SVIBOR - Project code: 1-07-099


Strossmayerov trg 4, HR - 10000 ZAGREB
tel.: +385 1 459 44 44, fax: +385 1 459 44 69


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Project code: 1-07-099

Interaction of metal ions with biomolecules

Main researcher: PRIBANIĆ, MARIJAN (38805)

Type of research: basic
Duration from: 01/01/91. to 12/31/93.

Papers on project (total): 14
Papers on project quoted in Current Contents: 12
Institution name: Farmaceutsko-biokemijski fakultet, Zagreb (6)
Department/Institute: Department of Chemistry
Address: Ante Kovačića 1
City: 10000 - Zagreb, Croatia
Phone: 385 (0) 449 444
Fax: 385 (0)445 117

Summary: The aims include characterization of iron(III), aluminum(III) gallium(III) and vanadium(IV) complexes with siderophore ligands and theit models. Mechanisms of their formation, hydrolysis and ligand substitution will be studied. Such processes undoubtedly play an important role in biological systems in transport, storage and function of metal ions. These reactions are of interest for understanding of basis of the therapy of certain disfunctions in which such metal ions are involved (for example therapy of the patients who sufer from overload iron or aluminium). In addition, the results obtained may provide a better understanding of the metal ion transport and storage processes in microorganisms. The techniques that will be used will include spectrophotometry, potentiometry and conventional, "stopped-flow" and "rapid-scan" kinetic procedures.

Keywords: Siderophores, hydroxamic acids, complexes, iron(III), aluminum(III), gallium(III), vanadium(IV), reaction mechanisms, kinetics

Research goals: Siderophore molecules are naturally occuring compounds produced by microorganisms to transfer iron from the enviroment into the cell. Siderophore desferrioxamine B (DFB) is used in medicine to remove the excess of iron in patients who suffer from Cooley's anemia. DFB is also used to remove excess iron during accidental iron poisoning of children. Removal of exess aluminum from the human body appears to be of equal importance to that of iron, particularly in those patients who must undergo permanent hemodialysis. Chemical studies of interactions of DFB with Al(III) ions is proposed in this project and the results obtained may provide a better understanding of the mechanism of the complexation of Al(III) in patients suffering from kidney disease. At the same time the results may contribute to the fundamental aspects of the mechanism of complexation of metal ions by polydentante ligands. DFB binds oxovanadium ions quite strongly. Since V is also a bioelement its biological concentrations may be influenced in those patients who are undergoing treatment with DFB. The dominant form of V in the human body is VO2+, and therefore, we propose a detailed study of the interactions of VO2+ with DFB as well as with synthetic monohydroxamic acids as models. The third element to be studied in this project is Ga(III) because its interactions with DFB is of biological importance. Scanning of Ga-67 is used in clinical radiological diagnosis, since Ga accumulates in cancer tissues. The increase in Ga concentration is a result of its chemical similarity to iron(III) and rapidly developing tissues can not discriminate between Ga(III) and Fe(III). Further substantiation of this hypothesis would be similarities in the interactions of Ga(III) and Fe(III) with siderophore molecules, the study which is proposed in this project. We intend to study the role od NH2 group in the complexation. The characterization of the new hydroxamic acids as beta-methyl-D-glucofururonohydroxamic acid and the mechanism of the formation of N-fenylacetohydroxamic acid from pyruvic acid and nitroso compounds in the presence of metal ions will also be studied.

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Last update: 10/16/95