Invited Talk 21st International Conference on Biological Inorganic Chemistry 2025

Discovery and characterization of reactive high-valent Fe(IV)-oxo complexes (120943)

Marcel Swart 1 , Faiza Ahsan 2 , Mursaleem Ansari 2 , Mehmet Jahja 2 , Sahmi Mahri 2 , Jin Xiong 3 , Yisong Guo 3 , Bittu Chandra 4 , Abhishek Das 4 , Nabhendu Pal 4 , Chupeng Li 4 , Alex Lovstedt 4 , Yuan Sheng 4 , Victor Young 4 , Lawrence Que Jr 4
  1. ICREA and Universitat de Girona, Girona, GI, Spain
  2. IQCC, Universitat de Girona, Girona, Spain
  3. Chemistry, Carnegie Mellon University, Pittsburgh, USA
  4. Chemistry, University of Minnesota, Minneapolis, USA

Nature has chosen high-spin iron(IV)=O oxidants for nonheme iron enzymes with mononuclear active sites to cleave strong substrate C–H bonds, as well as the epoxidation of olefins. The versatile reactivity of enzymatic Fe(IV)=O intermediates has inspired efforts to obtain synthetic analogues that mimic the structures and functions of these enzymes. Tracing back the rate enhancement to changes made in the ligand framework has proven to be a difficult task, requiring a joint effort by experiments and theory. Nevertheless, changes in the electronic structure and accessibility of the iron-oxo moiety, and involvement of different spin states in different synthetic complexes, have hampered a generalization in terms of a simple model to rationalize rate enhancements.

In recent years we have shown that substantial rate enhancements in OAT reactions for topological anti vs. syn isomers based on the 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane (TMC) ligand can be traced back to the dissociation of the axial acetonitrile during the reaction.[1] Likewise, the electronic structure of benzimidazole ligands was not affected by peripheral modifications, and instead entropic lowering of the reaction barrier was responsible for the rate enhancement with benzimidazole derivatives.[2] Only in the case of modifications of the N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine (N4Py) ligand was the enhancement directly related to the electronic structure, leading to larger electrophilicity.[3]

The paradigm that ligands providing quintet ground states should be favoured[4] seems to be challenged by our latest results, which emphasize the role of small changes in ligand geometry that can dictate the reactivity in different ways. It is this diversification, and the ability to trace it back to the origin of the rate enhancement through a combination of state-of-the-art synthesis, catalysis, spectroscopy and theory that new ligands for oxidative reactions, such as hydrogen or oxygen atom transfer (HAT, OAT), can be discovered and characterized.

Here I will discuss our latest results with rate enhancements up to million-fold, and an oxidative potency that surpasses that observed with the tris(2-quinolylmethyl)amine (TQA) ligand.[5]

  1. Chandra, Ahsan, Sheng, Swart, Que Jr., Proc. Natl. Acad. Sci. USA 2024, 121, e2319799121, DOI 10.1073/pnas.2319799121
  2. Das, Pal, Xiong, Young, Guo, Swart, Que Jr., J. Am. Chem. Soc. 2025, 147, 292-304, DOI 10.1021/jacs.4c10120
  3. Pal, Xiong, Jahja, Mahri, Young, Guo, Swart, Que Jr., Proc. Natl. Acad. Sci. USA 2025, 122, e2414962122, DOI 10.1073/pnas.2414962122
  4. Shaik, Chen, Janardanan, Nat. Chem. 2011, 3, 19-27, DOI 10.1038/nchem.943
  5. Biswas, Puri, Meier, Oloo, Rohde, Bominaar, Münck, Que Jr., J. Am. Chem. Soc. 2015, 137, 2428–2431, DOI 10.1021/ja511757j