Solubility of crystalline nonelectrolyte solutes in organic solvents: Mathematical correlation of acetylsalicylic acid solubilities with the Abraham general solvation model

The Abraham general solvation model is used to calculate the numerical values of the solute descriptors for acetylsalicylic acid from experimental solubilities in organic solvents. The mathematical correlations take the form of log(C-S/ C-W) = c + rR(2) + spi(2)(H) + aSigmaalpha(2)(H) + bSigmabeta(2)(H) + upsilonVx log(C-S/ C-G) = c + r R-2 + spi(2)(H) + aSigmaalpha(2)(H) + bSigmabeta(2)(H) + l log L-(16) where C-S and C-W refer to the solute solubility in the organic solvent and water, respectively, C-G is a gas phase concentration, R-2 is the solute excess molar refraction, V-x is McGowan volume of the solute, Sigmaalpha(2)(h) and Sigmabeta(2)(h) are measures of the solute hydrogen-bond acidity and hydrogen-bond basicity, pi(2)(H) 2 denotes the solute dipolarity/polarizability descriptor, and L-(16) is the solute gas-phase dimensionless Ostwald partition coefficient into hexadecane at 298 K. The remaining symbols in the above expressions are known solvent coefficients, which have been determined previously for a large number of gas-solvent and water-solvent systems. We estimate R-2 as 0.781 and calculate V-x as 1.2879 and then solve a total of 48 equations to yield pi(2)(H) = 1.6900, Sigmaalpha(2)(H) = 0.7100, Sigmabeta(2)(H) = 0.6700, and log L-(16) = 6.2789. These descriptors reproduce the 48 observed log (C-S/C-W) and log (C-S/C-G) values with a standard deviation of only 0.131 log units. The calculated descriptors differ significantly from two earlier sets of values that were deduced from experimental data for the partitioning of acetylsalicylic acid between water and a very limited number of organic solvents.