Łukasiewicz Research Network─PORT Polish Center for Technology Development, Stabłowicka 147, 54-066 Wroclaw, Poland.
Department of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wroclaw, Poland.
ACS Biomater Sci Eng. 2024 Jun 10;10(6):3727-3738. doi: 10.1021/acsbiomaterials.4c00456. Epub 2024 May 28.
The development of precision polymer synthesis has facilitated access to a diverse library of abiotic structures wherein chiral monomers are positioned at specific locations within macromolecular chains. These structures are anticipated to exhibit folding characteristics similar to those of biotic macromolecules and possess comparable functionalities. However, the extensive sequence space and numerous variables make selecting a sequence with the desired function challenging. Therefore, revealing sequence-function dependencies and developing practical tools are necessary to analyze their conformations and molecular interactions. In this study, we investigate the effect of stereochemistry, which dictates the spatial location of backbone and pendant groups, on the interaction between sequence-defined oligourethanes and bisphenol A ligands. Various methods are explored to analyze the receptor-like properties of model oligomers and the ligand. The accuracy of molecular dynamics simulations and experimental techniques is assessed to uncover the impact of discrete changes in stereochemical arrangements on the structures of the resulting complexes and their binding strengths. Detailed computational investigations providing atomistic details show that the formed complexes demonstrate significant structural diversity depending on the sequence of stereocenters, thus affecting the oligomer-ligand binding strength. Among the tested techniques, the fluorescence spectroscopy data, fitted to the Stern-Volmer equation, are consistently aligned with the calculations, thus validating the developed simulation methodology. The developed methodology opens a way to engineer the structure of sequence-defined oligomers with receptor-like functionality to explore their practical applications, e.g., as sensory materials.
精密聚合物合成的发展使得人们能够获得各种非生物结构的文库，其中手性单体位于大分子链的特定位置。这些结构预计具有类似于生物大分子的折叠特性，并具有相当的功能。然而，广泛的序列空间和众多变量使得选择具有所需功能的序列具有挑战性。因此，揭示序列-功能关系并开发实用工具来分析它们的构象和分子相互作用是必要的。在这项研究中，我们研究了立体化学的影响，立体化学决定了主链和侧基的空间位置，对序列定义的聚尿烷与双酚 A 配体之间的相互作用的影响。探索了各种方法来分析模型低聚物和配体的受体样性质。评估分子动力学模拟和实验技术的准确性，以揭示立体化学排列的离散变化对所得配合物的结构及其结合强度的影响。提供原子细节的详细计算研究表明，形成的配合物表现出显著的结构多样性，这取决于手性中心的序列，从而影响低聚物-配体的结合强度。在测试的技术中，拟合到 Stern-Volmer 方程的荧光光谱数据与计算结果一致，从而验证了所开发的模拟方法。所开发的方法为具有受体样功能的序列定义的低聚物的结构工程开辟了道路，以探索其实际应用，例如作为感测材料。
