimics potential candidates for fast release of hydrophobic cargo, for example, in drug delivery applications.
Polymer Chemistry, 2018
Photo-reactive poly(phosphoester)s (PPEs) forming surface-attached PPE-networks and hydrogels are... more Photo-reactive poly(phosphoester)s (PPEs) forming surface-attached PPE-networks and hydrogels are presented.
Chemical Society Reviews, 2018
Functional polymers are reviewed which are accessible by the polymerization of reactive monomers.... more Functional polymers are reviewed which are accessible by the polymerization of reactive monomers. Their synthesis, polymerization, and post-polymerization modification are discussed.
Macromolecular Bioscience, 2017
studied as promising surfactants for emulsions. [10] Furthermore, vinyl-terminated polyglycerols ... more studied as promising surfactants for emulsions. [10] Furthermore, vinyl-terminated polyglycerols were used as surfmers to synthesize stable polystyrene (PS) microspheres for medical diagnostics for possible postfunctionalization with proteins. [11,12] Hyperbranched and linear surfmers based on polyglycerols were additionally used to generate stable PS nanoparticles. [13] However, for the miniemulsion approach only less multifunctional PG-based surfactants or surfmers are known. Here, we use the versatility of the anionic polymerization of glycidyl ethers to prepare a series of multifunctional (additional OH-groups or polymerizable CC-groups) surfactants with adjustable hydrophiliclipophilic balance (HLB) that allows the stabilization of direct (oil-in-water) or inverse (water-in-oil) (mini)emulsions or can be used simultaneously for both systems. Two known orthogonal protection strategies, reported by Möller and coworkers, [14] were used to synthesize linear completely poly glycerol-based block copolymers as surfactants or surfmers for direct, inverse, or both types of miniemulsions (Scheme 1). The orthogonal-protected block copolymers were generated by anionic ring-opening polymerization in bulk using ethoxyethyl glycidyl ether (EEGE) and allyl glycidyl ether (AGE) or tert-butyl glycidyl ether (tBuGE) with defined block length ratios to tune their HLB. After acidic hydrolysis of the acetal groups, the water-soluble allyl-functionalized PG block copolymers were established as surfmers in the radical miniemulsion poly merization of styrene to generate polystyrene nanoparticles with decreased protein adsorption behavior due to incorporated PG surfactants (Scheme 1). In addition, oil-soluble allyl-functionalized block copolymers were introduced as surfmers to produce polyurea/urethane nanocapsules by interfacial polyaddition reactions of hydroxyethyl starch (HES) with toluene diisocyanate (TDI) (Scheme 1). [15] Furthermore, the allyl-protection groups on the polyurethane nanocarrier surface were utilized for surface functionalization by thiol-ene addition in water. For this purpose, the nanocarriers were transferred into water including a tert-butyl-protected poly glycerol block copoly mer. The tert-butyl-protected polyglycerol block copolymers were applied as surfactant to generate polystyrene nanoparticles in direct miniemulsions for comparison with the allyl-protected surfmer and in inverse miniemulsions to produce stable poly(hydroxyethyl methacrylate) (PHEMA) Polyglycerol Surfactants Poly(ethylene glycol)-based surfactants are a prominent example for nonionic surfactants. Poly(glycerol) (PG) is discussed as a polyfunctional alternative, however, it is not yet used to stabilize miniemulsions. The anionic polymerization of glycidyl ethers is used to prepare surfactants for direct or inverse emulsions and ambident surfactants by adjusting the copolymer composition. Orthogonal-protected poly(glycerol) block copolymers, using ethoxyethyl glycidyl ether and allyl glycidyl ether (AGE) or tert-butyl glycidyl ether (tBuGE), are synthesized. After cleavage of the acetal groups, these all-polyglycerol surfactants (PG-b-PtBuGE) or multifunctional surfmers (PG-b-PAGE), are used in direct and inverse miniemulsion polymerizations. Polystyrene nanoparticles are obtained by free-radical miniemulsion polymerization, in which the allyl-functionalized copolymers act as surfmer. In inverse miniemulsion, hydroxyethyl starch nanocarriers are synthesized with PG-b-PAGE as surfmer, transferred into aqueous PG-b-PtBuGE solution, and functionalized by thiolene addition. The PG-b-PtBuGE with equal block length ratio is used as a surfactant for direct and inverse miniemulsions. With the PG being covalently bound to the nanocarriers, a desorption during protein adsorption does not occur. It is believed that these surfactants are promising alternatives to conventional surfactants with additional functionality.
Polymer Chemistry, 2017
The living anionic polymerization of sulfonyl aziridines is systematically studied by variation o... more The living anionic polymerization of sulfonyl aziridines is systematically studied by variation of solvents, temperatures, gegenions, and novel initiators.
