Effect of Hydrogen-Bond on Aggregation Kinetics of Hydrophobic Molecules in Aqueous Solution

Molecular aggregation of amphiphile or partially hydrophobic molecules is prevalent in many processes e.g. cellular mechanisms, drug delivery, etc. It is generally observed to reduce the performance and efficiency of their functions. A major driving force for molecules to aggregate in an aqueous medium is hydrophobicity. While molecule-specific aggregations of such molecules are known in the literature, the link between the aggregation kinetics and the molecular underpinning of hydrophobicity has not been explored. In the present work, a combined modeling and characterization method has been developed using different rhodamine dyes to correlate their aggregation kinetics with the nonbonded interaction to understand the aggregation process. The kinetics were examined by measuring diffusivity using MD simulation, Fluorescent Correlation Spectroscopy, and NMR. It was observed that the level of hydrophobicity is strongly correlated to the hydrogen bonds between water molecules and dye. In addition, the aggregation process is inversely related to the hydrogen bonds between water and dye. This study has been further extended to predict protein (Amyloid β-42) aggregation rates, demonstrating strong alignment with the existing literature. The model developed here could be used to investigate the aggregation process of amphiphiles and the quantification of parameters to control it. This model could aid the development of drug molecules, which have implications for healthcare and pharmaceuticals.