title: Synthesis, X-ray Structures, Electronic Properties, and O2/NO Reactivities of Thiol Dioxygenase Active-Site Models.
abstract: Mononuclear non-heme iron complexes that serve as structural and functional mimics of the thiol dioxygenases (TDOs), cysteine dioxygenase (CDO) and cysteamine dioxygenase (ADO), have been prepared and characterized with crystallographic, spectroscopic, kinetic, and computational methods. The high-spin Fe(II) complexes feature the facially coordinating tris(4,5-diphenyl-1-methylimidazol-2-yl)phosphine (Ph2TIP) ligand that replicates the three histidine (3His) triad of the TDO active sites. Further coordination with bidentate l-cysteine ethyl ester (CysOEt) or cysteamine (CysAm) anions yielded five-coordinate (5C) complexes that resemble the substrate-bound forms of CDO and ADO, respectively. Detailed electronic-structure descriptions of the [Fe(Ph2TIP)(LS,N)]BPh4complexes, where LS,N= CysOEt (1) or CysAm (2), were generated through a combination of spectroscopic techniques [electronic absorption, magnetic circular dichroism (MCD)] and density functional theory (DFT). Complexes 1 and 2 decompose in the presence of O2to yield the corresponding sulfinic acid (RSO2H) products, thereby emulating the reactivity of the TDO enzymes and related complexes. Rate constants and activation parameters for the dioxygenation reactions were measured and interpreted with the aid of DFT calculations for O2-bound intermediates. Treatment of the TDO models with nitric oxide (NO)-a well-established surrogate of O2-led to a mixture of high-spin and low-spin {FeNO}7species at low temperature (-70 °C), as indicated by electron paramagnetic resonance (EPR) spectroscopy. At room temperature, these Fe/NO adducts convert to a common species with EPR and infrared (IR) features typical of cationic dinitrosyl iron complexes (DNICs). To complement these results, parallel spectroscopic, computational, and O2/NO reactivity studies were carried out using previously reported TDO models that feature an anionic hydrotris(3-phenyl-5-methyl-pyrazolyl)borate (Ph,MeTp-) ligand. Though the O2reactivities of thePh2TIP- andPh,MeTp-based complexes are quite similar, the supporting ligand perturbs the energies of Fe 3d-based molecular orbitals and modulates Fe-S bond covalency, suggesting possible rationales for the presence of neutral 3His coordination in CDO and ADO.
authors: Department of Chemistry, Marquette University , Milwaukee, Wisconsin 53201, United States.
authors: Anne A
authors: AA
authors: Fischer
authors: Department of Chemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
authors: Nuru
authors: N
authors: Stracey
authors: Department of Chemistry, Marquette University , Milwaukee, Wisconsin 53201, United States.
authors: Sergey V
authors: SV
authors: Lindeman
authors: Department of Chemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
authors: Thomas C
authors: TC
authors: Brunold
authors: Department of Chemistry, Marquette University , Milwaukee, Wisconsin 53201, United States.
authors: Adam T
authors: AT
authors: Fiedler
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D049308:Dioxygenases / Q000737:chemistry*; D004583:Electrons; D008956:Models, Chemical; D009569:Nitric Oxide / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D049308:Dioxygenases; D010100:Oxygen