Enthalpic interaction, hydrophobic groups

MR still is the chameleon [91] amongst the physicochemical parameters, despite its broad application in QSAR studies. It has been correlated with lipophilicity, molar volume, and steric bulk. Of course, due to its MW/q component it is indeed related to volume and size of a substituent. But two recent statements that MR is only based on these properties [91, 291] cannot be accepted. The refractive index-related correction term in MR accounts for the polarizability and thus for the size and the polarity of a certain group [158, 173, 286]. The larger the polar part of a molecule is, the larger its MR value will be. Even hydrophobic substituents have a weak enthalpic interaction due to dispersion forces, in addition to their entropic... 

Earlier literature has used the term hydrophobic bond, but it is clear from the above discussion that no special hydrophobic force exists. Nonpolar groups self-associate in water because their dispersal throughout the solvent would be entropically unfavorable. Once they come together and water is largely excluded, enthalpically favorable interactions are possible, but these are just (for nonaromatic hydrocarbons) the normal weak London forces between any polarizable groups. There is no bonding that is specifically hydrophobic. The correct term is hydrophobic effect. 

The interest in hydrophobic interactions was stimulated by their unusual thermodynamic properties it was argued and believed that they are governed, not by enthalpic, but by entropic features, characterized by the undesirable entropy decrease of water in the vicinity of nonpolar groups (Frank and Evans, 1945 Kauzmann, 1959 Franks, 1975 Tanford, 1980). This conclusion was reached largely from consideration of solvation effects at room temperature. 

Although there is overwhelming experimental evidence that the hydrophobic interaction is entropy-driven , this classical view is still a matter of debate [79a, 167, 227, 229-231, 343-347]. For example, it has been claimed that the major eontribution to the hydrophobic interaction between the methylene groups of n-alkanes is an enthalpic and not an entropic effect [230]. In other words, the poor solubility of non-... 

Van der Waals attraction. Of course, this also occurs between groups and water molecules, but the net effect is likely to be stabilizing. Van der Waals attraction cannot be fully separated from hydrophobic interaction. Moreover, some dipole dipole interaction may be involved. It concerns an enthalpic contribution. 

The most direct way to factorize interaction energies of unpolar solutes with water is based on thermodynamic measurements of the solute transfer from gas or from a hydrocarbon medium to water. Such measurements with the transfer of linear alkanes from hexane to water yield, as increments for a CH2 group, AAG = 3.85, AAH = 2.75 kJ/inol. respectively the enthalpic contribution dominates for the CH2 group in contrast to the CH3 group, for which one observes AAC = 8.4, AAH =—5.4 and TAAS = -13.8 kJ/mol, respectively. Another often-used way to evaluate hydrophobic contributions of solutes is based on measurements of distribution coefficients between water and a lipophihc solvent, for which one traditionally... 

Hydrophobic effects arise from the exclusion of non-polar groups or molecules from aqueous solution. This situation is more energetically favourable because water molecules interact with themselves or with other polar groups or molecules preferentially. This phenomenon can be observed between dichloromethane and water which are immiscible. The organic solvent is forced away as the intersolvent interactions between the water molecules themselves are more favourable than the hole created by the dichloromethane. Hydrophobic interactions play an important role in some supramolecular chemistry, for example, the binding of organic molecules by cyclophanes and cyclodextrins in water (see Chapter 2, Sections 2.7.1 and 2.7.5, respectively). Hydrophobic effects can be split into two energetic components, namely an enthalpic hydrophobic effect and an entropic hydrophobic effect. 

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