Characterization of Mn(II) and Mn(III) binding capability of natural siderophores desferrioxamine B and desferricoprogen as well as model hydroxamic acids

Complexes formed between Mn(II) ion and acetohydroxamic acid (HAha), benzohydroxamic acid (HBha), N-methyl-acetohydroxamic acid (HMeAha), DFB model dihydroxamic acids (H₂(3,4-DIHA), H₂(3,3-DIHA), H₂(2,5-DIHA), H₂(2,5-H,H-DIHA), H₂(2,4-DIHA), H₂(2,3-DIHA)) and two trihydroxamate based natural siderophores, desferrioxamine B (H₄DFB) and desferricoprogen (H₃DFC) have been investigated under anaerobic condition (and some of them also under aerobic condition). The pH-potentiometric results showed the formation of well-defined complexes with moderate stability. Monohydroxamic acids not, but all of the dihydroxamic acids and trihydroxamic acids were able to hinder the hydrolysis of the metal ion up to pH ca. 11. Maximum three hydroxamates were found to coordinate to the Mn(II) ion, but presence of water molecule in the inner-sphere was also indicated by the corresponding relaxivity values even in the tris-chelated complexes. Moreover, prototropic exchange processes were found to increase the relaxation rate of the solvent water proton over the value of Mn_aqua]²⁺ in the protonated Mn(II)-siderophore complexes at physiological pH. The much higher stability of Mn(III)-hydroxamate (especially tris-chelated) complexes compared to the corresponding Mn(II)-containing species results in a significantly decreased formal potential compared to the Mn(III)_aqua/Mn(II)_aqua system. As a result, air oxygen becomes an oxidizing agent for these manganese(II)-hydroxamate complexes above pH 7.5. The oxidation processes, followed by UV-Vis spectrophotometry, were found to be stoichiometric only in the case of the tris-chelated complexes of siderophores, which predominate above pH 9. ESI-MS provided support about the stoichiometry and cyclic-voltammetry was used to determine the stability constants for the tris-chelated complexes, Mn(HDFB)]⁺ and MnDFC].