Hydration, hydrophobic

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 solvation thermodynamics have been interpreted in a classical study by Frank and Evans in terms of the iceberg model . This model states that the water molecules around an nonpolar solute show an increased quasi-solid structuring. This pattern would account for the strongly negative 

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. 

Recently, this observation has been confirmed experimentally through neutron scattering studies, making use of isotopic substitution . These studies have revealed that the water molecules in the 

Very recently the first x-ray study (EXAFS) has been performed on hydrophobic hydration.  

Historically, the first published observations pertaining to the hydrophobic effect were made by Benjamin Franklin in 1891 when he poured oil into a pond and found the oil to spread and make a thin layer of oil on the water. The same experiment was repeated by Lord Rayleigh, who used it to determine, for the first time, the size of a molecule. Lord Rayleigh assumed that oil forms a monolayer on the water surface. As he knew the volume of the oil poured and the area of the water surface, he knew the size of each surfactant molecule of the oil. Both experiments used the logic that oil does not mix with water. 

Interestingly, nature seems to use a combination of hydrophobic and hydrophilic interactions to perform many functions, such as enzyme kinetics, micelle formation, transport of materials across biological cells, and the formation of the double-helix structure of DNA, to name a few. Many chemically important molecules, such as DMSO, phenol, ethanol, and dioxane, contain both hydrophobic and hydrophilic groups and this combination is responsible for the unique properties of these solvents. It is thus fitting to study these two effects together. 

The observed hydrophobic effect is to be understood at two levels, as follows. First, we need to understand the hydrophobic interaction between one isolated non-polar solute molecule and the surrounding water moleeules. Seeond, we need to understand the interaction between two non-polar solute molecules, as a function of distance mediated by intervening water moleeules. Both are important and need to be understood together. There are also independent attributes that need to be studied separately. 

The term hydrophobic hydration means the first of the above, that is, the interaction between one solute moleeule and the surrounding water molecules. Hydrophobic hydration can be quantified by measuring the free energy of transfer of a non-polar molecule from its neat liquid state to water. It is straightforward to 

The left-hand side of the above expression gives us the change of chemical potential on transferring one mole of the solute from its pure liquid state to water. 

Explaining heat capacities associated with hydrophobic hydration or hydrophobic interactions is essential to validating any model of hydrophobicity. One approach to calculating heat capacities takes advantage of the relationship between free energy and heat capacity  

The second derivative in this expression may be evaluated by taking analytical derivatives of a function fit to temperature-dependent free-energy data or, 

While these expressions are simple, determination of heat capacities is so computationally intensive that very few such calculations have been reported to date. 

The origin of hydrophobicity, in even the most complicated biological systems, is due to the unique solvation properties of water. As a result, simulations of hydrophobic hydration are arguably among the most important computational investigations related to hydrophobicity. The systems studied to date have often been simple, such as noble gases in water, but in spite of this simplicity the observed behavior is surprisingly rich and complex. 

Several key issues have been addressed in these published simulations, but the one receiving most attention involves the structural origin of the entropy of hydrophobic hydration. The classic perspective on this issue, originally put forth by Frank and Evans as the iceberg hypothesis, involves an ordering of water molecules in the hydration shell of the nonpolar solute. 

---

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... 

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. 

In summary, a wealtli of experimental data as well as a number of sophisticated computer simulations univocally indicate that two important effects underlie the acceleration of Diels-Alder reactions in aqueous media hydrogen bonding and enforced hydrophobic interactionsIn terms of transition state theory hydrophobic hydration raises the initial state more tlian tlie transition state and hydrogen bonding interactions stabilise ftie transition state more than the initial state. The highly polarisable activated complex plays a key role in both of these effects. 

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. 

If one would ask a chemist not burdened with any knowledge about the peculiar thermodynamics that characterise hydrophobic hydration, what would happen upon transfer of a nonpolar molecule from the gas phase to water, he or she would probably predict that this process is entropy driven and enthalpically highly unfavourable. This opinion, he or she wo ild support with the suggestion that in order to create room for the nonpolar solute in the aqueous solution, hydrogen bonds between water molecules would have to be sacrificed. 

Finally, also size and shape of the nonpolar solute seem to influence the formation of hydrophobic hydration shells. Particularly the curvature of the nonpolar surface has been suggested to be... 

