The methyl group and other nonpolar substituents

The initial application of the anchor principle described by Page related to data on the selectivity of amino acid-tRNA synthetases, from which he estimated intrinsic 

CHAPTER 21 The Role of Functional Groups in Drug-Receptor Interactions 

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In water, the polarity of the substituents determined the enantiopreference [Ij. Placing a nonpolar substituent in water is unfavorable. Reactions in water involving methyl and nonpolar aryl substituents will favor the nonpolar aryl substituent in the S/ pocket, opposite to that predicted based on size alone. Thus, subtilisin favors the (S)-enantiomer of l-(p-tolyl)ethanol in organic solvents (p-tolyl is larger than methyl), but the (R)-enantiomer in water (methyl is more polar than p-tolyl). On the other hand, with a polar aryl group such as (4-pyridine N-oxide), the (S)-enantiomer is favored both in water, where solvation of the pyridine N-oxide is favorable, and in organic solvent, where placing the pyridine N-oxide in the solvent avoids steric interactions in the S/ pocket. 

The liquid stationary phases used with capillary columns are similar to those used in packed columns. The most common stationary phases are polysiloxanes (silicones) that contain various substituents that modify the polarity of the phase. Polydimethyl siloxane (methyl silicone) is nonpolar. Replacing methyl groups with increasing numbers of phenyl substituents increases the polarity of the silicone. For example, J W DB-1, or a similar stationary phase sold by other companies, has the same properties as methyl silicone (SE-30 or DC-200) and is used with nonpolar... 

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