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 (5À100%) with molecular weights in the range of 3,900À13,200 g/mol and narrow molecular weight distributions (M w /M n = 1.06À1.20) 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 reactions: (i) thiolÀene addition and (ii) acetal formation, employing various model compounds. Both strategies are very efficient, resulting in quantitative conversion. The rapid and complete acetal formation with alcohols results in an acid-labile bond and is thus highly interesting with respect to biomedical applications that require slow or controlled release of a drug, while the thiolÀene addition to a vinyl ether prevents cross-linking efficiently compared to other double bonds.
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 (M w /M n = 1.07−1.20). The ferrocene (fc) content was varied from 3 to 30 mol %, obtaining watersoluble materials up to 10 mol % incorporation of the apolar ferrocenyl comonomer. Despite the steric bulk of fcGE, random copolymers were obtained, as confirmed via detailed 1 H NMR kinetic measurements as well as 13 C NMR studies of the polymer microstructure, including detailed triad characterization. In addition, the poly(fcGE) homopolymer has been prepared. All water-soluble copolyethers with fc side chains exhibited a lower critical solution temperature (LCST) in the range 7.2−82.2 °C in aqueous solution, depending on the amount of fcGE incorporated. The LCST is further tunable by oxidation/reduction of ferrocene, as demonstrated by cyclic voltammetry. Investigation of the electrochemical properties by cyclovoltammetry revealed that the iron centers can be oxidized reversibly. Further, to evaluate the potential for biomedical application, cell viability tests of the fc-containing PEG copolymers were performed on a human cervical cancer cell line (HeLa), revealing good biocompatibility only in the case of low amounts of fcGE incorporated (below 5%). Significant cytotoxic behavior was observed with fcGE content exceeding 5%. The ferrocenesubstituted copolyethers are promising for novel redox sensors and create new options for the field of organometallic (co)polymers in general.
The first application of N,N -diallylglycidylamine (DAGA) as a monomer for anionic ring-opening polymerization is presented. The monomer is obtained in a one-step procedure using epichlorohydrin and N,N -diallylamine. Both random and block copolymers consisting of poly(ethylene glycol) and poly( N,N -diallylglycidylamine) with adjusted DAGA ratios from 2.5 to 24% have been prepared, yielding well-defined materials with low polydispersities (M w/M n) in the range 1.04–1.19. Molecular weights ranged between 2600 and 10 300 g mol–1. Isomerization of allylamine to enamine structures during polymerization depending on time, temperature, and counterion has been realized. The kinetics of the formation of the copolymer structure obtained by random copolymerization was investigated, using time-resolved 1H NMR measurements and 13C NMR triad sequence analysis. A tapered character of the monomer incorporation was revealed in the course of the concurrent copolymerization of EO and DAGA. The thermal behavior of the copolymers in both bulk and aqueous solution has been studied, revealing LCSTs in the range 29–94 °C. Quantitative removal of protective groups via double-bond isomerization mediated by Wilkinson’s catalyst and subsequent acidic hydrolysis yielded multiamino-functional PEG copolymers with tapered or block structure. Accessibility of liberated primary amines for further transformation was demonstrated in a model reaction by derivatization with acetic anhydride. In contrast to previous approaches, the DAGA monomer permits the synthesis of block copolymers with PEG block combined with multiamino-functional polyether block.
A multicomponent template reaction utilizing an air-stable phosphonium precursor leads initially to the first enantiopure bis-tridentate iron complexes mer-[Fe(P-N-N) 2] (2+) in high yield and then to new tetradentate iron complexes trans-[Fe(MeCN) 2(P-N-N-P)] (2+).
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, hydroxyl-containing, polymer-protein conjugates. The hydroxyl side chain functional polymers selected for this study are a library of amine end-functional, linear, midfunctional, hyperbranched, and linear-block-hyperbranched polyglycerol (PG) copolymers. These synthetic polymers have been used to prepare a diverse library of BSA and lysozyme polymer conjugates. In addition to exploring the scope and limitations of the squaric acid diethylester-mediated coupling strategy, the use of the library of polyglycerol copolymers also allows to systematically study the influence of molecular weight and architecture of the synthetic polymer on the biological activity of the protein. Comparison of the activity of PG-lysozyme conjugates generated from relatively low molecular weight PG copolymers did not reveal any obvious structure-activity relationships. Evaluation of the activity of conjugates composed of PG copolymers with molecular weights of 10000 or 20000 g/mol, however, indicated significantly higher activities of conjugates prepared from midfunctional synthetic polymers as compared to linear polymers of similar molecular weight.
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