The Hydrophobic Effect

Explain the difference between lyotropic and thermotropic phases. 

THE IMPORTANCE OF MOLECULAR SHAPE ON PHASE STRUCTURE AND MEMBRANE CURVATURE 

Show that by starting with a large uniform membrane sheet (i.e., we are using a continuum model and ignoring molecular details), the energy to form a unilamellar vesicle from the sheet is not dependent on radius. Now, consider a membrane unilamellar tubule in the same way—is radius important in this case  

Show that the packing parameter for cylindrical micelles cannot be more than 0.5. 

What is the difference between mean curvature and Gaussian curvature for a surfactant membrane Describe a shape for which the mean curvature is equal to zero but the Gaussian curvature is nonzero. 

It is necessary to remind ourselves, that the adsorption of humic acids or fulvic acids correspond to the adsorption of a mixture of adsorbates. Adsorption equations derived for the adsorption of a single adsorbate (Langmuir, Frumkin or Gibbs Equation) cannot be used for mechanistic interpretation of the data even if these data can be fitted to such equations (Tomaic and Zutic, 1988). 

Kinetically, the adsorption of humic acids at a solid-water interface is controlled by convection or diffusion to the surface. Even at concentrations as low as 0.1 mg/e near-adsorption equilibrium is attained within 30 minutes. At high surface densities, a relatively slow rearrangement of the adsorbed molecules may cause a slow attainment of an ultimate equilibrium (Ochs, Cosovic and Stumm, in preparation). The humic acids adsorbed to the particles modify the chemical properties of their surfaces, especially their affinities for metal ions (Grauer, 1989). 

In a simplified way the adsorption of organic matter, X, at a hydrated surface, S, may be viewed as  

This equation may be interpreted as the summation of the equations for the hydra- 

The lipophilicity of a substance, that is, the tendency of a substance to become dissolved in a lipid, is often measured by the tendency of a substance to become dissolved in a nonpolar solvent, for example, by the n-octanol-water distribution coefficient. The lipophilicity of a substance is inversely proportional to its water solubility. 

The hydrophobic force is related to the hydrophobic effect [1174, 1175]. Nonpolar molecules such as hydro- and fluorocarbons and nonpolar gases poorly dissolve in water (Table 10.2). If, for example, liquid octane is in contact with water and the system is allowed to equilibrate, only 5.4 [xM octane dissolves in water. Rather than being dissolved as individual molecules hydro- and fluorocarbons attract each other and tend to form intermolecular aggregates in an aqueous medium. This aggregation effect is called hydrophobic effect. The apparent attraction between hydrophobic molecules in water is sometimes referred to as hydrophobic interaction. At the macroscopic level, the hydrophobic effect is apparent when oil and water are mixed together and form separate phases. On solid, hydrophobic surfaces, water forms a high contact angle (Table 10.1). At the molecular level, the hydrophobic effect is 

Measurements of solid surface tensions, solid-liquid interfacial tensions, and contact angles vary by typically 4mNm or 3°. The parameters depend to a certain degree on how the samples are prepared. For a discussion, see Refs [1177, 1178]. 

The entropy is multiplied by the temperature T = 298.15 K for better comparison. Values for gases refer to a pressure of 1 atm. For materials that at 25 °C and normal pressure are in the gas phase, solubilities, AS , AH°, and AG° values are reported in terms of the process ideal gas (1 atm) — ideal solution in water (unit mole fraction solute). For substances that at 25 °C and normal pressure are in the liquid phase (starting with pentane), the values are reported in terms of the process pure liquid solute ideal solution in water. See also Exercise 10.3. 

If we try to mix oil and water, the poor solubility leads to a phase separation (unless one ofthe phases is present in only trace amounts). The hydrophobic effect manifests itself in a high interfacial tension between hydrocarbons and water. For example, the interfacial tension of n-hexane-water at 25 °C is 50.4 Nm and that of n-dodecane-water is 52.6 mNm [1182]. Such a high interfacial tension destabilizes oil-in-water or water-in-oil emulsions. The oil drops in water (or water drops in oil) coagulate and form a continuous water (or oil) phase. In practice, to prevent an emulsion from immediate separation into two continuous phases, surfactants have to be added to reduce the interfacial tension. 

