The Hydrophobic Interaction

To gain insight into the thermodynamic factors that contribute to the spontaneous 

Throughout the text we shall see how concepts of physical chemistry can be used to establish some of the known rules for the assembly of complex biological structures. Here, we describe how the Second Law can account for the formation of such organized assemblies as proteins and biological cell membranes. 

To understand the hydrophobic interaction more completely we need to know more about the energetics of the interaction of hydrophobic groups and water. Experiments indicate that the dissolution of a largely hydrophobic molecule in water is commonly endothermic 0) but that the entropy change is 

An important consequence of this analysis is that low temperatures disfavor the hydrophobic interaction. Thus, from AG = AH - TAS, lowering the temperature reduces the effect of AS and the AG can change from negative to positive. This is the reason why some proteins and viruses dissociate into their individual subunits as the temperature is lowered to 0°C. 

A further aspect of this discussion is that we can set up a scale of hydropho-bicities. The hydrophobicity of a small molecular group R is reported by defining the hydrophobicity constant, n, as 

The formation of amphiphilic aggregates can be seen as a compromise between the tendency of alkyl chains to avoid contact with water and the strong affinity of the polar groups to water. A thermodynamic description of micellar systems should thus include both these aspects. The electrostatic effects are discussed in Sect. 6 so we will concentrate here on the interactions involving the nonpolar part of the amphi-phile. 

The low solubility of hydrocarbons and other mainly apolar substances in water has been ascribed phenomenologically to the hydrophobic interaction. The hydro-phobic free energy can be defined4 as the difference between the standard chemical potentials of an apolar solute at infinite dilution in a hydrocarbon solvent juhc and in water 

A further insight into the nature of the hydrophobic interaction is obtained by separating the free energy into enthalpic and entropic parts 

A characteristic feature of the hydrophobic interaction is that it is dominated by entropy effects. Both the temperature dependence of alkane solubilities in water126,127) and direct calorimetric measurements128 show that Iihf is close to zero at room temperature. Some calorimetric data for heats of solution of hydrocarbons in water are shown in Table 3.2. A further noticeable feature is that Iihf is temperature dependent due to the rather large heat capacity, Cp F, associated with the hydrophobic interaction. From a systematic calorimetric study of a series of compounds with rather short alkyl chains129 it was found that 

On the basis of the regular behavior of the heat capacity, Gill and Wadso125) were able to summarize the thermodynamic data for the hydrophobic interaction of hydrocarbons as 

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Protein adsorption has been studied with a variety of techniques such as ellipsome-try [107,108], ESCA [109], surface forces measurements [102], total internal reflection fluorescence (TIRE) [103,110], electron microscopy [111], and electrokinetic measurement of latex particles [112,113] and capillaries [114], The TIRE technique has recently been adapted to observe surface diffusion [106] and orientation [IIS] in adsorbed layers. These experiments point toward the significant influence of the protein-surface interaction on the adsorption characteristics [105,108,110]. A very important interaction is due to the hydrophobic interaction between parts of the protein and polymeric surfaces [18], although often electrostatic interactions are also influential [ 116]. Protein desorption can be affected by altering the pH [117] or by the introduction of a complexing agent [118]. 

Hydrophobic effects include two distinct processes hydrophobic hydration and hydrophobic interaction. Hydrophobic hydration denotes the way in which nonpolar solutes affect the organisation of the water molecules in their immediate vicinity. The hydrophobic interaction describes the tendency of nonpolar molecules or parts thereof to stick together in aqueous media " . A related frequently encountered term is hydrophobicity . This term is essentially not correct since overall attractive interactions exist between water and compounds commonly referred to as... 

Chapter 5 also demonstrates that a combination of Lewis-acid catalysis and micellar catalysis can lead to accelerations of enzyme-like magnitudes. Most likely, these accelerations are a consequence of an efficient interaction between the Lewis-acid catalyst and the dienophile, both of which have a high affinity for the Stem region of the micelle. Hence, hydrophobic interactions and Lewis-acid catalysis act cooperatively. Unfortunately, the strength of the hydrophobic interaction, as offered by the Cu(DS)2 micellar system, was not sufficient for extension of Lewis-acid catalysis to monodentate dienophiles. 

