Kinetika, kataliza i redoks reakcije kompleksnih jedinjenja zlata(I) i zlata(III)

U okviru ove disertacije sprovedeno je sveobuhvatno izučavanje stabilnosti i reaktivnosti različitih kompleksa zlata, u cilju utvrđivanja uticaja koordinovanih liganada na redoks stabilnost zlata i reaktivnost prema biološki relevantnim molekulima, kao i katalitičku aktivnost. Hemijsko ponašanje ovih jedinjenja detaljno je ispitivano u vodenom rastvoru, ali i u metanolu, u cilju postizanja kompletnijih kinetičkih podataka. Dodatno je izvršeno i poređenje nekih rezultata sa rezultatima dobijenim za komplekse platine(II), kao strukturnih analoga i predstavnika metala d8 elektronske konfiguracije. Sposobnost zlata da formira stabilne komplekse od najvećeg je značaja za poboljšanje njegove stabilnosti pri fiziološkim uslovima. Napredak u oblasti sinteze zlato(III) kompleksa je podstaknut činjenicom da povećanje broja azot-donorskih atoma u koordinacionoj sferi jona zlata(III) dovodi do značajnog smanjenja redukcionog potencijala. Budući da jedinjenja zlata(III) i pored redoks nestabilnosti pokazuju izvanredne citotoksične sposobnosti na različitim linijama kancera,1,2 proučavali smo reakcije niza monofunkcionalnih zlato(III) kompleksa i jednostavne zlato(III) soli, u biološki relevantnim uslovima. Kinetička ispitivanja obuhvataju reakcije supstitucije kompleksa zlata sa različitim nukleofilima, kao što su jodid (I-), bromid (Br-), nitrit (NO2 -), tiourea (tu), piridin (py), dimetil sulfoksid (DMSO), kao i biološki releventnim molekulima: L-cisteinom (L-Cys), L-metioninom (L-Met), glutationom (GSH, γ-Glu-L-Cys-Gly), L-histidinom (L-His). Poseban akcenat dat je mogućnosti detektovanja supstitucionog koraka u reakcijama u kojima dominira redoks proces. Utvrđeno je da spori redoks proces ima izražen uticaj na konstantu brzine veoma brze inicijalne reakcije supstitucije. U cilju izučavanja uticaja karbenskih liganada na stabilnost i reaktivnost jona zlata, sintetisan je niz zlato(I) i zlato(III) kompleksa koji sadrže N-heterociklične-karbenske (NHC-) i N-heterociklične-okso-karbenske (NHOC-) ligande. Ovo istraživanje daje kompletan pregled i poređenje zlato(I)-mono-karbenskih, zlato(I)-bis-karbenskih i zlato(III)-bis-karbenskih kompleksa, u pogledu stabilnosti i reaktivnosti. Dodatno je ispitan i uticaj različitih karbenskih supstituenata na katalitičku aktivnost zlata(III).In the framework of this thesis a comprehensive study of the stability and reactivity of various complexes of gold was carried out in order to determine the impact of the coordinated ligands on the redox stability and reactivity toward biologically relevant molecules, and further on catalytic activity. Chemical behavior of these compounds has been thoroughly investigated in an aqueous solution, but also in methanol, in order to achieve more complete kinetic data. An additional comparison of some results was made with those obtained for the platinum(II) complexes, as they are structural analogs and representatives metals with d8 electronic configuration. It is known that the ability of gold to form stable complexes is of the most importance in order to improve its stability under physiological conditions. The development of gold(III) complexes has been encouraged by the fact that an increase in the number of nitrogen-donor atoms in the coordination sphere of gold(III) leads to a significant decrease in the reduction potential. Motivated by the observation that gold(III) compounds despite redox instability show outstanding cytotoxic properties on different cancer lines,1,2 we have studied the reactions of a series of gold(III) complexes and a simple gold(III) salt, within biologically relevant conditions. Kinetic studies have been focused on examination of the substitution reactions of the gold complexes with a variety of nucleophiles, such as iodide (I-), bromide (Br-), nitrite (NO2 -), thiourea (tu), pyridine (py), dimethyl sulfoxide (DMSO), as well as with the biologicaly relevant molecules: L-cysteine (L-Cys), L-methionine (L-Met), glutathione (GSH, γ-Glu-L-Cys-Gly), L-histidine (L-His). Special emphasis is given to the opportunities of detecting the substitution step within reaction where the redox process is dominant. It is shown that the slow redox processes have a strong influence on the rate constant of a very quick initial substitution reaction. Additionally, in order to study the influence of carbene ligands on the stability and reactivity of gold ions, a series of gold(I) and gold(III) complexes containing N-heterocyclic-carbene (NHC-) and N-heterocyclic-oxo-carbene (NHOC) ligands has been synthesized. This study includes a complete overview and comparison of gold(I)-mono-carbene, gold(I)-bis-carbene and gold(III)-bis-carbene complexes, in terms of stability and reactivity. Additionally, we tested the effect of different carbene substituents on the catalytic activity of gold(III)