Determination of the thermodynamics of hydroxyl and carboxyl groups in solutions of drug molecules

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Abstract
The contributions of hydroxyl and carboxyl groups to solute activity and partition coefficients have been investigated using literature data. Both polar functions give rise to a reduced activity coefficient for aromatic solutes in water and differences exist between ring and asubstitution. Partition coefficients are similarly affected but the magnitude of the group contribution to the free energy of transfer is dependent on the nature of the solute and the organic partition solvent. The contribution for the groups in the terminal position in aliphatic compounds can be obtained by an extrapolation procedure where the group value is a composite of the polar function and a term that takes into account the inequality of aliphatic CH2 and CH3 groupings (H. .OH, H. .COOH). For a range of solvents there is good correlation between hydroxyl and carboxyl group values. In addition an attempt has been made to correlate group values for CH2, CH3, H. .OH, H. .COOH, with physico-chemical parameters that are characteristic of the partition system. The best correlations are obtained between group values and the solubility of water in the organic partition solvent. The H. .OH and H. .COOH group values can also be correlated with infrared spectroscopy data and self-association constants respectively.