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·亚历克斯·坎德尔博士正在探索分子如何以簇和单分子的形式在表面自组装。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，获得的数据被用于调整理论计算，最终获得分子如何自组装的现实模型，并提供对分子间相互作用在这一过程中的作用的洞察。该项目的一个特别重点是氨基酸，这是蛋白质的基本组成部分，因为正是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。虽然单个氨基酸之间的相互作用很简单，但扩展的氨基酸系统，如蛋白质，随着大小的增加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，同时改进对广泛生物过程的计算机模拟。在实施该项目的过程中，将对研究生、本科生和高中生进行先进的科研方法培训。该项目的仪器开发侧重于快速成型和三维打印，以便使科学工具的复制既便宜又简单，因此即使是社区中那些没有获得广泛科学基础设施的人，包括本科生机构和高中，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，还利用一个可浏览和可搜索的数据库组织了一个公开网站，其中载有该实验室的全部科学成果。该项目的研究活动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，其中多个亚稳态结构形成的结果是动力学控制。这与典型的自组装实验不同，典型的自组装实验通常寻求在单一的热力学稳定状态下准备系统。我们的目标是利用产生的多个亚稳态结构来推断分子间势能面的更大区域，而不是通常通过实验探索的区域。正因为如此，这项研究提供了改进和改进极化力场的可能性，用于对强相互作用分子的大规模模拟。在实验方面，将利用扫描隧道显微镜在超高真空和低温下研究表面的团簇和单分子膜。作为一种补充技术，电喷雾电离质谱仪将被用来研究气相团簇离子，因为过去的结果表明，在气相中优先形成特定的团簇尺寸与在表面观察到该团簇尺寸之间往往是一致的。实验将探索氨基酸和相关分子的自组装，并将与理论计算齐头并进，努力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阿米巴力场中感兴趣的分子的参数，实验观察到的结构与模拟产生的结构的比较应该允许调整参数，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优势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.