Lanthanide(III) complexes of some natural siderophores: a thermodynamic, kinetic and relaxometric study

Stability constants of the complexes formed between the natural trihydroxamic acids desferrioxamine B (DFB) and desferricoprogen (DFC) with Nd(III), Gd(III) and Yb(III) ions were determined using pH-potentiometry. The equilibrium in these systems can be described by models containing mononuclear protonated (Ln(HL), Ln(H2L) and Ln(H3L)), deprotonated (LnL) and ternary hydroxo Ln(H-1L) complexes, but for both ligands dinuclear complexes of low stability were also detected. The stability constants for the Ln(HDFB)(+) complexes are 11.95 (Nd(III)), 13.16 (Gd(III)) and 14.67 (Yb(III)), while these values of the Ln(DFC) complexes are considerably higher (14.42 (Nd(III)), 15.14 (Gd(III)) and 16.49 (Yb(III))). The stability constants of the complexes of DFB and DFC are much lower than those of the Ln(L)3 complexes formed with some aromatic hydroxamic acids indicating that the relatively long spacer between the hydroxamic acid moieties in DFB and DFC is unfavorable for Ln(III) complexation. The relaxometric study conducted for the Gd(HDFB)(+) species revealed an interesting pH dependence of the relaxivity associated with a large hydration number (bishydrated complex) and fast water exchange (kex=(29.9±0.4)×10(6)s(-1)), which would be favorable for CA use. However the dissociation of Gd(HDFB)(+) is fairly fast (<2ms) under all conditions employed in the present work thus the kinetically labile Gd(HDFB)(+) is not suitable for in vivo CA applications. Some low stability ternary complexes were also detected with K(Gd(HDFB)(HCO3))=17.5±1.9 and K(Gd(HDFB)(Lactate))=8.4±3.2 but in the presence of citrate and phosphate ions the Gd(HDFB)(+) complex was found to dissociate.