Hydrophobic Effect

Abstract

The term ‘hydrophobic effect’ refers to the poor solubility of nonpolar substances in water compared to organic solvents or to polar substances. The transfer of small nonpolar molecules from the gas phase or organic solvents to water has a characteristic thermodynamic signature: positive free energy, negative enthalpy, large negative entropy and positive heat capacity. This thermodynamic signature can be explained by considering the structure of water around nonpolar substances, which depends on the size and shape of the nonpolar solute. The poor solubility of nonpolar groups in water leads to aggregation of these groups (hydrophobic interaction) and the formation of self‐assembled structures such as miscelles and lipid bilayers. The hydrophobic interaction is also the major contributor to protein folding. The origin of the hydrophobic effect lies in the fact that water interacts with itself much more strongly than it does with nonpolar groups.

Key Concepts:

  • The origin of hydrophobicity lies in the strong water–water interactions.

  • The hydrophobic effect is entropic or enthalpic depending on temperature and the geometry of the associating solutes.

  • The characteristics of hydrophobic hydration differ depending on the length scale of the solute.

  • The hydrophobic effect is responsible for the formation of lipid bilayers and the folding of proteins.

  • Interaction between small hydrophobic solutes is in many ways different from transfer to a bulk phase.

  • Most studies find anticooperativity in the interaction between three small nonpolar solutes.

  • Very long‐range attractions between hydrophobic surfaces are probably due to macroscopic phenomena, such as air bubbles.

Keywords: water; hydrophobic; nonpolar; solvation; hydration; hydrogen bonding

Figure 1.

The thermodynamics of transfer of ethane from carbon tetrachloride to water. Th and Ts represent the temperatures at which ΔH° and ΔS° of transfer are zero, respectively. At Ts, ΔG° is at its maximum and at Th, ΔG°/T is at its maximum and the partition coefficient Kd=exp (–ΔG°/RT) is at its minimum.

Figure 2.

Representation of a single water molecule and the structure of ice I. (a) Water's two hydrogen atoms and two electron pairs are oriented tetrahedrally. (b) In ice I, the tetrahedra are oriented so each water molecule is hydrogen bonded to its four neighbours.

Figure 3.

Favourable orientations of water at the surface of a solute that is (a) nonpolar, (b) hydrogen bonding and (c) polar but not hydrogen bonding (the dashed line indicates the dipole axis).

close

References

Abraham MH (1982) Free energies, enthalpies, and entropies of solution of gaseous nonpolar nonelectrolytes in water and nonaqueous solvents. The hydrophobic effect. Journal of the American Chemical Society 104: 2085–2094.

Ashbaugh HS and Paulaitis ME (2001) Effect of solute size and solute‐water attractive interactions on hydration water structure around hydrophobic solutes. Journal of the American Chemical Society 123(43): 10721–10728.

Attard P (2003) Nanobubbles and the hydrophobic attraction. Advances in Colloid and Interface Science 104: 75–91.

Ben‐Naim A (1968) Solubility and thermodynamics of solution of argon in the water–ethylene glycol system. Journal of Physical Chemistry 72: 2998–3001.

Ben‐Naim A (1987) Solvation Thermodynamics. New York: Plenum Press.

Ben‐Naim A and Marcus Y (1984a) Solubility and thermodynamics of solution of xenon in liquid n‐alkanes. Journal of Chemical Physics 80: 4438–4440.

Ben‐Naim A and Marcus Y (1984b) Solvation thermodynamics of nonionic solutes. Journal of Chemical Physics 81: 2016–2027.

Berne BJ, Weeks JD and Zhou RH (2009) Dewetting and hydrophobic interaction in physical and biological systems. Annual Review of Physical Chemistry 60: 85–103.

Cabani S, Gianni P, Mollica B and Lepori L (1981) Group contributions to the thermodynamic properties of non‐ionic organic solutes in dilute aqueous solution. Journal of Solution Chemistry 10: 563–595.

Carey C, Cheng YK and Rossky PJ (2000) Hydration structure of the alpha‐chymotrypsin substrate binding pocket: the impact of constrained geometry. Chemical Physics 258(2–3): 415–425.

Chang ET, Gokcen NA and Poston TM (1968) Thermodynamic properties of gases in propellants. II. Solubilities of helium, nitrogen, and argon gas in hydrazine, methylhydrazine, and unsymmetrical dimethylhydrazine. Journal of Physical Chemistry 72: 638–642.

Clever HL, Battino R, Saylor JH and Gross PM (1957) The solubility of helium, neon, argon, and krypton in some hydrocarbon solvents. Journal of Physical Chemistry 61: 1078–1082.

