Interactions hydrophobic

These are long-ranged attractive interactions between non-polar groups separated by water. The interactions are moderately strong (5-40 kJ/mol) and endothermic (up to around 60 °C). 

Hydrophobic interactions are of entropic origin. That is to say, their formation is driven by the gain in the entropy of the system, especially involving the local structuring of the water molecules in the vicinity of the non-polar groups (Jenks, 1969 Cantor and Schimmel, 1980 Dickinson and McClements, 1995 McClements, 2005). A consequence of this entropic character is that the interactions become stronger with increasing temperature up to 60 °C. 

In an aqueous medium these wtermolecular attractive interactions make a strong contribution to biopolymer self-association and inclusion complex formation, as well as to the flocculation of biopolymer-coated colloidal particles. // //Y/molecular hydrophobic interactions commonly influence the level of folding/unfolding of macromolecules as well as their detailed conformations. 

It is clear that hydrophobic interactions are essential to the formation of the native structure of globular proteins. Again, thermodynamic studies [20] on such systems plus the analysis of protein crystal structures [30] are strong evidence for the essential role of these hydrophobic interactions. Globular proteins in their native conformation do have their hydrophobic atoms on the inside , away from the water, and the addition of non-aqueous solvents to the water tends to destabilize this structure, since the exposure of non-polar groups is not so energetically costly in e.g., mixed alcohol/water solvents as it is in pure water. 

It was recognized some time ago that the binding and catalysis of a-chymotrypsin substrates correlated with their hydrophobicity [32] and subsequent X-ray studies 

A second very interesting example was the difference in the QSAR for identical triazine analogs binding to two different (L. casei and chicken liver) dihydrofolate reductases. In one case, the dependence of binding on octanol partition coefficient w for long O-alkyl chains 0-(CH2) was 1, indicating an active site similar in 

It appears that the most important attractive non-covalent forces for biological association in aqueous solution are electrostatic, dispersion and hydrophobic. Electrostatic interactions are probably more important in providing specificity than in contributing to the overall thermodynamic driving force for association. It is likely that dispersion is important and hydrophobic terms essential in most protein-ligand interactions. 

More extensive discussions on the nature of intermolecular interactions and thermodynamics in biological systems are given by Jencks [39] and Fersht [22]. 

In the traditional view hydrophobic interactions are assumed to be driven by the release of water molecules from the hydrophobic hydration shells upon the approach of one nonpolar solute to another. Although the ideas about the structure of the hydrophobic hydration shell have changed, this view is essentially unaltered 

Surprisingly, some authors claim that methane molecules have a smaller tendency to associate in 

The distinction between pairwise and bulk hydrophobic interactions is often made, although some authors doubt the existence of an intrinsic difference between the two . Pairwise hydrophobic interactions denote the interactions behveen two isolated nonpolar solutes in aqueous solution. They occur in the regime where no aggregation takes place, hence below the critical aggregation concentration or solubility limit of the particular solute. If any breakdown of the hydrophobic hydration shell occurs, it will be only transient. 

What distinguishes water from ordinary organic solvents and justifies the term hydrophobic interaction is the molecular origin of the effect, being entropy driven in pure water at room temperature and resulting primarily from the strong water-water interactions. 

In the brief account below we summarise what we knew of hydrophobic interactions [42-45] in the context of this overview of complex molecular forces imtil 1993, so as not to deviate too far from our main theme. Recent work to be discussed in Appendix 3C, has opened up a whole new perspective. The consequences of that work affect our understanding in profound ways not yet fully comprehended. 

Two further forces operate in any colloidal suspension or self-organised system. The first is due to Onsager and to Langmuir [54-56] who explained colloidal stability of clays and cylindrical particles in terms of purely repulsive 

The term hydrophobic interaction refers to the solvent-induced interaction between nonpolar solutes in water. While experimental information on hydrophobic hydration is readily available, comparable information is nearly nonexistent for hydrophobic interactions, particularly for simple systems where interpretation of data would be unambiguous. This is due to the very low solubility of nonpolar solutes in water. Computational investigations have therefore been used extensively to investigate the nature of hydrophobic interactions. Early calculations in this area dealt primarily with the free energy of association, or potential of mean force (PMF), between pairs of nonpolar solutes in water, and have been reviewed by Blokzijl and Engberts. More recent calculations have included evaluations of the entropy and heat capacity of association. 

