Manipulating Supramolecular Assembly in Water and Aqueous Mixtures

深腔空穴是容器形的超分子复合物，其包含一个纳米、刚性、非极性的结合口袋和赋予良好水溶性的亲水性外部涂层。空穴已被证明是有用的“宿主”，因为它们能够在口袋内结合其他分子或“客人”，并以明确的化学计量组装。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中具有应用。 对这些超分子复合物的基本理解需要在分子水平上理解溶液中主体和客体之间的相互作用。提出了一个合作研究项目，结合分子模拟和实验研究，旨在调查的影响，水性混合物与助溶剂和聚合物添加剂的驱动力cavitand association.The拟议的研究的总体目标是开发分子工具，通过操纵溶剂的属性，介导的主/客体相互作用控制超分子cavitand组装。本论文主要研究了以下几个方面的问题：1）醇类共溶剂如何调节一系列两亲性和非极性客体的空穴结合和组装热力学？2)如何改变的疏水性和亲水性的功能基团环的cavitand主机口袋门户网站的影响口袋水合热力学，干燥/填充动力学，和客人的结合亲和力？ 3)水溶性聚合物拥挤剂对中等稳定的二聚空穴配合物的稳定性有什么影响？ 分子动力学模拟的客体结合和空穴复合物的形成将在一系列的溶剂条件和空穴功能，以检查水和醇的结构相关性与主/客体复合物，络合热力学，润湿的主机结合口袋，和渗透应力，以获得分子尺度的洞察力稳定这些组件。将进行补充实验，以检查主机功能和水性混合物组合物对所得的空穴复合物的影响，使用核磁共振和光散射，和底层的组装热力学，使用量热法。 除了研究生和本科生的培训，拟议的项目将包括一个外展计划，以新奥尔良特许科学和数学高中，服务于一个主要代表性不足的少数民族学生基地。这个奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

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.