Pillararene Sulfates: Understanding and Using their Ultratight Binding

在化学系大分子，超分子和纳米化学项目的支持下，马里兰大学帕克分校的Lyle Isaacs教授将研究一类被称为柱芳烃硫酸盐的分子容器的制备和分子识别特性。 在日常生活中，集装箱用于储存饮料和食物，将物品运送到特定目的地，以及组织物体。 类似地，当分子容器封装更小的分子时，可以发生化学和生物性质的有利改善，包括更好的溶解性、更明亮的颜色和更低的毒性。 Isaacs小组发现，柱芳烃硫酸盐在水中包封的小分子格外强烈，并将进行研究，以了解这种强结合的起源，并将其用于化学和生物传感以及环境修复等原型应用。 这项工作具有重大的广泛影响，因为本科生和研究生将被培养为对美国劳动力至关重要的跨学科科学家。 此外，Isaacs小组生成的数据集将允许计算化学家通过SAMPL（蛋白质和配体建模的统计评估）挑战来改进他们的计算方法。 Isaacs博士将把虚拟现实耳机纳入他的研究生课程，以提高学生在三维空间中可视化分子的能力。最后，Isaacs小组制备的柱芳烃硫酸盐可能会被其他研究人员用于各种应用，包括用于聚合物的包封，以及用于药物递送和生物成像。在过去的十年中，带有羧酸基团的水溶性柱[6]芳烃衍生物WP 6已经得到了很好的研究。 Isaacs教授和他的学生发现，柱[6]芳烃硫酸盐与水溶液中的阳离子客人的结合比阴离子水溶性柱芳烃WP 6紧密10，000倍。 Isaacs教授的研究小组将通过合成有机化学系统地改变柱芳烃硫酸盐的每个结构组分，随后通过NMR光谱学，X射线晶体学，UV/维斯和荧光光谱学以及等温滴定量热法的组合来研究它们对疏水阳离子面板的分子识别能力，以揭示它们异常强大的结合能力的起源。 将制备具有单一反应性官能团的柱芳烃硫酸盐;这将使它们能够附加到更复杂的系统中，如聚合物和固相载体。 新的柱芳烃硫酸盐的能力将在化学和生物相关的背景下探索，作为新型传感，分离和封存系统的组成部分。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估。

With the support of the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Professor Lyle Isaacs of the University of Maryland-College Park will study the preparation and molecular recognition properties of a class of molecular containers known as pillararene sulfates. In everyday life, containers are used to store beverages and food, to ship items to specific destinations, and to organize objects. Similarly, when a molecular container encapsulates a smaller molecule, advantageous improvements in chemical and biological properties can occur including better solubility, brighter colors, and lower toxicity. The Isaacs group has found that pillararene sulfates encapsulate smaller molecules exceptionally strongly in water and will perform studies to understand the origins of this strong binding and use them in prototypical applications such as chemical and biological sensing and environmental remediation. The work has significant broader impacts in that undergraduates and graduate students will be trained as interdisciplinary scientists crucial for the US workforce. Furthermore, the data sets generated by the Isaacs group will allow computational chemists to improve their computational methods via SAMPL(statistical assessment of the modeling of proteins and ligands) challenges. Dr. Isaacs will incorporate Virtual Reality headsets into his (under)graduate courses to enhance the students ability to visualize molecules in three dimensions. Finally, the pillararene sulfates to be prepared by the Isaacs group are likely to be adapted by other researchers for diverse applications including for the encapsulation of polymers, as well as for drug delivery, and biological imaging.The water soluble pillar[6]arene derivative WP6 bearing carboxylic acid groups has been well studied over the past decade. Professor Isaacs and his students found that pillar[6]arene sulfates bind up to 10,000-fold more tightly than the anionic, water-soluble pillararene, WP6, toward cationic guests in aqueous solution. Professor Isaacs' research group will systematically vary each structural component of pillararene sulfates by synthetic organic chemistry and subsequently investigate their molecular recognition capabilities toward panels of hydrophobic cations by a combination of NMR spectroscopy, X-ray crystallography, UV/vis and fluorescence spectroscopy, and isothermal titration calorimetry to uncover the origins of their exceptionally strong binding abilities. Pillararene sulfates that feature a single reactive functional group will be prepared; this will allow them to be appended to more complex systems such as polymers and solid phase supports. The abilities of the new pillararene sulfates will be explored in chemically and biologically relevant contexts as components of novel sensing, separation, and sequestration systems.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.