Hydrophobic effect

From Wikipedia, the free encyclopedia
Jump to: navigation, search
A droplet of water forms a spherical shape, minimizing contact with the hydrophobic leaf.

The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in aqueous solution and exclude water molecules.[1][2] This occurs because interactions between the hydrophobic molecules allow water molecules to bond more freely, increasing the entropy of the system. The word hydrophobic literally means "water-fearing," and it describes the segregation and apparent repulsion between water and nonpolar substances.

The hydrophobic effect is responsible for the separation of a mixture of oil and water into its two components. The hydrophobic effect is also responsible for the stability of cell membranes, drives protein folding as well as the insertion of membrane proteins into the nonpolar lipid environment and finally stabilizes protein-small molecule interactions. Hence the hydrophobic effect is essential to life.[3][4][5][6] Substances for which this effect is observed are known as hydrophobes.


Amphiphiles are molecules that have both hydrophobic and hydrophilic domains. Detergents are composed of amphiphiles that allow hydrophobic molecules to be solubilized in water by forming micelles and bilayers (as in soap bubbles). They are also important to cell membranes composed of amphiphilic phospholipids that prevent the internal aqueous environment of a cell from mixing with external water.

Folding of macromolecules[edit]

In the case of protein folding, the hydrophobic effect is important to understanding the structure of proteins that have hydrophobic amino acids (such as alanine, valine, leucine, isoleucine, phenylalanine, tryptophan and methionine) clustered together within the protein. Structures of water-soluble proteins have a hydrophobic core in which side chains are buried from water, which stabilizes the folded state. Charged and polar side chains are situated on the solvent-exposed surface where they interact with surrounding water molecules. Minimizing the number of hydrophobic side chains exposed to water is the principal driving force behind the folding process,[7] although formation of hydrogen bonds within the protein also stabilizes protein structure.[8]

The energetics of DNA tertiary structure assembly were determined to be driven by the hydrophobic effect, in addition to Watson-Crick base pairing, which is responsible for sequence selectivity, and stacking interactions between the aromatic bases.[9][10]

Protein purification[edit]

In biochemistry, the hydrophobic effect can be used to separate mixtures of proteins based on their hydrophobicity. Column chromatography with a hydrophobic stationary phase such as phenyl-sepharose will cause more hydrophobic proteins to travel more slowly, while less hydrophobic ones elute from the column sooner. To achieve better separation, a salt may be added (higher concentrations of salt increase the hydrophobic effect) and its concentration decreased as the separation progresses.

The origin of hydrophobic effect[edit]

Dynamic hydrogen bonds between molecules of liquid water

The origin of the hydrophobic effect is not fully understood. Some argue that the hydrophobic interaction is mostly an entropic effect originating from the disruption of highly dynamic hydrogen bonds between molecules of liquid water by the nonpolar solute.[11] A hydrocarbon chain or a similar nonpolar region of a large molecule is incapable of forming hydrogen bonds with water. Introduction of such a non-hydrogen bonding surface into water causes disruption of the hydrogen bonding network between water molecules. The hydrogen bonds are reoriented tangentially to such surface to minimize disruption of the hydrogen bonded 3D network of water molecules, and this leads to a structured water "cage" around the nonpolar surface. The water molecules that form the "cage" (or solvation shell) have restricted mobility. In the solvation shell of small nonpolar particles, the restriction amounts to some 10%. For example, in the case of dissolved xenon at room temperature a mobility restriction of 30% has been found.[12] In the case of larger nonpolar molecules, the reorientational and translational motion of the water molecules in the solvation shell may be restricted by a factor of two to four; thus, at 25 °C the reorientational correlation time of water increases from 2 to 4-8 picoseconds. Generally, this leads to significant losses in translational and rotational entropy of water molecules and makes the process unfavorable in terms of the free energy in the system.[13] By aggregating together, nonpolar molecules reduce the surface area exposed to water and minimize their disruptive effect.

