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In this work, attention is focused on the non-essential amino acid L-Tyrosine (TYR) hydroxylated to L-DOPA, which is the precursor to the neurotransmitters dopamine, noradrenaline (norepinephrine; NE) and adrenaline (epinephrine; EP) known as catecholamines and their interactions with redox-active Cu(II). Catecholamines have multiple functions in biological systems, including the regulation of the central nervous system, and free (unbound) redox metal ions are present in many diseases with disturbed metal homeostasis. The interaction between catecholamines and Cu(II) has been studied by means of Electron Paramagnetic Resonance spectroscopy (EPR), EPR spin trapping and UV-vis spectroscopy. The obtained spectroscopic results are supported by Density Functional Theory calculations. Only minor qualitative and quantitative changes in the UV-vis spectra of all the studied compounds have been observed following their interactions with Cu(II) ions. The low-temperature EPR spectra were more convincing and confirmed the interaction between Cu(II) ions and all the studied compounds, involving hydroxyl groups and amino nitrogens. The use of an ABTS assay revealed that the compounds under study possessed radical-scavenging activities against ABTS•+ in the order TYR < EP < DA < NE~L-DOPA. The neurotransmitters DA, NE and EP, following their interaction with Cu(II), exhibit the ability to (partially) reduce Cu(II) to Cu(I) species which was confirmed using the Cu(I) specific chelator neocuproine. EPR spin-trapping experiments revealed the suppressed formation of hydroxyl radicals (•OH) in a copper(II) catalyzed Fenton-like system in the presence of catecholamines. Only in the case of EP was autooxidation in a stock solution observed. Furthermore, the oxidation of EP is enhanced in the presence of Cu(II) ions. In conclusion, it has been confirmed that the oxidation of catecholamines in the presence of copper promotes the redox cycling process, resulting in the formation of ROS, which may, in turn, cause damage to neuronal systems. [ABSTRACT FROM AUTHOR]

Cyclam derivatives and their metal complexes have been found to exhibit an anti‐HIV effect and stimulate the activity of stem cells from bone marrow. The strength of their binding to the CXCR4 receptor correlates with anti‐HIV and stem‐cell activities. Knowledge of the conformation and crystal packing of various macrocyclic metal complexes has become important in developing new effective anti‐HIV drugs. The synthesis and preparation of single crystals of a new Cu2+‐doped macrocyclic compound, (3,14‐diethyl‐2,6,13,17‐tetraazatricyclo[16.4.0.07,12]docosane)copper(II) bis(perchlorate)–3,14‐diethyl‐2,13‐diaza‐6,17‐diazoniatricyclo[16.4.0.07,12]docosane bis(perchlorate) (0.69/0.31), {[Cu(C22H44N4)](ClO4)2}0.69·(C22H46N42+·2ClO4−)0.31, is reported. Characterization by X‐ray diffraction analysis shows that the asymmetric unit contains half of a centrosymmetric molecule. The macrocyclic ligand in the compound adopts the most stable trans‐III conformation. The Cu—N distances of 2.015 (3) and 2.047 (3) Å are normal, but the long axial Cu—O bond of 2.795 (3) Å may be due to a combination of the Jahn–Teller effect and the strong in‐plane ligand field. The crystal structure is stabilized by hydrogen bonding between secondary N—H groups, the N atoms of the macrocycle and the O atoms of the perchlorate anions. Hirshfeld surface analysis with 2D (two‐dimensional) fingerprint plots indicates that the main contributions to the crystal packing are from H...H (58.0%) and H...O/O...H (41.9%) interactions. Electron paramagnetic resonance (EPR) properties are also described. [ABSTRACT FROM AUTHOR]