Intramolecular vibrational motion is too rapid to permit adjustment of the relative positions and orientations of neighbouring molecules, so their contribution to the entropic force TdS R)/dRi may normally be neglected. 

Much is known of the hydrophobic effect from experimental studies of solutions of hydrocarbons in water and from computer simulations [15-17], and it remains an area of active research. 

The magnitude of this contribution to the free energy of interaction of hydrocarbons in water is estimated to be 0.017 x 10 J for every square Angstrom of buried hydrophobic surface [19,20]. 

Computer simulations of methane in water have provided a potential of average force for two CH molecules in water and the entropy of association [21 ]. A change of temperature from 275 to 317 K leads to a large increase in the clustering probability [22]. Such entropy-driven attraction may play an important role in molecular recognition of flexible molecules in aqueous solution. 

Paulaitis, J. Phys. Chem., 96, The term hydrophobic effect refers to the un-3847 (1992) and ref. 108] usual behavior of water towards nonpolar solutes. 

In the cavity-based model the hard core of water molecules is more important to the hydrophobic effect than H-bonding of water. The process of solvation is dissected into two components, the formation of a cavity in the water to accommodate the solute and the interaction of the solute with the water molecules. The creation of a cavity reduces the voliune of the translational motion of the solvent particles. This causes an imfavorable entropic effect. The total entropy of cavity formation at constant pressme  

Finally, the contribution of solute-water correlations to the hydrophobic effect may be displayed, for example, in the framework of the equation 

Recently, this behavioral difference of nonpolar and polar solutes could be reproduced by heat capacity calculations using a combination of Monte Carlo simulations and the random network model (RNM) of water. It was found that the hydrogen bonds between the water molecules in the first hydration shell of a nonpolar solute are shorter and less bent (i.e., are more ice-like) compared to those in pure water. The opposite effect occurs around 

Only at first glance, the two approaches, the clathrate cage model and the cavity-based modeL looked very different, the former based on the hydrogen bonding of water, and the later on the hard core of water. But taken all results together it would appear that both are just different perspectives on the same physics with different diagnostics reporting consequences of the same shifted balance between H bonds and vdW interactions. Actually, in a 

AScavj cavity formation entropy at constant pressure 

Walter Kauzmaim was perhaps the first to introduce the term hydrophobic bonding to describe the observed tendency of oils in water to aggregate together to form a separate entity. The term hydrophobic effect was popularized by Charles Tanford through his influential book The Hydrophobic Effect. This term literally means water-fearing , and, as discussed below, arises from a naive, pictorial (and wrong) explanation of the phenomenon in terms of an apparent repulsion between water and hydrocarbons. The often-quoted example of hydrophobic effect 

F igure 15.1. A schematic representation of a reaction at an oil-water interface. The transition state (AB ) is stabiUzed through the formation of strong HBs offered from the free dangling -OH groups. Here the transition state becomes more stabilized than the reactants. Adapted with permission from J. Am. Chem. Soc., 129 (2007), 5492-5502. Copyright (2007) American Chemical Society. 

The hydrophobic effect plays an important role in chemistry. It fosters the formation of micelles and reverse micelles and many other structures and gives rise to the unique solvation properties of aqueous binary mixtures (such as water-urea, water-DMSO, water-ethanol, to name just a few). The hydrophobic effect is also centrally important in biological systems. It is partly responsible for protein folding, micellar aggregation, lipid bilayer formation, cell membrane formation, the assembly of proteins into functional complexes, etc. 

Very recently the adsorption and aggregation of a P-amyloid fragment at the air/ water interface has been investigated by the combination of second harmonic generation (SHG) spectroscopy, Brewster angle microscopy (BAM), and MD simulation studies. It was found that in P-amyloid the hydrophobic residue-rich amino acid sequence 1-16 not only induces aggregation, but also exhibits a strong preference for the air-water interface relative to the bulk. [6]. 

