Partitioning of tryptophan side-chain analogs between water and cyclohexane.
We have measured the partitioning of the tryptophan side-chain analogs 3-methylindole and N-methylindole between water and cyclohexane over the temperature range 8-55 degrees C to investigate the relative contribution of the imine-NH- to the free energy of transfer. We take advantage of the fact that the indole imine nitrogen is blocked by a methyl group in N-methylindole. Unlike previous studies, we take into account the water present in the cyclohexane phase. Free energies of partitioning were calculated using mole-fraction, volume-fraction, and Flory-Huggins-corrected volume-fraction partition coefficients [De Young, L. R., & Dill, K. A. (1990) J. Phys. Chem. 94, 801-809; Sharp, K. A., Nicholls, A., Friedman, R., & Honig, B. (1991) Biochemistry 30, 9686-9697]. These approaches account for configurational entropy changes in different ways and thus lead to different values for the calculated free energies of transfer. There is a 2-3-fold difference in the free energies calculated from our measurements, using the different units. Independent of units, the partitioning of both compounds involves identical entropy changes. However, 3-methylindole has an additional unfavorable enthalpic contribution to partitioning into cyclohexane of +1.6 kcal/mol (independent of units) which is presumably the cost of removing the indole -NH- group from water and transferring it to cyclohexane. In cyclohexane, 3-methylindole forms hydrogen bonds with water that cause water to copartition into cyclohexane with the solute. A method is described which allows the partitioning process to be examined independent of subsequent interactions with water in the solvent.
Wimley
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Department of Physiology and Biophysics, University of California, Irvine 92717.
White
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D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003510:Cyclohexanes / Q000737:chemistry*; D006860:Hydrogen Bonding; D007211:Indoles / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
D003510:Cyclohexanes; D007211:Indoles; D014867:Water; D014364:Tryptophan; D009584:Nitrogen