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
Communication
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.
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. Other information about the project.