Cucurbiturils and Glycoluril-based Baskets Mimicked by Hard Sphere Fluids: A Novel Model Applied to Supramolecular Catalysis in Water

With the support of the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Professor Eric Masson of Ohio University will develop a new theoretical model to quantify the strength of interactions between synthetic host molecules and small molecule guests, when both host and guest are dissolved in water. This research aims to gain fundamental chemistry knowledge important for understanding molecular interactions in biological systems and for informing the design of new selective and potent drugs.

Masson will also use this model to identify guest molecules that are most likely to react with each other inside the host molecules. The host molecules will thus become miniature vessels that will catalyze these reactions. The project will expose students to core theoretical organic chemistry concepts, to synthetic chemistry especially with the preparation of new basket-shaped hosts, to molecular modeling, and to analytical chemistry techniques.

Masson will also engage in domestic and international collaborative programs that he spearheaded in Spain, France, Germany and the Czech Republic, as well as outreach activities at English-French bilingual high schools in the US.

The chosen hosts will be Cucurbiturils, a family of hollow, pumpkin-shaped molecules that can tightly encapsulate guest molecules; and tailor-made molecules resembling empty baskets. To quantify intermolecular interactions, the Masson team will mimic host molecules with hard-sphere fluids of low polarity. The unique advantage of this model is that it does not invoke the host structure explicitly.

The only required input is the volume of the guest, and its free energy of solvation in both water and the low polarity solvent; both solvation energies will be calculated rapidly. The scope and limitations of this model will be thoroughly tested as part of Aim 1. In Aim 2, the selectivity and packing predictions from the model will be used to identify suitable reaction partners inside hosts.

In Aim 3, a new family of glycoluril-based baskets for neutral and positively charged amphiphilic guest recognition in water will be synthesized. The flexibility and physico-chemical properties of the hosts are expected to be highly tunable. The hard-sphere fluid model will be tested again toward these hosts.

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.