Sumanene meets 5-fluorouracil: curved π-conjugated biointerfaces through covalent and supramolecular integration

The integration of 5-fluorouracil (5-FU) with a curved π-conjugated sumanene scaffold for biologically relevant biointerfaces is demonstrated. To this end, covalent and non-covalent conjugates of bowl-shaped sumanene and 5-FU were obtained. Spectrofluorimetric studies on supramolecular assembly of sumanene and 5-FU by molecular recognition ([sumanene·5-FU] associate), supported with umbrella sampling computations, revealed a good association constant for the system (10⁴ M^-1), which was improved in comparison with a flat triphenylene analog, along with an effect of sumanene binding on the anticancer properties of 5-FU. A covalent sumanene-5-FU conjugate (8) was effectively obtained via a click chemistry approach and was found to demonstrate no detectable toxicity in the zebrafish embryo assay. Data from the Alamar Blue assay and the reactive oxygen species (ROS) assay indicate that the cytotoxic effects of the designed curved π-conjugated systems (conjugate 8 and the [sumanene·5-FU] associate) may involve pathways distinct from those typically associated with ROS-driven cytotoxicity, with a more diverse mode of interaction, which may reflect the influence of the curved π-framework on cell-relevant molecular recognition processes. Collectively, our findings contribute to the development of new curved π-platforms in biologically relevant environments, with the potential for the coexistence of covalent and supramolecular interactions in these systems.