Time-dependent increase in aqueous solubility caused by the gradual disruption of hydrophobic aggregation

Abstract

We report the preparation of a thermoresponsive polymer whose solubility in water can be controlled simply by time elapse. Most importantly, we showed that the gradual disruption of hydrophobic aggregation originated from strong pi-pi stacking between side chain triazole rings resulting in an increase in the cloud point. As time progressed, hydrogen bonds between one of the triazole ring nitrogen atoms and water molecules became dominant. This caused disruption of the hydrophobic domains by breaking pi-pi stacking between the triazole rings, leading to a thermodynamically stable hydration state. The gradual disruption of hydrophobic aggregation induced a time-dependent increase in the apparent cloud point. This time-dependent increase in aqueous solubility was not driven by hydrolytic degradation of ester linkages. This behavior was carefully characterized using a number of techniques, including percent transmission analysis, UV-Vis spectroscopy and H-1-NMR spectroscopy, and dynamic light scattering (DLS) measurements, all supporting our hypothesis. This macromolecule, which offers tailored control over aqueous solubility, may be a unique potential platform for drug delivery scaffolds where the release of encapsulated molecules is controlled simply by time.