Hydrophobic effects molecular interactions

An experimental complication is the difficulty in effecting molecular interaction between the components. The usual technique for preparing lipid-protein phases in an aqueous environment is to use components of opposite charge. This in turn means that the lipid should be added to the protein in order to obtain a homogeneous complex since a complex separates when a certain critical hydrophobicity is reached. If the precipitate is prepared in the opposite way, the composition of the complex can vary since initially the protein molecule can take up as many lipid molecules as its net charge, and this number can decrease successively with reduction in available lipid molecules. It is thus not possible to prepare lipid— protein—water mixtures, as in the case of other ternary systems, and to wait for equilibrium. Systems were prepared that consisted of lecithin-cardiolipin (L/CL) mixtures with (a) a hydrophobic protein, insulin, and with (b) a protein with high water solubility, bovine serum albumin (BSA). 

Absorption, metaboHsm, and biological activities of organic compounds are influenced by molecular interactions with asymmetric biomolecules. These interactions, which involve hydrophobic, electrostatic, inductive, dipole—dipole, hydrogen bonding, van der Waals forces, steric hindrance, and inclusion complex formation give rise to enantioselective differentiation (1,2). Within a series of similar stmctures, substantial differences in biological effects, molecular mechanism of action, distribution, or metaboHc events may be observed. Eor example, (R)-carvone [6485-40-1] (1) has the odor of spearrnint whereas (5)-carvone [2244-16-8] (2) has the odor of caraway (3,4). 

Hydrophobicity ( water-hate ) can dominate the behavior of nonpolar solutes in water. The key observations are (1) that very nonpolar solutes (such as saturated hydrocarbons) are nearly insoluble in water and (2) that nonpolar solutes in water tend to form molecular aggregates. Some authors refer to item 1 as the hydrophobic effect and to item 2 as the hydrophobic interaction. Two extreme points of view have been taken to account for these observations. 

The stereoelectronic features produce actions at a distance by the agency of the recognition forces they create. These forces are the hydrophobic effect, and the capacity to enter ionic bonds, van der Waals interactions and H-bonding interactions. The most convenient and informative assessment of such recognition forces is afforded by computahon in the form of MIFs, e.g. lipophilicity fields, hydrophobicity fields, molecular electrostatic potentials (MEPs) and H-bonding fields (see Chapter 6) [7-10]. 

The concept of micelles consists of aggregation of amphiphilic molecules that contain polar and non-polar moieties, which associate in a manner that minimizes hydrophobic and lipophilic interactions. However, a cascade molecule consisting of an internal lipophilic framework and a external hydrophilic surface would effectively be a unimolecular micelle [59] capable of hosting molecular guest(s). 

Here we present and discuss an example calculation to make some of the concepts discussed above more definite. We treat a model for methane (CH4) solute at infinite dilution in liquid under conventional conditions. This model would be of interest to conceptual issues of hydrophobic effects, and general hydration effects in molecular biosciences [1,9], but the specific calculation here serves only as an illustration of these methods. An important element of this method is that nothing depends restric-tively on the representation of the mechanical potential energy function. In contrast, the problem of methane dissolved in liquid water would typically be treated from the perspective of the van der Waals model of liquids, adopting a reference system characterized by the pairwise-additive repulsive forces between the methane and water molecules, and then correcting for methane-water molecule attractive interactions. In the present circumstance this should be satisfactory in fact. Nevertheless, the question frequently arises whether the attractive interactions substantially affect the statistical problems [60-62], and the present methods avoid such a limitation. 

Second, P-gp differs from other transporters in that it recognizes its substrates when dissolved in the lipid membrane [52], and not when dissolved in aqueous solution. The site of recognition and binding has been shown to be located in the membrane leaflet facing the cytosol [53, 54], This implies that the membrane concentration of the substrate, Csm, determines activation [57]. Since the nature of a molecular interaction is strongly influenced by the solvent, the lipid membrane must be taken into account as the solvent for the SAR analysis of P-gp. Under certain conditions, the effect of additional solvents or excipients (used to apply hydrophobic substrates or inhibitors) on the lipid membrane and/or on the transporter must also be considered. Lipophilicity of substrates has long been known to play an important role in P-gp-substrate interactions nevertheless, the correlation of the octanol/water partition coefficients with the concentration of half-maximum... 

It is important to propose molecular and theoretical models to describe the forces, energy, structure and dynamics of water near mineral surfaces. Our understanding of experimental results concerning hydration forces, the hydrophobic effect, swelling, reaction kinetics and adsorption mechanisms in aqueous colloidal systems is rapidly advancing as a result of recent Monte Carlo (MC) and molecular dynamics (MO) models for water properties near model surfaces. This paper reviews the basic MC and MD simulation techniques, compares and contrasts the merits and limitations of various models for water-water interactions and surface-water interactions, and proposes an interaction potential model which would be useful in simulating water near hydrophilic surfaces. In addition, results from selected MC and MD simulations of water near hydrophobic surfaces are discussed in relation to experimental results, to theories of the double layer, and to structural forces in interfacial systems. 

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. 

To a greater or lesser degree the spectra of all C-6 ionic salts, whether they are substituted with a covalent group at C-2 or not, are comprised of a mixture of the spectra of C-6 ionic and C-6 covalent forms. Differences among the spectra of the compounds result from secondary effects on the structure of the bare anions such as hydrogen bonding and dimerization due to hydrophobic dye/dye molecular interactions. This is particularly obvious when the fluorescence spectra of the ammonium salts at room temperature of the C-2, C-6 bis trimethylammonium salt shows a triad of broad peaks centered at 583 nm. At reduced temperature the same compound shows three sharper peaks at 538, 583, and 605 nm. The shortest wavelength of these... 

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