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submitted on 07.11.2020, 20:42 and posted on 10.11.2020, 07:06by Zoltán Garda, Enikő Molnár, Nadège Hamon, Jose Barriada, David Esteban-Gómez, Balázs Váradi, Viktória Nagy, Kristof Pota, Ferenc K. Kalman, Imre Tóth, Norbert Lihi, Carlos Platas-Iglesias, Eva Toth, Raphael Tripier, Gyula Tircso
We report the Mn(II) complexes with two pyclen-based ligands (pyclen = 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene) functionalized with acetate pendant arms either at positions 3,6 (3,6-PC2A) or 3,9 (3,9-PC2A) of the
macrocyclic fragment. The 3,6-PC2A ligand was synthesized in five steps from pyclen-oxalate by protecting one of the
secondary amine groups of pyclen using Alloc protecting chemistry. The complex with 3,9-PC2A is characterized by a higher
thermodynamic stability (logKMnL = 17.09(2) than the 3,6-PC2A analogue (logKMnL = 15.53(1), 0.15 M NaCl). Both complexes
contain a water molecule coordinated to the metal ion, which results in relatively high 1H relaxivities (r1p = 2.72 and 2.91
for the complexes with 3,6- and 3,9-PC2A, respectively, 25 ºC, 0.49 T). The coordinated water molecule displays fast
exchange kinetics with the bulk in both cases; the rates (kex
298) are 140106 and 126106
for [Mn(3,6-PC2A)] and [Mn(3,9-
PC2A)], respectively. The two complexes were found to be remarkably inert with respect to their dissociation, with halflives of 63 and 21 h, respectively, at pH 7.4 in the presence of excess Cu(II). The r1p values recorded in blood serum remain
constant at least over a period of 120 h. Cyclic voltammetry experiments show irreversible oxidation features shifted to
higher potentials with respect to [Mn(EDTA)]2- and [Mn(PhDTA)]2-
, indicating that the PC2A complexes reported here have
a lower tendency to stabilize Mn(III). The superoxide dismutase activity of the Mn(II) complexes was tested using the
xanthine/xanthine oxidase/NBT assay at pH 7.8. The Mn(II) complexes of 3,6-PC2A and 3,9-PC2A are capable to assist the
decomposition of superoxide anion radical. The kinetic rate constant of the complex of 3,9-PC2A is smaller by one order of
magnitude than that of 3,6-PC2A.