József S. Pap

Bio-inspired flavonol and quinolone dioxygenation by a non-heme iron catalyst modeling the action of flavonol and 3-hydroxy-4(1H)-quinolone 2,4-dioxygenases

The mononuclear complex, Fe(III)(O-bs)(salen) (salenH(2)=1,6-bis(2-hydroxyphenyl)-2,5-diaza-hexa-1,5-diene; O-bsH=O-benzoylsalicylic acid) was synthesized as synthetic enzyme-depside complex, and characterized by spectroscopic methods and X-ray crystal analysis. The dioxygenation of flavonol (flaH) and 3-hydroxy-4-quinolone (quinH(2)) derivatives in the presence of catalytic amounts of Fe(III)(O-bs)(salen) results in the oxidative cleavage of the heterocyclic ring to give the corresponding O-benzoylsalicylic and anthranilic acid derivatives with concomitant release of carbon monoxide. These reactions can be regarded as biomimetic functional models with relevance to the iron-containing flavonol and the cofactor-independent 3-hydroxy-4(1H)-quinolone 2,4-dioxygenases.

Branched peptide with three histidines for the promotion of CuII binding in a wide pH range – complementary potentiometric, spectroscopic and electrochemical studies

Modifications in linear and cyclic peptides have been widely explored in relation with the associated effects on the coordination of CuII. Branching of peptides is yet another innovative conception to promote metal binding. The three dimensional (3D), quasi-tripodal structure of the new ligand, H-His-Dap(H-His)-His-NH2 (3H, where Dap = L-2,3-diaminopropionic acid), which is created by the vicinal two N-terminal and one C-terminal functions of Dap allows triple-arm extension and offers new options in metal binding. A strategy is presented for the characterization of 3H focusing on the role of structural domains in CuII binding by comparison of analogous tetrapeptides that involve a varying number of His and Gly residues. Potentiometric, spectroscopic (UV-Vis, CD and EPR), mass spectrometric and electrochemical data indicate that in monomeric CuII–3H complexes the metal is bound with higher affinity compared to its structural domains indicating that the effect of 3D branching should be taken as an important factor for future studies on CuII peptide constructs.

The Cu2+ binding properties of branched peptides based on l -2,3-diaminopropionic acid

Three new branched peptides, namely, H-Gly-Dap(H-Gly)-Gly-NH2 (3G), H-His-Dap(H-His)-Gly-NH2 (2HG), and H-Gly-Dap(H-Gly)-His-NH2 (2GH), where Dap stands for the 2,3-diaminopropionic acid residue, were synthesized by solid phase procedures. Because of the junction at Dap these peptides have three available pending arms for metal chelation. The complex formation between these peptides and 1 equiv of Cu(2+) was investigated as a function of pH by potentiometry ultraviolet-visible absorption, circular dichroism, and X-band electron paramagnetic resonance spectroscopy in aqueous medium. Our results clearly demonstrate that cooperation between all three peptide arms essentially contributes to the stability of copper(II) complexes.

Transition metal complexes bearing flexible N3 or N3O donor ligands: Reactivity toward superoxide radical anion and hydrogen peroxide

Mononuclear complexes of N-methylpropanoate-N,N-bis-(2-pyridylmethyl)amine (MPBMPA) and N-propanoate-N,N-bis-(2-pyridylmethyl)amine (HPBMPA) with first row transition metals from Mn to Cu were synthesized and characterized by spectroscopy (infrared, UV-visible), electrochemistry (cyclic voltammetry), microanalysis and in four cases X-ray crystallography. Structure of the complexes revealed high flexibility of these ligands that can adopt facial (Fe) and meridional (Cu) geometry. Activity in the degradation of reactive oxygen species (superoxide radical anion: superoxide dismutase (SOD)-like activity and hydrogen peroxide: catalase-like activity) was tested throughout the complex series in aqueous solutions. In connection with the catalytic dismutation of H(2)O(2), bleaching tests with morin were also conducted in water. Comparison of the two ligands helped in elucidating the possible role of the carboxylate moiety in the different catalytic reactions. Although no general trends could be revealed between reactivity and constitution of the first coordination sphere, plausible explanations for differences are discussed individually for SOD like, catalase-like and bleaching activity.

Stabilisation of μ-peroxido-bridged Fe(III) intermediates with non-symmetric bidentate N-donor ligands

The spectroscopic characterisation of the (μ-1,2-peroxido)diiron(iii) species formed transiently upon reaction of [Fe(ii)(NN)3](2+) complexes with H2O2 by UV/vis absorption and resonance Raman spectroscopy is reported. The intermediacy of such species in the disproportionation of H2O2 is demonstrated.

