Polar hydrophobicity

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... 

In amphiphilic molecules, the polar, hydrophilic part is known as the head and the non-polar, hydrophobic part the tail of the molecule. Hydrophilic molecules, or parts of molecules, try to interact with polar water molecules, while hydrophobic moieties try to avoid them. 

Thus, a molecule can be characterized in terms of its potential hydrogen bonding, polar, hydrophobic and ionic interactions in 3D space. The size and the spatial distribution of these molecular interaction contours is translated into a quantitative scheme, the VolSurf descriptors, without the need to align the molecules in 3D space [8, 9] (Fig. 17.1). 

Calculated molecular properties from 3D molecular fields of interaction energies are a novel approach to correlate 3D molecular structures with pharmacodynamic, pharmacokinetic and physico-chemical properties. The novel VolSurf descriptors quantitatively characterize size, shape, polarity, hydrophobicity and the balance between them. 

Valsaraj, K.T. (1988) On the physico-chemical aspects of partitioning of non-polar hydrophobic organics at the air-water interface. Chemosphere 17, 875-887. 

Each micelle has a polar periphery and an oil-like core. When molecules of monomer collide with the solid surface of, say, a dirty plate, the non-polar ( hydrophobic ) end adsorbs to the non-polar grease. Conversely, the polar ( hydrophilic ) end readily solvates with water. Soon, each particle of oil or grease is surrounded with a protective coating of surfactant monomer, according to Figure 10.13. 

Solvent-laden air (SLA), 70 95 Solvent mixtures flash point of, 23 116 viscosity of, 23 99 Solvent Orange 107, 60, 63, 7 colorant for plastics, 7 374t Solvent polarity/hydrophobicity probing, polymethine dyes in, 20 517 Solvent polarity/temperature, in initiating systems, 74 268 Solvent power, 23 89 Solvent preparation, for Grignard reactions, 72 823 Solvent properties... 

The adsorption of fatty acids on the non-polar hydrophobic surface (Hg) is dominated by their hydrophobic properties. The extent of adsorption increases with increasing chain length. The following relationship of the free energy of adsorption, AGacis. and the number of C atoms, nc, of the fatty acids can be established ... 

Robertson and Yeager used Py and Ru(bpy)3 probes for the purpose of locating the locations of Cs+ and 1 ions in the nanophase-separated morphology. It is known that these probes take residence in the intermediate polarity hydrophobic—hydrophilic interfacial regions. The studies concluded that Cs+ ions were located in the aqueous regions, but I ions were in the interfacial regions. 

This surface area classification notion naturally can be extended to other properties. For example, a collection of pharmacophore-type VS A descriptors can be calculated by summing the V, contribution of each in a molecule of a specific type. For example, if the atom classes are donor, acceptor, polar, hydrophobe, anion, and cation, then six VSA descriptors can be calculated such that for any given molecule the sum of the six descriptors is the VSA of the entire molecule and each descriptor is the VSA of all atoms one of the six classes. Such descriptors can be used for rough pharmacophore-based similarity measures. 

It was early discovered that enzyme activity in organic solvents depends very much on the nature of the solvent. It was realized that the polarity or hydrophobicity of the solvent had a large influence, with non-polar hydrophobic solvents often providing higher reaction rates than more polar, hydrophilic solvents. When the kinetics of enzymatic reactions is studied, it is often found that Km values in organic solvents are much higher than those in water for the corresponding... 

Molecular complexity is defined by the number of pharma-cophoric triangles, where compounds with more triangles are more deemed complex. This is done by first identifying the phar-macophoric elements contained within each molecule, and then a triangle is identified by three features and the shortest bond path between each pair of features (Fig. 11.3). There are eight pharmacophoric features used H-bond donor, H-bond acceptor, polar, hydrophobic, pi donor, pi acceptor, pi polar, and pi hydrophobic. The Molecular Operating Environment ( )... 

The introduction of asymmetry, followed by resolution, can be used to gain selectivity from a promiscuous molecule. Closely related receptors may differ only in the shape or size of their non-polar (hydrophobic) areas. Because of this, it makes sense to try to exploit differences in hydrophobic binding. Ariens (1986) exemplifies this by referring to derivatives of diphenhydramine (44, Ri = R2 = H). Table 3 is compiled from the data of Rekker et al. (1971) and shows how a 10-fold selectivity of diphenhydramine for the histamine receptor has been translated into an increase in potency and more than 100-fold selectivity towards the histamine receptor in the (-F)-methyl derivative, and to an increase in potency and more than 100-fold increase in selectivity towards the acetylcholine receptor in the (-)-r-butyl derivative. The data provide a good example of Pfeiffer s Rule (Pfeiffer, 1956) that enantiomeric potency ratios increase with potency. Many examples of this rule have been reviewed by Lehmann (1986). 

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