Creating metastable clusters and assemblies and characterizing their intermolecular interactions

在化学系高分子、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。 设计了一种实验和理论相结合的方法，其中实验探测分子的自组装，获得的数据用于调整理论计算，最终获得分子自组装的现实模型，并深入了解分子间相互作用在该过程中的作用。 该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重要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（例如蛋白质）很快变得具有挑战性。 该项目旨在改进氨基酸的理论模型，增进我们对这些基本分子的理解，同时改进对各种生物过程的计算机模拟。在该项目的实施过程中，研究生、本科生和高中生将接受先进科学研究方法的培训。 该项目的仪器开发强调快速原型制作和三维打印，以便使科学工具的复制变得廉价且简单，因此即使对于那些无法获得广泛科学基础设施的社区（包括本科机构和高中）来说也可以使用。所有仪器的组装计划和说明将在网上免费发布。此外，还使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。该项目的研究活动探索分子自组装成表面上的簇和单层。 重点是非平衡自组装，其中由于动力学控制而形成多个亚稳态结构。 这与典型的自组装实验相反，典型的自组装实验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态结构来推断比通常实验探测的更大的分子间势能表面区域。正因为如此，该研究提供了细化和改进可极化力场以用于强相互作用分子的大规模模拟的可能性。 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簇和单层。作为补充技术，电喷雾电离质谱将用于研究气相团簇离子，因为过去的结果表明，气相中特定团簇尺寸的优先形成与表面上该团簇尺寸的观察之间经常存在重合。 实验将探索氨基酸和相关分子的自组装，并将与理论计算齐头并进，以获得这些系统中分子间相互作用的更好模型。 从头计算最初将用于获得 AMOEBA 力场感兴趣分子的参数，并将实验观察到的结构与模拟产生的结构进行比较，以便调整参数以更好地捕捉分子间相互作用的影响。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力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.