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

生物体，从单细胞到人类，都是由于蛋白质、DNA、糖和脂质等分子之间的大量相互作用和反应而茁壮成长的。药物也与这些化学结构相互作用，以抵消症状和疾病。对不同化学结构如何相互作用（或“粘在一起”）的更精确的了解，有可能使人们更好地理解与疾病有关的生化过程，并促进药物设计。在美国国家科学基金会（NSF）大分子、超分子和纳米化学（MSN）项目的支持下，俄亥俄大学埃里克·马森教授的研究小组设计并合成了空心的南瓜形分子，这种分子可以在空心中心容纳两种化学实体。通过将两种化学实体结合在一起，马森团队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），并对他们进行有机化学、分析化学和计算化学方面的培训。除其他外展活动外，Masson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讲习班。研讨会汇集了来自这两个机构的化学、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，学生们学会向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腔中的非共价相互作用，Masson教授的团队设计了与水兼容的超分子系统，可用于评估广泛的非共价相互作用；而且几何上定义良好，远没有自然系统复杂，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，Cucurbituril （CB[n]）家族的大环被用来包裹高度亲水的客体，并确定在CB[n]的疏水腔内形成的分子内氢键的强度。在第二个目标中，设计了多种4'-取代铂（II）三吡啶配合物在curcubit[8] （CB[8]）上的“2:1堆叠”三元配合物。这些三元配合物作为自分选探针用于定量多肽之间的库仑相互作用以及芳基-芳基“pi-pi”和芳基-环烯基CH-pi在水介质中的相互作用。最后一个目标是利用“2:1堆叠”三元配合物作为超分子平衡来量化水介质中色散“pi-pi”和CH-pi相互作用。超分子平衡是由CB[8]中与三泰烯单元（“轮”）相连的铂配合物与另一个不含三泰烯的铂配合物（“轴”）的自分选形成的。由CB[8]中的一个“轴”和一个“轮”或CB[8]中的两个“轮”组成的新型三元配合物可能代表着超分子制动器和正齿轮的新家族。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。

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.