The observation that in the activated complex the reaction centre has lost its hydrophobic character, can have important consequences. The retro Diels-Alder reaction, for instance, will also benefit from the breakdown of the hydrophobic hydration shell during the activation process. The initial state of this reaction has a nonpolar character. Due to the principle of microscopic reversibility, the activated complex of the retro Diels-Alder reaction is identical to that of the bimoleciilar Diels-Alder reaction which means this complex has a negligible nonpolar character near the reaction centre. O nsequently, also in the activation process of the retro Diels-Alder reaction a significant breakdown of hydrophobic hydration takes placed Note that for this process the volume of activation is small, which implies that the number of water molecules involved in hydration of the reacting system does not change significantly in the activation process. 

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. 

It is established, that the natural and synthetic polymers influence on spectrophotometrical, protolytical and complex-formating properties of azodyes in different degree. The result of interaction between anions of organic dyes and polymers is formation of specifical hydrophobic-hydrated adducts. Express spectrophotometrical methods of polymer content determination in water solutions with the help of polymer adducts have been elaborated. 

Furthermore it can be shown that besides the direct influence of hydrophilic and hydrophobic hydration on the conformation, the interaction of charged groups with ions is also strongly influenced by the hydration of the groups involved. Such studies were made largely by using relatively simple poly-a-aminoacids with ionogenic side chains as model substances. 

Water is a special liquid that forms unique bonds involving protons between the oxygen atoms of neighboring molecules, the so-called hydrogen bond. The solvation forces are then due not simply to molecular size effects, but also and most importantly to the directional nature of the bond. They can be attractive or hydrophobic (hydration forces between two hydrophobic surfaces) and repulsive or hydrophilic (between two hydrophilic surfaces). These forces arise from the disruption or modification of the hydrogen-bonding network of water by the surfaces. These forces are also found to decay exponentially with distance [6]. 

Thus, for a hydrophobic solute is determined by quantifying the probability po of successfully inserting a hard-core solute of the same size and shape into equilibrium configurations of water, as illustrated in Figure 4. A virtue of this approach is that the thermodynamics of hydrophobic hydration characterized by is determined from the properties of pure water alone. The solute enters only through its molecular size and shape (see Fig. 4). 

Fig. 4. A schematic two-dimensional illustration of the idea for an information theory model of hydrophobic hydration. Direct insertion of a solute of substantial size (the larger circle) will be impractical. For smaller solutes (the smaller circles) the situation is tractable a successful insertion is found, for example, in the upper panel on the right. For either the small or the large solute, statistical information can be collected that leads to reasonable but approximate models of the hydration free energy, Eq. (7). An important issue is that the solvent configurations (here, the point sets) are supplied by simulation or X-ray or neutron scattering experiments. Therefore, solvent structural assumptions can be avoided to some degree. The point set for the upper panel is obtained by pseudo-random-number generation so the correct inference would be of a Poisson distribution of points and = kTpv where v is the van der Waals volume of the solute. Quasi-random series were used for the bottom panel so those inferences should be different. See Pratt et al. (1999).

The simplicity and accuracy of such models for the hydration of small molecule solutes has been surprising, as well as extensively scrutinized (Pratt, 2002). In the context of biophysical applications, these models can be viewed as providing a basis for considering specific physical mechanisms that contribute to hydrophobicity in more complex systems. For example, a natural explanation of entropy convergence in the temperature dependence of hydrophobic hydration and the heat denaturation of proteins emerges from this model (Garde et al., 1996), as well as a mechanistic description of the pressure dependence of hydrophobic... 

Okazaki, S. Nakanishi, K. Touhara, H., Monte Carlo studies on the hydrophobic hydration in dilute aqueous solutions on nonpolar molecules, J. Theor. Biol. 1979, 71, 2421-2429... 

Straatsma, T. R Berendsen, H. J. C. Postma, J. P. M., Free energy of hydrophobic hydration. A molecular dynamics study of noble gases in water, J. Chem. Phys. 1986, 85, 6720-6727... 

Smith, P. E., Computer simulation of cosolvent effects on hydrophobic hydration, J. Phys. Chem. B 1999,103, 525-534... 

Grossman, J. C. Schwegler, E. Galli, G., Quantum and classical molecular dynamics simulations of hydrophobic hydration structure around small solutes, J. Phys. Chem. B 2004,108, 15865-15872... 

---