Electron transfer mechanism of catalytic superoxide dismutation via Cu(ii/i) complexes: evidence of cupric–superoxo/–hydroperoxo species

Abstract

To understand the electron transfer mechanisms (outer versus inner sphere) of catalytic superoxide dismutation via a Cu(ii/i) redox couple such as occur in the enzyme copper-zinc superoxide dismutase, the Cu(ii/i) complexes [(L1)2Cu](ClO4)2·CH3CN, (1·CH3CN) and [(L1)2Cu](ClO4), (2) supported by a bis-N2Sthioether ligand, 2-pyridyl-N-(2'-methylthiophenyl)methyleneimine (L1) have been synthesized and structurally characterised. Both 1 and 2 display the same cyclic voltammogram (CV) featuring a quasireversible response at E1/2 = +0.33 V vs. SCE that falls in the SOD potential window of -0.04 V to +0.99 V. These complexes catalytically dismutate superoxide radicals at 298 K in aqueous medium (the IC50 for 1 is 2.15 μM). Electronic absorption spectra (233 K and 298 K), FTIR, ESI mass spectra, CV (233 K and 298 K) and DFT calculations collectively indicate formation of [(L1)2Cu(O2˙(-))](+), [(L1)2Cu(O2(2-))] and [(L1)2Cu(OOH(-))](+) species and help to elucidate the electron transfer mechanism for the SOD function of 1 and 2. Once O2˙(-) binds to Cu(II) (evident at 233 K), the first step of the catalytic cycle (Cu(II) + O2˙(-)→ Cu(I) + O2) does not follow but the second step (Cu(I) + O2˙(-) + 2H(+)→ H2O2 + Cu(II)) does follow. Therefore, the catalytic disproportionation of superoxide radicals via1 and 2 at 298 K indicates that the first and second steps of the catalytic cycle proceed through outer and inner sphere electron transfer mechanisms, respectively. Feasibility of the first step to occur in pure aprotic solvent (where 18-crown-6-ether is used to solubilise KO2) was tested and also supports the same notion of the electron transfer mechanisms as stated above.

Activation of dioxygen by copper metalloproteins and insights from model complexes

“…A recent model study contrasts this proposed enzymatic mechanism (Scheme 19, bottom) [260]. At room temperature, addition of ${\mathrm{normalO}}_2^{·-}$ to a Cu II model complex resulted in 97% formation of O 2 , as confirmed via electrochemical studies.…”

“…Middle the proposed enzymatic mechanism of CuZnSOD [258, 259]. Bottom the proposed mechanism for a model complex of CuZnSOD [260]…”

Investigating the cytotoxic redox mechanism of PFOS within Hep G2 by hyperspectral-assisted scanning electrochemical microscopy

“…To investigate the role of SOD 1 and superoxide anion radical, Hep G2 cells were treated with a 5 µM solution of a SOD 1 inhibitor (i.e., LCS-1, which is a 2-phenylpyridazin-3(2H)-one based non-copper chelater that selectively inhibits SOD 1 (Cu/Zn-SOD) with an IC 50 of 1.07 µM). Following treatment, the activity of SOD 1 was suspended to prohibit the following mechanism for the dismutation of superoxide (eqn (3)-( 5)): 43 Cu…”

“…Upon recognition of a Cu II -redox species, the first reaction mechanism (eqn (3)) executed by SOD 1 is an outer-sphere electron transfer, 43 making it feasible for electrons lost via superoxide dismutation to be gained by Fc + CH 2 OH to facilitate the regeneration of FcCH 2 OH. Alternatively, superoxide anion radicals have been implicated in the regeneration of ferrocene analogs.…”

Design and reactivity of Ni-complexes using pentadentate neutral-polypyridyl ligands: Possible mimics of NiSOD

“…Following a reported procedure, sodium iodide assays were employed to detect and quantify the amount of hydrogen peroxide produced by 1 – 3 . 59 The assays were done in the presence of perchloric acid (HClO 4 ) due to the stability it affords to any liberated H 2 O 2 . All three complexes show evidence for H 2 O 2 production by this assay (Figure S9), with comparable yields of H 2 O 2 (~ 15 – 20%).…”