Pillararene-Basket Conjugates, Deeper Cavity Baskets and Covalent Basket Cages for Allosteric Complexation of Toxicants

在化学系大分子、超分子和纳米化学（MSN）项目的支持下，俄亥俄州立大学的Jovica badjiki教授致力于开发能够与包括毒素在内的各种分析物结合的新型隔离分子。使用计算化学和实验化学方法制备、功能化和测试花瓶状化合物（即篮子）以捕获小分子。这些研究旨在扩大对在复杂的生物环境中捕获特定分析物（包括毒素）的过程的基本理解。该项目将教育研究生、本科生和公众有关我们社会中与健康相关的中毒问题，以及如何使用超分子化学来解决这些问题。提供给学生的跨学科研究培训将有助于为化学工业或学术界准备熟练的劳动力。该计划的第一个目标是检查分子篮到柱芳烃的共轭。篮柱芳烃（BPr）杂合体的一个刚性、深度和定义明确的芳香口袋被设计成有利于目标生物相关的客体配体的完全包裹和溶解，包括烟草吡啶生物碱、兴奋剂、阿片类药物和致幻剂，有助于形成紧密配合物。顶部和中间的两个官能团带的位置产生良好的主-客体接触，以提高稳定性和结合选择性。该计划的第二个目标是了解强效抗癌药物甲氨蝶呤的封装，甲氨蝶呤可以抑制二氢叶酸还原酶，从而干扰嘧啶的生物合成，从而影响DNA复制。这种相当大的带负电荷的化合物有望折叠，从而补充含有负羧酸盐的更深空腔篮的内部空间。该项目的第三个目标是开发四种抗癌药物在水溶性共价筐笼内的变构包封，其形状为截断四面体，四角处有四个筐。预计在一个狭窄的浓度窗口内发生的合作封装机制将允许对毒性物质的隔离进行前所未有的控制。该奖项反映了美国国家科学基金会的法定使命，并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，被认为值得支持。

With support from the Macromolecular, Supramolecular and Nanochemistry (MSN) Program in the Division of Chemistry, Professor Jovica Badjić at Ohio State University aims to develop novel sequestering molecules capable to binding to a variety of analytes includes toxins. Vase-shaped compounds (i.e., baskets) are to be prepared, functionalized, and tested for trapping small molecules using methods of both computational and experimental chemistry. These studies are aimed to broaden fundamental understanding about the process by which specific analytes, including toxins, can be captured in complex biological environment. The program will educate graduate, undergraduate students, and public about health-related intoxications in our society and ways to use supramolecular chemistry to address them. The interdisciplinary research training to be provided to students will help to prepare a skilled workforce for the chemical industry or academia.The first objective of the program is to examine conjugation of molecular baskets to pillararenes. A rigid, deep, and well-defined aromatic pocket of basket-pillararene (BPr) hybrids is designed to favor a full inclusion and desolvation of targeted biologically relevant guest ligands, including tobacco pyridine alkaloids, stimulants, opioids, and hallucinogens contributing to the formation of tight complexes. Two belts of functional groups, at the top and in the middle, are positioned to generate favorable host-guest contacts to improve stability and binding selectivity. The second objective of the program is to learn about encapsulation of the potent anticancer drug, methotrexate, that inhibits dihydrofolate reductase, thereby interfering with pyrimidine biosynthesis, and hence DNA replication. This sizeable and negatively charged compound is expected to fold and thus complement the inner space of deeper cavity baskets holding negative carboxylates. The third objective of the program is to develop allosteric encapsulation of four anti-cancer drugs within water-soluble covalent basket cages, having the shape of a truncated tetrahedron with four baskets at the corners. A projected mechanism of cooperative encapsulation occurring over a narrow concentration window is anticipated to permit an unprecedented level of control in the sequestration of toxicants.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.