Supramolecular Assemblies of Deep-Cavity Cavitands Stabilized by the Hydrophobic Effect

Since the mid-20th century supramolecular chemistry has become a thriving field in synthetic chemistry. Supramolecular assemblies are assemblies of molecules formed and stabilized by non-covalent interactions. Deep-cavity cavitands, bowl-shaped molecules, are one such class of molecules that form assemblies using the hydrophobic effect when in the presence of suitable hydrophobic guests in an aqueous environment. Computer simulations allow us to study these assemblies at the molecular level and provide valuable insight into both the thermodynamics of assembly as well as provide information relevant to the design of the next generation of deep-cavity cavitands.;This research begins by investigating dimeric capsules of a deep-cavity cavitand known as Octa-acid (OA). We use Molecular Dynamics to study a homologous series of n-alkane guests in order to learn some of the "rules" of guest packing. Additionally we use a machine learning technique to harvest a dominant conformation from each simulation and compare computed chemical shifts of that structure with experimental chemical shifts.;The second part of this dissertation looks into multimeric systems formed by one of OA's derivatives known as Tetra-endomethyl Octa-acid (TEMOA). The entrance to the binding pocket of TEMOA is narrower than OA due to four methyls being added to its rim. TEMOA forms not only dimers, but also tetramers and hexamers, depending on the guest size. We use free energy techniques to show that guest packing primarily drives the transitions between each assembly state. Additionally we obtain the interior volumes of each multimer and demonstrate that they now approach that of structures formed by other means. We give insight into why TEMOA forms multimeric systems and OA does not.;The last section of this dissertation compares the interior hydration characteristics of OA and TEMOA. We show that the small structural changes from OA to TEMOA promote a large change in wetting/dewetting behavior inside the binding pocket. Normally OA is full of water in its interior, but TEMOA exhibits a two-phase behavior. Here we also demonstrate a simple bridge between simulation and experiment to validate our findings by using partial molar volume calculations.