In the hope of having done away with these misunderstandings, we now address the molecular origin of the hydrophobic hydration as well as the hydrophobic interaction. Note that comprehension of hydrophobic hydration is a prerequisite for understanding hydrophobic interactions, since hydrophobic interactions always involve a (partial) reversal of the hydrophobic hydration. 

In HIC, the hydrophobic interactions are relatively weak, often driven by salts in moderate concentration (I to 2 M), and depend primarily on the exposed residues on or near the protein surface preservation of the native, biologically active state of the protein is an important feature of HIC. Elution can be achieved differentially by decreasing salt concentration or increasing the concentration of polarity perturbants (e.g., ethylene glycol) in the eluent. 

Chemists often call upon certain chemical types of interaction to account for solvent-solvent, solvent-solute, or solute-solute interaction behavior, and we should eon-sider how these ehemical interactions are related to the long-range noncovalent forces discussed above. The important chemical interactions are charge transfer, hydrogen bonding, and the hydrophobic interaction. 

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. 

Upon formulating these relationships, phenols with branched alkyl substituents were not included in the data of a-cyclodextrin systems, though they were included in (3-cyclodextrin systems. In all the above equations, the n term was statistically significant at the 99.5 % level of confidence, indicating that the hydrophobic interaction plays a decisive role in the complexation of cyclodextrin with phenols. The Ibrnch term was statistically significant at the 99.5% level of confidence for (3-cyclo-dextrin complexes with m- and p-substituted phenols. The stability of the complexes increases with an increasing number of branches in substituents. This was ascribed to the attractive van der Waals interaction due to the close fitness of the branched substituents to the (3-cyclodextrin cavity. The steric effect of substituents was also observed for a-cyclodextrin complexes with p-substituted phenols (Eq. 22). In this case, the B parameter was used in place of Ibmch, since no phenol with a branched... 

Macrocyclic tetraammonium compounds VIII and IX 611 form stable 1 1 inclusion complexes with anionic molecules in aqueous solutions 62). The anions are halides, carbonate, phosphate, AMP, ATP etc. The stability of the inclusion complexes hepends on electrostatic as well as hydrophobic interactions. Whereas the complexes of VIII are dominated by the electfostatic component, the hydrophobic interaction plays the main part in complexes of IX. 

It can be seen from the figure that the electrostatic repulsive forces between the macrocations are overwhelmed, probably by hydrophobic attractive forces between their hydrophobic side groups. It should be noted that the complimentary base-base pairing is unimportant in the present case. If this is not the case, the mixtures of APVP and TPVP should show the largest hypochromicity. This, however, is not the case. The importance of the hydrophobic interactions between nucleic acid bases has been proposed by Ts o et al.I9 from thermodynamic parameters of various nucleic acid bases or nucleosides in aqueous media. 

Cordes et al995 carried out alkaline hydrolyses of p-nitrophenylhexanoate 55 (PNPH) in the presence of poly-4-vinylpyridine partially quaternized with dodecyl-bromide and ethylbromide (QPVP). They also found that the polyelectrolytes are increasingly effective as catalysts with an increasing ratio of dodecyl to ethyl groups, and the hydrophobic interactions are important in determining the catalytic efficiency. They observed the inhibitory effects of several gegen-anions fluoride ions are the weakest inhibitor, and nitrate is the strongest (F- < Cl < S04 [Pg.159]

The hydrophobic interaction results in the existence of a lower critical solution temperature and in the striking result that raising the temperature reduces the solubility, as can be seen in liquid-liquid phase diagrams (see Figure 5.2a). In general, the solution behaviour of water-soluble polymers... 

In this case, the hydrophobic interaction is very weak compared to that of aq.KOH-graphite system. In spite of this, it still dominates the disjoining pressure. 

Another important interaction that needs to be considered is the hydrophobic interaction. This can be most easily thought of in terms of two immiscible liquids such as oil and water being induced to mix by adding surfactants, to form (micro) emulsions. The exact structure of the phase formed depends heavily on the relative compositions of the various phases and the structure of the surfactant (see Figure 6.4). 

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