Supramolecular assembly state switching and water absorption of deep-cavity cavitands
Description
Inspired by the study of supramolecular self-assembly behaviors, hydrophobic effect has been identified as one of the prominent driving forces behind these assemblies. To have a better understanding of the molecular scale forces associated with supramolecular host-guest binding processes, and the guest packing motifs within confinement, a family of water-soluble deep-cavity cavitand host molecules were developed. They possess bowl-shaped binding pockets and can form into distinct assembly states with presence of suitably-sized guest molecules in aqueous environment. Besides, their assembly properties can be tuned by changing the guest molecules and the functionalization on their hydrophobic rim. And the hydration states within their hydrophobic pockets, which are also sensitive to different functionalization, can have significant impact on the binding process. We used Molecular Dynamics (MD) simulation to study the thermodynamics of cavitand’s host-guest binding process, and the water absorption within the pockets efficiently. This research begins by a small application of molecular dynamics simulation to predict Second osmotic viral coefficients of small molecules like methane, ethane, and their alcohol counterparts. The second and third parts of this dissertation are studying the different assembly states progression behaviors of different cavitands with minor structural modification. We used advanced sampling method to evaluate the association free energy of all the different complexes and therefore quantitatively characterize their stabilities. From that, we built up a network reaction model to describe this whole process and used this model to reproduce and predict the distinct assembly states progression trends for cavitands with different structures. The fourth part of this dissertation provides a systematic study of the hydration states within cavitand pockets and its correlation to different functionalities on the rim. A unique self-dewetting behavior were promoted by further methylation on the cavitand portal. Several analytic models were developed to give a deeper insight into this special two-state like behavior. In the last part of this dissertation, we applied a newly developed advanced sampling technique (INDUS) to measure the different responses of water within cavitand pockets with different functionalization. In addition, the different hydrophobicity in different regions of the cavitand can be qualitatively characterized by this method.