Thermodynamic Group Contributions for Hydroxyl, Amino, and Methylene Groups

Abstract

The hydroxyl, amino, and methylene group contributions to the free energy of transfer from water to the organic phase, from water to the vapor phase, and from heptane to the vapor phase were determined from the Henry constants of aliphatic series of hydrocarbons, alcohols, and amines in dilute aqueous and heptane solutions. The Henry constant of each solution was measured using a vapor headspace GLC method with very dilute aqueous and organic solutions. Plotting the log of the Henry constant versus carbon number yielded a straight line from which the methylene group contribution was calculated. This value was −150cal/ mole for water to vapor, 760cal/mole for heptane to vapor, and −910cal/mole for water to the organic phase. The hydroxyl contribution was 6890cal/mole for water to vapor, 1320cal/mole for organic to vapor, and 5570cal/mole for the transfer of a hydroxyl group from water to the organic phase. For the amino group, the free energy of transfer was 6470cal/mole for water to vapor, 1490cal/mole for heptane to vapor, and 4980cal/mole for water to the organic phase. The values determined were in reasonable agreement with literature data. Such data can be used to predict the effects of various functional groups on the distribution and transport tendencies of drugs.