Elzbieta Lodyga-Chruscinska

Synthesis and Characterization of VIVO Complexes of Picolinate and Pyrazine Derivatives. Behavior in the Solid State and Aqueous Solution and Biotransformation in the Presence of Blood Plasma Proteins

Oxidovanadium(IV) complexes with 5-cyanopyridine-2-carboxylic acid (HpicCN), 3,5-difluoropyridine-2-carboxylic acid (HpicFF), 3-hydroxypyridine-2-carboxylic acid (H2hypic), and pyrazine-2-carboxylic acid (Hprz) have been synthesized and characterized in the solid state and aqueous solution through elemental analysis, IR and EPR spectroscopy, potentiometric titrations, and DFT simulations. The crystal structures of the complexes (OC-6-23)-[VO(picCN)2(H2O)]·2H2O (1·2H2O), (OC-6-24)-[VO(picCN)2(H2O)]·4H2O (2·4H2O), (OC-6-24)-Na[VO(Hhypic)3]·H2O (4), and two enantiomers of (OC-6-24)-[VO(prz)2(H2O)] (Λ-5 and Δ-5) have been determined also by X-ray crystallography. 1 presents the first crystallographic evidence for the formation of a OC-6-23 isomer for bis(picolinato) V(IV)O complexes, whereas 2, 4, and 5 possess the more common OC-6-24 arrangement. The strength order of the ligands is H2hypic ≫ HpicCN > Hprz > HpicFF, and this results in a different behavior at pH 7.40. In organic and aqueous solution the three isomers OC-6-23, OC-6-24, and OC-6-42 are formed, and this is confirmed by DFT simulations. In all the systems with apo-transferrin (VO)2(apo-hTf) is the main species in solution, with the hydrolytic V(IV)O species becoming more important with lowering the strength of the ligand. In the systems with albumin, (VO)(x)HSA (x = 5, 6) coexists with VOL2(HSA) and VOL(HSA)(H2O) when L = picCN, prz, with [VO(Hhypic)(hypic)](-), [VO(hypic)2](2-), and [(VO)4(μ-hypic)4(H2O)4] when H2hypic is studied, and with the hydrolytic V(IV)O species when HpicFF is examined. Finally, the consequence of the hydrolysis on the binding of V(IV)O(2+) to the blood proteins, the possible uptake of V species by the cells, and the possible relationship with the insulin-enhancing activity are discussed.

Oxovanadium(IV) complexes of quinoline derivatives

Abstract Complex formation between oxovanadium(IV) and five quinoline derivatives, 8-hydroxyquinoline (8-HQ), 8-hydroxyquinoline-5-sulphonic acid (8-HQS), 2-methyl-8-hydroxyquinoline (8-HQD), 8-hydroxyquinoline-N-oxide (8-HQNO), and 8-quinolinecarboxylic acid (8-QC), was studied in aqueous solution through the combined application of potentiometric and spectroscopic (electronic absorption and EPR) techniques. The results indicate that all the ligands form mono and bis chelated complexes with the VO(IV) ion. The bis chelated complexes are neutral and poorly soluble. In solution 8-HQ and 8-HQS form two cis isomers bearing a water molecule in the equatorial plane. This water molecule deprotonates with a pKa of 8.76 (8-HQ) to give the corresponding EPR-active mono hydroxo species. Four five-coordinated complexes were isolated in the solid state: [VO(8-HQ)2], [VO(8-HQD)2], [VO(8-HQNO)2] and [VO(8-QC)2]. They were characterised by IR spectroscopy and diffuse reflectance electronic absorption, and by solution studies in coordinating (DMSO) or non-coordinating (toluene and CH2Cl2) solvents. Moreover, the corresponding species with Zn2+, GaCl2+ or TiO2+ were doped with different amounts of VO2+. The structures of [VO(8-HQ)2] and [VO(8-HQD)2] show a distortion toward the trigonal bipyramid, whilst those of [VO(8-HQNO)2] and [VO(8-QC)2] are closer to the square pyramid. In coordinating solvents, [VO(8-HQ)2] shows a trans–cis isomerisation and re-originates the structure displayed in aqueous solution. The features of five-coordinated VO(IV) complexes in solution and in solid state are discussed.

Can the 1,5-disubstituted tetrazole ring modify the co-ordinating ability and biological activity of opiate-like peptides?

The copper(II) complexing ability and the biological activity of beta-casomorphin-7 tetrazole analogues have been investigated. Potentiometric and spectroscopic (UV-Vis, CD and EPR) studies have been used to establish the thermodynamic stability, speciation and structure of Cu(II) complexes with YP-psi(CN4)-FPGPI-NH2 (1), YPF-psi(CN4)-AGPI-NH2 (2) and YPFP-psi(CN4)-GPI-NH2 (3). Comparison of the binding ability of the tetrazole analogues reveals that the most effective ligand for copper(II) is YPF-psi(CN4)-AGPI-NH2. The effectiveness of this ligand comes from its particular conformation suited for the Cu(II) 2N co-ordination mode in the physiological pH region. The ability of casomorphin tetrazole analogues to activate rat mast cells to histamine release in vitro in the presence of copper(II) has been studied.

Effect of the tetrazole cis-amide bond surrogate on the complexing ability of some enkephalin analogues toward Cu(II) ions

A study of the effect of the tetrazole moiety, a cis-amide bond surrogate, on the Cu(II) coordinating properties of oligopeptides is reported. The insertion of the tetrazole moiety psi (CN4) into the peptide sequence of [Leu5]enkephalin considerably changes the coordination ability of the ligand. Potentiometric and spectroscopic results indicate that if the tetrazole moiety is in a suitable position in the peptide chain, i.e. if it follows the third residue, an unusual stable CuH-1L species involving 4N coordination is formed in the physiological pH region. The tetrazole psi (CN4) ring provides one of these nitrogens. The data indicate that Cu(II) ions are strongly trapped inside a bent peptide backbone. However, the coordination mode involving the tetrazole ring nitrogen does not prevent the hydrolysis process under strongly basic conditions.

CAN THE ALPHA -HYDROXYMETHYLATED AMINO ACID RESIDUE INFLUENCE THE PEPTIDE BINDING ABILITY TOWARDS COPPER(II) IONS?

Abstract Complexing ability of tetrapeptides Phe– ( R,S )HmR–Arg–Lys, Phe–( R )HmR–Arg–Lys and Phe–( R,S )HmO–Arg–Lys containing potential multi-donor systems provided by the novel amino acid α-hydroxymethylarginine or by α-hydroxymethylornithine has been investigated by potentiometry and the spectroscopic methods (EPR, UV-VIS and CD). Their complexes with copper(II) ions were compared with those of the parent peptides Phe–Ala–Ala–Lys, Phe–Ser–Ala–Lys, Phe–Arg–Arg–Lys and Phe–Orn–Arg–Lys. The significant enhancement of thermodynamic stability is observed for the 2N and 3N species. The CD and EPR spectra support square-planar geometry in 3N species formed at physiological pH. The distortion of the metal environment is induced through the bend conformation adopted by the peptide molecule. The Lys residue is the critical factor influencing this geometry distortion in the 3N species. However, the presence of a α-hydroxymethyl group affects the stability of the complexes, most likely by stabilizing conformations suitable for metal complexation.