Structural characterization of a highly active superoxide-dismutase mimic

Abstract

A lot of effort has been put into the synthesis of copper complexes with superoxide-dismutase (SOD) activity because of their potential pharmaceutical applications. In this work, we study a model for these so-called SOD mimics (SODm), namely a copper complex of 6-(2-hydroxy-benzaldehyde) hydrazono-as-triazine-3,5-dione, which shows an extremely high SOD-like activity in solution. X-Ray diffraction reveals that the complex adopts a di-copper structure in the solid state. However, in solution, the chloride bridges are broken, forming a mono-copper center as follows from UV/Vis absorption and electron paramagnetic resonance (EPR) experiments. Using pulsed EPR techniques in combination with DFT (density functional theory) computations, the electronic structure of the complex in solution is analyzed in detail and related to its high SOD activity. The structure-activity analysis serves to orient further synthetic efforts to obtain the optimum geometry around the metal essential for SOD-like activity.

Mononuclear copper (II) salicylate complexes with 1,2-dimethylimidazole and 2-methylimidazole: Synthesis, spectroscopic and crystal structure characterization and their superoxide scavenging activities

“…Although these IC 50 values are still larger than the value reported for native Cu, Zn-SOD (0.04 M) but are comparable with the IC 50 values reported for the best copper complex mimics [12,15,[29][30][31][32][45][46][47][48]. These complexes are considered potent SOD mimics considering their very low molecular weights when compared to that of the native Cu, Zn-SOD enzyme.…”

“…The SOD-like activities which are measured by IC 50 values of the complexes under investigations are comparable with those IC 50 values reported for the most active SOD mimics [12,15,[29][30][31][32][45][46][47][48]. The IC 50 for complex 1 is comparable with that reported for the trans-bis (benzimidazole) 2 bis (salicylato) copper (II) complex (Table 2) [15].…”

Synthesis, structure and superoxide dismutase-like activity of copper(II) complexes based on N,N′-bis(2-quinolinylmethyl)amantadine

“…Due to the limitations of solution instability, immunogenicity, bell-shaped dose response curves, short half-lives, costs of production and proteolytic digestion, the direct utilization of Cu,Zn-SOD as a pharmaceutical agent still has many problems [6]. Therefore, considerable endeavors on Cu,Zn-SOD mimics of low-molecular weight copper complexes have been carried out due to the advantages of overcoming the immunogenicity problems associated with protein administration and tissue permeability, and for the potential for greater in vivo stability [7]. Many copper(II) complexes of bipod/tripod ligands containing three N donor atoms have been extensively applied as SOD mimics due to their redox activity, flexible configuration and relative stability [8][9][10][11].…”

Artificial Organelles: Reactions inside Protein–Polymer Supramolecular Assemblies

“…We introduced a novel approach to detoxify superoxide radicals by designing nanoreactors with superoxide dismutase (SOD) or its mimics inside the cavity of polymersomes equipped with OmpF. [26][27][28][29] Another interesting approach for providing appropriate conditions for the development of complex reaction systems, as in molecular factories, is to design stimulicreates an opportunity for developing biohybrid desalination membranes that are necessary for translational applications.…”