| Despite the successful use of fluorine in pharmaceutical applications, most of the underlying principles governing the peculiar properties of fluorine substituents in a molecule are still unanswered. Both fundamental studies and applications of organic fluorine in pharmaceutical sciences are addressed in this manuscript.; The X-ray structure of the complex of a cyclic urea inhibitor (DMP323) and HIV-1 protease shows that the benzyl alcohol groups of the inhibitor only accept H-bonds from the enzyme backbone amide groups of Asp30 and Asp30 '. The hydroxyl groups were replaced with fluorine to study the changes in binding affinities. Investigating enzyme inhibition by fluorinated ligands allows a comprehensive understanding of the effect of fluorinated groups on the binding of specific molecules to the active sites of enzymes. As the interaction between enzymes and their substrates is extremely sensitive to minimal changes in the structure and in the electronic properties of the substrate, this methodology allows a qualitative and quantitative understanding of the participation by organic fluorine in a variety of non-covalent interactions. The binding affinities of these molecules to HIV-1 protease show that the added fluorine atoms can effectively engage in a hydrogen bond with the backbone of the protein.; In a different project, we have designed and synthesized semifluorinated block copolymers that can self-assemble into nanoscopic micellar structures. A semifluorinated block copolymer consisting of a hydrophilic segment (PEG, Mn = 6000 a.m.u.) and a perfluorooctyl segment was synthesized and shown to self-assemble into nanoscopic micelles in aqueous solution by fluorine-19 nuclear magnetic resonance, dynamic light scattering, and fluorescence correlation spectroscopy. The micelles have also been proven to efficiently encapsulate sevoflurane (an example of a volatile and non-polar drug) inside their fluorous core. Thus, it is possible to formulate sevoflurane for intravenous injection via polymeric micelle systems based on perfluoroalkyl block PEG. |
