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 part… Show more
“…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.…”
Section: Limitations and Alternativesmentioning
confidence: 99%
“…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.…”
Section: Limitations and Alternativesmentioning
confidence: 99%
“…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.…”
We all know that to enhance solubility using greener chemistry we should harness sound principles of molecular-based thermodynamics. The problem is that even for simple systems it can be hard to know how to use fundamental tools for formulation benefit, and for the more complex systems that we must often use, calculations required for molecular thermodynamics can often be quite involved. In this paper we show that a fundamental, assumption-free statistical thermodynamics approach, the Kirkwood-Buff theory, can be used in practical, complex aqueous systems to provide the insights we need to optimise formulations. The theory itself is not that difficult, but its implementation, which requires many steps of thermodynamic calculations, has up to now not been straightforward. Taking full advantage of an interactive approach, here we review what the Kirkwood-Buff theory can provide for formulators; we use the power of modern web browsers to provide open-source, user-friendly, responsive-design apps to do the hard work of data analysis, leaving formulators to focus on the interpretation of the results for their specific optimisation task. Indeed the apps are intended to be used by researchers and formulators for specific systems of interest to them.
“…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.…”
Section: Limitations and Alternativesmentioning
confidence: 99%
“…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.…”
Section: Limitations and Alternativesmentioning
confidence: 99%
“…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.…”
We all know that to enhance solubility using greener chemistry we should harness sound principles of molecular-based thermodynamics. The problem is that even for simple systems it can be hard to know how to use fundamental tools for formulation benefit, and for the more complex systems that we must often use, calculations required for molecular thermodynamics can often be quite involved. In this paper we show that a fundamental, assumption-free statistical thermodynamics approach, the Kirkwood-Buff theory, can be used in practical, complex aqueous systems to provide the insights we need to optimise formulations. The theory itself is not that difficult, but its implementation, which requires many steps of thermodynamic calculations, has up to now not been straightforward. Taking full advantage of an interactive approach, here we review what the Kirkwood-Buff theory can provide for formulators; we use the power of modern web browsers to provide open-source, user-friendly, responsive-design apps to do the hard work of data analysis, leaving formulators to focus on the interpretation of the results for their specific optimisation task. Indeed the apps are intended to be used by researchers and formulators for specific systems of interest to them.
“…[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 the present contribution, the pre-structuring of binary mixtures of hydrotropes and HO is linked to the solubilisation of poorly water miscible compounds. We have chosen a series of short-chain alcohols as hydrotropes and benzyl alcohol, limonene and a hydrophobic azo-dye (Disperse Red 13) as organic compounds to be dissolved. A very weak pre-structuring is found for ethanol/HO and 2-propanol/HO mixtures. Pre-structuring is most developed for binary 1-propanol/HO and tert-butanol/HO mixtures and supports the bicontinuity model of alcohol-rich and water-rich domains as already postulated by Anisimov et al. Such a pre-structuring leads to a high solubilisation power for poorly water miscible components (limonene and Disperse Red, characterized by high octanol/water partition coefficients, log(P) values of 4.5 and 4.85), whereas a very weak pre-structuring leads to a high solubilisation power for slightly water miscible components (benzyl alcohol). This difference in solubilisation power can be linked to (i) the formation of mesoscale structures in the cases of ethanol and 2-propanol and (ii) the extension of pre-structures in the cases of 1-propanol and tert-butanol. Three different solubilisation mechanisms could be identified: bulk solubilisation, interface solubilisation and a combination of both. These supramolecular structures in binary and ternary systems were investigated by small-and-wide-angle X-ray and neutron scattering, dynamic light scattering and conductivity measurements (in the presence of small amounts of salt).
“…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.…”
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