Triazole-tethered ferrocene-quinoline conjugates: solid-state structure analysis, electrochemistry and theoretical calculations

Ferrocenyl-, triazole- and quinoline-containing compounds are known to possess potential for biological activities. The synthesis and biological activities of O-alkylated quinoline derivatives, attached to the ferrocene moiety through 1,2,3-triazole bridge, have been reported earlier. Compounds in which triazole ring is directly bonded to ferrocene skeleton were more active in terms of cytotoxicity and reactive oxygen species generation, as compared to those analogues which contain a spacer between triazole ring and ferrocene skeleton. The first aim of this paper was to explore how small difference on surface of the molecules influence their supramolecular assembling. For these reasons, we performed detailed X-ray crystal structure analysis of five ferrocene-quinoline conjugates. In addition, as electronic structure and electrochemical properties could be important for antiproliferative activities of these conjugates, electrochemical measurements and computational analysis have been performed. In all structures, C-H···N and C-H···F hydrogen bonds form one-dimensional or two-dimensional networks, which are further linked by C-H···π and π···π interactions into higher order supramolecular structures. Conformational search at the M06L level revealed that crystal structures of ferrocene conjugates retained their geometries in solution. This confirmed that solid-state structural properties are relevant for electrochemistry and bioactivity discussion. Derivatives in which triazole ring is directly coupled to the ferrocene have lower redox potential values, which suggest higher antioxidant capacity. This was supported by DFT calculation in which frontier molecular orbitals were used as descriptors for redox behaviour of the respective ferrocene conjugates.