The design and investigation of transition metal complexes incorporating distinct ligand scaffolds is of immense significance, considering the possibility of obtaining unique structures featuring intriguing specificities [1,2]. These specificities include the ability of the complex to undergo effective catalytic reactions, efficient biomimicking functionalities, potential drugs, and other day-to-day life applications. Excellent activities have been observed with N/O-containing heteroaryl ligands like imidazole, benzimidazole, and phenol derivatives [3]. These compounds have been identified as important cores in a wide range of therapeutic reagents, including antimicrobial, anticancer, antidiabetic, antiinflammatory, antioxidants, hormone modulators, CNS stimulants, proton pump inhibitors, as well as lipid and depressant level modulators [4]. Moreover, these ligands, when combined with appropriate metal ions, can function as enzyme-mimicking models, replicating the biochemical reactions typically catalyzed by natural enzymes [5]. For example, numerous studies have been conducted on various copper-containing enzymes, including catechol oxidase [6], particulate methane monooxygenase [7], tyrosinase [8], phenoxazinone synthase [9], quercetin-2,3-dioxygenase [10], superoxide dismutase [11], galactose and glyoxal oxidases [12], and so on. Notably, many different metal complexes with various ligand architectures were studied as functional models of these enzymes [[5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]].

Among the enzymes listed above, phenoxazinone synthase (PHS) is a multi‑copper oxidase enzyme with an enigma in its mechanism; it demands more attention to comprehend the actual reactivity as well as the mode of action in each step [9]. To address the conundrum and broaden the range of reactions for wider applications, different metal complexes have been synthesized and studied [[13], [14], [15], [16], [17], [18], [19], [20]]. Among them, copper complexes of various denticity were widely studied and proved as impressive mimics [[13], [14], [15], [16], [17]]. Additionally, other metal complexes such as manganese, iron, and cobalt have also been investigated as PHS mimics [[18], [19], [20]]. Although the studies utilising these complexes exhibited PHS activity, they often showed very low reaction rates or failed to proceed effectively in aqueous media. Moreover, iron complexes have rarely been used as models for this study [20]. Bipyridine-mediated 1D-polymeric iron(III) complex demonstrated a mimicking study with a kcat of 32.36 h−1 in methanol.[21(a)] Iron(III) complexes featuring a naphthol-based Schiff base and a secondary ligand were reported to catalyze the same reaction, with reaction rates ranging from 157.57 to 209.52 h−1 in acetonitrile.[21(b)] In a subsequent study, a pair of iron(III) complexes of pyridine and phenolate-based ligands showed a kcat of 8.6 and 11.1 h−1 in methanol.[21(c)]

As alluded to above, these studies reveal that the oxidative coupling activity of the reported iron complexes is either moderate or low when conducted in non-aqueous solvents. In contrast, the enzyme PHS oxidatively catalyses 3-hydroxy-4-methylanthranilic acid to produce phenoxazinone chromophore through a six-electron oxidation process in aqueous medium (Scheme 1). This key distinction underscores a critical limitation of synthetic iron complexes, which rely on organic solvents and fail to replicate the biologically relevant aqueous environment. This limitation extends to all other synthetic metal complexes studied in organic media. The reliance on organic solvents not only restricts their practical applicability but also poses significant environmental concerns. Consequently, an ideal biomimetic system should typically function in an aqueous medium to address these challenges and to align more closely with natural enzymatic processes.

To triumph over these obstacles, we designed, synthesized and characterized a new set of iron(III) complexes (1–3) using the ligands 2-(1-(pyridin-2-yl)imidazo[1,5-a]pyridin-3-yl)phenol (L1(H)), 4-methoxy-2-(1-(pyridin-2-yl)imidazo[1,5-a] pyridin-3-yl)phenol (L2(H)), and 4-bromo-2-(1-(pyridin-2-yl)imidazo[1,5-a]pyridin-3-yl)phenol (L3(H)) (Scheme 2). We have found that the newly synthesized iron(III) complexes function as highly efficient mimics of phenoxazinone synthase, catalysing the conversion of model substrates; o-aminophenol (APOH), 2-amino-6-chlorophenol (6Cl-APOH), and 2-amino-6-methylphenol (6Me-APOH), to obtain the oxidative coupled products 2-amino-phenoxazin-3-one (APX), 2-amino-4,6-dichloro-phenoxazin-3-one (6Cl-APX), and 2-amino-4,6-dimethyl-phenoxazin-3-one (6Me-APX) in aqueous medium under ambient conditions. Remarkably, the studies reveal that even subtle variations in the ligand systems of these complexes result in catalytic activity at rates higher than all the known studies. We have also comprehended the mechanism by trapping and characterizing the complex-substrate intermediates presumed to form during the catalytic process. Moreover, radical trapping experiments with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) reveal the involvement of a radical in the reaction.