New Perspectives on Fluorine Interactions: Revealing the Supramolecular Profile of Fluorine–Oxygen Interactions

This study investigates the supramolecular properties of fluorinated compounds by analyzing fluorine–oxygen (F···O) intermolecular interactions, which play a subtle but important role in molecular packing. Combining data from crystal structures with high-level quantum-mechanical calculations and QTAIM topological analysis, the geometric and energetic characteristics of F···O interactions were examined. Over 52,000 interactions were identified using a 3.5 Å cutoff, ranking them as the third most common fluorine-based interactions in crystal structures after C–H···F and F···F interactions. The influence of the surrounding chemical environment, as well as the nature of substituents on the interacting atoms, was assessed. Quantum mechanical analyses, including high-level CCSD(T)/CBS calculations, show that these interactions are weak (−0.77 to −2.55 kcal/mol) but stronger than F···F and C–H···F interactions and comparable to C–H···O interactions, with more geometric flexibility. The observed geometry is influenced by crystal packing, cooperativity, and the presence of multiple simultaneous interactions. Energy minima typically occur between 2.9 and 3.5 Å, often with antiparallel orientations. Together, the statistical and computational results establish F···O interactions as meaningful contributors to supramolecular organization and provide a framework for their inclusion in crystal engineering and computational modeling.