A Facially Coordinating Tris-Benzimidazole Ligand for Nonheme Iron Enzyme Models: Biomimetic or Radical Aerobic Oxidation? Parami S. Gunasekera, † Preshit C. Abhyankar, † Samantha N. MacMillan, § David C. Lacy* † † Department of Chemistry, University at Buffalo, State University of New York, Buffalo, New York 14260, United States. § Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States. Supporting Information Placeholder ABSTRACT: Herein, we report a rationally designed tripodal tris-benzimidazole ligand (Tbim) that structur- ally mimics the 3-His coordination environment of cer- tain nonheme mono-nuclear iron oxygenases. The coor- dination chemistry of Tbim was explored with iron(II) and the ability of the iron complexes to oxidize biomi- metic model substrates lithium diethyl 2-phenylmalonate and sodium thiocresolate was studied. Molecular oxygen (O2) is the most sustainable oxi- dant in oxidative transformation. It is no surprise then that the design of new catalysts take inspiration from (di)oxy- genases, which are enzymes that incorporate O-atoms from O2 into a substrate. Many of these enzymes are iron- dependent and contain a two-histidine one-carboxylate (2-His-1-C) facial triad binding pocket. 1,2 Recently, addi- tional binding modes have been discovered, and these in- clude the three-histidine (3-His), three-histidine one-car- boxylate, and four histidine binding modes. 3 Modelling the 3-His coordination has been attempted through various nitrogen donor ligands such as 1,4,7- triazacyclononane (tacn), 4 tris(2-pyridyl)methane (Tpym), 5 trispyrazolyl variants namely trispyrazol- ylborates (Tp), 6 trispyrazolylmethanes (Tpm) 7 and tri- simidazolylphosphines (TIP), 8 and other ligands. 9, 10 Some of these facially coordinating ligands have been used to prepare Fe-based O2 derived oxidants, such as su- peroxo and oxo species, 11-16 and there are a few catalytic examples. 17,18 In our pursuit to prepare structurally faithful 3-His mononuclear nonheme iron model complexes, we noted that despite similar coordination geometry, most of the ligands contain donor groups that are not representative of those in nature (Figure 1). For instance, histidine do- nors are imidazole nitrogen groups with sp 2 hybridization and in an aromatic ring. In contrast, tacn has sp 3 hybridi- zation and is not conjugated. Accordingly, we noted that Gebbink and coworkers modeled the 2-His-1-C facial triad using imidazole and benzimidazole ligands Figure 1. Natural two-histidine one-carboxylate enzyme bind- ing site (left) compared to tridentate ligands with representative “mono-dentate” ligand donor groups and their respective [NH] + pKa in water (see Fig. S19 and Table S1 for more examples). (2bim1C) with surprising structural precision and also functional chemistry. 19,20 In addition to the electronic similarity (i.e. sp 2 hybridized and aromatized) with the donor groups in Gebbink’s 2bim1C and histidine, ben- zimidazole and imidazole have excellent pKa similarities to histidine. For instance, the pKa of the nitrogen donor of histidine is 6.0 in water, 21 which is close to the pKa of 6.6 for 1,2-dimethylbenzimidazole that is the donor moiety in Gebbink’s 2bim1C ligand. 22,23 Ligands with similar co- ordination modes and electronic properties are thought to impart the appropriate thermodynamic requirements for functional chemistry. 24 Therefore, inspired by Gebbink’s 2bim1C ligand, we report herein the synthesis of a novel 3-His model with a tris-benzimidazole ligand, 2,2’-(2-(1- ethylbenzimidazol-2yl)ethane-1,1-diyl)bis(1-methylben- zimidazole) (Tbim), its coordination with iron and a brief foray into catalysis. Synthesis. Our synthesis of the new ligand Tbim used a strategy similar to the one Gebbink used to prepare 2bim1C (Scheme 1). 20, 25,26 With ligand in hand, we ex- plored the coordination chemistry of Tbim using a vari- ety of FeX2 salts (X = OAc, Cl, OTf). Inspired from cer- tain successful work with Tp* to afford mono-ligated complexes, 11 we performed an analogous reaction with Tbim and Fe(OAc)2 in a dichloromethane/acetonitrile solvent mixture (Scheme 2). Crystals suitable for diffrac- tion revealed the mono-ligated complex [Fe{Tbim}(OAc)2] (1) (Figure 2). Both acetates are k-2 and Tbim is bound through the two benzimidazole arms