Czaplewski C, Rodziewicz‐Motowidlo S, Dabal M et al. (2003) Molecular simulation study of cooperativity in hydrophobic association: clusters of four hydrophobic particles. Biophysical Chemistry 105(2–3): 339–359.

Dill KA (1990) Dominant forces in protein folding. Biochemistry 29: 7133–7155.

Frank HS and Evans MW (1945) Free volume and entropy in condensed systems III. Entropy in binary liquid mixtures. Journal of Chemical Physics 13: 507–532.

Ghosh T, Garcia AE and Garde S (2003) Water‐mediated three‐particle interactions between hydrophobic solutes: Size, pressure, and salt effects. Journal of Physical Chemistry B 107(2): 612–617.

Glew DN (1962) Aqueous solubility and the gas hydrates. The methane‐water system. Journal of Physical Chemistry 66: 605–609.

Haselmeier R, Holz M, Marbach W and Weingärtner H (1995) Water dynamics near a dissolved noble gas. First direct experimental evidence for a retardation effect. Journal of Physical Chemistry 99: 2243–2246.

Horiuti J (1931) On the solubility of gas and coefficient of dilatation by absorption. Scientific Papers of the Institute of Physical and Chemical Research 17(341): 125.

Hummer G, Garde S, Garcia AE, Pohorille A and Pratt LR (1996) An information theory model of hydrophobic interactions. Proceedings of the National Academy of Sciences of the USA 93: 8951–8955.

Israelachvili J and Pashley R (1982) The hydrophobic interaction is long‐range, decaying exponentially with distance. Nature 300(5890): 341–342.

Jencks WP (1969) Catalysis in Chemistry and Enzymology. New York: Dover.

de Jong PHK, Wilson JE, Neilson GW and Buckingham AD (1997) Hydrophobic hydration of methane. Molecular Physics 91: 99–103.

Jorgensen WL, Gao J and Ravimohan C (1985) Monte Carlo simulations of alkanes in water: hydration numbers and the hydrophobic effect. Journal of Physical Chemistry B 89: 3470–3473.

Kauzmann W (1959) Some factors in the interpretation of protein denaturation. Advances in Protein Chemistry 1: 14–63.

Lazaridis T (2001) Solvent size vs cohesive energy as the origin of hydrophobicity. Accounts of Chemical Research 34(12): 931–937.

Lazaridis T and Paulaitis ME (1992) Entropy of hydrophobic hydration – a new statistical mechanical formulation. Journal of Physical Chemistry 96(9): 3847–3855.

Lazaridis T and Paulaitis ME (1994) Simulation studies of the hydration entropy of simple, hydrophobic solutes. Journal of Physical Chemistry 98(2): 635–642.

Lee B (1985) The physical origin of the low solubility of nonpolar solutes in water. Biopolymers 24: 813–823.

Lee CY, McCammon JA and Rossky PJ (1984) The structure of liquid water at an extended hydrophobic surface. Journal of Chemical Physics 80(9): 4448–4455.

Lee ME and van der Vegt NFA (2006) Does urea denature hydrophobic interactions? Journal of the American Chemical Society 128(15): 4948–4949.

Lum K, Chandler D and Weeks JD (1999) Hydrophobicity at small and large length scales. Journal of Physical Chemistry B 103: 4570–4577.

Madan B and Sharp K (1997) Molecular origin of hydration heat capacity changes of hydrophobic solutes: perturbation of water structure around alkanes. Journal of Physical Chemistry B 101: 11237–11242.

Makhatadze GI and Privalov PL (1990) Heat capacity of proteins I. Partial molar heat capacity of individual amino acid residues in aqueous solution: hydration effects. Journal of Molecular Biology 213: 375–384.

Mao M, Zhang JH, Yoon RH and Ducker WA (2004) Is there a thin film of air at the interface between water and smooth hydrophobic solids? Langmuir 20(5): 1843–1849.

Meyer EA, Castellano RK and Diederich F (2003) Interactions with aromatic rings in chemical and biological recognition. Angewandte Chemie – International Edition 42(11): 1210–1250.

Mezger M, Reichert H, Ocko BM, Daillant J and Dosch H (2011) Comment on ‘How water meets a very hydrophobic surface’. Physical Review Letters 107(24): 249801

Mezger M, Sedlmeier F, Horinek D et al. (2010) On the origin of the hydrophobic water gap: an x‐ray reflectivity and md simulation study. Journal of the American Chemical Society 132(19): 6735–6741.

Naghibi H, Dec SF and Gill SJ (1987) Heats of solution of ethane and propane in water from 0 to 50°C. Journal of Physical Chemistry 91: 245–248.

