Institute for Complex Molecular Systems, Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
J Am Chem Soc. 2013 Jan 9;135(1):501-10. doi: 10.1021/ja310422w. Epub 2012 Dec 27.
We herein report the synthesis and characterization of ABA triblock copolymers that contain two complementary association motifs and fold into single-chain polymeric nanoparticles (SCPNs) via orthogonal self-assembly. The copolymers were prepared using atom-transfer radical polymerization (ATRP) and possess different pendant functional groups in the A and B blocks (alcohols in the A block and acetylenes in the B block). After postfunctionalization, the A block contains o-nitrobenzyl-protected 2-ureidopyrimidinone (UPy) moieties and the B block benzene-1,3,5-tricarboxamide (BTA) moieties. While the protected UPy groups dimerize after photoinduced deprotection of the o-nitrobenzyl group, the BTA moieties self-assemble into helical aggregates when temperature is reduced. In a two-step thermal/photoirradiation treatment under dilute conditions, the ABA block copolymer forms both BTA-based helical aggregates and UPy dimers intramolecularly. The sequential association of the two self-assembling motifs results in single-chain folding of the polymer, affording nanometer-sized particles with a compartmentalized interior. Variable-temperature NMR studies showed that the BTA and UPy self-assembly steps take place orthogonally (i.e., without mutual interference) in dilute solution. In addition, monitoring of the intramolecular self-assembly of BTA moieties into helical aggregates by circular dichroism spectroscopy showed that the stability of the aggregates is almost independent of UPy dimerization. Size-exclusion chromatography (SEC) and small-angle X-ray scattering analysis provided evidence of significant reductions in the hydrodynamic volume and radius of gyration, respectively, after photoinduced deprotection of the UPy groups; a 30-60% reduction in the size of the polymer chains was observed using SEC in CHCl(3). Molecular imaging by atomic force microscopy (AFM) corroborated significant contraction of individual polymer chains due to intramolecular association of the BTA and UPy groups. The stepwise folding process resulting from orthogonal self-assembly-induced supramolecular interactions yields compartmentalized SCPNs comprised of distinct microdomains that mimick two secondary-structuring elements in proteins.
我们在此报告了 ABA 三嵌段共聚物的合成与表征，该共聚物包含两个互补的缔合基序，通过正交自组装折叠成单链聚合物纳米颗粒（SCPN）。该共聚物通过原子转移自由基聚合（ATRP）制备，并在 A 和 B 嵌段中具有不同的侧基官能团（A 嵌段中的醇和 B 嵌段中的炔）。后功能化后，A 嵌段含有邻硝基苄基保护的 2-脲嘧啶酮（UPy）部分，B 嵌段含有苯-1,3,5-三羧酸酰胺（BTA）部分。虽然保护的 UPy 部分在光诱导去保护邻硝基苄基后二聚化，但 BTA 部分在温度降低时自组装成螺旋聚集体。在两步热/光辐照处理下，在稀溶液中，ABA 嵌段共聚物形成基于 BTA 的螺旋聚集体和 UPy 二聚体的混合物。两种自组装基序的顺序缔合导致聚合物的单链折叠，赋予具有分隔内部的纳米级颗粒。变温 NMR 研究表明，BTA 和 UPy 自组装步骤在稀溶液中是正交进行的（即，没有相互干扰）。此外，通过圆二色光谱监测 BTA 部分自组装成螺旋聚集体的过程表明，聚集体的稳定性几乎与 UPy 二聚化无关。尺寸排阻色谱（SEC）和小角 X 射线散射分析分别提供了 UPy 基团光诱导去保护后水动力体积和回转半径显著减小的证据；使用 SEC 在 CHCl3 中观察到聚合物链尺寸减小 30-60%。原子力显微镜（AFM）的分子成像证实了由于 BTA 和 UPy 基团的分子内缔合，单个聚合物链的显著收缩。由于正交自组装诱导的超分子相互作用导致的逐步折叠过程产生了具有不同微域的分隔 SCPN，这些微域模拟了蛋白质中的两个二级结构元件。
