Untitled

Abstract

The thermodynamics of mobile disorder rejects the static model of the quasi-lattice for liquids. Because cause of the perpetual change of neighbors, during the observation time of thermodynamics of the order of seconds, each molecule of a given kind in a solution has experienced the same environment and had at its disposal the same mobile volume. This domain is not localizable and not orientable. Each molecular group perpetually "visits" successively all parts of this domain. The highest entropy is obtained when the groups visit all the parts of the domain without preference. H-bonds are preferential contacts with given sites of the neighbors that cause deviations with respect to such "random" visiting, thereby decreasing the entropy. The quantitative development of these ideas leads to equations describing the effect of solvent-solvent, solute-solvent, and solute-solute hydrogen bonds on the chemical potential of the solute. A universal equation predicting the solubility of drugs in a given solvent is derived. The effect of H-bonds is governed not by "solubility parameters" but by stability constants from which the order of magnitude can be estimated. From the sole knowledge of the solubility of methylparaben in pentane, the method predicts correctly the order of magnitude of its solubility in 26 other solvents, including alcohols and water.

Understanding the volume-solubility dependence: the mobile order and disorder view

“…The quantitative development 34 of the MOD theory is at the basis of a new thermodynamic treatment of nonassociated and associated solutions. The development led in particular to a general predictive solubility model [Eqn.…”

“…More exact values for protic solvents can be calculated from particular expressions issued from the quantitative development of the MOD theory. 34,50 The term O expresses the effect on solubility of the Hbonds formed between proton-acceptor sites of the solute and proton-donor solvents. Each particular H-bond interaction such as ketone-alcohol contributes to increase solubility, and is characterized by the group interaction stability constant, K O i .…”

“…Remember that in the case of solid solutes, the molar volume to be considered is not that of the crystalline substance, but the volume of the molecule in its hypothetical subcooled liquid state. Such volumes are readily estimated from the addition of group contributions 34,52 whose values were obtained to fit best the experimental molar volumes of a large number of liquids.…”

“…Such a solubility model is then applicable to predict the solubility of any liquid or solid substance in any apolar, polar or protic solvent including water, and may in particular shed light on the molecular origin of the empirically observed dependence of the solubility with respect to particular physicochemical properties. In fact, the general solubility model 34 based on the non-ergodic thermodynamics of the mobile order and disorder (MOD) theory for Hbonded liquids, developed by Huyskens and co-workers, [35][36][37] fullfils these objectives. To date, the MOD theory-derived solubility equation has been successfully applied to predict the solubility of low-polarity substances in individual and binary solvent systems, [38][39][40][41][42][43][44][45][46][47][48][49] the mutual solubility of water and hydrocarbons 50,51 and the solubility of solid and liquid proton-acceptor substances and alcohols in aprotic and protic solvents.…”

Thermodynamic Modeling of Solubility

“…B. Korrelationen auf Basis der QSPR-(Quantitative Structure-Property Relationship) Methode [1], werden aus zahlreichen Messdaten gewonnen und sind in der Regel nur in der Lage, die berücksichtigten Löslichkeiten wiederzuge-ben, nicht jedoch Löslichkeiten in neuen Lösungsmitteln vorauszuberechnen. Die Methode Thermodynamics of mobile disorder zur Vorhersage von Löslichkeiten in reinen Lösungs-mitteln von Ruelle et al [2,3] benötigt zusätzlich zu Schmelztemperatur und -enthalpie das molare Flüssigvolu-men des Feststoffes, den modifizierten Löslichkeitspara-meter des Feststoffes (angepasst an einen Löslichkeitspunkt) und einige Konstanten zur Beschreibung der spezifischen Wechselwirkungen (z. B. Wasserstoffbrückenbindung) zwischen den Molekülen.…”