Department of Chemistry, College of Science, North University of China, Taiyuan 030051, China.
J Mater Chem B. 2019 Apr 21;7(15):2474-2483. doi: 10.1039/c9tb00056a. Epub 2019 Mar 15.
Molecularly imprinted polymers (MIPs) capable of selectively recognizing small organic analytes in complex biological samples hold great promise in many real-world bioanalytical and biomedical applications, but development of such advanced synthetic receptors remains a challenging task. Herein, a facile and highly efficient new approach to obtaining well-defined complex biological sample-compatible MIP microspheres is developed by combining RAFT polymerization and thiol-epoxy coupling chemistry. Its proof-of-principle has been demonstrated by the first synthesis of propranolol-imprinted polymer microspheres with surface epoxy groups (briefly MIP-EP) via the combined use of reversible addition-fragmentation chain transfer (RAFT) precipitation polymerization and surface-initiated RAFT polymerization and their subsequent coupling reaction with a hydrophilic macromolecular thiol (i.e., thiol-terminated poly(2-hydroxyethyl methacrylate) (PHEMA-SH)). MIP-EP proved to show good propranolol recognition ability in an organic solvent but not in aqueous solution. The coupling reaction between PHEMA-SH and MIP-EP readily led to MIP microspheres with densely grafted PHEMA brushes, which greatly enhanced the surface hydrophilicity of MIP particles and transformed water-incompatible MIP-EP particles into biological sample-compatible ones (i.e., the resulting hydrophilic MIP microspheres exhibited specific template binding almost as good as they showed in the organic solvent and high template selectivity in biological samples including undiluted pure milk and pure bovine serum). In sharp contrast, the simple ring-opening of the epoxy groups on MIP-EP particles by using perchloric acid (following a previously reported method for obtaining water-compatible MIPs) only provided MIPs with propranolol recognition ability in pure water instead of in the complex biological samples.
分子印迹聚合物（MIPs）能够选择性地识别复杂生物样品中的小分子有机分析物，在许多实际的生物分析和生物医学应用中具有广阔的应用前景，但开发这种先进的合成受体仍然是一项具有挑战性的任务。在此，通过将 RAFT 聚合和巯基-环氧偶联化学相结合，开发了一种获得具有良好定义的复杂生物样品相容性的 MIP 微球的简便、高效的新方法。通过可逆加成-断裂链转移（RAFT）沉淀聚合和表面引发的 RAFT 聚合的联合使用，以及随后与亲水性大分子巯基（即巯基封端的聚（2-羟乙基甲基丙烯酸酯）（PHEMA-SH））的偶联反应，首次合成了具有表面环氧基团的普萘洛尔印迹聚合物微球（简称 MIP-EP），证明了其原理。MIP-EP 被证明在有机溶剂中具有良好的普萘洛尔识别能力，但在水溶液中则不然。PHEMA-SH 与 MIP-EP 之间的偶联反应很容易导致 MIP 微球上接枝有密集的 PHEMA 刷，这极大地提高了 MIP 颗粒的表面亲水性，并将不兼容水的 MIP-EP 颗粒转化为生物样品相容的颗粒（即，所得的亲水 MIP 微球表现出与在有机溶剂中几乎相同的模板结合特异性，以及在包括未稀释的纯牛奶和纯牛血清在内的复杂生物样品中的高模板选择性）。相比之下，通过使用高氯酸（按照以前报道的获得水兼容 MIPs 的方法）简单地开环 MIP-EP 颗粒上的环氧基团，只能在纯水中提供具有普萘洛尔识别能力的 MIPs，而不是在复杂的生物样品中。
