Linear Well-Defined Polyamines via Anionic Ring-Opening Polymerization of Activated Aziridines: From Mild Desulfonylation to Cell Transfection.
Linear Well-Defined Polyamines via Anionic Ring-Opening Polymerization of Activated Aziridines: From Mild Desulfonylation to Cell Transfection.
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DOI：
10.1021/acsmacrolett.9b00792
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发表时间：
2019-12
影响因子：
5.8
通讯作者：
Tassilo Gleede;Fangzhou Yu;Yingli Luo;Youyong Yuan;Jun Wang;F. Wurm
中科院分区：
文献类型：
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作者：
Tassilo Gleede;Fangzhou Yu;Yingli Luo;Youyong Yuan;Jun Wang;F. Wurm
线性聚乙烯亚胺（L-PEI）是一种非病毒基因传递的标准材料，通常由聚（2-恶唑啉）s水解而成。最近，磺胺活化的叠氮嘧啶的阴离子聚合被报道为一种用于定义良好的L-PEI和线性多胺的替代途径。然而，聚（磺酰基氮吡啶）的脱硫通常依赖于恶劣的条件（酸，微波）或使用有毒溶剂（例如，六甲基磷酰胺）。此外，极性的剧烈变化需要溶剂，这些溶剂可以保持溶液中的聚（磺酰基氮吡啶）s和L-PEI，目前报道的策略有限。本文制备了1-（4-氰苯磺基）2-甲基叠氮吡啶(1)单体，用于阴离子开环聚合。它被聚合成定义明确的线性聚磺酰基氮吡啶。在温和条件下将4-三苯基磺酰活化基团脱除为线性聚丙烯胺（L-PPI）。使用十二硫醇和二氮杂环十一烯（DBU）可实现≥98%的脱硫，对多胺的纯化可靠，纯度高，避免主链断裂。与以前用于聚合后脱硫的方法相比，这种方法代表了一种快速的方法，并产生线性定义良好的多胺。通过活阴离子聚合实现对分子量和分散度的高度控制是我们策略的关键优势，特别是如果用于生物医学应用，其中分子量可能与毒性相关。合成的聚丙烯亚胺作为细胞转染剂进行了进一步的测试，结果证明，阳离子纳米颗粒的转染效率为16.1%，可以替代2-恶唑啉途径获得的L-PEI。这种总体策略将允许制备包含多胺片段的复杂大分子结构，这在以前是无法实现的。
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 4-cyanobenzenesulfonyl-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.