Reactive Copolymers Based on N-Vinyl Lactams with Pyridyl Disulfide Side Groups via RAFT Polymerization and Postmodification via Thiol–Disulfide Exchange Reaction,Macromolecules

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Reactive Copolymers Based on N-Vinyl Lactams with Pyridyl Disulfide Side Groups via RAFT Polymerization and Postmodification via Thiol–Disulfide Exchange Reaction
Macromolecules ( IF 5.1 ) Pub Date : 2016-09-22 00:00:00 , DOI: 10.1021/acs.macromol.6b01210
Huan Peng ₁ , Kristin Rübsam ₁ , Xiaobin Huang ₂ , Felix Jakob ₁ , Marcel Karperien ₂ , Ulrich Schwaneberg ₁ , Andrij Pich ₁

Affiliation

Herein, we report the synthesis of a series of novel pyridyl disulfide (PDS)-functionalized statistical reactive copolymers that enable facile access to complex polymeric architectures through highly selective thiol–disulfide exchange reaction with thiol-containing ligands or proteins. Functional reactive poly(N-vinyl lactam)-based copolymers including poly(N-vinylpyrrolidone-co-pyridyl disulfide ethyl methacrylate) (PVPD), poly(N-vinylpiperidone-co-pyridyl disulfide ethyl methacrylate) (PVPID), and poly(N-vinylcaprolactam-co-pyridyl disulfide ethyl methacrylate) (PVD) with PDS side groups were synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization at 60 °C in anisole with methyl 2-(ethoxycarbonothioylthio)propanoate as chain transfer agent. The PDS contents in the synthesized copolymers were varied from 2 to 10 mol % (as confirmed by systematical characterization with FTIR/Raman and ¹H NMR spectroscopy) using well-controlled continuous feeding method. The kinetics study suggested that copolymerizations were less favored with the enlargement of the lactam rings, indicated by lower conversions and larger dispersity indexes (Đ). The PDS-functionalized reactive polymers were amenable to functionalization with a variety of thiol-containing molecules, including 3-mercaptopropionic acid (3M), 2-phenylethanethiol (2P), methyl 3-mercaptopropionate (M3), 2-mercaptoethanol (2M), 2-aminoethanethiol (2A), poly(ethylene glycol) methyl ether thiol (PEG-SH), and enhanced green fluorescent protein (EGFP) via thiol–disulfide exchange reaction under mild conditions, confirmed by ¹H NMR and SDS-PAGE. The conversions in all cases were higher than 95%, displaying that the thiol–disulfide exchange reaction to PDS groups with thiol-containing molecules is highly selective and tolerant to different ligands including amine, carboxyl, hydroxyl, phenyl, PEG and even polypeptides, providing a versatile scaffold for facile conjugation of various biological components. The contact angle measurement results and fluorescence microscopy study indicated that the reactive films based on the PDS-functionalized copolymers allowed facile, direct, and environmental-friendly surface engineering of surfaces from aqueous solution suggesting potential application in surface decoration of tissue-engineering scaffolds and medical implants. The initial cell culture experiments with HeLa cells displayed that the unmodified PVPD film was nontoxic and biocompatible while the film modified with PEG (a type of antifouling polymer) showed diminished cell attachment and growth, indicating that elegant engineering of the film surface can meet demands of particular applications.

中文翻译：

基于N-乙烯基内酰胺与吡啶基二硫键侧基通过RAFT聚合和通过巯基-二硫键交换反应进行后改性的反应性共聚物

在这里，我们报告了一系列新型的吡啶二硫醚（PDS）-官能化的统计反应性共聚物的合成，这些共聚物能够通过与含硫醇的配体或蛋白质的高度选择性的硫醇-二硫键交换反应，轻松地进入复杂的聚合物结构。功能性反应性基于聚（N-乙烯基内酰胺）的共聚物，包括聚（N-乙烯基吡咯烷酮-共-吡啶基二硫化甲基丙烯酸甲酯）（PVPD），聚（N-乙烯基哌啶酮-共-吡啶基二硫化甲基丙烯酸乙酯）（PVPID）和聚（ñ -vinylcaprolactam-合作通过在60°C下于苯甲醚中以2-（乙氧基碳硫代硫代硫代）丙酸甲酯为链转移剂的可逆加成-断裂链转移（RAFT）聚合反应，合成了具有PDS侧基的-吡啶基二硫化甲基丙烯酸乙酯（PVD）。使用良好控制的连续进料方法，合成共聚物中的PDS含量在2到10 mol％之间变化（通过FTIR / Raman和¹ H NMR光谱系统表征得到证实）。动力学研究表明，内酰胺环的扩大不利于共聚反应，这表明较低的转化率和较大的分散指数（Đ）。经PDS官能化的反应性聚合物适合用各种含硫醇的分子进行官能化，包括3-巯基丙酸（3M），2-苯基乙硫醇（2P），3-巯基丙酸甲酯（M3），2-巯基乙醇（2M）， 2-氨基乙硫醇（2A），聚（乙二醇）甲醚硫醇（PEG-SH）和增强的绿色荧光蛋白（EGFP）通过在温和条件下的硫醇-二硫键交换反应得到了¹1 H NMR和SDS-PAGE。在所有情况下，转化率均高于95％，这表明具有含硫醇分子的PDS基团的巯基-二硫键交换反应具有高度选择性，并能耐受不同的配体，包括胺，羧基，羟基，苯基，PEG甚至多肽。一种多功能支架，可轻松结合各种生物成分。接触角测量结果和荧光显微镜研究表明，基于PDS-官能化共聚物的反应膜可实现水溶液水溶液表面的简便，直接和环保的表面工程设计，从而潜在地应用于组织工程支架和医学的表面装饰植入物。

更新日期：2016-09-22

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