Multicomponent Domino Synthesis of Bis(imidazo[1,5‐ <i>a</i> ]pyridine) Triarylmethane Iron(II) Complexes: Reaction Process Tracking and Photoactivated Cytotoxicity Evaluation

ABSTRACT We report the facile synthesis of nine novel iron(II) complexes ( Fe‐1 ∼ Fe‐9 ) featuring the in situ‐formed bis(imidazo[1,5‐ a ]pyridine)‐based triarylmethane ligands via a multicomponent domino reaction of pyridine‐2‐methamine, pyridine‐2‐aldehyde derivates, salicylaldehyde derivates and FeCl 3 . The structures of all iron(II) complexes were unambiguously confirmed by single‐crystal X‐ray diffraction analysis, and the domino reaction process was tracked by time‐dependent electrospray ionization mass spectrometry, which supports a highly organized domino reaction sequence that includes: (i) aldimine condensation between pyridine‐2‐methamine and pyridine‐2‐aldehyde; (ii) intramolecular cyclization to form the imidazo[1,5‐ a ]pyridine intermediate; and (iii) sequential intermolecular nucleophilic addition of imidazo[1,5‐ a ]pyridine to salicylaldehyde, yielding the bis(imidazo[1,5‐ a ]pyridine)‐based triarylmethane scaffold. Moreover, all complexes exhibited photoactivated cytotoxicity against melanoma cells (B16F10 and A375). Notably, Fe‐8 showed potent photocytotoxicity (IC 50 = 0.36 ± 0.06 µM for B16F10; 1.06 ± 0.42 µM for A375) under irradiation, via light‐triggered dual ROS generation: hydroxyl radicals from a Fenton‐like pathway and singlet oxygen from photooxidation.