Interactions of anti-Parkinson drug benserazide with Zn(II), Cu(II), Fe(II) ions

One of the treatments of Parkinson disease is based on increasing the brain dopamine level by L-DOPA (LD) applications. To prevent the peripheral degradation of levodopa, another drug, benserazide is applied. On the other hand, during this neurodegenerative disease changes in the homeostasis of metals are observed and the increasing brain zinc levels are postulated to have therapeutic effects. Here we present studies on interactions of Zn(II), Cu(II), Fe(II) ions with benserazide and with benserazide/levodopa in ternary system. By applying mass spectrometry and UV-vis methods we describe the interactions between selected metal ions and the drug additives in the investigated systems. The results show forming of equimolar complexes in the binary and ternary systems.

Armed by Asp? C-terminal carboxylate in a Dap-branched peptide and consequences in the binding of CuII and electrocatalytic water oxidation

The imidazole ring of histidine (His) and the methylcarboxylate function of aspartic acid (Asp) are crucial for Cu coordination in enzymes, artificial proteins and other bioinspired systems. In order to elucidate the effect of Asp at the C-terminus, a new branched peptide, H-Gly-Dap(H-Gly)-Asp-NH2 (2GD, Dap = 2,3-diaminopropionic acid) has been synthesized to ligate CuII. While at pH < 8, 2GD favours dimeric complexes at 1 : 1 metal-to-ligand ratio, at increasingly alkaline pH the Asp at the C-terminus creates a {NH2,N−,N−,O−}eq set and the dominance of mononuclear CuLH−2 and CuLH−3 species, according to potentiometry, molecular spectroscopy (UV-visible, circular dichroism and X-band electron paramagnetic resonance) and ESI-MS analysis. The changes in speciation with pH are accompanied by shifts in the CuIII/II redox current peaks that were analyzed by square wave voltammetry (SWV) and allowed the calculation of the pKa values for the CuII and CuIII forms. The 2GD complex exhibits electrocatalytic activity in water oxidation in phosphate buffer. However, when Asp residues are present at all three termini to produce 3D (H-Asp-Dap(H-Asp)-Asp-NH2), the electrocatalysis of water oxidation decreases and, if present only at the N-termini in 2DG (H-Asp-Dap(H-Asp)-Gly-NH2), it ceases. As for CuII ligated by 2GD, a TOF of ∼16 s−1 was calculated at pH = 11 in 0.2 M phosphate electrolyte, which is crucial for catalysis, but also acts as inhibitor anion according to cyclic voltammetry observations. The system is highly tolerant to the presence of chloride, which is a feature of practical importance in efficient water oxidation catalysis.

On the Cu(III)/Cu(II) Redox Chemistry of Cu-Peptide Complexes to Assist Catalyst Design

Graphical Abstract The versatility of copper-peptide complexes offers several options for adjusting their pH-dependent speciation, stability, and redox properties. In context, their bio-inspired and prospective catalytic applications receive distinguished attention. There are a number of Cu-catalysts (including some Cu-peptides) that utilize Cu(III) as part of the catalytic cycle and, in those cases, this oxidation state has been thoroughly characterized. However, the Cu(III) state for peptide complexes in general has been less studied. Compared to the sophisticated characterization of the Cu(II) equilibrium species, the precise evaluation of their Cu(III)/Cu(II) redox processes is scarce. Considering their potential catalytic applications, understanding their redox behavior would be essential. In this brief comment, a methodology and its background are discussed that aim to highlight relations between the Cu(III)/Cu(II) formal potentials, the difference in the association constants (stability) of the oxidized and reduced forms, and the ligand constitution for a number of mononuclear copper-peptide complexes.

Iron and Manganese-Containing Flavonol 2,4-Dioxygenase Mimics

Oxygenases are enzymes which play key roles in the metabolism of essential substances for vital functions, and in the biodegradation of aromatic compounds in the environment. Two types of oxygenases are known, namely monoand dioxygenases: one atom oxygen is incorporated into a substrate by the former accompanied with the formation of water, and two atoms of dioxygen into one or two substrates by the latter (Eqs. 1-3).

SOD-Like Activity of Copper(II) Containing Metallopeptides Branched By 2,3-Diaminopropionic Acid: What the N-Termini Elevate, the C-Terminus Ruins

Relations between structural modifiactions and SOD-like activity of four branched CuII-metallopeptides based on l-2,3-diaminopropionic acid are reported. The IC50 values (McCord–Fridovich method) illustrate that enhanced SOD-like activity is warranted by exclusive N-terminal His localization that surmounts the driving force by the CuII/I formal potential.