Creating metastable clusters and assemblies and characterizing their intermolecular interactions

在化学系大分子、超分子和纳米化学项目的支持下，圣母大学的S. Alex Kandel博士正在探索分子如何在表面上自组装成簇和单层。设计了一种结合实验和理论的方法，其中实验探测分子的自组装，所获得的数据用于调整理论计算，以最终获得分子如何自组装的现实模型，并提供分子间相互作用在该过程中的作用。这个项目的一个特别重点是氨基酸，它是蛋白质的基本组成部分，因为氨基酸之间的相互作用决定了这些基本生物分子的结构和功能。虽然单个氨基酸的相互作用很简单，但随着尺寸的增加，扩展的氨基酸系统（如蛋白质）迅速变得具有挑战性。该项目旨在改进氨基酸的理论模型，促进我们对这些基本分子的理解，同时改进计算机对广泛生物过程的模拟。在开展项目的过程中，将对研究生、本科生和高中生进行先进科研方法的培训。这个项目的仪器发展重点是快速制作原型和三维印刷，以便使科学工具的复制既便宜又简单，从而使社区中没有广泛的科学基础设施，包括大学院校和高中的人也能获得。所有仪器的组装计划和说明将在网上免费发布。此外，还利用可浏览和可搜索的数据库组织了一个包含实验室全部科学成果的公开网站。本项目的研究活动是探索分子在表面上自组装成簇和单层。重点是非平衡自组装，其中多个亚稳结构形成作为动力学控制的结果。这与典型的自组装实验相反，后者通常寻求在单一的热力学稳定状态下制备系统。目标是利用产生的多个亚稳结构来推断分子间势能表面的更大区域，而不是通常通过实验来探测。正因为如此，该研究提供了精炼和改进极化力场的可能性，以用于强相互作用分子的大规模模拟。在实验方面，将使用扫描隧道显微镜在超高真空和低温下研究表面上的团簇和单层。作为一种补充技术，电喷雾电离质谱法将被用于研究气相簇离子，因为过去的结果表明，在气相中优先形成特定簇大小的离子与在表面上观察到的簇大小往往是一致的。实验将探索氨基酸和相关分子的自组装，并将与理论计算携手努力，以获得这些系统中分子间相互作用的更好模型。最初将使用从头计算来获得对AMOEBA力场感兴趣的分子的参数，并将实验观察到的结构与模拟产生的结构进行比较，应该允许调整参数，以更好地捕获分子间相互作用的影响。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Macromolecular, Supramolecular and Nanochemistry program in the Division of Chemistry, Dr. S. Alex Kandel of the University of Notre Dame is exploring how molecules self-assemble as clusters and as monolayers on surfaces. A combined experimental and theoretical approach is devised where experiments probe self-assembly of molecules and the data obtained is used to tune the theoretical calculations to ultimately obtain realistic models for how molecules self-assemble and provide insight on the role of intermolecular interactions in the process. A special focus of the project is on amino acids, which are the basic building blocks of proteins, because it is the interactions between amino acids is what determine the structure and thus the function of these essential biological molecules. While the interactions of individual amino acids are simple, extended amino acid systems such as proteins rapidly become challenging with increasing size. The project seeks to improve theoretical models of amino acids, advancing our understanding of these fundamental molecules, while at the same time improving computer simulations of a wide range of biological processes. In the course of conducting the project, graduate, undergraduate and high-school students will be trained in advanced scientific research methods. Instrument development for this project places an emphasis on rapid prototyping and three-dimensional printing, in order to make reproduction of scientific tools inexpensive and simple, and thus accessible even for those in the community without access to extensive scientific infrastructure, including undergraduate institutions and high schools. Plans and instructions for assembly for all instruments will be published freely online. Also a publicly available website containing the entire scientific output of the laboratory has been organized using a browsable and searchable database.The research activities of this project explore molecular self-assembly into clusters and monolayers on surfaces. The emphasis is on non-equilibrium self-assembly, where multiple metastable structures form as the result of kinetic controls. This is in contrast to typical self-assembly experiments, which generally seek to prepare the system in a single, thermodynamically stable state. The goal is to use the multiple metastable structures produced to draw inferences about a larger region of the intermolecular potential energy surface than is ordinarily probed by experiments. Because of this, the research affords the possibility of refining and improving polarizable force fields to be used in large-scale simulations of strongly interacting molecules. On the experimental side, clusters and monolayers on surfaces will be studied in ultra-high-vacuum and at low temperature using scanning tunneling microscopy. As a complementary technique, electrospray ionization mass spectrometry will be employed to study gas-phase cluster ions, as past results have shown that there is often coincidence between preferential formation of a particular cluster size in the gas phase and the observation of that cluster size on the surface. Experiments will probe self-assembly of amino acids and related molecules, and will proceed hand-in-hand with theoretical calculations in an effort to obtain a better model of intermolecular interactions in these systems. Ab initio calculations will initially be used to obtain parameters for molecules of interest for the AMOEBA force field, and comparison of experimentally observed structures to those arising from simulations should allow parameters to be adjusted to better capture the effect of intermolecular interactions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.