Małgorzata Jeżowska-Bojczuk

Coordination of heavy metals by dithiothreitol, a commonly used thiol group protectant.

D,L-Dithiothreitol (DTT), known also as Cleland reagent, is a thiol group protectant, used commonly in peptide and protein chemistry. Therefore, it is often added at high concentrations in preparations of proteins relevant to heavy metal biochemistry. The coordination of five of these metal ions, Zn(II), Cd(II), Pb(II), Ni(II) and Cu(I) to DTT was studied by means of potentiometric titrations, and UV-Vis and NMR spectroscopies. It was found that DTT forms specific and very stable polymeric and monomeric complexes with all of these metal ions, using both of its sulfur donors. The quantitative description of these complexes in solution and the solid state provides the basis for predictions of interference from DTT in studies of metal ion binding of thiol-containing biomolecules.

Complexes of aminophosphonates - 10. Copper(II) complexes of phosphonic derivatives of iminodiacetate and nitrilotriacetate

Abstract pH-Metric and spectroscopic (absorption and EPR) studies were made on the proton and copper(II) complexes of phosphonic and mixed carboxylic-phosphonic derivatives of iminodiacetic acid and nitrilotriacetic acid. The stoichiometries and stability constants of the complexes formed were determined at 25°C and at an ionic strength of 0.20 mol dm −3 (KCl). Stability data and spectroscopic measurements revealed that in spite of the increased basicity of the coordinating phosphonate donors, the carboxylic analogues remain more efficient copper(II) binders as the larger space requirement and higher electrostatic repulsion between the binegative phosphonate donors overcompensate the former effect. The PO 3 2− /CO 2 − substitution results in a significant rhombic distortion in the geometry of the complexes.

Copper(II) binding by kanamycin A and hydrogen peroxide activation by resulting complexes

Protonation and copper(II) coordination properties of kanamycin A were studied in solution by potentiometry, UV-Vis, circular dichroism (CD), EPR and cyclic voltammetry (CV). Only mononuclear complexes of stoichiometries ranging from CuH2L to CuH−2L were found. Kanamycin A anchors Cu(II) ions with an {NH2, O−} chelate of the C-ring of its molecule. At pH higher than 6 the amino and hydroxyl groups of the A-ring of kanamycin A also participate in binding. The resulting structure, similar to that of complexes of other unsubstituted aminoglycosides studied previously, involves Cu(II) coordination by donors of terminal aminosugar rings, rather than those of the central unit. The results of cyclic voltammetry investigations, kinetic studies of H2O2 disproportionation and ROS detection experiments, further supported the mechanism of oxidative reactivity of cupric complexes of aminoglycosides, proposed by us recently [M. Jezowska-Bojczuk, W. Leśniak, W. Bal, H. Kozlowski, K. Gatner, A. Jezierski, J. Sobczak, S. Mangani and W. Meyer-Klaucke; Chem. Res. Toxicol., 2001, 14, 1353–1362], which involves Cu(I) and Cu(III) redox states and both metal-bound and free ROS.

Biological activity and structure dependent properties of cuprous iodide complexes with phenanthrolines and water soluble tris (aminomethyl) phosphanes.

This paper presents the biological activity of copper(I) iodide complexes with 1,10-phenanthroline (phen) or 2,9-dimethyl-1,10-phenanthroline (dmp) and three tris (aminomethyl) phosphanes: P(CH2N(CH2CH2)2NCH3)3 (1), P(CH2N(CH2CH2)2O)3 (2) and P (CH2N(CH3)CH2CH2OH)3 (3). Crystallographic and DFT data indicate a significantly stronger binding ability of 3 in the complexes [CuI (phen) P (CH2N (CH3)CH2CH2OH)3] (3P) and [CuI(dmp)P(CH2N(CH3)CH2CH2OH)3] (3N) in comparison to the 1 or 2 ligands. Most probably, this is caused by the relatively small steric requirements of 3. The complexes with dmp exhibit a very high in vitro activity against the Staphylococcus aureus strain (MIC - minimal inhibitory concentration: 2.5-5 μg/mL) and Candida albicans diploid fungus (MIC: 1.25-2.5 μg/mL). All the tested complexes also show a strong in vitro antitumor activity against human ovarian carcinoma cell lines: MDAH 2774 (IC50: 7-2 μM) and cisplatin-resistant SCOV3 (IC50: 3-2 μM). Interestingly, the complexes with dmp of higher biological activity more weakly interact with bovine serum albumin (BSA) and less efficiently cleave the pBluescriptSK+ plasmid.

COPPER(II) BINDING TO TOBRAMYCIN : POTENTIOMETRIC AND SPECTROSCOPIC STUDIES

Protonation and Cu(II) binding by tobramycin, an aminoglycosidic antibiotic, was studied by potentiometry and UV-vis, CD and EPR spectroscopies. A range of mononuclear complexes of a general formula CuHnL was found, with n between 3 and -2. Tobramycin anchors Cu(II) with an ¿NH2, O-¿ chelate of the C-ring of its molecule. The amino and hydroxyl groups of the A-ring of tobramycin also participate in the binding at pH 7 and higher. The resulting structure involves both terminal aminosugar rings but eliminates the donors of the central streptamine unit from the coordination. A comparison between tobramycin and its close analog, kanamycin B [M. Jezowska-Bojczuk, W. Bal and H. Kozłowski, Inorg. Chim. Acta, 275-276 (1998) 541-545] reveals the importance of the A3-OH group for the binding properties of these aminoglycosides.