The hydrophobic effect is relatively easy to understand, at least semi-quantitatively. It arises because water, at room temperature, makes sufficiently strong HBs among its molecules that are energetically favorable. So, water reorganizes itself around a non-polar solute to maintain its HB network and this costs entropy. This physical picture changes at higher temperature, as we discuss below. At room temperature (around 25°C), the enthalpy of solvation of a non-polar solute 

This aggregation of organic molecules in water actually leads to accelerated rates for some organic reactions in water. Diels-Alder and other sigmatropic reactions work very well in water, despite not being soluble or miscible in that solvent. This effect is discussed further in Chapter 7. 

It is well known that water is a good solvent for ions and polar molecules. On the other hand, it is a poor solvent for nonpolar molecules such as hydrocarbons. Perhaps surprisingly, the insolubility of hydrocarbons and other nonpolar compounds is not due to a positive enthalpy effect. The enthalpy of mixing hydrocarbons with water is foimd to be either very small or negative. Therefore, the positive value for AG must arise from a negative entropy change. This effect, called the hydrophobic effect, assumes importance in many processes, including solubilization and the adsorption of compounds at interfaces. 

If the solute is nonpolar, there is only weak van der Waals attraction with water, and water molecules arrange around the nonpolar solute such that they form the most extensive number of hydrogen bonds, with the ice clathrates (Part IV, Chap. 21) the extreme case. The ordering of water molecules is entropically unfavorable, since they lose orientational and translational freedom. This can be compensated for if the solvated solute molecules aggregate and the ordered water molecules are released from their surface into bulk water, a process which is entropically favorable and the main driving force for the hydrophobic effect [128 to 134]. 

The hydrophobic effect can be measured in terms of transfer of a molecule from gaseous phase or dissolved in nonpolar solvent to water. Since the change in Gibbs free energy AG is associated with changes in ethalpy JH, and entropy JS according to 

The transfer cycle for methane ([135], Ihble 2.10) shows that transfer from the inert solvent to the gas phase is favorable due to the large increase in entropy (JS = +14 kcal/mol-1 K-1) which compensates for the loss in van der Waals contacts indicated by a positive enthalpy (JH= +0.5 kcal mol-1). The transfer from the inert solvent and from the gas phase to water is unfavorable due to the large decrease in entropy (the water molecules arrange around methane in clathrate form), which outweighs the favorable change in enthalpy AH--2.7 and -3.2 kcal mol-1) arising from the increase in van der Waals contacts with water. 

A hydrophobidty scale for amino adds. The free energy of transfer from organic solvent to water depends linearly on the accessible surface area of a solute molecule [136 to 138], as illustrated for a number of hydrocarbons and amino adds in Fig. 2.11. For the hydrocarbons and the amino adds with nonpolar side chains Ala, Val, Leu, Phe, the lines with a slope of 25 cal A-2 and 22 cal A-2 respectively pass through the origin. The line for the amino adds with polar side chains Ser, Thr, His, Met, Tyr, Tip also has a slope of about 25 cal A-2, but the free energy of transfer is systematically lower than expected from their surface areas. 

We can associate these data directly with the concept of ordered water molecules around a nonpolar solute molecule, viz. the larger the surface area, the more water molecules are arranged around the solute molecule, with a loss in energy of 22 to 25 cal A-2. Based on arguments similar to those given above, the hydropho-bicity scale was extended to all amino acids and is compared in Ihble 2.11 with a scale derived on the basis of the actual distribution of amino acids in the interior or at the surface of a sample of 46 monomeric proteins. 

STUDIES OF WATER AND SOLUTION PHENOMENA A Cellular Automata Model of Water 

The hydrophobic effect is a term describing the influence of relatively nonpolar (lipophilic) substances on the collective behavior of water molecules in their vicinity. The common expression is that water is more structured or organized when in contact with a lipophilic solute. This behavior was observed in a cellular automata model of a solute in water,42,43 which led to a study in more detail.44 The hydrophobic effect was modeled by systematically increasing the breaking probability, PB(WS), value, encoding an increasing probability of a solute molecule, S, not to associate with water. 

