Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)



Committee Chair

Dor Ben-Amotz

Committee Member 1

Lyudmila Slipchenko

Committee Member 2

Mary Wirth

Committee Member 3

Jianguo Mei


Water mediated hydrophilic and hydrophobic interactions are important for biological systems, atmospheric, geological, and environmental chemistry, and pharmaceuticals formulation development. Open questions remain regarding the degree of water restructuring in hydrophobic cavities, the extent of hydration in self-assembled aggregates, and the influence of water restructuring on hydrophobic interactions. Here, we use Raman spectroscopy combined with multivariate curve resolution (Raman-MCR), partial molar volume, and fluorescence spectroscopic methods to detect and quantify changes in hydration extent and structure due to hydrophobic aggregation and hydrophobic cavity structure. Raman-MCR decomposes an aqueous solution spectrum into solvent (pure water) and solute-correlated spectra, the latter of which contains vibrational features from the solute as well as any water molecules that are perturbed by the solute. This hydration-shell spectrum therefore contains evidence of hydrophobic aggregation by changes in the solute vibrational features as well as information on the extent and structure of water perturbed in the hydration shell of the solute. Partial molar volume measurements are also sensitive to changes in hydration-shell structure due to solute shape differences or aggregation, and, when combined with complementary simulation results, can provide detailed information on water structure. The results presented here aid in understanding outstanding questions concerning hydration of micelles, cavity hydration and dewetting transitions, and crystallization and host-guest binding processes in aqueous environments. In particular, Raman-MCR is used to observe the presence and extent of water penetration into micelle interiors, and partial molar volume results from density measurements of deep-cavity cavitands demonstrate experimental observation of a hydrophobic cavity dewetting transition. In addition, Raman-MCR is used to detect changes in solute structure and cavity hydration upon host-guest complexation. These results demonstrate the possibility of quantifying the effect of host structure on hydration to better understand hydration of protein interiors and cavities as well as development of selective pharmaceutical excipients.