Capsular Assemblies Driven by the Hydrophobic Effect

描述(由申请人提供)： 项目摘要 这项建议的长期目标是：1)了解分子结构和疏水效应如何结合起来促进纳米胶囊在水溶液中的组装；2)利用这些信息来了解四元蛋白质结构，并设计作为药物输送系统的自组装纳米胶囊。 这项提议的目的是合成和分析组装成纳米级胶囊的水溶性空穴，并在这样做的过程中将客体分子困在它们的中空内部。将合成四个空腔形状和大小不同的空穴，以及促进组装的疏水表面面积。每一种材料都可以“涂覆”一层调节其组装性能的外部功能层。将这些变量结合在一起，就会产生数百个同质和异质胶囊。胶囊的形成将作为客人的功能进行检查，以确定它们如何影响组装。此外，我们还将研究胶囊是如何动态稳定正常活性化合物的。在这方面特别令人感兴趣的将是对潜在的抗疟疾药物的分析，这些药物太不稳定或太难溶解，无法单独证明活性。这些体系的分析将使用核磁共振(核磁共振)光谱、等温滴定量热法(ITC)和荧光光谱。 相关性 新药物输送系统的发展为攻击疾病状态提供了新的途径。在模仿自然界最有效的药物传递系统--病毒--的过程中，这项提议概述了对纳米胶囊的形成和性质的研究。到目前为止，人们对纳米胶囊如何在水中组装知之甚少。因此，这些研究将为这一新的研究领域提供有价值的信息。

DESCRIPTION (provided by applicant): Project Summary The long-term objectives of this proposal are: 1) to learn how molecular structure and the hydrophobic effect combine to promote the assembly of nano-capsules in aqueous solution; 2) to use this information to both gain an understanding of quaternary protein structure, and devise self-assembling nano-capsules that function as drug delivery systems. The aim of this proposal is the synthesis and analysis of water-soluble cavitands that assemble into nano-scale capsules, and in doing so entrap guest molecules within their hollow interiors. Four cavitands that differ in cavity shape and size, and the area of hydrophobic surface that promotes assembly, will be synthesized. Each can be "coated" with an external layer of functionality that modulates their assembly properties. In combination these variables engenders hundreds of homo- and hetero-capsules. Capsule formation will be examined as a function of guest to determine how they influence assembly. In addition, we will examine how the capsules kinetically stabilize normally reactive compounds. Of particular interest in this regard will be the analysis of potential anti-malarial drugs that are too unstable or insoluble to individually demonstrate activity. Analysis of the systems will be carried out with Nuclear Magnetic Resonance (NMR) spectroscopy, Isothermal Titration Calorimetry (ITC), and fluorescence spectroscopy. Relevance The development of new drug delivery systems allows new avenues for attacking disease states. In mimicry of Nature's most efficient drug delivery systems - viruses - this proposal outlines investigations into the formation and properties of nano-capsules. To date, little is known about how nano-capsules assemble in water. Hence, these studies will provide valuable information pertaining to this novel field of research.