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莱尔·艾萨克斯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性能。在日常生活中，集装箱被用来储存饮料和食物，将物品运送到特定的目的地，并组织物品。同样，当分子容器包裹较小的分子时，可以在化学和生物性能方面发生有利的改善，包括更好的溶解度、更鲜艳的颜色和更低的毒性。Isaacs团队发现，柱芳烃硫酸盐在水中包裹的小分子非常强烈，并将进行研究，以了解这种强烈结合的来源，并将它们用于典型应用，如化学和生物传感以及环境修复。这项工作具有重大的更广泛的影响，因为本科生和研究生将被培养成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。艾萨克斯博士将把虚拟现实耳机融入他(本科)的研究生课程中，以增强学生在三维空间可视化分子的能力。最后，Isaacs小组将制备的柱芳烃硫酸盐很可能被其他研究人员用于不同的应用，包括聚合物的封装，以及药物输送和生物成像。在过去的十年中，含有羧酸基的水溶性柱状[6]芳烃衍生物WP6得到了很好的研究。艾萨克斯教授和他的学生发现，在水溶液中，柱状[6]芳烃硫酸盐与阳离子客体的结合比阴离子、水溶性的柱状芳烃WP6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成分，并随后通过结合核磁共振光谱、X射线结晶学、UV/VIS和荧光光谱以及等温滴定热法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来源。将制备具有单一反应性官能团的环芳烃硫酸盐；这将使它们能够添加到更复杂的体系中，如聚合物和固相载体。新的柱芳烃硫酸盐的能力将作为新型传感、分离和隔离系统的组件在化学和生物相关的背景下进行探索。该奖项反映了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。

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.