As discussed in the methods section, computational techniques used to study hydrophobic interactions are similar to those used for hydrophobic hydration. Most commonly, TI and FEP methods have been adapted to yield a PMF by equating the coupling parameter A, or the perturbation coordinate, respectively, to the radial distance between two solute particles. The application of a test particle approach or of Eq. [28] is also possible. Methods for decomposition of the free energy of association into its entropic and energetic (enthalpic) parts are equivalent to those discussed above, as are techniques for determining the heat capacity. 

Models of hydrophobic hydration including the iceberg hypothesis and its more modern variants have led to several qualitative predictions for pairwise hydrophobic interactions. The first and simplest prediction based on free-energy arguments is that nonpolar solutes should tend to associate 

Water is an excellent solvent for ions and for substances that contain polarized bonds (see p.20). Substances of this type are referred to as polar or hydrophilic ( water-loving ). In contrast, substances that consist mainly of hydrocarbon structures dissolve only poorly in water. Such substances are said to be apolar or hydrophobic. 

The spontaneous separation of oil and water, a familiar observation in everyday life, is due to the energetically unfavorable formation of clathrate structures. When a mixture of water and oil is firmly shaken, lots of tiny oil drops form to begin with, but these quickly coalesce spontaneously to form larger drops—the two phases separate. A larger drop has a smaller surface area than several small drops with the same volume. Separation therefore reduces the area of surface contact between the water and the oil, and consequently also the extent of clathrate formation. The AS for this process 

Molecules that contain both polar and apolar groups are called amphipathic or amphiphilic. This group includes soaps (see p.48), phospholipids (see p. 50), and bile acids (see p. 56). 

The separation of oil and water (B) can be prevented by adding a strongly amphipathic substance. During shaking, a more or less stable emulsion then forms, in which the surface of the oil drops is occupied by amphipathic molecules that provide it with polar properties externally. The emulsification of fats in food by bile acids and phospholipids is a vital precondition for the digestion of fats (see p.314). 

Koolman, Color Atlas of Biochemistry, 2nd edition 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. 

The qualitative discussion of solubility has focussed so far on the attractive forces in solute-solvent interactions. However, where water is concerned, it is also important to consider the forces of repulsion due to the so-called hydrophobic interactions that may arise in certain cases (Franks, 1975). These hydrophobic interactions may be explained in terms of thermodynamic concepts. 

Measuring enthalpy changes for the dissolution of hydrocarbons, such as alkanes, in water shows that heat is evolved, i.e., A/f is negative and energetically water and alkanes attract each other. However, such attraction does not make alkanes soluble in water to any appreciable extent. This is because the free energy change AGsomtion opposes the process and is positive. 

In cases where the solvation energies are large, as for example when ionic compounds dissolve in water, these hydrophobic effects, based on adverse changes in entropy, are swamped. Dissolving such compounds can be readily accomplished due to the very large energies released when the ions become hydrated. 

As mentioned above, an additional type of interaction, which is considered to be crucial for the integrity of biopolymers, is that which has been termed the hydrophobic or apolar interaction. The driving force for hydrophobic interactions appears to be largely entropic. By forming an oil-droplet-like structure, hydrophobic side chains avoid the increased order and unfavorable, decreased entropy that would occur were they to be incorporated into a water lattice. The genesis of these forces has been a subject of great interest, and several accounts are available (Tanford, 1973 Franks, 1975 Lewin, 1974). 

In the previous section we have seen that the formation of hydrophobic hydration shells aids the dissolution of apolar solutes in water. Upon increasing concentration and/or size of the solute it is inevitable that, at a critical concentration, the large hydrophobic hydration shells start to overlap, leading to mutually destructive breakdown of these water arrangements (Fig. 2.6). This sacrifice of H-bonding interactions results in a solvent-induced sticking 

It should be emphasized here that hydrophobic hydration shells are quite voluminous. Computer simulations can be used for estimating hydration numbers. For example, Jorgensen has reported hydration numbers of 20 and 34 for, respectively, methane and n-pentane. A C-NMR study gave a hydration number of 20 for aqueous methane. 

HI between aromatic molecules have a different thermodynamic signature and are driven by favorable enthalpy effects rather than entropy effects ( nonclassical HI ).  

For HI between two r-systems the heat capacity changes are relatively small and negative. For aromatics London dispersion interactions involving the polarizable n electrons contribute more significantly than in the case of aliphatic solutes.  

