Our research program focuses on understanding how thiolate ligands promote N-O and O-O (O2- and O2) bond activation. Nitric oxide (NO) is frequently used to probe O2 binding sites, and form stable analogues of key metastable Fe-O2 intermediates. The ?NO stretching frequency provides a measure of N-O, and thus O-O bond activating properties. A growing number of metalloenzymes use Mn and Fe interchangeably without altering function, and a majority of these promote O-O bond activation and cleavage, and involve M-dioxygen, -superoxo, -peroxo, and -oxo (M= Mn, Fe) species as key intermediates. These enzymes function to remove toxic O2- radicals implicated in cancer, Alzheimer's, Parkinson's disease, and synthesize key biomolecules such as DNA, neurotransmitters, fatty acids, and steroids. The spectroscopic and reactivity properties of thiolate-ligated Fe- and Mn-peroxo, superoxo, and oxo species remain largely unexplored, and the O2 and O2- chemistry of Mn and Fe is complementary with respect to the spectroscopic visibility and stability of reactive intermediates. For the proposed project period we will design and synthesize new, readily derivatized thiolate ligands, and their corresponding Mn and Fe complexes. By systematically altering substituents we will fine-tune the electronic and steric properties of the molecule, and adjust the redox potential, metal ion Lewis acidity, and relative pKa of the distal versus proximal peroxo oxygens. Using a systematic approach we will attempt to determine which properties are key to promoting reactivity and function. By probing redox potentials and ?NO of structurally analogous Mn/Fe pairs we will examine the tunable nature of the M- SR bond, and establish whether cysteinates can facilitate the interchangeability of Mn and Fe while maintaining function. We will fully characterize our new pyridine/thiolate-ligated Fe-peroxo intermediates formed via O2- reduction, and continue to explore the O2- reactivity of additional pyridine- substituted derivatives. Ultimately we will be looking for correlations between Hammett parameters and reactivity, and determining which properties are key to promoting Fe-O versus O-O bond cleavage. We will continue to look for M3+ (M= Mn, Fe) promoted O2- oxidation activity by monitoring for O2 evolution. Ultimately we will be looking for a catalytic SOD mimic. We will fully characterize our new Mn-dioxygen and Mn-OOR (R= tBu, Cm) intermediates using XAS, MCD, resonance Raman, parallel- mode EPR, and DFT, and examine the kinetics and mechanism of the Mn-dioxygen species formation. We wil attempt to stabilize these intermediates, as well as our new Mn=O, by incorporating steric bulk into the ligand. We will continue to explore the reactivity of our new Mn-dioxygen, Mn-oxo, and Mn- OOR intermediates with oxidizable substrates.
Our research program focuses on understanding how thiolate ligands promote O-O bond activation in Mn- and Fe-containing enzymes that function to remove toxic O2- radicals (implicated in cancer, Alzheimer's, Parkinson's disease), and synthesize key biomolecules (e.g., DNA, and neurotransmitters). The proposed project will determine the metal ion properties that are key to promoting function, and establish whether the tunable nature of M-SR bonds can facilitate the interchangeable use of Mn and Fe without altering function. The spectroscopic and reactivity properties of thiolate-ligated Fe- and Mn-peroxo, superoxo, and oxo species remain largely unexplored, and the O2 and O2- chemistry of Mn and Fe is complementary with respect to the spectroscopic visibility and stability of reactive intermediates.
|Kowalska, Joanna K; Nayyar, Brahamjot; Rees, Julian A et al. (2017) Iron L2,3-Edge X-ray Absorption and X-ray Magnetic Circular Dichroism Studies of Molecular Iron Complexes with Relevance to the FeMoco and FeVco Active Sites of Nitrogenase. Inorg Chem 56:8147-8158|
|Villar-Acevedo, Gloria; Lugo-Mas, Priscilla; Blakely, Maike N et al. (2017) Metal-Assisted Oxo Atom Addition to an Fe(III) Thiolate. J Am Chem Soc 139:119-129|
|Rees, Julian A; Martin-Diaconescu, Vlad; Kovacs, Julie A et al. (2015) X-ray Absorption and Emission Study of Dioxygen Activation by a Small-Molecule Manganese Complex. Inorg Chem 54:6410-22|
|Brines, Lisa M; Coggins, Michael K; Poon, Penny Chaau Yan et al. (2015) Water-soluble Fe(II)-H2O complex with a weak O-H bond transfers a hydrogen atom via an observable monomeric Fe(III)-OH. J Am Chem Soc 137:2253-64|
|Kovacs, Julie A (2015) Tuning the Relative Stability and Reactivity of Manganese Dioxygen and Peroxo Intermediates via Systematic Ligand Modification. Acc Chem Res 48:2744-53|
|Coggins, Michael K; Martin-Diaconescu, Vlad; DeBeer, Serena et al. (2013) Correlation between structural, spectroscopic, and reactivity properties within a series of structurally analogous metastable manganese(III)-alkylperoxo complexes. J Am Chem Soc 135:4260-72|
|Coggins, Michael K; Sun, Xianru; Kwak, Yeonju et al. (2013) Characterization of metastable intermediates formed in the reaction between a Mn(II) complex and dioxygen, including a crystallographic structure of a binuclear Mn(III)-peroxo species. J Am Chem Soc 135:5631-40|
|Coggins, Michael K; Toledo, Santiago; Kovacs, Julie A (2013) Isolation and characterization of a dihydroxo-bridged iron(III,III)(?-OH)2 diamond core derived from dioxygen. Inorg Chem 52:13325-31|
|Coggins, Michael K; Brines, Lisa M; Kovacs, Julie A (2013) Synthesis and structural characterization of a series of Mn(III)OR complexes, including a water-soluble Mn(III)OH that promotes aerobic hydrogen-atom transfer. Inorg Chem 52:12383-93|
|Coggins, Michael K; Toledo, Santiago; Shaffer, Erika et al. (2012) Characterization and dioxygen reactivity of a new series of coordinatively unsaturated thiolate-ligated manganese(II) complexes. Inorg Chem 51:6633-44|
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