Determination of thermodynamics of halogen groups in solutions of drug molecules

Abstract

The contribution of the halogen groups (F, Cl, Br, I) to solute activity and partition coefficients has been investigated using literature data. The activity coefficient for an aromatic solute at infinite dilution is increased as the size of the halogen group increases. Partition coefficients are affected similarly but there is variation among group values for a given halogen. This is related to group position and the partition solvent. Preferred group values for partition have been selected and for different solvent systems mean preferred values can be calculated for two general solvent classifications; polar and non-polar. There is excellent correlation between group values and the size of the halogen function as given by surface area. The group values for non-polar solvents are related to those of the polar solvents through the Hammett electronic substituent constant. The use of the group values in structure-activity relations is discussed with reference to the thermodynamic model of Higuchi and Davis.