Jump to main content
Jump to site search


Spectroscopic and computational studies of reversible O2 binding by a cobalt complex of relevance to cysteine dioxygenase

Author affiliations

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+(TpR2)(CysOEt)] (R = Ph (3) or Me (4); TpR2 = 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 TpR2 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.

Graphical abstract: Spectroscopic and computational studies of reversible O2 binding by a cobalt complex of relevance to cysteine dioxygenase

Back to tab navigation

Supplementary files

Publication details

The article was received on 02 May 2017, accepted on 27 Jun 2017 and first published on 07 Jul 2017


Article type: Paper
DOI: 10.1039/C7DT01600J
Citation: Dalton Trans., 2017, Advance Article
  •   Request permissions

    Spectroscopic and computational studies of reversible O2 binding by a cobalt complex of relevance to cysteine dioxygenase

    A. A. Fischer, S. V. Lindeman and A. T. Fiedler, Dalton Trans., 2017, Advance Article , DOI: 10.1039/C7DT01600J

Search articles by author

Spotlight

Advertisements