Manipulating Supramolecular Assembly in Water and Aqueous Mixtures

深腔空穴是一种容器形状的超分子复合体，它包含一个一纳米的、刚性的、非极性的结合口袋和一层亲水的外部涂层，赋予了良好的水溶解能力。洞穴已经被证明是有用的“宿主”，因为它们能够结合口袋里的其他分子或“客人”，并以明确的化学计量比聚集在一起。它们在蛋白质溶解度的研究、药物的控制释放、分离、光化学反应的精确控制以及作为胶凝剂方面都有应用。要从根本上理解这些超分子络合物，需要在分子水平上了解溶液中主客体之间的相互作用。提出了一项将分子模拟和实验研究相结合的合作研究项目，旨在研究含共溶剂和聚合物添加剂的水性混合物对驱动空穴和组装的作用力的影响。该研究的总体目标是开发分子工具，通过操纵介导主/客体相互作用的溶剂性质来控制超分子空穴和组装。将研究以下主题：1)醇共溶剂如何调节一系列两亲性和非极性客体的空穴和结合和组装热力学？2)环状空穴和主体口袋入口的官能团的疏水性和亲水性的变化如何影响口袋水化热力学、干燥/填充动力学和客体结合亲和力？3)水溶性聚合物排泄剂对中等稳定的二聚体空穴和络合物的稳定性有何影响？将在一系列溶剂条件和空穴和功能范围内对客体结合和空穴和络合物的形成进行分子动力学模拟，以考察水和醇与主客体络合物的结构相关性、络合热力学、宿主结合口袋的润湿和渗透压力，以获得对稳定这些组装的力的分子尺度的洞察。将进行补充实验，使用核磁共振和光散射，以及基本的组装热力学，使用量热法，检查主体功能和水混合物组成对生成的空穴和复合体的影响。除了研究生和本科生培训，拟议的项目还将包括一项针对新奥尔良特许科学和数学高中的外展计划，该计划服务于占多数的少数族裔学生基础。这一奖项反映了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。

Deep cavity cavitands are container-shaped supramolecular complexes that contain a one-nanometer, rigid, non-polar binding pocket and a hydrophilic exterior coating that bestows good water solubility. Cavitands have proven useful "hosts" because of their ability to bind other molecules, or "guests", within their pockets and assemble in well-defined stoichiometries. They have applications in studies of protein solubility, in controlled release of pharmaceuticals, in separations, in the precise control of photochemical reactions, and as gelling agents. The fundamental understanding of these supramolecular complexes requires a molecular-level understanding of the interactions between hosts and guests in solution. A collaborative research project is proposed that combines molecular simulation and experimental studies aimed at investigating the impact of aqueous mixtures with co-solvent and polymeric additives on the forces driving cavitand assembly.The overarching goal of the proposed research is to develop molecular tools for controlling supramolecular cavitand assembly by manipulating the solvent properties that mediate host/guest interactions. The following topics will be studied: 1) How do alcoholic co-solvents moderate cavitand binding and assembly thermodynamics for a series of amphiphilic and non-polar guests? 2) How do changes in the hydrophobicity and hydrophilicity of the functional groups ringing the cavitand host pocket portals impact pocket hydration thermodynamics, drying/filling kinetics, and guest binding affinities? 3) What is the impact of water-soluble polymer crowding agents on the stability of moderately stable dimeric cavitand complexes? Molecular dynamics simulations of guest binding and cavitand complex formation will be performed over a range of solvent conditions and cavitand functions to examine water and alcohol structural correlations with host/guest complexes, complexation thermodynamics, wetting of host binding pockets, and osmotic stresses to gain molecular-scale insights into the forces stabilizing these assemblies. Complementary experiments will be performed to examine the effects of host functions and aqueous mixture compositions on the resulting cavitand complexes, using Nuclear Magnetic Resonance and light scattering, and the underlying assembly thermodynamics, using calorimetry. In addition to graduate and undergraduate student training, the proposed project will include an outreach program to the New Orleans Charter Science and Mathematics High School that serves a predominantly underrepresented minority student base.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.