The hydrophobic effect can be quantified by measuring the partition coefficients of non-polar molecules between water and non-polar solvents. The partition coefficients can be transformed to free energy of transfer which includes enthalpic and entropic components, ΔG = ΔH - TΔS. These components are experimentally determined by calorimetry. The hydrophobic effect was found to be entropy-driven at room temperature because of the reduced mobility of water molecules in the solvation shell of the non-polar solute; however, the enthalpic component of transfer energy was found to be favorable, meaning it strengthened water-water hydrogen bonds in the solvation shell due to the reduced mobility of water molecules. At the higher temperature, when water molecules become more mobile, this energy gain decreases along with the entropic component. The hydrophobic effect increases with temperature, which leads to "cold denaturation" of proteins.[14]

See also[edit]


  1. ^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version:  (2006–) "hydrophobic interaction".
  2. ^ Chandler D (2005). "Interfaces and the driving force of hydrophobic assembly". Nature 437 (7059): 640–7. doi:10.1038/nature04162. PMID 16193038. 
  3. ^ Kauzmann W (1959). "Some factors in the interpretation of protein denaturation". Advances in Protein Chemistry 14: 1–63. doi:10.1016/S0065-3233(08)60608-7. PMID 14404936. 
  4. ^ Charton M, Charton BI (1982). "The structural dependence of amino acid hydrophobicity parameters". Journal of Theoretical Biology 99 (4): 629–644. doi:10.1016/0022-5193(82)90191-6. PMID 7183857. 
  5. ^ Lockett MR, Lange H, Breiten B, Heroux A, Sherman W, Rappoport D, Yau PO, Snyder PW, Whitesides GM (2013). "The binding of benzoarylsulfonamide ligands to human carbonic anhydrase is insensitive to formal fluorination of the ligand". Angew. Chem. Int. Ed. Engl. 52 (30): 7714–7. doi:10.1002/anie.201301813. PMID 23788494. 
  6. ^ Breiten B, Lockett MR, Sherman W, Fujita S, Al-Sayah M, Lange H, Bowers CM, Heroux A, Krilov G, Whitesides GM (2013). "Water networks contribute to enthalpy/entropy compensation in protein-ligand binding". J. Am. Chem. Soc. 135 (41): 15579–84. doi:10.1021/ja4075776. PMID 24044696. 
  7. ^ Pace CN, Shirley BA, McNutt M, Gajiwala K (1 January 1996). "Forces contributing to the conformational stability of proteins". FASEB J. 10 (1): 75–83. PMID 8566551. 
  8. ^ Rose GD, Fleming PJ, Banavar JR, Maritan A (2006). "A backbone-based theory of protein folding". Proc. Natl. Acad. Sci. U.S.A. 103 (45): 16623–33. doi:10.1073/pnas.0606843103. PMC 1636505. PMID 17075053. 
  9. ^ Gilbert HF (2001). Basic concepts in biochemistry: a student's survival guide (2nd, International ed. ed.). Singapore: McGraw-Hill. p. 9. ISBN 978-0071356572. 
  10. ^ Ho PS, van Holde KE, Johnson WC, Shing P (1998). Principles of physical biochemistry. Upper Saddle River, N.J.: Prentice-Hall. p. 18. ISBN 978-0137204595. See also thermodynamic discussion pages 137-144 
  11. ^ Silverstein TP (January 1998). "The Real Reason Why Oil and Water Don't Mix". Journal of Chemical Education 75 (1): 116. doi:10.1021/ed075p116. 
  12. ^ Haselmeier R, Holz M, Marbach W, Weingaertner H (1995). "Water Dynamics near a Dissolved Noble Gas. First Direct Experimental Evidence for a Retardation Effect". The Journal of Physical Chemistry 99 (8): 2243. doi:10.1021/j100008a001. 
  13. ^ Tanford C (1973). The hydrophobic effect: formation of micelles and biological membranes. New York: Wiley. ISBN 978-0-471-84460-0. 
  14. ^ Jaremko M, Jaremko Ł, Kim HY, Cho MK, Schwieters CD, Giller K, Becker S, Zweckstetter M (2013). "Cold denaturation of a protein dimer monitored at atomic resolution". Nat. Chem. Biol. 9 (4): 264–70. doi:10.1038/nchembio.1181. PMID 23396077. 

Further reading[edit]