Naslov
Chelation, oxydo-reduction and transport mechanisms of metals by antibiotic and siderophore analogues

Autori
Budimir, Ana

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, doktorska disertacija

Fakultet
Farmaceutsko-biokemijski fakultet

Mjesto
Zagreb ; Strasbourg

Datum
27.11

Godina
2007

Stranica
209

Mentor
Biruš, Mladen ; Albrecht-Gary, Anne-Marie

Ključne riječi
8-hydroxyquinoline; pyridine; clioquinol; hydroxyurea; metallic complexes; molecular switches; Alzheimer's disease; free radicals.

Sažetak
The main objective of this PhD dissertation is focused on the coordination properties of new 8-hydroxyquinoline derivatives and on the oxidation mechanism of hydroxyurea, a hydroxamate based compound.The two first chapters deal with the ionic recognition properties of two pyridine-oxine ligands (2-(pyridin-2-yl)quinolin-8-ol L1 and 6'-(8-hydroxyquinolin-2-yl)picolinic acid L2) towards a series of divalent (Cu, Zn, Co, Ni) and trivalent lanthanide cations (Eu, Tb). The presence of N, O- and N, N-bis-compartmental binding sites, as well as the conformational changes of the bipyridyl moiety, allowed the observation by spectrophotometry of the translocation of metals driven by protons in L1 bischelate metallic complexes. With lanthanide ions, L1 acts as a strict tridentate binding unit and affords mono-, bis- and trischelates. The introduction of an additional carboxylate unit in L2 drastically modifies its binding properties, and thus confers to L2 the binding properties of a tetradentate chelator. L2 is a low molecular weight and a moderate chelator of divalent cations, which could find applications in neurodegenerative therapy (Alzheimer's disease ; AD).In the third part, we have revisited the coordination properties of clioquinol, an oxine-type active neurological drug in Alzheimer's disease, toward biologically relevant divalent metal ions (Cu, Zn, Ni, Co and Mn). The determination of the stability constants showed an especially strong complexation of the cupric cations. Our data are discussed in the framework of AD.The last part of this thesis is focused on the oxidation reaction by Fe(CN)63- of hydroxyurea, a hydroxamic acid used in the treatment of sickle cell anemia. Hydroxyurea reduces Fe(CN)63- into Fe(CN)64- via the formation and subsequent fading out of a free radical. Spectroscopic and kinetic techniques were used to elucidate the mechanism and allowed us to raise the question of production of NO.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA