Luo Xubo, Roncoroni Fabrice, Yu Tianyi, Li Nan K, Zuckermann Ronald N, Jiang Xi, Balsara Nitash P, Prendergast David
Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.
Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.
ACS Appl Nano Mater. 2025 Jun 16;8(25):12909-12919. doi: 10.1021/acsanm.5c01381. eCollection 2025 Jun 27.
Peptoids, or polypeptoids, are biomimetic polymers that can self-assemble into nanocrystals for biomedical and biotechnological applications. Polypeptoid nanocrystals can be prepared by evaporation-induced self-assembly, but the roles of solvent components for this process have long been overlooked at the molecular level, leaving a tunable parameter for improving self-assembly protocols. This work utilized molecular dynamics simulations to study the effects of water and the commonly used tetrahydrofuran (THF) on the assembly of nanosheets from molecules of acetylated diblock polypeptoid, poly-(-decylglycine)--poly-(-2-(2-(2-methoxyethoxy)-ethoxy) ethylglycine), abbreviated as Ac-Ndc-Nte. To probe the stages of self-assembly, isolated molecules and preassembled nanofibers/nanosheets were simulated in pure THF, water, and their mixtures, respectively. The assembly energies show that the THF/water mixture has a greater tendency to form nanosheets than pure water. In a THF/water mixture, polypeptoids were found more uncoiled in isolated states, less compact in disordered agglomerates, and with reduced requirement for the Nte block to cover hydrophobic Ndc surfaces in the nanocrystals. Mixed solvent is vital to initiating self-assembly, as THF assists in the opening of coiled polypeptoid molecules, while water provides the thermodynamics to aggregate and ultimately form nanocrystals. To obtain wider nanosheets, it is recommended that some THF be maintained in the aqueous solvent before it becomes exhausted by evaporation. Near the nanosheet surface, the THF concentration is higher than that in bulk solution (3-4 times in 4 M THF/water). The strong adsorption of THF indicates the self-assembly in a mixed solvent. These results are expected to guide the refinement of evaporation-induced self-assembly protocols for polypeptoid nanocrystals.
类肽，即聚类肽，是一种仿生聚合物，可自组装成纳米晶体，用于生物医学和生物技术应用。聚类肽纳米晶体可通过蒸发诱导自组装制备，但该过程中溶剂成分在分子水平上的作用长期以来一直被忽视，这使得改善自组装方案有了一个可调节的参数。这项工作利用分子动力学模拟研究了水和常用的四氢呋喃（THF）对由乙酰化二嵌段聚类肽分子，即聚（-癸基甘氨酸）-聚（-2-（2-（2-甲氧基乙氧基）-乙氧基）乙基甘氨酸）（简称为Ac-Ndc-Nte）组装纳米片的影响。为了探究自组装阶段，分别在纯THF、水及其混合物中模拟了孤立分子和预组装的纳米纤维/纳米片。组装能量表明，THF/水混合物比纯水更倾向于形成纳米片。在THF/水混合物中，发现聚类肽在孤立状态下更舒展，在无序聚集体中更松散，并且在纳米晶体中覆盖疏水Ndc表面对Nte嵌段的需求降低。混合溶剂对于启动自组装至关重要，因为THF有助于打开盘绕的聚类肽分子，而水提供聚集并最终形成纳米晶体的热力学条件。为了获得更宽的纳米片，建议在水溶剂中保留一些THF，直到其因蒸发而耗尽。在纳米片表面附近，THF浓度高于本体溶液中的浓度（在4 M THF/水体系中高3-4倍）。THF的强吸附表明在混合溶剂中发生了自组装。这些结果有望指导聚类肽纳米晶体蒸发诱导自组装方案的优化。