Nakahara M, Wakai C, Yoshimoto Y and Matubasasi N (1996) Dynamics of hydrophobic hydration of benzene. Journal of Physical Chemistry 100: 1345–1349.

Nozaki Y and Tanford C (1970) Solubility of amino acids, diglycine, and triglycine in aqueous guanidine hydrochloride solutions. Journal of Biological Chemistry 245(7): 1648–1652.

Owicki JC and Scheraga HA (1977) Monte Carlo calculations in the isothermal‐isobaric ensemble. 2. Dilute aqueous solution of methane. Journal of the American Chemical Society 99: 7413–7418.

Paul S and Patey GN (2008) Hydrophobic interactions in urea – Trimethylamine‐N‐oxide solutions. Journal of Physical Chemistry B 112(35): 11106–11111.

Poynor A, Hong L , Robinson IK et al. (2006) How water meets a hydrophobic surface. Physical Review Letters 97(26): 266101.

Pratt LR and Chandler D (1977) Theory of the hydrophobic effect. Journal of Chemical Physics 67: 3683–3704.

Seelig J and Ganz P (1991) Nonclassical hydrophobic effect in membrane binding equilibria. Biochemistry 30: 9354–9359.

Setny P, Baron R and McCammon JA (2010) How can hydrophobic association be enthalpy driven? Journal of Chemical Theory and Computation 6(9): 2866–2871.

Shimizu S and Chan HS (2001) Configuration‐dependent heat capacity of pairwise hydrophobic interactions. Journal of the American Chemical Society 123(9): 2083–2084.

Shimizu S and Chan H‐S (2002a) Anti‐cooperativity and cooperativity in hydrophobic interactions: three‐body free energy landscapes and comparison with implicit‐solvent potential functions for proteins. Proteins 48: 15–30.

Shimizu S and Chan HS (2002b) Origins of protein denatured state compactness and hydrophobic clustering in aqueous urea: Inferences from nonpolar potentials of mean force. Proteins: Structure, Function and Genetics 49(4): 560–566.

Smith DE and Haymet ADJ (1993) Free energy, entropy, and internal energy of hydrophobic interactions: computer simulations. Journal of Chemical Physics 98: 6445–6454.

Tanford C (1979) Interfacial free energy and the hydrophobic effect. Proceedings of the National Academy of Sciences of the USA 76: 4175–4176.

Tanford C (1980) The Hydrophobic Effect: Formation of Micelles and Biological Membranes. New York: John Wiley & Sons.

Tsao YH, Evans DF and Wennerstrom H (1993) Long‐range attractive force between hydrophobic surfaces observed by atomic‐force microscopy. Science 262(5133): 547–550.

Wallqvist A, Covell DG and Thirumalai D (1998) Hydrophobic interactions in aqueous urea solutions with implications for the mechanism of protein denaturation. Journal of the American Chemical Society 120(2): 427–428.

Wilhelm E and Battino R (1973) Thermodynamic functions of the solubilities of gases in liquids at 25°C. Chemical Reviews 73: 1–9.

Wimley WC and White SH (1993) Membrane partitioning: distinguishing bilayer effects from the hydrophobic effect. Biochemistry 32: 6307–6312.

Wood RH and Thompson PT (1990) Differences between pair and bulk hydrophobic interactions. Proceedings of the National Academy of Sciences of the USA 87: 946–949.

Zangi R, Zhou RH and Berne BJ (2009) Urea's action on hydrophobic interactions. Journal of the American Chemical Society 131(4): 1535–1541.

Further Reading

Blokzijl W and Engberts JBFN (1993) Hydrophobic effects. Opinions and facts. Angewandte Chemie – International Edition 32: 1545–1579.

Chandler D (2005) Interfaces and the driving force of hydrophobic assembly. Nature 437(7059): 640–647.

Hummer G, Garde S, Garcia AE, Paulaitis ME and Pratt LR (1998) Hydrophobic effects on a molecular scale. Journal of Physical Chemistry B 102: 10469–10482.

Pollack GL (1991) Why gases dissolve in liquids. Science 251: 1323–1330.

Pratt LR (2002) Molecular theory of hydrophobic effects: ‘she is too mean to have her name repeated’. Annual Review of Physical Chemistry 53: 409–436.

Ragone R and Colonna G (1994) The role of conditional hydration on the thermodynamics of protein folding. Journal of the American Chemical Society 116: 2677–2678.

Schellman JA (1997) Temperature, stability and the hydrophobic interaction. Biophysical Journal 73: 2960–2964.

Southall NT, Dill KA and Haymet ADJ (2002) A view of the hydrophobic effect. Journal of Physical Chemistry B 106(3): 521–533.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Lazaridis, Themis(Jan 2013) Hydrophobic Effect. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002974.pub2]