Effect hydrophobic

This is quite a peculiar type of interaction, which appears mainly (not only) in water solutions. The hydrophobic interaction does not represent any particular new interaction (beyond those we have already considered), because at least potentially they could be explained by the electrostatic, induction, dispersion, valence repulsion and other interactions already discussed, cf. pp. 718 and 695. 

The problem may be seen from a different point of view. The basic interactions have been derived as if operating in vacuum. However, in a medium the molecules interact with one another through the mediation of other molecules, including those of the solvent. In particular, a water medium creates a strong network of 

We may say m a rather simplistic way mat liydropliobic molecules aggregate not because they attract particularly strongly, but because water strongly prefers them to be out of its hydrogen bond net structure. 

The molecular architecture described above was first planned by a chemist. The system fulfilled all the points of the plan and self-organized in a spontaneous process.  

Hydrophobic interactions involve not only the molecules on which we focus our attention, but also, to an important extent, the water molecules of the solvent. The hydrogen bond network keeps the hydrophobic objects together, as a shopping bag keeps latd slabs together. 

Polar compounds and compounds that ionize can dissolve readily in water. These compounds are said to be hydrophilic. In contrast to hydrophilic substances, hydrocarbons and other nonpolar substances have very low solubihty in water because it is energetically more favorable for water molecules to interact with other water molecules rather than with nonpolar molecules. As a result, water molecules tend to exclude nonpolar substances, forcing them to associate with themselves in forming drops, thereby minimizing the contact area between 

In thermodynamic terms, solutes can be divided into two classes. For hydrophobic solutes in dilute solution in water, the partial Gibbs free energy of solution is positive. This is because water molecules that surround a less polar molecule in solution are more restricted in 

TABLE 1.2 Internal Pressures and Cohesive Energy Densities for Some Common Soivents (25° C)  

Hydrophobic interaction, however, is a relatively weak interaction. For example, the energy required to transfer a -CH2- unit from a hydrophobic to an aqueous environment is about 3 kJ mol .  

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Pratt L 1997 Molecular theory of hydrophobic effects Encyclopedia of Computational Chemistry... 

Flummer G, Garde S, Garcia A E, Paulitis M E and Pratt L R 1998 Hydrophobic effects on a molecular scale J. Phys. Chem. 102 10 469... 

The work by Hammett and Taft in the 1950s had been dedicated to the separation and quantification of steric and electronic influences on chemical reactivity. Building on this, from 1964 onwards Hansch started to quantify the steric, electrostatic, and hydrophobic effects and their influences on a variety of properties, not least on the biological activity of drugs. In 1964, the Free-Wilson analysis was introduced to relate biological activity to the presence or absence of certain substructures in a molecule. 

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. 

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... 

The ideas of Frank, Evans and Kauzmann had a profound influence on the way chemists thought about hydrophobic effects in the decades that followed However, after the study of the hydrophobic hydration shell through computer simulations became feasible, the ideas about the hydrophobic hydration gradually changed. It became apparent that the hydrogen bonds in the hydrophobic hydration shell are nof or only to a minor extent, stronger than in normal water which is not compatible with an iceberg character of the hydration shell. 

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 ". ... 

Three years after the Breslow report on the large effects of water on the rate of the Diels-Alder reaction, he also demonstrated tliat the endo-exo selectivity of this reaction benefits markedly from employing aqueous media . Based on the influence of salting-in and saltirg-out agents, Breslow pinpoints hydrophobic effects as the most important contributor to the enhanced endo-exo... 

Apart from the thoroughly studied aqueous Diels-Alder reaction, a limited number of other transformations have been reported to benefit considerably from the use of water. These include the aldol condensation , the benzoin condensation , the Baylis-Hillman reaction (tertiary-amine catalysed coupling of aldehydes with acrylic acid derivatives) and pericyclic reactions like the 1,3-dipolar cycloaddition and the Qaisen rearrangement (see below). These reactions have one thing in common a negative volume of activation. This observation has tempted many authors to propose hydrophobic effects as primary cause of ftie observed rate enhancements. 

Niek Buurma and Theo Rispens are most gratefully acknowledged for the inspiring discussions on hydrophobic effects. These discussions have contributed significantly to a better understanding of this topic and form the basis of what is described in Section 1.3. 

Hydrophobic effects. Implications for organic reactivity in water... 

Throughout this thesis reference has been made to hydrophobic effects. Enforced hydrophobic interactions are an important contributor to the acceleration of uncatalysed and also of the Lewis-acid catalysed Diels-Alder reactions which are described in this thesis. Moreover, they are likely to be involved in the beneficial effect of water on the enantioselectivity of the Lewis-acid catalysed Diels-Alder reaction, as described in Chapter 3. Because arguments related to hydrophobic effects are spread over nearly all chapters, and ideas have developed simultaneously, we summarise our insights at the end of this thesis. 

In the case of the retro Diels-Alder reaction, the nature of the activated complex plays a key role. In the activation process of this transformation, the reaction centre undergoes changes, mainly in the electron distributions, that cause a lowering of the chemical potential of the surrounding water molecules. Most likely, the latter is a consequence of an increased interaction between the reaction centre and the water molecules. Since the enforced hydrophobic effect is entropic in origin, this implies that the orientational constraints of the water molecules in the hydrophobic hydration shell are relieved in the activation process. Hence, it almost seems as if in the activated complex, the hydrocarbon part of the reaction centre is involved in hydrogen bonding interactions. Note that the... 

Also the arene-arene interactions, as encountered in Chapter 3, are partly due to hydrophobic effects, which can be ranked among enforced hydrophobic interactions. Simultaneous coordination of an aromatic oc amino acid ligand and the dienophile to the central copper(II) ion offers the possibility of a reduction of the number of water molecules involved in hydrophobic hydration, leading to a strengthening of the arene-arene interaction. Hence, hydrophobic effects can have a beneficial influence on the enantioselectivity of organic reactions. This effect is anticipated to extend well beyond the Diels-Alder reaction. 

The type of enforced hydrophobic effect that is operative in the retro Diels-Alder reaction cannot be referred to an enforced hydrophobic interaction, since there is no coming together, but rather a separation of nonpolar molecules during the reaction. It is better to refer to this process as an enforced hydrophobic effect. 

Finally, we summarise our insight into hydrophobic effects that have developed during the work described in this thesis. The discussion focuses on the influence of hydrophobic effects on organic reactivity. 

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...

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