Complexation of desferricoprogen with trivalent Fe, Al, Ga, In and divalent Fe, Ni, Cu, Zn metal ions: effects of the linking chain structure on the metal binding ability of hydroxamate based siderophores

Complexes of the natural siderophore, desferricoprogen (DFC), with several trivalent and divalent metal ions in aqueous solution were studied by pH-potentiometry, UV–Vis spectrophotometry and cyclic voltammetry. DFC was found to be an effective metal binding ligand, which, in addition to Fe(III), forms complexes of high stability with Ga(III), Al(III), In(III), Cu(II), Ni(II) and Zn(II). Fe(II), however, is oxidized by DFC under anaerobic conditions and Fe(III) complexes are formed. By comparing the results with those of desferrioxamine B (DFB), it can be concluded that the conjugated b-double bond slightly increases the stability of the hydroxamate chelates, consequently increases the stability of mono-chelated complexes of DFC. Any steric effect by the connecting chains arises only in the bis- and tris-chelated complexes. With metal ions possessing a relatively big ionic radius (Cu(II), Ni(II), Zn(II), In(III)) DFC, containing a bit longer chains than DFB, forms slightly more stable complexes. With smaller metal ions the trend is the opposite. Also a notable difference is that stable trinuclear complex, [Cu3L2], is formed with DFC but not with DFB. Possible bio-relevance of the Fe(II)/Fe(III) results is also discussed in the paper

Új sziderofór modellek fémmegkötő sajátságainak vizsgálata: Hidroxámsavak és fémionok közötti kölcsönhatás szelektivitását befolyásoló tényezők = Studies on metal binding ability of new siderophore models: Factors affecting the interaction between hydroxamic acids and metal ions

A kutatás során (1) multikelátor típusú természetes sziderofórok (deszferrioxamin B és deszferrikoprogén) és analógok (pl. EDTA származék hidroxipiridinon), valamint modelljeik fémmegkötő sajátságainak, ezen belül a szelektivitást befolyásoló tényezőknek a vizsgálata, továbbá (2) a fémionokkal relatíve kisebb stabilítású kompexeket képező, "oldalláncukban" imidazolcsoportot tartalmazó új monohidroxámsavak előállítása és fémkomplexeiknek a tanulmányozása folyt. Az (1) témában több rendszernél is feltártuk a fémion-szelektivítást befolyásoló legfontosabb molekulaszerkezeti tényezőket. Bizonyítottuk és értelmeztük, hogy miért lehet pl. ólommérgezés esetén fémionkivonásra hatásosabb a DFC, mint a DFB. Egy lisszaboni laboratóriummal való együttműködésben néhány új hidroxipiridinon, pl. EDTA származék, fémkomplexeinek részletes oldategyensúlyi vizsgálata történt. Eredményeink szerint ezen ligandumok az M3+ és Mo(VI) fémionokat igen nagy hatékonysággal képesek komplexbe vinni, szelektíven kötni . (2) Számos imidazolcsoportot is tartalmazó új monohidroxámsav (mint potenciális metalloenzim inhibítor) előállítása és fémkomplexeik vizsgálata történt. Nemzetközi együttműködésben elindultak azok a vizsgálatok, melyek a monohidroxámsavaink metalloenzimek katalitikus centrumát modellező komplexekkel való kölcsönhatásának felderítésére irányulnak. | (1) Metal complexation of multichelator type natural siderophores (desferrioxamine B and desferricoprogen), their analogues (such as hydroxypyridinone derivative of EDTA) and some of their models have been investigated. Within this subject, characterization of the main factors determining the metal ion selectivity of these very effective metal binding agents was in the focus of the work. One of the most interesting results helped us to answer the question: Why can be the desferricoprogen a better lead-sequestering agent than desferrioxamine B' (2) Metal binding ability of potentially metalloenzyme inhibitor monohydroxamic acids has been also investigated. As a continuation of the previous work, the effect of the imidazole situating in various distances compared to the hydroxamic function was studied. Following the examination of the binary systems, the interaction of the imidazole containing monohydroxamic acids with model complexes for catalytic centre of metalloenzymes is planned to study nowadays

Some factors affecting metal – ion monohydroxamate interaction in aqueous solution

The chelating properties exhibited by a series of monohydroxamic acids (propanohydroxamic acid (Pha), hexanohydroxamic acid (Hha), benzohydroxamic acid (Bha), N-methyl-acetohydroxamic acid (MAha), N-phenyl-acetohydroxamic acid (PhAha) and 2-hydroxypyridine- N-oxide (PYRha)) towards copper(II), nickel(II), zinc(II), calcium(II), magnesium(II) and aluminium(III) ions were studied by pHmetric, spectrophotometric and, in one case, by 27Al NMR methods. The results were compared with the corresponding data for metal ion– acetohydroxamate (Aha) and metal ion–desferrioxamine B (DFB) complexes. Changes of the substituents either on the carbon or on the nitrogen of the hydroxamate moiety caused a measurable effect on the chelate stability only in the case of aluminium(III) complexes. The aromatic derivative, PYRha, formed significantly more stable complexes than expected on the basis of the ligand basicity. The higher complexforming ability of DFB compared to monohydroxamic acids diminishes in the case of the largest calcium(II) ion

New insight into the oxidation of Fe(II) by desferrioxamine B (DFB): spectrophotometric and capillary electrophoresis (CE) study

