Bioinspired Non-Heme Iron Complexes: The Evolution of Facial N, N, O Ligand Design

Abstract

Iron-containing metalloenzymes that contain the 2-His-1-Carboxylate facial triad at their active site are well known for their ability to activate molecular oxygen and catalyse a broad range of oxidative transformations. Many of these reactions are synthetically challenging, and developing small molecular iron-based catalysts that can achieve similar reactivity and selectivity remains a long-standing goal in homogeneous catalysis. This review focuses on the development of bioinspired facial N,N,O ligands that model the 2-His-1-Carboxylate facial triad to a greater degree of structural accuracy than many of the polydentate N-donor ligands commonly used in this field. By developing robust, well-defined N,N,O facial ligands, an increased understanding could be gained of the factors governing enzymatic reactivity and selectivity.

Structurally Modelling the 2‐His‐1‐Carboxylate Facial Triad with a Bulky N,N,O Phenolate Ligand

“…Based on these results, Im Ph2 NNO t Bu can be regarded as a heteroscorpionate ligand that imparts a metallobicyclo[2.2.3]nonane topology to each complex. The ability of the ligand to monoligate is proposed to be principally due to the steric demands of its constituent groups, where the 4,5‐diphenyl‐substituted imidazole groups hinder the coordination of a second ligand equivalent and the ortho ‐ t Bu substituent on the phenolate reduces the accessibility of the lone pair of the phenolic oxygen atom and prevents any bridging coordination modes from occurring [23, 28, 35] . Together, these bulky groups contribute to the relatively large buried volume of the ligand (58.9 and 59.6 % V buried in 1 and 2 , Figure 6).…”

“…While the ligand's imidazole groups are the most biologically relevant heterocycle for modelling histidine residues, the incorporation of a phenol deviates somewhat from the carboxylate residue of the 2H1C due to its redox‐active properties. However, the ease with which phenols can be functionalised opens up more possibilities for ligand design and helps avoid certain drawbacks associated to carboxylic acids, such as decarboxylation, poor solubility, [31] or the formation of coordination oligomers [23] . Moreover, the tert‐ butyl substituents on the 2,4‐positions of the phenol can help prevent radical side reactions.…”

“…The robustness of the ligands’ facial N , N,O coordination to iron in solution therefore remains largely unknown, making the use of their respective complexes disadvantageous from a practical point of view compared to the well‐established coordination chemistry of polydentate N‐donor ligands. Previously, our group has explored the facial capping potential of bis‐imidazole derived N , N,O phenolate ligands, ImNNO and BenzImNNO [23, 25] . However, these were shown to readily form bis‐ligated complexes in the absence of a co‐ligand.…”

“…In order to structurally model the 2H1C with greater accuracy,i tr emains of interestt od evelop facial, tridentate N,N,O ligands.W hile numerouse xamples of such ligands with system-atically varied donor group constituents have been reported, [23] the number of N,N,O ligandst hat can coordinate in at ripodal manner and support the formation of mononuclear,m onoligated metal complexes is small. Typically,d ifficulties in achieving the desired coordinationm ode are encountered due to the formation of homoleptic bis-ligand complexes, [24][25][26] the increase in nuclearity due to anionic O-donorb ridging modes, [27][28][29][30] or rupture of the N,N,O coordination due to lability of an eutralN -/O-donor.…”

Facile Synthesis and Characterization of a Bromine-Substituted (Chloromethyl)Pyridine Precursor towards the Immobilization of Biomimetic Metal Ion Chelates on Functionalized Carbons

“…Ligands containing two bis [2-(2-pyridyl)ethyl]amine (pye) moieties have been used on copper(I) to mimic copper containing oxygenases or hemocyanin by promoting dioxygen oxidation chemistry or reversible dioxygen binding, respectively, depending on the type of central linker [11][12][13]. Many non-haem iron containing metalloenzymes bind iron through moieties known as the 2-His-1-carboxylate, 3-His facial triads or other combinations of histidine and carboxylate endogenous ligating residues [14][15][16][17]. These structural motifs have been extensively modeled using pyridyl based ligands (Figure 1) that have been shown to support high valent metal-oxo species capable of activating C-H bonds of substrates similarly to their enzymatic counterparts [18][19][20][21][22][23].…”