CARBON-FLUORINE BOND IN COMPOUNDS OF BIOLOGICAL INTEREST

The principles learned from studies of nuoroacetate and the application of these principles in the use of fluorouracil tend to emphasize the value of organic fluorine compounds in the design of selective inhibitors of enzymes. This important application may obscure other uses that organic fluorine compounds can have in various areas of biological science. The alterations in the properties of a molecule that can often be predicted from a fluorine substituent are valuable in the development of correlations between structure and function, particularly when fluorine is compared systematically to other substituents on the basis of size or electronegativity. Recent studies which show the changes in physical and chemical properties of RNA and proteins after the incorporation of fluoro analogs indicate that structure-function correlations of this kind may be extended to macromolecules. A particularly challenging area with potentially wide practical application in therapeutics is the use of fluorinated analogs as probes to elucidate subtle differences in the biochemistry of different tissues. It is hoped that the recent finding of carbon-fluorine bond cleavage by enzymes will give more insight into the biochemical properties of this bond and also contribute to an understanding of the mechanism of certain kinds of enzyme catalysis. It seems clear that the availability of judiciously designed fluoro analogs will be of considerable value in the development of these approaches.