Phenyl-substituted copper di-Schiff base, a potent Cu 2Zn 2 superoxide dismutase mimic surviving competitive biochelation

Abstract

[ N, N′-bis(2-pyridyl-phenyl)methylene-1,4-butanediamine]-( N, N′, N″, N‴)-copper( II), Cu(II)PuPhePy, a copper(II) di-Schiff base in both its chloride and perchlorate form, has been prepared and crystallized with a yield of 50 ± 10%. IR spectra confirmed the successful preparation. The electronic absorption ϵ 690 was 136 M −1 cm −1. The EPR parameters g ⊥ = 2.048 and g ∥ = 2.217 were in close agreement with the respective values of intact Cu 2Zn 2 SOD. Comparison of the crystal structures of this complex and the copper binding centre of Cu 2Zn 2 SOD revealed a virtually identical coordination chemistry. The pulse-radiolytically-determined superoxide dismutation proceeded even in the presence of a fourfold molar excess of EDTA at a rate of 0.48 × 10 9 M −1 s −1. In the indirect nitroblue tetrazolium assay 0.27 μM of Cu(II)PuPhePy(ClO 4) 2 were required to cause 50% inhibition. The thermodynamic stability constant log K = 18.33 ± 0.77 was calculated from CD data. The stability being two orders of magnitude higher than that of serum albumin, a competitive biological Cu(II) chelator and its ‘model’ EDTA was deduced. Of all the many superoxide dismutase mimics examined, the present Cu complex is in closest agreement in both structure and catalytic function with the active centre of intact Cu 2Zn 2 SOD.