Spectroscopic and Computational Comparisons of Thiolate-Ligated Ferric Nonheme Complexes to Cysteine Dioxygenase: Second-Sphere Effects on Substrate (Analogue) Positioning

Authors

Anne A. Fischer, Marquette University
Joshua R. Miller, University of Wisconsin - MadisonFollow
Richard J. Jodts, University of Wisconsin - Madison
Danushka M. Ekanayake, Marquette UniversityFollow
Sergey V. Lindeman, Marquette UniversityFollow
Thomas C. Brunold, University of Wisconsin - Madison
Adam T. Fiedler, Marquette UniversityFollow

Document Type

Article

Language

eng

Publication Date

12-2-2019

Publisher

American Chemical Society Publications

Source Publication

Inorganic Chemistry

Source ISSN

0020-1669

Abstract

Parallel spectroscopic and computational studies of iron(III) cysteine dioxygenase (CDO) and synthetic models are presented. The synthetic complexes utilize the ligand tris(4,5-diphenyl-1-methylimidazol-2-yl)phosphine (^Ph2TIP), which mimics the facial three-histidine triad of CDO and other thiol dioxygenases. In addition to the previously reported [Fe^II(CysOEt)(^Ph2TIP)]BPh₄ (1; CysOEt is the ethyl ester of anionic l-cysteine), the formation and crystallographic characterization of [Fe^II(2-MTS)(^Ph2TIP)]BPh₄ (2) is reported, where the methyl 2-thiosalicylate anion (2-MTS) resembles the substrate of 3-mercaptopropionate dioxygenase (MDO). One-electron chemical oxidation of 1 and 2 yields ferric species that bind cyanide and azide anions, which have been used as spectroscopic probes of O₂ binding in prior studies of Fe^III-CDO. The six-coordinate Fe^III-CN and Fe^III-N₃ adducts are examined with UV–vis absorption, electron paramagnetic resonance (EPR), and resonance Raman (rRaman) spectroscopies. In addition, UV–vis and rRaman studies of cysteine- and cyanide-bound Fe^III-CDO are reported for both the wild-type (WT) enzyme and C93G variant, which lacks the Cys-Tyr cross-link that is present in the second coordination sphere of the WT active site. Density functional theory (DFT) and ab initio calculations are employed to provide geometric and electronic structure descriptions of the synthetic and enzymatic Fe^III adducts. In particular, it is shown that the complete active space self-consistent field (CASSCF) method, in tandem with n-electron valence state second-order perturbation theory (NEVPT2), is capable of elucidating the structural basis of subtle shifts in EPR g values for low-spin Fe^III species.

Synopsis

The geometric and electronic structures of thiolate-ligated Fe^III complexes of relevance to the active sites of thiol dioxygenases have been elucidated with spectroscopic and computational methods. Data collected for the synthetic models are compared to those previously obtained for the analogous enzymatic species, and newly collected resonance Raman spectra of Cys- and CN-bound Fe^III-CDO are presented. The combined enzymatic/synthetic approach reveals that second-sphere residues perturb the positions of substrate (analogues) coordinated to the nonheme iron site of CDO.

Comments

Accepted version. Inorganic Chemistry, Vol. 58, No. 24 (December 2, 2019): 16487-16499. DOI. © 2019 American Chemical Society Publications. Used with permission.

Recommended Citation

Fischer, Anne A.; Miller, Joshua R.; Jodts, Richard J.; Ekanayake, Danushka M.; Lindeman, Sergey V.; Brunold, Thomas C.; and Fiedler, Adam T., "Spectroscopic and Computational Comparisons of Thiolate-Ligated Ferric Nonheme Complexes to Cysteine Dioxygenase: Second-Sphere Effects on Substrate (Analogue) Positioning" (2019). Chemistry Faculty Research and Publications. 991.
https://epublications.marquette.edu/chem_fac/991