Duality of Hydrotropes in Solution and at Interface

Mikhail Anisimov, University of Maryland- College Park

Hydrotropes are substances containing small amphiphilic molecules, which increase solubility of
nonpolar (hydrophobic) substances in water. Hydrotropes are used in many technological
applications. Typical examples of nonionic hydrotropes with well-balanced amphiphilicity are
tertiary butanol and 3-methyl pyridine. Hydrotropes do not form stable micelles in aqueous
solutions, but they may form dynamic clusters (less or about 1 ns lifetime) with water molecules;
such clusters can be viewed as “pre-micelles” or as pre-micellization fluctuations of solution
structure. This molecular clustering causes pronounced thermodynamic anomalies,
experimentally observed in dilute and semi-dilute aqueous solutions of hydrotropes. Molecular
dynamics simulations demonstrate that the origin of the clustering is associated with formation
of hydrogen bonds between the water and hydrotrope molecules. Most recently, experimental
and simulation studies of water-hydrotrope-oil ternary solutions have revealed remarkable
duality in hydrotropes’ actions in the bulk and at the oil/water interface. At low concentrations,
the hydrotrope acts as a surfactant, while at higher concentration after the interface is saturated it
acts as a co-solvent toward complete mixing. Crossover between these limits is described by a
universal function interpolating the Gibbs adsorption theory and scaling theory of smooth nearcritical
interface. In bulk, a spectacular phenomenon, “mesoscale solubilization”, intermediate
between molecular solubility and macroscopic phase separation, is also observed. It is proved
that mesoscale solubilization is a nonequilibrium phenomenon, though extremely long-lived.
Making practically stable colloids from small hydrotrope molecules has an untapped potential for
applications in material science and medicine, in particular, in controlled drug delivery.