Polymers, 2017
Partially degradable, nonionic AB and ABA type di-and triblock copolymers based on poly(propylene... more 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)-CoOBzF 5 as a catalyst in a solvent-free one-pot procedure. The amphiphilic surfactants were prepared with molecular weights (M n) between 2800 and 10,000 g•mol −1 with narrow molecular weight distributions (1.03-1.09). The copolymers were characterized using 1 H-, 13 C-and DOSY-NMR spectroscopy and size exclusion chromatography (SEC). Surface-active properties were determined by surface tension measurements (critical micelle concentration, CMC; CMC range: 1-14 mg•mL −1). Degradation of the acid-labile polycarbonate blocks was investigated in aqueous solution using online 1 H-NMR spectroscopy and SEC. The amphiphilic polymers were used as surfactants in a direct miniemulsion polymerization for poly(styrene) (PS) nanoparticles with mean diameter of 270 to 940 nm. The usage of an acid-triggered precipitation of the emulsion simplified the separation of the particles from the surfactant and purification of the nanoparticles.
Biomaterials, Nov 1, 2016
Targeting antigen combined with adjuvants to hepatic antigen-presenting cells (APCs) is essential... more 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 dendritic cells (DCs) and the potential to induce intrahepatic immune responses in a mouse model. Maturation of DCs was significantly increased by application of NS5A+MPLA-NCs compared to non-functionalized NS5A-NCs promoting a vigorous expression of CD40, CD80, CD86 and a strong secretion of the...
Bioconjugate chemistry, Mar 13, 2016
A popular strategy to overcome the limited plasma half-life of peptide heptad repeat 2 (HR2) fusi... more A popular strategy to overcome the limited plasma half-life of peptide heptad repeat 2 (HR2) fusion inhibitors against HIV-1 is through conjugation with biocompatible polymers such as poly(ethylene glycol) (PEG). However, despite improved resistance to proteolysis and reduced renal elimination, covalent attachment of polymers often causes a loss in therapeutic potency. In this study, we investigated the molecular origins of the loss in potency upon conjugation of linear, mid-functional and hyperbranched PEG-like polymers to peptides that inhibit HIV-1 - host cell membrane fusion. Fluorescence binding assays revealed that polymer conjugation imparted mass transport limitations that manifested as coexistent slower association and dissociation rates from the gp41 target on HIV-1. Furthermore, reduced association kinetics rather than affinity disruption was responsible for the loss in antiviral potency. Finally, the binding assays indicated that the unmodified HR2-derived peptide demons...
Polymers, 2016
Inverse (water-in-oil) miniemulsions are an important method to encapsulate hydrophilic payloads ... more Inverse (water-in-oil) miniemulsions are an important method to encapsulate hydrophilic payloads such as oligonucleotides or peptides. However, the stabilization of inverse miniemulsions usually requires block copolymers that are difficult to synthesize and/or cannot be easily removed after transfer from a hydrophobic continuous phase to an aqueous continuous phase. We describe here a new strategy for the synthesis of a surfactant for inverse miniemulsions by radical addition-fragmentation chain transfer (RAFT) polymerization, which consists in a homopolymer with triisopropylsilyl protecting groups. The protecting groups ensure the efficient stabilization of the inverse (water-in-oil, w/o) miniemulsions. Nanocapsules can be formed and the protecting group can be subsequently cleaved for the re-dispersion of nanocapsules in an aqueous medium with a minimal amount of additional surfactant.
Macromolecular rapid communications, 2016
Poly ((ethylene oxide)-b-(propylene oxide)-b-(ethylene oxide)) triblock copolymers commonly known... more 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 molecular weight distributions (Ð = 1.06-1.08). Surface tension measurements reveal surface-active behavior in aqueous solution comparable to established noncleavable poloxamers. Complete hydrolysis of the labile junctions after acidic treatment is verified by size exclusion chromatography. The block c...
Chemical Reviews, 2016
The review summarizes current trends and developments in the polymerization of alkylene oxides in... more 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 phosphazene bases. In addition, the commercially relevant double-metal cyanide (DMC) catalyst systems are discussed. Besides the synthetic progress, new types of multifunctional linear PEG (mf-PEG) and PPO structures accessible by copolymerization of EO or PO with functional epoxide comonomers are presented as well as complex branched, hyperbranched, and dendrimer like polyethers. Amphiphilic block copolymers based on PEO and PPO (Poloxamers and Pluronics) and advances in the area of PEGylation as the most important bioconjugation strategy are also summarized. With the ever growing toolbox for epoxide polymerization, a "polyether universe" may be envisaged that in its structural diversity parallels the immense variety of structural options available for polymers based on vinyl monomers with a purely carbon-based backbone.
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Papers by Frederik R Wurm
Volltext hier: https://onlinelibrary.wiley.com/doi/epdf/10.1002/ciuz.201900875