Quantitative assessment of non-covalent interactions in aqueous medium and in hydrophobic cavities using Cucurbiturils

活着的生物体，从单细胞到人类，由于包括蛋白质、DNA、糖和脂类在内的分子之间极其大量的相互作用和反应而蓬勃发展。药物还与这些化学结构相互作用，以对抗症状和疾病。更精确地了解不同的化学结构如何相互作用(或“粘连”在一起)有可能使人们能够更好地了解疾病中涉及的生化过程，并促进药物设计。在NSF大分子、超分子和纳米化学(MSN)计划的支持下，俄亥俄大学埃里克·马森教授的研究小组设计并合成了中空的南瓜形状的分子，可以在其中空中心容纳两个化学实体。通过将两种化学实体结合在一起，马森小组试图确定它们相互作用的程度，并在分子水平上量化它们相互作用的强度。该研究项目涉及研究生和本科生(包括来自贫困家庭的学生)，并对他们进行有机、分析和计算化学方面的培训。在其他外展活动中，马森教授还共同组织了在俄亥俄大学和德国莱比锡大学举行的年度科学传播和政策研讨会。研讨会聚集了两所大学化学、新闻和国际研究的学生，围绕社会感兴趣的科学主题。通过研讨会，学生学习如何与非科学家交流科学概念。为了量化水介质和被水环境包围的疏水空腔中的非共价相互作用，马森教授的团队设计了超分子体系，这些体系与水相容，可用于评估广泛的非共价相互作用；几何上定义明确，远低于自然体系，以避免二次扰动。这个项目有三个具体目标。在第一个目标中，大环葫芦环(CB[n])家族被用来包裹高度亲水的客体，并确定CB[n]疏水空腔内形成的分子内氢键的强度。在第二个目标中，设计了各种4‘-取代铂(II)-联吡啶配合物(CB[8])的“2：1堆积”三元配合物。这些三元络合物作为自分类探针用于定量多肽之间的库仑相互作用以及水介质中芳基-芳基“pi-pi”和芳基-环烯基CH-pi的相互作用。最后一个目的是利用“2：1堆积”的三元络合物作为超分子天平来定量水介质中分散的“pi-pi”和CH-pi相互作用。超分子平衡是由CB[8]中连接到三茂铁单元(“轮”)的铂络合物与另一不含三叔丁烯的铂络合物(“轴”)自分类形成的。由CB[8]中的一个“轴”和一个“轮”或CB[8]中的两个“轮”组成的新型三元复合体可能代表了超分子制动器和正齿轮的新家族。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。

Living organisms, from single cells to human beings, thrive as a result of an extremely large number of interactions and reactions between molecules that include proteins, DNA, sugars and lipids. Drugs also interact with these chemical structures to counteract symptoms and diseases. A more precise knowledge of how different chemical structures interact (or "stick" together) has the potential to enable a better understanding of biochemical processes involved in diseases and to facilitate drug design. With the support of the NSF Macromolecular, Supramolecular and Nanochemistry (MSN) Program, the research group of Professor Eric Masson at Ohio University designs and synthesizes hollow, pumpkin-shaped molecules that can accommodate two chemical entities in its hollow center. By bringing two chemical entities together, the Masson group seeks to determine how well they interact and to quantify the strength of their interactions at the molecular level. The research project involves graduate and undergraduate students (including students from underprivileged backgrounds) and trains them in organic, analytical and computational chemistry. Among other outreach activities, Professor Masson also co-organizes a yearly science communication and policy workshop held at Ohio University and at the University of Leipzig, Germany. The workshop brings together students from chemistry, journalism and international studies at both institutions around scientific themes of societal interest. Through the workshop, students learn to communicate scientific concepts to non-scientists.For the purpose of quantifying non-covalent interactions in both aqueous medium and in hydrophobic cavities surrounded by an aqueous environment, Professor Masson's group designs supramolecular systems that are water-compatible, versatile for evaluating a wide range of non-covalent interactions; and geometrically well-defined and far less complex than natural systems, to avoid secondary perturbations. There are three specific aims in this project. In the first aim, the Cucurbituril (CB[n]) family of macrocycles is used to encapsulate highly hydrophilic guests and determine the strengths of the intramolecular hydrogen bonds formed inside the hydrophobic cavity of CB[n]. In the second aim, "2:1 stacked" ternary complexes of a variety of 4'- substituted platinum(II) terpyridyl complexes in curcubit[8]urils (CB[8]) are designed. These ternary complexes serve as self-sorting probes for quantifying Coulombic interactions between peptides as well as aryl-aryl "pi-pi" and aryl-cycloalkenyl CH-pi interactions in aqueous medium. The last aim exploits the use of the "2:1 stacked" ternary complexes as supramolecular balances for quantifying dispersive "pi-pi" and CH-pi interactions in aqueous medium. The supramolecular balance is formed by self-sorting of a platinum complex connected to a triptycene unit (the "wheel") with another platinum complex without triptycene (the "shaft") in CB[8]. The novel ternary complexes that are composed of one "shaft" and one "wheel" in CB[8] or two "wheels" in CB[8] may represent new families of supramolecular brakes and spur gears.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.