Spectroscopic and Computational Studies of Reversible O₂ Binding by a Cobalt Complex of Relevance to Cysteine Dioxygenase

Authors

Anne A. Fischer, Marquette University
Sergey V. Lindeman, Marquette UniversityFollow
Adam T. Fiedler, Marquette UniversityFollow

Document Type

Article

Language

eng

Publication Date

10-21-2017

Publisher

Royal Society of Chemistry

Source Publication

Dalton Transactions

Source ISSN

1477-9226

Abstract

The substitution of non-native metal ions into metalloenzyme active sites is a common strategy for gaining insights into enzymatic structure and function. For some nonheme iron dioxygenases, replacement of the Fe(II) center with a redox-active, divalent transition metal (e.g., Mn, Co, Ni, Cu) gives rise to an enzyme with equal or greater activity than the wild-type enzyme. In this manuscript, we apply this metal-substitution approach to synthetic models of the enzyme cysteine dioxygenase (CDO). CDO is a nonheme iron dioxygenase that initiates the catabolism of L-cysteine by converting this amino acid to the corresponding sulfinic acid. Two mononuclear Co(II) complexes (3 and 4) have been prepared with the general formula [Co²⁺(Tp^R2)(CysOEt)] (R = Ph (3) or Me (4); Tp^R2 = hydrotris(pyrazol-1-yl)borate substituted with R-groups at the 3- and 5-positions, and CysOEt is the anion of L-cysteine ethyl ester). These Co(II) complexes mimic the active-site structure of substrate-bound CDO and are analogous to functional iron-based CDO models previously reported in the literature. Characterization with X-ray crystallography and/or ¹H NMR spectroscopy revealed that 3 and 4 possess five-coordinate structures featuring facially-coordinating Tp^R2 and S,N-bidentate CysOEt ligands. The electronic properties of these high-spin (S = 3/2) complexes were interrogated with UV-visible absorption and X-band electron paramagnetic resonance (EPR) spectroscopies. The air-stable nature of complex 3 replicates the inactivity of cobalt-substituted CDO. In contrast, complex 4 reversibly binds O₂ at reduced temperatures to yield an orange chromophore (4-O₂). Spectroscopic (EPR, resonance Raman) and computational (density functional theory, DFT) analyses indicate that 4-O₂ is a S = 1/2 species featuring a low-spin Co(III) center bound to an end-on (η¹) superoxo ligand. DFT calculations were used to evaluate the energetics of key steps in the reaction mechanism. Collectively, these results have elucidated the role of electronic factors (e.g., spin-state, d-electron count, metal–ligand covalency) in facilitating O₂ activation and S-dioxygenation in CDO and related models.

Comments

Accepted version. Dalton Transactions, No. 39, (June 27, 2017). DOI. © 2017 The Royal Society of Chemistry. Used with permission.

Recommended Citation

Fischer, Anne A.; Lindeman, Sergey V.; and Fiedler, Adam T., "Spectroscopic and Computational Studies of Reversible O₂ Binding by a Cobalt Complex of Relevance to Cysteine Dioxygenase" (2017). Chemistry Faculty Research and Publications. 889.
https://epublications.marquette.edu/chem_fac/889