It was observed that low PB(WS) values, modeling a polar molecule, produced configurations in which the solute molecules were extensively surrounded by water molecules, a pattern simulating hydration or electrostric-tion. Conversely, with high values of PB(WS) most of the solute molecules were found outside of the water clusters and within the cavities. This configuration leaves the water clusters relatively free of solute hence they are more 

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Water-soluble globular proteins usually have an interior composed almost entirely of non polar, hydrophobic amino acids such as phenylalanine, tryptophan, valine and leucine witl polar and charged amino acids such as lysine and arginine located on the surface of thi molecule. This packing of hydrophobic residues is a consequence of the hydrophobic effeci which is the most important factor that contributes to protein stability. The molecula basis for the hydrophobic effect continues to be the subject of some debate but is general considered to be entropic in origin. Moreover, it is the entropy change of the solvent that i... 

The hydrophobic effect. Water molecules around a non-polar solute form a cage-like structure, which ices the entropy. When two non-polar groups associate, water molecules are liberated, increasing the entropy. 

Jorgensen W L, J Gao and C Ravimohan 1985. Monte Carlo Simulations of Alkanes in Water Hydratior Numbers and the Hydrophobic Effect. Journal of Physical Chemistry 89 3470-3473. 

Higher alcohols become more hydrocarbon like and less water soluble 1 Octanol for example dissolves to the extent of only 1 mL m 2000 mL of water As the alkyl chain gets longer the hydrophobic effect (Section 2 17) becomes more important to the point that It more than hydrogen bonding governs the solubility of alcohols... 

Fig. 5. Protein folding. The unfolded polypeptide chain coUapses and assembles to form simple stmctural motifs such as -sheets and a-hehces by nucleation-condensation mechanisms involving the formation of hydrogen bonds and van der Waal s interactions. Small proteins (eg, chymotrypsin inhibitor 2) attain their final (tertiary) stmcture in this way. Larger proteins and multiple protein assembhes aggregate by recognition and docking of multiple domains (eg, -barrels, a-helix bundles), often displaying positive cooperativity. Many noncovalent interactions, including hydrogen bonding, van der Waal s and electrostatic interactions, and the hydrophobic effect are exploited to create the final, compact protein assembly. Further stmctural...

Modem understanding of the hydrophobic effect attributes it primarily to a decrease in the number of hydrogen bonds that can be achieved by the water molecules when they are near a nonpolar surface. This view is confirmed by computer simulations of nonpolar solutes in water [15]. To a first approximation, the magnimde of the free energy associated with the nonpolar contribution can thus be considered to be proportional to the number of solvent molecules in the first solvation shell. This idea leads to a convenient and attractive approximation that is used extensively in biophysical applications [9,16-18]. It consists in assuming that the nonpolar free energy contribution is directly related to the SASA [9],... 

C. Tanford. The Hydrophobic Effect Formation of Micelles and Biological Membranes. New York Wiley, 1980. 

For a recent review on the hydrophobic effect, see M. E. Paulaitis, S. Garde,... 

Hydrophobicity ( water-hate ) can dominate the behavior of nonpolar solutes in water. The key observations are (1) that very nonpolar solutes (such as saturated hydrocarbons) are nearly insoluble in water and (2) that nonpolar solutes in water tend to form molecular aggregates. Some authors refer to item 1 as the hydrophobic effect and to item 2 as the hydrophobic interaction. Two extreme points of view have been taken to account for these observations. 

Tanford. C. The Hydrophobic Effect", 2nd ed. Wiley-Interscience New York, 1980. 

Segel, I. H., 1976. Biochemical Calculations, 2nd ed. New York John Wiley. Tanford, C., 1980. The Hydrophobic Effect, 2nd ed. New York John Wiley. 

Tanford, C. (1980). The Hydrophobic Effect (2nd edition). New York Wiley-lnterscience. 

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