A Series of Ni Complexes Based on a Versatile ATCUN-Like Tripeptide Scaffold to Decipher Key Parameters for Superoxide Dismutase Activity

Abstract

The cellular level of reactive oxygen species (ROS) has to be controlled to avoid some pathologies, especially those linked to oxidative stress. One strategy for designing antioxidants consists of modeling natural enzymes involved in ROS degradation. Among them, nickel superoxide dismutase (NiSOD) catalyzes the dismutation of the superoxide radical anion, O 2•− , into O 2 and H 2 O 2 . We report here Ni complexes with tripeptides derived from the amino-terminal Cu II -and Ni II -binding (ATCUN) motif that mimics some structural features found in the active site of the NiSOD. A series of six mononuclear Ni II complexes were investigated in water at physiological pH with different first coordination spheres, from compounds with a N3S to N2S2 set, and also complexes that are in equilibrium between the N-coordination (N3S) and S-coordination (N2S2). They were fully characterized by a combination of spectroscopic techniques, including 1 H NMR, UV−vis, circular dichroism, and X-ray absorption spectroscopy, together with theoretical calculations and their redox properties studied by cyclic voltammetry. They all display SOD-like activity, with a k cat ranging between 0.5 and 2.0 × 10 6 M −1 s −1 . The complexes in which the two coordination modes are in equilibrium are the most efficient, suggesting a beneficial effect of a nearby proton relay.

Reduction-cleavable desferrioxamine B pulldown system enriches Ni(ii)-superoxide dismutase from a Streptomyces proteome

“…The model showed the displacement of the His1 residue upon mono-hydroxamate binding, with the mobility of this residue established as part of the NiSOD mechanism. 28,30,49–52 The modelling was informative, but alone was insufficient to support the proposed ternary complex.…”

The role of the terminal cysteine moiety in a metallopeptide mimicking the active site of the NiSOD enzyme

“…16 Since NiSODs exhibit a rather unusual active site, significant efforts have been made to understand the fundamental spectroscopic and catalytic features of these compounds. Accordingly, several Ni-based metallopeptides [17][18][19][20][21] and low-molecular-weight synthetic nickel complexes [22][23][24][25] have been studied. Our work focused on how the stability of Ni II and Ni III complexes as well as the catalytic activity can be tuned by altering the primary coordination sphere of nickel.…”