TY - JOUR
T1 - Estimation of aqueous solubility by the General Solubility Equation (GSE) the easy way
AU - Sanghvi, Tapan
AU - Jain, Neera
AU - Yang, Gang
AU - Yalkowsky, Samuel H.
PY - 2003/4
Y1 - 2003/4
N2 - The General Solubility Equation (GSE) provides a simple method of estimating the molar aqueous solubility of an organic non-electrolyte in water (Sw) as a function of its celsius melting point (MP) and octanol-water partition coefficient (Kow): log Sw = -0.01(MP-25) - log Kow + 0.5 The melting term of the GSE is based upon the Clausius-Clapyron equation and Walden's rule. The aqueous activity coefficient is assumed to be the reciprocal of the octanol-water partition coefficient. The constant is based upon the molarity of pure octanol. There are no fitted parameters in the GSE. Extension of the GSE to weak electrolytes in buffered aqueous solutions is straightforward. The concentration of the ionized species, Si, is accounted for by incorporating one additional term, which contains the pKa of the solute and pH of the solution. For a weak acid, Stotal = Sw + Si = Sw [1 + 10(PH-pKa)] The solubility of a weak electrolyte in unbuffered water requires further consideration because the solute will determine the pH of the solution. It is shown that in unbuffered media Stotal = Sw + Si = Sw + (SwKa)1/2 Thus, it is not necessary to explicitly know the pH of the saturated solution to estimate the solubility of a weak electrolyte in water. The GSE is validated on data set of over a thousand compounds, covering a wide range of structural categories. The GSE is compared to a number of other solubility estimation techniques using the criteria of accuracy of fit, applicability, parsimony, convenience, and elegance.
AB - The General Solubility Equation (GSE) provides a simple method of estimating the molar aqueous solubility of an organic non-electrolyte in water (Sw) as a function of its celsius melting point (MP) and octanol-water partition coefficient (Kow): log Sw = -0.01(MP-25) - log Kow + 0.5 The melting term of the GSE is based upon the Clausius-Clapyron equation and Walden's rule. The aqueous activity coefficient is assumed to be the reciprocal of the octanol-water partition coefficient. The constant is based upon the molarity of pure octanol. There are no fitted parameters in the GSE. Extension of the GSE to weak electrolytes in buffered aqueous solutions is straightforward. The concentration of the ionized species, Si, is accounted for by incorporating one additional term, which contains the pKa of the solute and pH of the solution. For a weak acid, Stotal = Sw + Si = Sw [1 + 10(PH-pKa)] The solubility of a weak electrolyte in unbuffered water requires further consideration because the solute will determine the pH of the solution. It is shown that in unbuffered media Stotal = Sw + Si = Sw + (SwKa)1/2 Thus, it is not necessary to explicitly know the pH of the saturated solution to estimate the solubility of a weak electrolyte in water. The GSE is validated on data set of over a thousand compounds, covering a wide range of structural categories. The GSE is compared to a number of other solubility estimation techniques using the criteria of accuracy of fit, applicability, parsimony, convenience, and elegance.
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U2 - 10.1002/qsar.200390020
DO - 10.1002/qsar.200390020
M3 - Article
AN - SCOPUS:0038745774
SN - 1868-1743
VL - 22
SP - 258
EP - 262
JO - Molecular Informatics
JF - Molecular Informatics
IS - 2
ER -