Hydrophobic interactions, still the least understood representative of noncovalent interactions, are of great importance in (bio)chemistry. They contribute to protein folding, the formation of enzyme-substrate and enzyme-inhibitor complexes, the formation and functioning of cell membranes, just to mention processes of crucial biological importance. But HI also occur between ordinary apolar organic molecules and operate in many molecular 

The attraction between hydrocarbons or fluorocarbons in air (mainly van der Waals) increases very much when we place these molecules in water. For example, for two contacting methane molecules in free space the interaction pair potential energy is —2.5 x 10 21J, whereas in water it is —14 x 10 21J. On the other hand, experimental evidence 

Hydrophobic attraction is also very important in understanding molecular self-assembly, micelle-formation, biological membrane structure and protein conformations, which will be discussed in Chapters 5, 7, 9 and 10. 

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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]. 

Both the structural and kinetic aspects of the protein-folding problem are complicated by the fact that folding takes place within a bath of water molecules. In fact, hydrophobic interactions are almost certainly crucial for both the relation of the sequence and the native structure, and the process by which a good sequence folds to its native structure. 

Hummer G, Garde S, Garcia A E, Pohorille A and Pratt L R 1996 An information theory model of hydrophobic interactions Proc. Natl Acad. Sc/. 93 8951... 

As with SCRF-PCM only macroscopic electrostatic contribntions to the Gibbs free energy of solvation are taken into account, short-range effects which are limited predominantly to the first solvation shell have to be considered by adding additional tenns. These correct for the neglect of effects caused by solnte-solvent electron correlation inclnding dispersion forces, hydrophobic interactions, dielectric saturation in the case of... 

D. E. Smith and A. D. J. Haymet. Free energy, entropy and internal energy of hydrophobic interactions computer simulations. J. Chem. P/iys., 98 6445-6454,... 

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... 

Breslow immediately grasped the significance of his observation. He interpreted this discovery in terms of a hydrophobic effect Since in the Diels-Alder reaction. .. the transition state. .. brings together two nonpolar groups, one might expect that in water this reaction could be accelerated by hydrophobic interactions ". ... 

Tire importance of hydrophobic interactions in the aqueous acceleration is further demonstrated by a qualitative study described by Jenner on the effect of pressure on Diels-Alder reactions in water and a number of organic solvents. Invariably, the reactions in water were less accelerated by pressure than those in organic solvents, which is in line with the notion that pressure diminishes hydrophobic interactions. 

In conclusion, the special influence of water on the endo-exo selectivity seems to be a result of the fact that this solvent combines in it three characteristics that all favour formation of the endo adduct (1) water is a strong hydrogen bond donor, (2) water is polar and (3) water induces hydrophobic interactions. 

Breslow studied the dimerisation of cyclopentadiene and the reaction between substituted maleimides and 9-(hydroxymethyl)anthracene in alcohol-water mixtures. He successfully correlated the rate constant with the solubility of the starting materials for each Diels-Alder reaction. From these relations he estimated the change in solvent accessible surface between initial state and activated complex " . Again, Breslow completely neglects hydrogen bonding interactions, but since he only studied alcohol-water mixtures, the enforced hydrophobic interactions will dominate the behaviour. Recently, also Diels-Alder reactions in dilute salt solutions in aqueous ethanol have been studied and minor rate increases have been observed Lubineau has demonstrated that addition of sugars can induce an extra acceleration of the aqueous Diels-Alder reaction . Also the effect of surfactants on Diels-Alder reactions has been studied. This topic will be extensively reviewed in Chapter 4. 

What is the effect of water on the rate and selectivity of the Lewis-acid catalysed Diels-Alder reaction, when compared to oiganic solvents Do hydrogen bonding and hydrophobic interactions also influence the Lewis-acid catalysed process Answers to these questions will be provided in Chapter 2. 

The relative extents to which enforced hydrophobic interactions and hydrogen bonding influence the rate of the Diels-Alder reaction depends on the particular reaction under study". 

Appreciating the beneficial influences of water and Lewis acids on the Diels-Alder reaction and understanding their origin, one may ask what would be the result of a combination of these two effects. If they would be additive, huge accelerations can be envisaged. But may one really expect this How does water influence the Lewis-acid catalysed reaction, and what is the influence of the Lewis acid on the enforced hydrophobic interaction and the hydrogen bonding effect These are the questions that are addressed in this chapter. 

In summary, there are indications that neither hydrophobic interactions, nor donor- acceptor interactions are predominantly driving the arene - arene interaction. Osnsequently, we contend that these interactions are mainly governed by London - dispersion and electrostatic forces. 

The beneficial effect of water in the arene - arene interaction can be explained by the fact that this solvent is characterised by a low polarisability so that interactions of the aromatic rings with water are less efficient than with most organic solvents. Also the high polarity of water might lead to a polarisation of the aromatic rings, thereby enhancing electrostatic interactions. Finally, hydrophobic interactions may be expected to play a modest role. 

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