Results on the previously described irreversible redox reaction taking place between iron(II) and desferrioxamine B (DFB) under anaerobic conditions have been complemented by additional capillary electrophoresis (CE) and kinetic studies in the present work. Reduction of the oxidizing agent, DFB to monoamide derivative, was confirmed by CE technique and suggestion for the most probable kinetically active species and mechanism of the initial step is discussed in the paper. (C) 2002 Elsevier Science B.V. All rights reserved

Új, funkcionalizált peptidszármazékok előállítása és oldategyensúlyi vizsgálata = Synthesis and solution equilibrium studies of new, functionalised derivatives of peptides

A pályázat keretében 15 új peptidhidroxámsavat állítottunk elő és szisztematikusan megvizsgáltuk azt, hogy a ligandumok építőelemeinek (terminális aminocsoport jelenléte, a hidroxámsavcsoport nitrogénjének szubsztituense, a peptidlánc hossza, az oldalláncban jelenlevő erősen koordinálódni képes donorcsoport jelenléte) megváltoztatása hogyan befolyásolja fémionmegkötő képességüket. A ligandumok esszenciális (Fe3+, Cu2+, Ni2+, Zn2+, Mo(VI)) és toxikus (Al3+) fémionokkal való kölcsönhatásának tanulmányozására pH-potenciometriát, ESI-MS-t és spektrális módszereket (UV-VIS, NMR, CD, ESR) alkalmaztunk, meghatározva az oldatbeli részecskék összetételét, stabilitási szorzat értékeit és legvalószínűbb oldatszerkezetét. | Fifteen new peptide hydroxamic acids have been synthesized, characterized and a systematic study has been carried out to explore the effect of the change of the building blocks (presence of the terminal amino group, substituent at the nitrogen of the hydroxamic moiety, length of the peptide chain, presence of strongly coordinating donor in the side chain) of the ligands on their metal binding capability. The interaction of the peptide hydroxamic acids with essencial (Fe3+, Cu2+, Ni2+, Zn2+, Mo(VI)) and toxic (Al3+) metal ions has been studied using pH-potentiometry, ESI-MS and different spectroscopic (UV-VIS, NMR, CD, ESR) techniques

Coordination modes of hydroxamic acids in copper(II), nickel(II) and zinc(II) mixed-ligand complexes in aqueous solution

The stability constants and coordination modes of the mixed-ligand complexes formed by Cu(II), Ni(II), Zn(II), ethylenediamine (en), 2,2%-bipyridine (bpy), glycinate (Gly), disodium salt of 4,5-dihydroxybenzene 1,3-disulfonate (Tiron), diethylenetriamine (dien) or 2,2%:6,2¦-terpyridine (terpy) (ligand B) and acetohydroxamate (Aha), N-methylacetohydroxamate (MeAha) or N-phenylacetohydroxamate (PhAha) (ligand A) were determined in water (25°C, I0.2 M KCl) by pH-metric, spectrophotometric, EPR and calorimetric methods. Mixed-ligand complexes with typical hydroxamate type chelation mode involving the NHO moiety are formed in all systems. However, further copper(II) induced deprotonation of the NHO moiety of Aha in the presence of en or bpy results in the formation of mixed-ligand complexes with hydroximato chelates at high pH. The results show the favoured coordination of a hydroxamate to metal(II)–en and especially to a metal(II)–bpy moiety. If ligand B is Gly, the increase of stability of the mixed-ligand complexes is as expected on statistical basis, whereas the formation of complexes involving O,O-coordinated hydroxamate and O,O-coordinated Tiron is unfavoured. The tridentate coordination of dien or terpy results in five-coordinated mixed-ligand copper(II) complexes in which, most probably, the hydroxamate moiety adopts an equatorial–axial coordination mode. This quite unstable hydroxamate chelate can not hinder the hydrolysis of the complex above pH 8. Under very basic conditions acetohydroximato moieties (CONO2) displace the rigid terpy ligand from the coordination sphere and complexes, [Cu(AhaH1)2]2 involving hydroximato chelates are formed

Interaction between iron(II) and hydroxamic acids: oxidation of iron(II) to iron(III) by desferrioxamine B under anaerobic conditions

Interaction between iron(II) and acetohydroxamic acid (Aha), a-alaninehydroxamic acid (a-Alaha), b-alaninehydroxamic acid (b-Alaha), hexanedioic acid bis(3-hydroxycarbamoyl-methyl)amide (Dha) or desferrioxamine B (DFB) under anaerobic conditions was studied by pH-metric and UV–Visible spectrophotometric methods. The stability constants of complexes formed with Aha, a-Alaha, b-Alaha and Dha were calculated and turned out to be much lower than those of the corresponding iron(III) complexes. Stability constants of the iron(II)–hydroxamate complexes are compared with those of other divalent 3d-block metal ions and the Irving–Williams series of stabilities was found to be observed. Above pH 4, in the reactions between iron(II) and desferrioxamine B, the oxidation of the metal ion to iron(III) by the ligand was found. The overall reaction that resulted in the formation of the tris–hydroxamato complex 1 [Fe(HDFB)] and monoamide derivative of DFB at pH 6 is: 21 1 1 1 1 2Fe 13H DFB 52[Fe(HDFB)] 1H DFB–monoamide 1H O14H 4 3 2 Based on these results, the conclusion is that desferrioxamine B can uptake iron in iron(III) form under anaerobic conditions