Mechanism of dye solubilization and de-aggregation by urea

Urea is an effective solubilizer for dyes with low aqueous solubility. To establish, at a molecular level, the reason behind the action of urea as an effective solubilizer, we employ a rigorous statistical thermodynamics approach based on the Kirkwood-Buff theory of solutions. We show that (i) contrary to the classical hypothesis on “water structure breaking”, the effect of urea on dye hydration makes a minor contribution to solubilization; (ii) the driving force of solubilization is the accumulation of urea around hydrophobic dye molecules. • Why urea is an effective dye solubilizer was clarified using statistical thermodynamics. • The effect of urea on dye hydration makes a minor contribution to solubilization. • The accumulation of urea around hydrophobic dye molecules drives solubilization.