Hydrophobic effect, in the

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. 

Hansch, C. et al. (1986) A quantitative structure-activity relationship and molecular graphics analysis of hydrophobic effects in the interactions of inhibitors with alcohol dehydrogenase. J. Med. Chem., 29 (5), 615-620. 

Occasionally, however, the ions are deviants and associate preferentially with the nonelectrolyte solute, shunning the water (hydrophobic effects). In the rare instances where these deviants appear, there is a rapid departure of the nonelectrolyte from the parent lattice and the solubility of the former is enhanced rather than deaeased. The phenomenon is called salting in. 

The importance of the hydrophobic effect in the self-association of amphiphilic solutes means that any factor which disrupts three-dimensional solvent structure also disrupts normal micelles. For example, addition of relatively large amounts of such organic solvents as ethanol or acetone to water makes the micelles smaller, and eventually they disappear and the surfactant behaves as a simple solute. On the other hand apolar solutes can enter the micelle and stabilize it and so lower the cmc, and added electrolytes also lower the cmc [15]. 

Table 11.6. Hydrophobic Effects in the Diels-Alder Reaction of Cyclopentadiene and Methyl Vinyl Ketone in Aqueous Media...

Macalady, D. L. and N. L. Wolfe. 1992. Hydrophobic effects in the reduction of anthropogenic organic chemicals by natural organic matter, paper presented at... 

Scott et al. [44] have designed two types of flow cells (1) parallel flow channel arrangement and (2) a spot design of a flow bed. These two types of flow cells are designed to test with electrodes made of Teflon and carbon with ruthenium and platinum as catalysts on electrodes. Teflon was used for the purpose of providing hydrophobic effect in the electrode. By making the electrode hydrophobic, the flow of methanol is improved. 

Figure 12. Proposed hydrophobic effect in the coupling of peptides activated by diisothio-cyanate or hydroxybenzotriazole ester.

One of the more challenging locations, therefore, for consideration of the comprehensive hydrophobic effect in the panoply of biological energy conversions is the electron transport chain embedded within the inner mitochondrial membrane. Essential parts of these protein-based machines insert into and function in very hydrophobic lipid bilayers. Here the ingress and egress of protons for develop-... 

Koga K (2004) Hydrophobic effect in the pressure-temperature plane. J ChemPhys 121(15) 7304... 

Any interpretation based solely on the thermodynamic parameters can only represent one of the several alternatives and hence is disputable. Accordingly, here examination of the thermodynamic parameters will be confined to their compatibility with the foregoing contention that the hydrophobic effect in the hydrophilic gels stems from the intrinsic hydrophobicity of the monomeric residues of the constituent polymers and is cooperatively enhanced in the concentrated gels. 

Although the influence of water on the PEG conformational stmcture is widely accepted, it is less clear to what extent the water stmcture is modified by the presence of PEG. The density depression illustrated in Fig. 3 would suggest that a modified water stmcture potentially exists several nanometers beyond the nominal bmsh length. This is comparable to recent neutron-scattering observations (Schwendel et al., 2002) on ethylene-oxide self-assembled monolayers. The general idea is that this effect be linked to the hydrophobic effect in the vicinity of the amphiphilic PEG layer. 

Of equal importance, the use of RPC and HIC techniques provides a very powerful avenue to explore the molecular basis of the hydrophobic effect per se that these biomacromolecules exhibit. Since the time of the initial attempts, commencing over 50 years ago, to exploit the hydrophobic effect as part of robust separation procedures, RPC and HIC have thus come to assume a dominant position for the isolation and analysis of many proteins and now represent the techniques par excellence for the purification and analysis of polypeptides prepared by solid- or solution-phase synthetic procedures. Equally, these techniques provide an opportunity to explore the role of the hydrophobic effect in the stabilization and folding of proteins and polypeptides, the molecular forces that are involved in these processes, the thermodynamics of their interaction with relatively well-defined nonpolar surfaces, and the biophysics of peptide or protein nonpolar interactions in general. 

Three aromatic carboxylic acids, benzoic add (Arl), phenylacetic acid (Ar2), and 4-methoxyphenylacetic acid were selected as guests to probe the depth of penetration in host 1, and, as well, two aliphatic carboxylic acid guests, cydo-hexylacetic acid (All), and l-adamantanecarboxyHc acid (A12), were also used to further study the importance of hydrophobic effects in the molecular recognition process with host 1. According to their plQ values, all of these carboxylic adds existed in the anionic form at pH 7 [4a, b]. The CICS values of the three guests, Arl, Ar2, and 4-methoxyphenylacetic acid, by host 1 are presented in a similar fashion as described above for the substituted aromatic carboxylic acids (Fig. 10.6). 

