CAS Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences , Beijing 100190, People's Republic of China.
J Phys Chem B. 2017 Nov 2;121(43):10064-10072. doi: 10.1021/acs.jpcb.7b09067. Epub 2017 Oct 24.
Foldamer, inspired by the structures and functions of biopolymers, is defined as an artificial molecular architecture that can fold into a three-dimensional structure in solution and has been a growing and active field in supramolecular chemistry. The central issue in foldamer science is to understand how the primary sequence of oligomer folds into conformationally ordered structures as well as how individual subunits self-associate into assembly. For duplex structures, these two issues are always interrelated and inseparable with each other. Although the emergence of new foldamer keeps growing, the detailed mechanism remains elusive. On the basis of an artificially synthesized arylamide oligoamide foldamer with its crystal structure available, we constructed a set of four foldamers with a similar backbone but different substituents and aimed at dissecting the folding and self-association mechanisms of a double-helical foldamer with computations. Using molecular simulations at a microsecond time scale, we observed very consistent processes of the spontaneous self-assembly of two single-helical motifs into an entwined complex. Our results reveal that aggregation of two single-helical motifs driven by extensive π-π interactions is energetically favorable and that this spontaneous self-assembly proceeds through an "unwinding-threading-rewinding" mechanism. The detailed mechanisms about the folding and self-assembly in an aromatic oligoamide foldamer we present here disclose how the sequence is associated with a well-ordered three-dimensional structure at atomic level and therefore may have implications for designing new foldamers with versatile functions.
折叠体受生物聚合物结构和功能的启发，被定义为一种可以在溶液中折叠成三维结构的人工分子结构，它是超分子化学中一个不断发展和活跃的领域。折叠体科学的核心问题是理解低聚物的一级序列如何折叠成构象有序的结构，以及如何使单个亚基自组装成组装体。对于双链结构，这两个问题总是相互关联和不可分割的。尽管新的折叠体不断涌现，但详细的机制仍然难以捉摸。在具有晶体结构的人工合成芳酰胺寡酰胺折叠体的基础上，我们构建了一组具有相似骨架但不同取代基的四个折叠体，旨在通过计算来剖析双链折叠体的折叠和自组装机制。使用微秒时间尺度的分子模拟，我们观察到两个单链构象自发组装成缠绕复合物的非常一致的过程。我们的结果表明，由广泛的π-π相互作用驱动的两个单链构象的聚集在能量上是有利的，并且这种自发的自组装通过“解旋-穿线-重绕”机制进行。我们在这里介绍的关于芳香族寡酰胺折叠体的折叠和自组装的详细机制揭示了序列如何与原子水平上的有序三维结构相关联，因此可能对设计具有多种功能的新型折叠体具有启示意义。
