Fluorinated analogues of many bioorganic compounds have become important pharmacological and medicinal agents. The advantages of fluorine substitution arise from its small van der Waals radius (1.35 A). As a result, fluorine bonded to a trigonal carbon is used effectively as a C-H replacement. Because of similar aliphatic C-F and C-0 bond lengths (1.39 and 1.43 A, respectively), the halogen bonded to a tetrahedral carbon has been used frequently as an OH surrogate, particularly in studies with nucleoside analogues. These steric similarities allow fluorinated compounds to mimic their nonfluorinated parents with respect to recognition by various biological macromolecules such as enzymes, transport proteins and receptors. On the other hand, the high electronegativity of fluorine (4.0) can drastically alter electron density distribution in the molecule which, in turn, affects pK values in neighboring groups and molecular dipole moments. All these altered physicochemical properties, as a result of fluorine substitution, can result in drastically modified biological properties such as potency, transport and receptor selectivity. Furthermore, recent advances in 19-F NMR and electron energy-loss spectroscopic techniques, and 18-F positron- emission tomography (18-F PET), have increased the significance and application of fluorinated molecules as biological markers and diagnostic agents. We have used acetyl hypofluorite for fast, efficient and regiospecific introduction of fluorine into the phenolic ring of tyrosine within its peptides. By use of a different fluorinating agent, N-fluoropyridinium triflate, fluorination at the C-2 position of tryptophan has been achieved. Extension of this method to tryptophan-containing peptides is in progress. Studies are under way to determine whether different fluorinating agents, by virtue of differences in reaction mechanism, can achieve selective fluorination of different amino acids.
