Control of structure, stability and catechol oxidase activity of copper(II) complexes by the denticity of tripodal platforms

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On the possible roles of N-terminal His-rich domains of Cu,Zn SODs of some Gram-negative bacteria

The Cu,Zn superoxide dismutases (Cu,Zn SOD) isolated from some Gram-negative bacteria possess a His-rich N-terminal metal binding extension. The N-terminal domain of Haemophilus ducreyi Cu,Zn SOD has been previously proposed to play a copper(II)-, and may be a zinc(II)- chaperoning role under metal ion starvation, and to behave as a temporary (low activity) superoxide dismutating center if copper(II) is available. The N-terminal extension of Cu,Zn SOD from Actinobacillus pleuropneumoniae starts with an analogous sequence (HxDHxH), but contains considerably fewer metal binding sites. In order to study the possibility of the generalization of the above mentioned functions over all Gram-negative bacteria possessing His-rich N-terminal extension, here we report thermodynamic and solution structural analysis of the copper(II) and zinc(II) complexes of a peptide corresponding to the first eight amino acids (HADHDHKK-NH2, L) of the enzyme isolated from A. pleuropneumoniae. In equimolar solutions of Cu(II)/Zn(II) and the peptide the MH2L complexes are dominant in the neutral pH-range. L has extraordinary copper(II) sequestering capacity (KD,Cu = 7.4×10–13 M at pH 7.4), which is provided only by non-amide (side chain) donors. The central ion in CuH2L is coordinated by four nitrogens {NH2,3Nim} in the equatorial plane. In ZnH2L the peptide binds to zinc(II) through a {NH2,2Nim,COO–} donor set, and its zinc binding affinity is relatively modest (KD,Zn = 4.8×10–7 M at pH 7.4). Consequently, the presented data do support a general chaperoning role of the N-terminal His-rich region of Gram-negative bacteria in copper(II) uptake, but do not confirm similar function for zinc(II). Interestingly, the complex CuH2L has very high SOD-like activity, which may further support the multifunctional role of the copper(II)-bound N-terminal His-rich domain of Cu,Zn SODs of Gram-negative bacteria. The proposed structure for the MH2L complexes have been verified by semiempirical quantum chemical calculations (PM6), too

A novel 1,3,5-triaminocyclohexane-based tripodal ligand forms a unique tetra(pyrazolate)-bridged tricopper(II) core: solution equilibrium, structure and catecholase activity

A polydentate tripodal ligand forms a series of tricopper(ii) complexes, that feature unique pyrazolate-bridged linear core. The Cu3H−3L2complex is an efficient catecholase mimic with a surprisingly low pH optimum at pH = 5.6.</p

Tuning the coordination properties of multi-histidine peptides by using a tripodal scaffold: solution chemical study and catechol oxidase mimicking

Two new tripodal peptides containing non-protected N-terminal (L1, tren3his) and C-terminal (L2, nta3his) histidines have been synthesized in order to combine the structuring effect of tripodal scaffolds and the strong metal binding properties of histidine moieties. In the present work the copper(ii) complexes of these ligands have been studied by combined pH-metric, UV-Vis, CD, EPR and MS methods. At a 1 : 1 metal-to-ligand ratio the two ligands behave as the corresponding dipeptides containing N/C-terminal histidines, but above pH 9 the participation of the tertiary amine in the fused chelate rings results in unique binding modes in the case of both ligands. Besides, the formation of oligonuclear complexes also confirms the positive influence of tripodal platforms on metal coordination, and provides the potential to be efficient functional models of oxidase enzymes. Accordingly, the oligonuclear complexes of both ligands exhibit considerable catecholase-like activity. The oxidation of 3,5-di-tert-butyl-catechol proceeds with the participation of separated Cu2+ centers in the presence of L1 complexes. However, the proximity of the two metal ions in the dinuclear complexes of L2 allows their cooperation along the catalytic cycle. Substrate binding modes, effects of reactants, intermediate and side product formation have also been studied, allowing us to propose a plausible catalytic mechanism for each copper(ii)-ligand system