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

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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.