The origin of cooperative solubilisation by hydrotropes

Abstract

The signature of hydrotropic solubilisation is the sigmoidal solubility curve; when plotted against hydrotrope concentration, solubility increases suddenly after the minimum hydrotrope concentration (MHC), and reaches a plateau at higher hydrotrope concentrations. This sigmoidal curve is characteristic of cooperative phenomena, yet the true molecular basis of hydrotropic cooperativity has long remained unclear. Here we develop a theory, derived from the first principles of statistical thermodynamics using partially-open ensembles, to identify the origin of hydrophobic cooperativity. Our theory bears a close resemblance to the cooperative binding model used for protein-ligand binding. The cause of cooperativity is the enhancement of the hydrotrope m-body interaction induced by the presence of the solute; m can be estimated from the experimental solubility data.

Practical molecular thermodynamics for greener solution chemistry

“…41 This operative solubilisation theory attributes the sigmoidal solubility increase to the enhancement of n-body hydrotrope association when the solute comes into the solution. 41 As can be demonstrated in the app featured in Fig.…”

“…41 This operative solubilisation theory attributes the sigmoidal solubility increase to the enhancement of n-body hydrotrope association when the solute comes into the solution. 41 As can be demonstrated in the app featured in Fig. 4, the overall sigmoidal shape can be reproduced using only three parameters described in the reference, including n. This theory is approximate, and does not contain all the KBIs, but may be useful for an overall understanding of hydrotrope action.…”

“…4, the overall sigmoidal shape can be reproduced using only three parameters described in the reference, including n. This theory is approximate, and does not contain all the KBIs, but may be useful for an overall understanding of hydrotrope action. 41 One of the many beautiful aspects of thermodynamics is that the same problem can be viewed from several different perspectives. Those who prefer to work with enthalpies and entropies (and the issue of entropy/enthalpy compensation) could, in principle, take the same experimental data and derive thermodynamic values that are equally valid.…”

The impact of the structuring of hydrotropes in water on the mesoscale solubilisation of a third hydrophobic component

“…[14][15][16][17] Only recently, the group of Shimizu et al developed an approach to describe hydrotropic solubilisation theoretically. [18][19][20][21] This approach derived from pure statistical thermodynamics uses the exact Kirkwood Buff theory to describe the cooperative phenomena in hydrotropic solubilisation such as (i) the sudden onset of solubilisation of hydrophobic compounds in H 2 O (commonly referred to as MHC) and (ii) solubility saturation of hydrophobic compounds at high hydrotrope concentrations. In a nutshell, they consider hydrotropic solubilisation to be the result of a subtle balance between solute-hydrotrope interaction and hydrotrope-hydrotrope interaction.…”

In search for novel functions of adenosine 5′-triphosphate (ATP) in the heart

“…13 In contrast to classical micelle-forming detergents, the surface-active and amphiphilic hydrotrope molecules have shorter hydrophobic regions and therefore do not cause spontaneous self-aggregation in the aqueous phase. To enhance the solubility of lipophilic proteins, the chemical structure of hydrotropes must consist of two essential parts, an anionic or polar group and an aromatic ring or ring system.…”