Hydrophobic substituent

GeneraHy, hydrophobic substituents on the pyridine ring reduce water solubHity, polar ones capable of hydrogen bonding as acceptor or donor, iacrease it. 

From the data reported in (63PMH(l)177) it was concluded that hydrophobic substituents reduce the solubility of pyrazole in water (at 20 °C pyrazole, 1 part in 2.5 3,5-dimethyl-pyrazole, 1 part in 52). Another determination gives the following values for the solubilities of pyrazole at 25 °C in water, benzene and cyclohexane (expressed as g/100 g of solvent) 130, 18 and 3 (66AHC(6)347). Indazole is soluble in hot water and most organic solvents, but less so in cold water. 

The binding site is located at the tip of the subunit within the jelly roll structure (Figure 5.23). The sialic acid moiety of the hemagglutinin inhibitors binds in the center of a broad pocket on the surface of the barrel (Figure 5.24). In addition to this groove there is a hydrophobic channel that can accomodate large hydrophobic substituents at the C2 position of sialic acid (Figures 5.22 and 5.24). 

Figure 5.24 Space-filling model (green) of the sialic acid binding domain of hemagglutinin with a bound inhibitor (red) Illustrating the different binding grooves. The sialic acid moiety of the Inhibitor binds in the central groove. A large hydrophobic substituent, Ri, at the Cz position of sialic acid binds in a hydrophobic channel that runs from the central groove to the bottom of the domain. (Adapted from S.J. Watowich et al.. Structure 2 719-731, 1994.)...

Hansch-Leo hydrophobic substituent parameter Hammett sigma constants Modtried Swam Lupton constants... 

TTx represents the hydrophobicity of the substituents at position 10. Its positive coefficient (+0.75) suggests that the presence of highly hydrophobic substituents at position 10 increases the activity. The outlier (X = OH) is much more active than expected by 11 times the standard deviation. This may be due to the formation of a phenoxyl radical that interacts with DNA [48]. The other derivative (X = NH2) is also considered as an outher due to being much more active than expected by 14 times the standard deviation. This anomalous behavior may be attributed to its nature as an aniline. This could result in hydrogen abstraction, or involve microsomal N-oxidation [48,49]. 

R. Franke, S. Dove and R. Kuehne, Hydrophobicity and hydrophobic interactions, 1. On the physical nature of aromatic hydrophobic substituent constants. Eur. J. Med. Chem., 14 (1979) 363-374. 

Suitable disperse dyes for polyester require good sublimation fastness and generally contain additional or more hydrophobic substituents compared with acetate dyes. Thus, for example, Cl Disperse Red 60 (6.42) is important for the dyeing of polyester fabrics but has only moderate sublimation fastness. It is, however, the most important red dye for transfer... 

Solubility of the polysilane(II) was completely unlike conventional polysilanes with hydrophobic substituents. The polysilane(II) was soluble in acetone, alcohols and acetonitrile, and insoluble in toluene and hexane. Table 1 also shows the ratio(quantum yield of... 

The mechanistic interpretation involves the interaction of a hydrophobic substituent in the ligand bound to Cu(II) with an aromatic ring in the dienophile exerting a favorable effect on the dienophile-Cu(II) interaction. Both the catalytic efficiency of Lewis-acid catalysis and the stereochemistry of the cycloaddition benefit from this water- induced interaction (Figure 7.9). 

A new class of water-soluble materials [10,11], was developed as a result of such design parameters that will be referred to as double substituted cationic cellulose ethers (DCEs). These materials contain both a cationic substituent and a hydrophobic substituent, attached to a cellulose ether backbone. The use of a double-substituted hydrophobe modified cationic polysaccharide is fundamentally different from current commercial vaginal formulations, which rely exclusively on nonionic or anionic vehicles. 

Water solubility is determined by polymer structure (linear, branched, etc.), concentration and placement of charged species [ionomeric (cationic or anionic) or amphoteric (cationic and anioiuc)], hydrophihc/hydrophobic substituents, and hydrogen bonding, to name the more commonly encountered factors. In general, polymer water solubility requires polar functional... 

In aromatic series, when hydrogen atoms are replaced by fluorine atoms or by fluoroalkyl groups, an enhancement of the log P occurs (Table 3) [13]. The CF3, CF3O and CF3S groups are the most hydrophobic substituents known. They are widely used in crop science [41]. 

Haloallyl amines also have been studied as inhibitors of SSAO. The 2-aryl-3-haloallylamines proved to be potent irreversible inhibitors of rat aorta SSAO. Hydrophobic substituents on the aryl ring enhanced activity, while phenolic groups decreased activity [78]. The MAO B selective ( )-2-(3, 4 -dimethoxyphe-nyl)-3-fluoroallylamine (22d) inhibited rat SSAO in vascular and brown adipose tissues and was selective relative to inhibition of MAO A [79]. MDL 72974A (25) is a potent irreversible inhibitor of both MAO B and SSAO with a 190-fold lower affinity for MAO A [80]. 

Amino acids with fluoroalkyl side chains have often been prepared for use in structural studies on the autoassembly of proteins. The presence of a highly hydrophobic substituent on the side chain, such as a fluoroalkyl group, of an amino acid of a polypeptide, may a priori deeply influence the interhelical interactions. 

It is well-established that in the case of short lipid chains such as famesyl and myristoyl, the binding affinity of monolipidated proteins to membranes, is not sufficient to promote stable association. 25 26 36 8°1 Among the various intracellular proteins that are covalently modified by an acyl group from a fatty acid or a prenyl group, several carry more than one such hydrophobic substituent per protein molecule. The addition of a second hydrophobic chain to a... 

The crystal structure of ERK2 complexed with 67 was determined. It is believed that the molecule can recognize small hydrophobic substituents but not hydrophilic ones <2006BML55>.The structure of the complex is shown in formula 68. 

---