Steric effects solubilization

Polar aprotic solvents solubilize cations well using their unshared electron pairs, but do not interact as strongly with anions because they cannot hydrogen bond with them and because the positive regions of the solvent are shielded by steric effects from the anion. This differential solvation leaves anions more free to act as nucleophiles because they are less encumbered by the cation and solvent, thus enhancing the rate of S]vi2 reaction. Sodium ions of sodium iodide, for example, can be solvated by DMSO as shown here, leaving the iodide anion more free to act as a nucleophile. 

The interactions between a lipophilic or hydrophilic drug and micellar phases are caused by weak physicochemical forces such as hydrophobic (unspecific) and electrostatic effects (specific dipole-dipole, dipole-mdacoA dipole) and steric effects, whereas the hydrophobic binding to the micellar systems is dominant. An indirect indication for the presence of interactions between the micellar phase and drugs is given by molecular and dynamic parameters of the drug and the micelles (ionic mobiUty, diffusion coefficient, hydrodynamic radius, apparent molecular mass), which are altered by the solubilization of lipophilic substances in a characteristic manner. 

The hydroxypropyl substituent, being larger yet, appears to require a lower DS to improve binding without sterically obscuring the cavity entrance. Muller and Brauns have studied the effect of the DS on complex-ing ability (Table 3) and have observed that lower degrees of hydroxypropyl substitution (2 to 5) are more conducive to complexation. As the DS increases, the solubilization of six different drugs decreases but when the DS is from 4 to 8 the solubilization is fairly consistent. 

These steric and ionization effects seriously limit the usefulness of substituted celluloses in site-of-action studies. Further uncertainties are introduced by the fact that the substitution reactions used to solubilize cellulose distribute the substituents randomly on the polysaccharide. As a consequence the reaction products become a very large family of variously substituted fragments rather than a single product or a few identifiable oligosaccharides. 

This concept for the cycle- and nnsatnration-free control of molecular shapes is likely to find multiple applications. For example, fonr stereoisomeric vicinal diflnorinated analogues of the natural cyclic heptapeptide unguisin A were found to adopt dramatically different secondary strnctnres as a function of stereoelectronic and steric interactions. The preferred conformations of PEG (polyethylene glycol) groups (popular solubilizing substitnents for many biomedical applications) are likely to be affected by the gauche effect as well. 

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