To explain the differentways of solubilization,we propose to have a
look at a typical phase diagramof a ternary systemwater – hydrophopic solute (organic solvent) – hydrotrope/co-solubilizer, see Fig. 3. Region 1
is typically used formost hydrotrope/co-solubilizer applications. At low
hydrotrope concentration (but nevertheless in the molar range), the
solubility of the organic solute is significantly enhanced. In the case of
a hydrotrope, there is typically a certain threshold, the MHC, which is
not observed for a co-solubilizer. So in Region 1, the phase diagram is
different for a hydrotrope and a co-solubilizer. For the sake of simplicity,
this difference is not included in Fig. 3. Figs. 2a and b illustrate the
expected structuring in Region 1 for a) neutral and b) charged
hydrotropes. Above theMHC, the hydrotrope molecules cluster around
the solute, thus rendering it water soluble. There are two driving forces
for this clustering: first, there is a slight attraction between the
hydrotrope and the solute (the enthalpic contribution), and second
there is a gain in entropy when water molecules are released from the
contact with the solute. Two parameters are thus necessary to describe
the effect. In the case of the approach by Abbott, Shimizu and coworkers,
these are the two parameters derived from Kirkwood–Buff integrals, in
which the contributions of enthalpy and entropy are mixed. The first
parameter describes the preferential hydrotrope–solute interaction
and the second one the hydrotrope–water interaction.