Influence of Cononsolvency on the Aggregation of Tertiary Butyl Alcohol in Methanol–Water Mixtures

The term cononsolvency has been used to describe a situation in which a polymer is less soluble (and so is more likely to collapse and aggregate) in a mixture of two cosolvents than it is in either one of the pure solvents. Thus, cononsolvency is closely related to the suppression of protein denaturation by stabilizing osmolytes. Here, we show that cononsolvency behavior can also influence the aggregation of tertiary butyl alcohol in mixtures of water and methanol, as demonstrated using both Raman multivariate curve resolution spectroscopy and molecular dynamics simulations. Our results imply that cononsolvency results from the cosolvent-mediated enhancement of the attractive (solvophobic) mean force between nonpolar groups, driven by preferential solvation of the aggregates, in keeping with Wyman-Tanford theory.