Dissociation kinetics of Mn2+ complexes of NOTA and DOTA.

The kinetics of transmetallation of Mn(nota) and Mn(dota) was investigated in the presence of Zn(2+) (5-50-fold excess) at variable pH (3.5-5.6) by (1)H relaxometry. The dissociation is much faster for Mn(nota) than for Mn(dota) under both experimental and physiologically relevant conditions (t(½) = 74 h and 1037 h for Mn(nota) and Mn(dota), respectively, at pH 7.4, c(Zn(2+)) = 10(-5) M, 25 °C). The dissociation of the complexes proceeds mainly via spontaneous (Mn(nota)k(0) = (2.6 ± 0.5) × 10(-6) s(-1); Mn(dota)k(0) = (1.8 ± 0.6) × 10(-7) s(-1)) and proton-assisted pathways (Mn(nota)k(1) = (7.8 ± 0.1) × 10(-1) M(-1) s(-1); Mn(dota)k(1) = (4.0 ± 0.6) × 10(-2) M(-1) s(-1), k(2) = (1.6 ± 0.1) × 10(3) M(-2) s(-1)). The observed suppression of the reaction rates with increasing Zn(2+) concentration is explained by the formation of a dinuclear Mn(2+)-L-Zn(2+) complex which is about 20-times more stable for Mn(dota) than for Mn(nota) (K(MnLZn) = 68 and 3.6, respectively), and which dissociates very slowly (k(3)∼10(-5) M(-1) s(-1)). These data provide the first experimental proof that not all Mn(2+) complexes are kinetically labile. The absence of coordinated water makes both Mn(nota) and Mn(dota) complexes inefficient for MRI applications. Nevertheless, the higher kinetic inertness of Mn(dota) indicates a promising direction in designing ligands for Mn(2+) complexation.