Using deep-cavity cavitands to study supramolecular chemistry in water

利用深腔空配体研究水中的超分子化学

• 批准号: 8627614
• 负责人: BRUCE C GIBB
• 金额: $ 28.29万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8627614
• 关键词: Affinity; Age; Anions; Binding; Biological Models; Calorimetry; Chemistry; Complex; Computer Simulation; Data; Documentation; Employee Strikes; Event; Goals; Inorganic Sulfates; Ions; Lead; Life; Modeling; Modus; Molecular; NMR Spectroscopy; Oils; Perchlorates; Precipitation; Property; Proteins; Research; Salts; Science; Series; Shapes; Sodium Chloride; Solubility; Solutions; Solvents; Structure; Surface Tension; Thermodynamics; Titrations; Unspecified or Sulfate Ion Sulfates; Viscosity; Water; Work; X-Ray Crystallography; aqueous; base; cavitand; driving force; mathematical model; molecular scale; programs; protein structure; research study; solute

DESCRIPTION (provided by applicant): The goal of this program of research is to contribute to Science's understanding of the Hydrophobic Effect. Water, the 'solvent of life' has a profound influence on the structure and assembly of proteins and other biomolecules, yet there are still many unknowns regarding the modus operandi of the Hydrophobic Effect. For example, our understanding of the Hofmeister Effect - why some salts (kosmotropes) decrease the solubility of organic solutes whilst others (chaotropes) increase solubility - is poorly understood; even though the phenomenon was first described by Hofmeister over 120 years ago. In studying the formation of a host-guest complex driven by the hydrophobic effect, we have observed that the strength of complexation varies as a function of co-solute salts, in a manner paralleling the ability of salts to induce either precipitation or solubilization of proteins. Thus, kosmotropic sats cause an apparent decrease in the solubility of the host-guest pair and lead to an enhancement of the binding affinity, whilst chaotropes have the opposite effect. Using a combination of Isothermal Titration Calorimetry (ITC) and Nuclear Magnetic Resonance (NMR) spectroscopy, we have traced the ability of chaotropes to weaken binding to the fact that anions have a surprisingly strong affinity for hydrophobic concavity. In other words, the reduced affinity between host and guest occurs because chaotropic anions compete with the hydrophobic guest for binding to the host. This is the first observation of anions binding to hydrophobic concavity. Furthermore, ITC and NMR spectroscopy allows the accurate determination of the thermodynamics of host-guest and host-anion binding. As a result, the data we are gathering is allowing us to build the first molecular-scale models of the Hofmeister Effect. The major hypothesis behind this program of study is that anion binding to concavity is one of the major driving forces behind the observation that chaotropes break up protein quaternary and tertiary structure to form the molten-globule state. To build on this idea, this proposal describes experiments to probe the thermodynamics of 1:1 complexation of organic guests to a series of cavitand hosts. These studies will utilize a combination of ITC, NMR, spectroscopy, in silico work, and X-ray crystallography, to examine how co solutes salts influence these binding events. This data will be used to build the first thermodynamic models of the Hofmeister Effect at the molecular level, and has the potential to unify current models of the Hofmeister Effect based on bulk properties such as solubility, viscosity, and surface tension.

描述（由申请人提供）：本研究项目的目标是促进科学对疏水效应的理解。水，作为“生命的溶剂”，对蛋白质和其他生物分子的结构和组装有着深远的影响，但关于疏水效应的运作方式仍有许多未知之处。例如，我们对霍夫迈斯特效应的理解——为什么有些盐（宇宙异色盐）会降低有机溶质的溶解度，而另一些盐（混沌异色盐）会增加溶解度——知之甚少；尽管这种现象最早是由霍夫迈斯特在120多年前描述的。在研究由疏水效应驱动的主-客体络合物的形成时，我们观察到络合的强度随共溶质盐的作用而变化，其方式与盐诱导蛋白质沉淀或增溶的能力相似。因此，共向卫星导致主-客体对溶解度的明显降低，并导致结合亲和力的增强，而混沌卫星则具有相反的效果。使用等温滴定量热法（ITC）和核磁共振（NMR）光谱的结合，我们已经追踪了混沌的能力削弱结合的事实，阴离子对疏水凹具有惊人的强亲和力。换句话说，宿主和客体之间的亲和力降低是因为向乱性阴离子与疏水性客体竞争与宿主的结合。这是首次观察到阴离子与疏水凹的结合。此外，ITC和核磁共振光谱可以准确地确定主-客体和主-阴离子结合的热力学。因此，我们正在收集的数据使我们能够建立霍夫迈斯特效应的第一个分子尺度模型。这个研究项目背后的主要假设是，阴离子与凹度的结合是观察到混沌物破坏蛋白质的四级和三级结构以形成熔融球状状态的主要驱动力之一。为了建立这一想法，本提案描述了探索有机客体与一系列空腔和宿主1:1络合的热力学实验。这些研究将结合ITC、核磁共振、光谱学、硅工作和x射线晶体学来研究co溶质盐如何影响这些结合事件。这些数据将用于在分子水平上建立霍夫迈斯特效应的第一个热力学模型，并有可能统一目前基于溶解度、粘度和表面张力等体积性质的霍夫迈斯特效应模型。