Reactivity of Manganese and Iron Metalloenzyme Models

Summary

Principal Investigator: David P Goldberg
Abstract: DESCRIPTION (provided by applicant): The goal of the proposed research is to investigate the reactivity of manganese and iron complexes as models of heme metalloenzymes that utilize dioxygen. Heme enzymes such as cytochrome P450, peroxidases, catalases, heme oxygenase, nitric oxide synthase and cytochrome C oxidase all rely upon Mn or Fe active sites to perform an impressive range of critical biological functions involving O2 or its derivatives. Although the functions of these enzymes are highly diverse, there are some mechanistic commonalities involving key intermediates that bring these systems together. These key intermediates involve high-valent metal-oxo (M=O) and metal-(hydro)peroxo (M-OO(H)) species. Understanding the reactivity and spectroscopic features of these species is critically important, yet many questions remain about these species in part because of challenges associated with studying what are unstable and often short-lived intermediates. We will address fundamental questions regarding high-valent M=O species and their precursors, M-OO(H), through a synthetic analog approach. We will utilize ligands known as corrolazines (Czs) and corroles (Cors) to carry out this research. These ligands are designed to stabilize high oxidation states (e.g. MVO). They also support lower-valent complexes such as MIII and MIV, which will be used to study O-O cleavage events. Aims of this proposal are 1) to synthesize novel high-valent (Cz)M(O) and (Cor)M(O) complexes, determine their structural and spectroscopic properties, and examine their reactivity in biologically relevant transformations and 2) to determine the reactivity of (Cz)M and (Cor)M toward O-O cleavage/O2 activation. Synthetic methods, including ligand design and coordination chemistry, will be used to construct new model complexes of interest. We will correlate the structural and electronic properties of the (Cz)M and (Cor)M (M = Mn, Fe) complexes with reactivity in reactions of direct biological relevance (e.g. hydrogen-atom-transfer (HAT), oxygen-atom-transfer (OAT), and electron-transfer (ET) processes). Reactivity and mechanism will be studied through analysis of products and kinetic measurements with a range of HAT substrates containing C-H and O-H bonds, O-atom acceptor substrates, and ET agents. Comparison of our Mn and Fe chemistry should yield insights regarding why Nature chooses Fe or Mn to perform specific functions. Fundamental information regarding the mechanisms of biomimetic HAT, OAT, ET and related reactions will be obtained.
Funding Period: 2013-09-01 - 2017-05-31
more information: NIH RePORT

Top Publications

  1. pmc Photochemical oxidation of a manganese(III) complex with oxygen and toluene derivatives to form a manganese(V)-oxo complex
    Jieun Jung
    Department of Material and Life Science, Graduate School of Engineering, ALCA, Japan Science and Technology Agency, Osaka University, Suita, Osaka 565 0871, Japan
    Inorg Chem 52:13594-604. 2013
  2. pmc Dramatically accelerated selective oxygen-atom transfer by a nonheme iron(IV)-oxo complex: tuning of the first and second coordination spheres
    Leland R Widger
    Department of Chemistry, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, United States
    J Am Chem Soc 136:2699-702. 2014
  3. ncbi Thioether-ligated iron(II) and iron(III)-hydroperoxo/alkylperoxo complexes with an H-bond donor in the second coordination sphere
    Leland R Widger
    Department of Chemistry, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA
    Dalton Trans 43:7522-32. 2014

Research Grants

  1. Synthetic Modeling of Copper Protein Active Sites
    William B Tolman; Fiscal Year: 2013

Detail Information

Publications3

  1. pmc Photochemical oxidation of a manganese(III) complex with oxygen and toluene derivatives to form a manganese(V)-oxo complex
    Jieun Jung
    Department of Material and Life Science, Graduate School of Engineering, ALCA, Japan Science and Technology Agency, Osaka University, Suita, Osaka 565 0871, Japan
    Inorg Chem 52:13594-604. 2013
    ....
  2. pmc Dramatically accelerated selective oxygen-atom transfer by a nonheme iron(IV)-oxo complex: tuning of the first and second coordination spheres
    Leland R Widger
    Department of Chemistry, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, United States
    J Am Chem Soc 136:2699-702. 2014
    ..However, direct S-oxygenation does occur in the reaction of 1 with mCPBA, yielding sulfoxide-ligated [Fe(II)(N3Py(amide)S(O)R)](BF4)2 (4). Catalytic OAT with 1 was also observed. ..
  3. ncbi Thioether-ligated iron(II) and iron(III)-hydroperoxo/alkylperoxo complexes with an H-bond donor in the second coordination sphere
    Leland R Widger
    Department of Chemistry, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA
    Dalton Trans 43:7522-32. 2014
    ..The influence of a thioether ligand and of one H-bond donor on the stability and spectroscopic properties of these complexes was investigated. ..

Research Grants30

  1. Synthetic Modeling of Copper Protein Active Sites
    William B Tolman; Fiscal Year: 2013
    ..In addition to aspiring to a deep understanding of copper enzyme structure/function relationships, the proposed work is aimed at developing novel copper chemistry of fundamental significance. ..