In order to further determine the relative importance of K-n and hydrophobic effects in the molecular recognition process, a competition study between aromatic guest Ar2, and its closely related aliphatic guest. All, was undertaken. During this study, the concentrations of both competitors were kept constant, while that of 1 increased from 0 to 1 equivalent. Two control experiments, which held constant the concentration of one guest while varying the concentration of 1, were also performed. The results show similar plots for the control and the competitive experiments for Ar2 and/or All, which suggest that the K-Kand hydrophobic effects may he of similar importance in aqueous solution. 

Deep-cavity cavitands that dimerize into capsules via the hydrophobic effect, in the presence of a suitable guest molecule and in aqueous solution, have been developed by the Gibb group [110,111], Such complexes possess hydrophilic outer coats, hydrophobic rims that favor self-assembly, and deep hydrophobic pockets (up to 1 nm wide to 2 nm long). They have been used to drive the formation of high-definition assemblies with a number of guest molecules, including steroid and hydrocarbon molecules [112]. Reactions within the capsule (eg, selective oxidation of substrates) and potential applications in hydrocarbon gas separation [111] have been also achieved or demonstrated [113]. 

The various solvent scales can be used to determine which property of a solvent has the greatest influence on reactivity or any other physical / chemical phenomena. An example of their use in a common reaction is given in the following Connections highlight, and we will also showcase their use in a Connections highlight concerned with the hydrophobic effect in the next chapter. 

C. Hansch, T. Klein, J. McClarin, R. Langridge, and N. W. Cornell, ]. Med. Chem., 29, 615 (1986). A Quantitative Structure-Activity Relationship and Molecular Graphics Analysis of Hydrophobic Effects in the Interactions of Inhibitors of Alcohol Dehydrogenase. 

E. T., Lockett, M.R., H roux, A., Sherman, W., and Whitesides, G.M. (2011) Mechanism of the hydrophobic effect in the biomolecular recognition of arylsulfonamides by carbonic anhydrase. Proceedings of the National Academy of Sciences of the United States of America, 108,17889-17894. 

In further studies of the remarkable water effects on Diels-Alder reactions, we examined the exo-endo selectivity of the processes. We saw that butenone added with a 95.7% preference for endo addition in water, but only an 80% endo preference in cyclopentadiene as solvent. Thus the endo addition is favored not only by secondary orbital overlap , it is even more strikingly favored by the hydrophobic effect. In the transition state for the addition reaction, the endo geometry diminishes the amount of water/hydrocarbon interface more than does the exo geometry. The high energy of a hydrocarbon/water interface is the cause of hydrophobicity, the tendency of nonpolar materials and segments to cluster in water so as to diminish the interface with water. 

As additional evidence for hydrophobic effects in the Diels-Alder reaction, there was a great inaease in the preference for an endo geometry in the Diels-Alder reactions in water [11], as expected if the transition state becomes more compact to minimize exposure of hydrocarbon segments to the water solvent. This endo preference was also inaeased to some extent when LiCl was added, and decreased when GnCl was the additive. Other evidence has also been cited for a hydrophobic effect on Diels-Alder reactions [12], and the water effect on geometric selectivity has been used in synthetic applications [13]. 

We also detected a hydrophobic effect in the benzoin condensation [14]. In this case, in contrast to the Diels-Alder reaction, it is not formally required that the two hydrophobic phenyl groups come together in the transition state, but our studies indicated that they do. Again there was a large increase in rate when water was the solvent, but in an ionic reaction of this sort such solvent effects could well be related only to the effect on the ions of the polar character of the medium. However, we saw that the reaction rate was increased with LiCl, but decreased when LiC104 was added. In this system LiC104 is a salting... 

The importance of hydrophobic effects in the catalysis by synthetic macromolecules is also discussed by Kunitake and Shinkai [34, 35]. We will once again mention the importance of hydrophobic effects in the next Section 2.2 regarding the influence of the overall chain conformation on catalysis. 

Table 2.1 Change in standard molar Gibbs energy, enthalpy and entropy (all in kj mot ) for the transfer of hydrocarbons from pure liquids into water at 25 °C (Prausnitz, Lichtenthaler and de Azevedo, 1999 Gill and Wadso, 1976). Notice the large negative entropy changes due to the hydrophobic effect, in the case of n-butane, the entropy decrease amounts to 85% of the Gibbs energy of solubilization, while for other hydrocarbons the entropic contribution is even larger...

An important part of the puzzle is that the most characteristic hydrophobic effects, the unfavorable entropies and large heat capacity changes, seem to be largely independent of the molecular details of solute-solvent interactions within broad families. This is an awkward point for computational chemistry that naturally invests great effort in accurately describing intermolecular interactions before entropies are considered. This point emphasizes the utility of studying model problems, primitive hydrophobic effects in the first place and modelistic expressions of those effects. It is helpful to identify the minimum that must be included in the model in order to get the interesting behavior and only after that to include all features actually present in specific cases. 

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