COMPLEXES OF Al(III) WITH HYDROXYAROMATIC LIGANDS

Abstract In order to assess the aluminium binding ability of humic and fulvic acids, important organic soil constituents, a pH-potentiometric study was made of the proton and aluminium(III) complexes of various bi-, tri- and tetradentate catechol and salicylic acid derivatives at 25°C and at an ionic strength of 0.20moldm−3 (KC1). The stability data revealed that at low pH the salicylate function, and at high pH the catecholate function, is preferentially bound to the aluminium ion. In the intermediate pH range, mixed hydroxo complexes and other di/oligomeric species are also formed. With an increase of the number of available coordinating sites in the molecule, the tendency to oligomeric complex formation increases, while the tendency to metal ion hydrolysis decreases.

Cu(II) binding by angiotensin II fragments: Asp-Arg-Val-Tyr-Ile-His and Arg-Val-Tyr-Ile-His. Competition between amino group and imidazole nitrogens in anchoring of metal ions.

Potentiometric and spectroscopic (absorption, circular dichroism and electron paramagnetic resonance) study on the coordination of two angiotensin II fragments (Asp-Arg-Val-Tyr-Ile-His and Arg-Val-Tyr-Ile-His) to Cu(II) ions has shown that competition between amino and imidazole nitrogens to anchor metal ions is a complicated process and may lead to formation of macrochelate rings. The important factor that influences this competition is the distance between competing His and N-terminal residues (number of spacer residues in a peptide sequence).

Kanamycin revisited: a combined potentiometric and spectroscopic study of copper(II) binding to kanamycin B

Abstract Coordination of Cu(II) to kanamycin B, an aminoglycosidic antibiotic, was studied by potentiometry and UV-Vis, circular dichroism and electron paramagnetic resonance spectroscopies. Mononuclear complexes with stoichiometries ranging from CuH 3 A to CuH −2 A were found. Kanamycin B binds Cu(II) through nitrogen and oxygen donors of two terminal aminosugar rings, but the central deoxystreptamine moiety does not participate in the binding. The complex mediates oxidation of 2′-deoxyguanosine by H 2 O 2 very effectively. These properties may contribute to biological properties of kanamycin B.

Copper(II) binding to geneticin, a gentamycin analog

Abstract Protonation and Cu(II) binding by geneticin, an aminoglycosidic antibiotic of the gentamycin family, was studied by potentiometry and spectroscopic techniques (UV–vis, CD and EPR). Mononuclear complexes of a general formula CuH n L were found, with n between 2 and −2. In contrast to previously studied aminoglycosides, an additional complex with two aminoglycoside molecules, CuH −3 L 2 , was found above pH 9. Geneticin binds Cu(II) primarily with an {NHCH 3 , O − } chelate of the C-ring of its molecule. The amino and hydroxyl groups of the A-ring of geneticin also participate in the binding above pH 7. The presence of the methyl substituent on the C-ring amine nitrogen decreases Cu(II) affinity to this ring slightly compared to other aminoglycosides sharing homologous Cu(II) binding sites (tobramycin, kanamycin B). This is more than compensated by the increased affinity of the A-ring, due to the absence of a C-6 amine in geneticin.

Revised Coordination Model and Stability Constants of Cu(II) Complexes of Tris Buffer

2-Amino-2-hydroxymethyl-propane-1,3-diol, or tris(hydroxymethyl)aminomethane (Tris), is probably the most common biochemical buffer used alone or in combination with other buffers because it is stable, unreactive, and compatible with most proteins and other biomolecules. Being nontoxic, it has even found applications in medicine. Tris is known, however, to coordinate transition metal ions, Cu(II) among them. Although often ignored, this feature affects interactions of Cu(II) ions with biomolecules, as Tris is usually used in high molar excess. Therefore, it is important to have precise knowledge on the stoichiometry, stability, and reactivity of cupric Tris complexes. The literature data are incoherent in this respect. We reinvestigated the complex formation in the Tris-Cu(II) system by potentiometry, UV-vis, ESI-MS, and EPR at a broad range of concentrations and ratios. We found, contrary to several previous papers, that the maximum stoichiometry of Tris to Cu(II) is 2 and at neutral pH, dimeric complexes are formed. The apparent affinity of Tris buffer for Cu(II), determined by the competitivity index (CI) approach [Krężel, A.; Wójcik, J.; Maciejczyk, M.; Bal, W. Chem. Commun. 2003, 6, 704-705] at pH 7.4 varies between 2 × 10(6) and 4 × 10(4) M(-1), depending on the Tris and Cu(II) concentrations and molar ratio.