Silicon Derivatives of Known Active Compounds

Substitution of a silicon atom for another atom in a biologically active compound should provide clues to structure-activity relationships. The structural and electronic effects of silicon substitution are, to a reasonable extent, predictable. For example, substitution of a silicon atom for a carbon atom places a slightly larger, more electropositive, atom in the 

Classes of Biologically Active Organic Compounds and Their Organosilicon Derivatives 

Selected Direct Silicon Analogs of Known Drugs 

Benzhydryl ether Ph2Z(CH3)OCH2CH2N(C2H5)2 NH3C1 I C,Si 34 

Silyl groups, which tend to increase lipid solubility, may be used as a substitute for alkyl branching in space-filling groups. Direct substitution of a silicon atom for a carbon atom increases the hydrophobic character of a compound, even without the addition of more alkyl groups. Table III lists the relative partition coefficients of two pairs of carbon and silicon compounds in octanol-water, a system used to approximate the lipid-water system within an organism. As may be seen from the table, the silicon compounds are two to five times more soluble in the octanol phase this effect falls off with an increasing number of carbon atoms in the parent structure (36). 

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