Redox active transition metal ions (e.g., iron and copper) have been implicated in the etiology of many oxidative stress-related diseases including also neurodegenerative disorders. Unbound copper can catalyze formation of reactive oxygen species (hydroxyl radicals) via Fenton reaction/Haber-Weiss chemistry and therefore, under physiological conditions, free copper is potentially toxic and very rarely exists inside cells. Copper(II) bound to the aminoacid L-histidine represents a species discovered in blood in the mid 60s and since then extensive research on this complex was carried out. Copper bound to L-histidine represents an exchangeable pool of copper(II) in equilibrium with the most abundant blood plasma protein, human serum albumin. The structure of this complex, in aqueous solution, has been a subject of many studies and reviews, however without convincing success. The significance of the (1:2) copper(II)-L-histidine complex at physiological pH documents its therapeutic applications in the treatment of Menkes disease and more recently in the treatment of infantile hypertrophic cardioencephalomyopathy. While recently the (1:2) Cu(II)-L-His complex has been successfully crystallized and the crystal structure was solved by X-ray diffraction, the structure of the complex in fluid solution at physiologicalpH is not satisfactorily known. The aim of this paper is to study the (1:2) Cu(II)-L-histidine complex at low temperatures by X-band and S-band EPR spectroscopy and at physiological pH at room temperature by Fourier transform CW-EPR spectroscopy. [ABSTRACT FROM AUTHOR]

The radical scavenging and metal chelating properties of flavonoids indicate that they may play a protective role in diseases with perturbed metal homeostasis such as Alzheimer's disease. In this work we investigated the effect of the coordination of quercetin to copper(II) in view of the formation of ROS in Cu-catalyzed Fenton reaction. ABTS and DPPH assays confirmed that the copper(II)-quercetin complex exhibits a stronger radical scavenging activity than does quercetin alone. EPR spin trapping experiments have shown that chelation of quercetin to copper significantly suppressed the formation of hydroxyl radicals in the Cu(II)-Fenton reaction. DNA damage experiments revealed a protective effect for quercetin, but only at higher stoichiometric ratios of quercetin relative to copper. DNA protective effect of quercetin against ROS attack was described by two mechanisms. The first mechanism lies in suppressed formation of ROS due to the decreased catalytic action of copper in the Fenton reaction, as a consequence of its chelation and direct scavenging of ROS by free quercetin. Since the Cu-quercetin complex intercalates into DNA, the second mechanism was attributed to a suppressed intercalating ability of the Cu-quercetin complex due to the mildly intercalating free quercetin into DNA, thus creating a protective wall against stronger intercalators. [ABSTRACT FROM AUTHOR]

The X-band Electron Spin Resonance spectra, ESR, of Cu(II) complexes with the carboxylic acids, HCOOH, CH3COOH, ClCH2COOH, Cl2CHCOOH, Cl3CCOOH, F2ClCOOH, CH3CH2COOH, niflumic acid and the ligands nicotinamide and papaverine have been studied. The compounds form either mononuclear or binuclear structures which can be qualitatively correlated with the strengths of the acid and base. Analysis of the spin Hamiltonian parameters for the monomeric species indicate that the molecule has nearly axial symmetry (g&par;>g⊥) with the unpaired electron in the dx2–y2 orbital. In many cases the perpendicular feature is sufficiently well resolved showing superhyperfine features due to the nitrogen ligand nuclei. A&par; varies over the range 130→188 G and the variation appears to arise as a consequence of changes in g&par;. The dimeric species show ESR spectra typical of Cu(II)-carboxylate complexes which consist of 3 (4 if E≠0) lines. These are assigned to Bz1, Bx2,y2 and Bz2 since the Q-band spectra of similar molecules indicate that the Bx1,y1 transition(s) lies below Bz2 which is itself near zero field. The observed seven-line hyperfine coupling on the Bz1 transition of some of the dimeric complexes is due to the two equivalent copper nuclei (I=I1+I2=3). The singlet–triplet separation has been estimated from the spin Hamiltonian parameters to give values of &z.sfnc;2J&z.sfnc; in the range of approximately 220–290 cm−1 which are typical of the compounds of this type. [Copyright &y& Elsevier]