It Is Getting Packed in Here: Synthesis, Structure and Biological Activity of Halogenated 1,10-Phenanthroline Epoxide Derivatives

1,10-Phenanthroline derivatives are versatile ligands whose structural and biological properties can be tuned by targeted functionalization. Here, a series of 2,9-dihalogenated 1,10-phenanthroline derivatives and their corresponding 5,6-epoxy-5,6-dihydro analogs were synthesized and characterized. Single-crystal X-ray diffraction experiments reveal pronounced substituent-dependent packing motifs. While 2,9-diiodo-1,10-phenanthroline forms a sandwich-herringbone arrangement dominated by short I···I contacts, the phenanthroline epoxides exhibit π-stacking combined with C–H···O and C–H···halogen interactions. For the brominated and iodinated epoxides, additional halogen···halogen contacts generate extended supramolecular networks. Biological evaluation in selected cell lines showed that both halogenation and epoxidation reduce the cytotoxicity of the parent phenanthroline scaffold, whereas no significant effects on Pseudomonas aeruginosa growth or biofilm formation were observed. These results demonstrate how simple structural modifications of 1,10-phenanthroline influence both solid-state organization and biological activity, providing insight into the role of halogen substituents and epoxide formation in phenanthroline-based systems.