Relative to free antibiotics, polymer-antibiotic conjugates (PACs) can possess modified solubility, sustained release behavior, and prolonged bioactivity in biological systems. As one of the most potent and ubiquitous antibiotics, clindamycin (Clin) has broad-spectrum antibiotic activity with versatile medical applications. However, polymer-Clin conjugates have not been reported yet. This can be partly ascribed to the difficulties in selective modification of Clin which possesses multiple reactive hydroxyl groups. In this study, we employed immobilized lipase as a bio-based catalyst for the facile and highly regioselective synthesis of a methacrylic-functionalized monomer-Clin conjugate via a one-step reaction. Reversible addition fragmentation chain transfer (RAFT) polymerization was then employed to synthesize copolymers of the monomer-Clin conjugate with 2-hydroxymethyl methacrylate or 3-[(3-acrylamidopropyl) dimethylammonio]propanoate to achieve water-insoluble and water-soluble Clin-containing PACs, respectively. These PACs possessed well-defined structures with high Clin content (33-46 wt%), as confirmed by ¹H NMR and gel permeation chromatography characterizations. Living nature of the RAFT process for the synthesis of PACs was verified by a chain-extension experiment. With sustained Clin release behavior, these PACs further demonstrated notable antibacterial activities against Streptococcus mutans, as verified by zone of inhibition tests. Collectively, this work presents an efficient method to synthesize different types of Clin-containing PACs, with potential for use in diverse antibacterial applications.

中文翻译：

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通过脂肪酶催化酯化反应和 RAFT 聚合合成聚合物-克林霉素偶联物


相对于游离抗生素，聚合物-抗生素偶联物 （PAC） 在生物系统中具有改性的溶解度、缓释行为和延长的生物活性。作为最有效和最普遍的抗生素之一，克林霉素 （Clin） 具有广谱抗生素活性，具有多种医学应用。然而，聚合物-Clin 偶联物尚未报道。这部分归因于具有多个反应性羟基的 Clin 选择性修饰的困难。在这项研究中，我们采用固定化脂肪酶作为生物基催化剂，通过一步反应简单且高度区域选择性地合成甲基丙烯酸官能化单体-Clin 偶联物。然后采用可逆加成碎裂链转移 （RAFT） 聚合合成单体-Clin 偶联物与 2-羟基甲基丙烯酸酯或 3-[（3-丙烯酰胺丙基）二甲基铵基]丙酸酯的共聚物，以分别获得水不溶性和水溶性含 Clin 的 PAC。这些 PAC 具有明确的结构，具有高 Clin 含量 （33-46 wt%），H NMR 和凝胶渗透色谱表征证实 ¹ 了这一点。通过链延伸实验验证了 PACs 合成的 RAFT 过程的活体性质。凭借持续的 Clin 释放行为，这些 PAC 进一步显示出对变形链球菌的显着抗菌活性，如抑制区试验所验证的那样。总的来说，这项工作提出了一种合成不同类型含 Clin 的 PAC 的有效方法，具有用于各种抗菌应用的潜力。