Synthesis, X-ray Structures, Electronic Properties, and O₂/NO Reactivities of Thiol Dioxygenase Active-Site Models

Authors

Anne A. Fischer, Marquette University
Nuru Stracey, University of Wisconsin - Madison
Sergey V. Lindeman, Marquette UniversityFollow
Thomas C. Brunold, University of Wisconsin - Madison
Adam T. Fiedler, Marquette UniversityFollow

Document Type

Article

Language

eng

Publication Date

11-21-2016

Publisher

American Chemical Society

Source Publication

Inorganic Chemistry

Source ISSN

0020-1669

Original Item ID

DOI: 10.1021/acs.inorgchem.6b01931

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)(L_S,N)]BPh₄ complexes, where L_S,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 O₂ to 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}⁷ species 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 O2 reactivities of the ^Ph2TIP- and ^Ph,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.

Comments

Accepted version. Inorganic Chemistry, Vol. 55, No. 22 (November 21, 2016): 11839-11853. DOI. © 2016 American Chemical Society. Used with permission.

Recommended Citation

Fischer, Anne A.; Stracey, Nuru; Lindeman, Sergey V.; Brunold, Thomas C.; and Fiedler, Adam T., "Synthesis, X-ray Structures, Electronic Properties, and O₂/NO Reactivities of Thiol Dioxygenase Active-Site Models" (2016). Chemistry Faculty Research and Publications. 538.
https://epublications.marquette.edu/chem_fac/538