Role of Fluorine in Weak Interactions in Co-crystals
The presence of the C–F bond (commonly referred to as organic fluorine) in a large number of pharmaceutically relevant compounds suggests that it may be used in the production of novel salts and co-crystals that have intermolecular interactions involving fluorine. There is an ongoing debate in this context as fluorine is characterized by its high electronegativity, relatively small size and very low polarizability. The propensity of hydrogen to participate in generating highly directional and energetically stable hydrogen bonds has been exploited in the design of co-crystals and salts of many pharmaceutical compounds. A direct extension of this property to fluorine, however, is not plausible and thus intermolecular interactions involving fluorine must be quantified. Recent results and new approaches designed to evaluate organic fluorine which provide useful inputs for the design of co-crystals and salts are discussed in this chapter.