The basis of the hydrophobic effect.
The property of a molecule that most reliably determines the magnitude of the hydrophobic effect that it will experience is the number of hydrogen-carbon bonds it contains not the accessible surface area of its nonpolar portions. This conclusion follows from an examination of the standard free energies of transfer of alkanes, alkenes, alkadienes, and arenes from water to hexadecane. When the standard free energies of transfer for hydrocarbons in these different classes are plotted as a function of the number of hydrogen-carbon bonds they contain, all of the data fall upon the same line. These standard free energies of transfer are also directly proportional to the number of hydrogen-carbon bonds the hydrocarbons contain. When the same standard free energies of transfer are plotted as a function of the accessible surface areas of the hydrocarbons, the data do not fall upon the same line nor are the standard free energies of transfer directly proportional to the accessible surface areas. An examination of the standard free energies of transfer for the different classes of hydrocarbons from the gas phase to water and from the gas phase to hexadecane reinforces the conclusion that the number of hydrogen-carbon bonds in a molecule rather than its accessible surface area is the basis of the hydrophobic effect. Consequently, estimates of the contribution of different functional groups to the hydrophobic effect providing the free energy of folding of a molecule of protein or providing the free energy of dissociation for the association of two proteins or the association of a ligand with a protein should be made by counting the number of hydrogen-carbon bonds excluded from water rather than computing the accessible surface areas excluded from water.
Kyte
Jack
J
Department of Chemistry 0506, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0506, USA. jkyte@ucsd.edu
D000465:Algorithms; D002244:Carbon / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D019277:Entropy; D006859:Hydrogen / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D013816:Thermodynamics
D002244:Carbon; D006859:Hydrogen