archives@tulane.edu / Enzymes are most powerful catalysts in Nature. Despite decades of research, there are still many open questions surrounding the mechanisms by which enzymes catalyze reactions. Supramolecular chemists have made lots of effort to designing a variety of host molecules to mimic enzymes over the last decade. They aim to understand the power of noncovalent forces and how local environment can be involved in enzymes’ catalytic functions. In our studies, two synthetic water-soluble deep cavity cavitands with different electrostatic potential (EP) that can provide well-defined nano-spaces and can be encapsulated with guests through hydrophobic effect were utilized to investigative the inner guests’ pKa shifts and reactions. First, pKa shifts of thiol guests in deep cavity cavitands have been examined. Here we utilize supramolecular capsules assembled via the hydrophobic effect to encapsulate guests and control their acidity. We found that the greatest impact on the acidity of the bound guests is the position of the acid group in the yotoliter space. Moreover, the nature of the electrostatic potential field (EPF) generated by charged solubilizing groups also plays an important role in acidity, as does the counter ion complexing to the outer surface of the capsule. In summary, these results suggest an electrostatic potential field (EPF) engendered by remote solubilizing groups can affect reactions inside of confined spaces. Second, macrocyclization reactions were investigated in two different electrostatic potential (EP) nano capsules. Here, we quantify these effects through acidity and cyclization rate by the size of the encapsulated guests, which confirmed primary role of Coulombic forces with a simple mathematical model approximating the capsules as Born spheres within a continuum dielectric. These results reveal the reaction rate accelerations possible under Coulombic control and highlight important design criteria for nanoreactors. / 1 / Xiaoyang Cai