SOLVENT SELECTION FOR WHOLE-CELL BIOTRANSFORMATIONS IN ORGANIC MEDIA

Although they were used historically as antimicrobial agents, there is a modem requirement to devise organic solvent systems for exploitatio n in the biotransformation by intact cells of substrates that are poor ly soluble in water. Water-immiscible solvents are normally less cytot oxic than are water-miscible ones. While a unitary mechanism is exclud ed, damage to the membrane remains the likeliest major mechanism of cy totoxicity, and may be conveniently assessed using an electronic bioma ss probe. Studies designed to account for the mechanisms of action of general anesthetics and of uncouplers parallel those designed to accou nt for the cytotoxicity of organic solvents. Although there are hundre ds of potential physical descriptors of solvent properties, many are b roadly similar to each other, such that the intrinsic dimensionality o f solvent space is relatively small (<10). This opens up the possibili ty of providing a rational biophysical basis for the optimization of t he solvents used for biotransformations. The widely used descriptor of solvent behavior, log P (the octanol:water partition coefficient), is a composite of more fundamental molecular descriptors; this explains why there are rarely good correlations between cytotoxicity and log P when a wide variety of solvents is studied. Although the intrinsic dim ensionality of solvent space is relatively small, pure solvents still populate it rather sparsely. Thus, mixtures of solvents can and do pro vide the opportunity of obtaining a solvent optimal for a biotransform ation of interest.