Self-Assembly of Nanocubic Molecular Capsules via Solvent-Guided Formation of Rectangular Blocks

We
investigate the mechanism underlying the self-assembly of gear-shaped
amphiphilic molecules into a highly ordered nanocubic capsule (“nanocube”)
in aqueous methanol. Simulation results show that the solvent molecules
play a significant role in the assembly process by directing the primitive
intermediates to orthogonal/rectangular shapes, thus creating appropriate
building blocks for cubic assembly while avoiding off-pathway stacked
aggregates. Free-energy analyses reveal that the interplay of the
direct intermonomer interaction and the solvent-mediated repulsion
between large aromatic cores (via preferential solvation of methanol
on hydrophobic surfaces) leads to the strong trend for perpendicular
binding of monomers and hence the solvent-guided formation of rectangular
blocks. Furthermore, we report the self-assembly simulation of the
nanocube using replica exchange with solute tempering and demonstrate
that the simulation can predict a highly ordered nanocapsule structure,
assembly intermediates, and encapsulated molecules, which helps promote
computer-aided design of functional molecular self-assemblies in explicit
solvent.

本研究探究了齿轮形两亲性分子（gear-shaped amphiphilic molecules）在甲醇水溶液中自组装为高度有序纳米立方胶囊（"纳米立方"）的内在机制。模拟结果表明，溶剂分子在组装过程中发挥关键作用：通过引导初级中间体形成正交/矩形结构，为立方组装构建合适的构筑基元，同时避免偏离组装路径的堆叠聚集体生成。自由能分析显示，单体间直接相互作用与大芳香核之间的溶剂介导排斥作用（通过甲醇在疏水表面的优先溶剂化实现）共同作用，使得单体呈现出强烈的垂直结合趋势，进而由溶剂引导形成矩形构筑基元。此外，本研究采用溶质温控副本交换法（replica exchange with solute tempering）开展了纳米立方的自组装模拟，结果表明该模拟方法可精准预测高度有序的纳米胶囊结构、组装中间体以及包封分子，有助于推动显式溶剂环境下功能性分子自组装体系的计算机辅助设计。