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Enrique Meléndez

Publications and source records attributed to Enrique Meléndez.

5 recordsLinked to original sources

Determination of the titanium content of human transferrin by inductively-coupled plasma-atomic-emission spectroscopy.

We report a simple method that combines dialysis, as a purification method, with the multielement capability of ICP to determine the titanium-to-transferrin mole ratio at physiological pH, under buffer conditions. The method, by means of which titanium and transferrin are determined simultaneously, enabled us to assess the binding capacities of different titanocene complexes.

Humans↗

Molybdenocene-oligonucleotide binding study at physiological pH using NMR spectroscopy and cyclic voltammetry.

The self-complementary oligonucleotide CGCATATATGCG was used as a model to establish the binding interactions of antitumor molybdenocene dichloride and DNA. The free dodecamer was first characterized using (1)H, NOESY, and DQF-COSY NMR experiments, which enable to pinpoint the guanines and adenines as well as the cytosines and thymines signals in the aromatic region. Molybdenocene dichloride was characterized in saline and buffer solutions as function of pH by (1)H NMR spectroscopy. In 10mM NaCl/D(2)O solution at pH of 6.5 and above, Cp(2)Mo(OD)(D(2)O)(+) is in equilibrium with its dimeric species, [Cp(2)Mo(mu-OH)(2)MoCp(2)](2+). In 25mM Tris/4mM NaCl/D(2)O at physiological pH, a new stable species is formed, coordinated by the buffer, Tris(hydroxymethyl)aminomethane. The interactions of molybdenocene dichloride species with CGCATATATGCG were studied at different pH. At pH 6.5, in 4mM NaCl/D(2)O solution, (1)H NMR spectra of CGCATATATGCG exhibit downfield shifts in the signals associated mainly to adenines and guanines, upon addition of molybdenocene dichloride. At pH 7.4, in 25mM Tris/4mM NaCl/D(2)O, molybdenocene species causes broadening and small downfield shifts to the purines and pyrimidine signals, suggesting that molybdenocene dichloride can get engaged in binding interactions with the oligonucleotide in a weak manner. (31)P NMR spectra of these interactions at pH 7.4 showed no changes associated to Mo(IV)-OP coordination, indicating that molybdenocene-oligonucleotide binding interactions are centered, most likely, on the bases. Cyclic voltammetry titration showed a 4.9% of molybdenocene-oligonucleotide interaction. This implicates that possible binding interactions with DNA are weak.

DNA↗

Water-soluble titanocene complexes with sulfur-containing amino acids: synthesis, spectroscopic, electrochemical and Ti(IV)-transferrin interaction studies.

Three new water soluble titanocene-amino acid complexes have been synthesized via the reaction of Cp(2)TiCl(2) and two equivalents of amino acid (L) in methanol, affording [Cp(2)TiL(2)]Cl(2), L = L-cysteine (2), D-penicillamine (3) and L-methionine (4). These complexes have been characterized by (1)H, IR and UV-Vis spectroscopies, elemental analysis and cyclic voltammetry. Kinetic studies of ligand hydrolysis have been monitored at low pH using UV-Vis and (1)H NMR spectroscopies to assess their stability in aqueous solution. At low pH, amino acid ligands are lost one order of magnitude faster than cyclopentadienyl. However, at physiological pH, in Tris buffer solution, the complexes decompose rapidly to form an insoluble titanium compound. The affinity of these complexes to apo-transferrin was also investigated to elucidate how the ancillary amino acid ligands affect the titanium intake by apo-transferrin.

Amino Acids, Sulfur↗

Study of titanocene-DNA and molybdenocene-DNA interactions by inductively coupled plasma-atomic emission spectroscopy.

Titanocene and molybdenocene dichlorides belong to a new class of organometallic antitumor agent. Although these complexes are isostructural, they behave differently under physiological conditions and hence have different mechanisms of action. It was initially proposed that these species interact with DNA, inhibiting the cell cycle. Recent studies using nucleotides and oligonucleotides suggest that molybdenocene does not bind DNA constituents at physiological pH whereas titanocene apparently interacts weakly with nucleotides through the phosphoesters. The evidence for this was, however, obtained under non-physiological conditions. Herein we report an analytical method that enables determination of the amount of metal bound to DNA under physiological conditions (pH 7.4 and buffer solution) and with sample preparation (dialysis) that resembles the cell environment. It was found that more than 90% titanium was bound to DNA after 46 h whereas binding of molybdenum was no more than 5%.

Animals↗

Titanium complexes in cancer treatment.

A series of complexes containing titanium, Ti, as a metal center has shown to possess a wide spectrum of antitumor properties. This series belongs to the non-platinum metal antitumor agents which has been developed mainly in the past 20 years. The bis(beta-diketonato)titanium(IV) and titanocene derivatives appear to offer a different alternative for cancer chemotherapy which do not follow the rationale and mechanism of action of the platinum complexes. The hydrolysis of these complexes in aqueous and pseudo aqueous solutions is discussed and the interaction studies of titanium complexes with biomolecules are also presented to unravel the mechanism of action at molecular levels.

Animals↗