Mn Complexes Containing Sulfonamide Groups with pH-Responsive Relaxivity.

We present two ligands containing a -ethyl-4-(trifluoromethyl)benzenesulfonamide group attached to either a 6,6'-(azanediylbis(methylene))dipicolinic acid unit (HDPASAm) or a 2,2'-(1,4,7-triazonane-1,4-diyl)diacetic acid macrocyclic platform (HNO2ASAm). These ligands were designed to provide a pH-dependent relaxivity response upon complexation with Mn in aqueous solution. The protonation constants of the ligands and the stability constants of the Mn complexes were determined using potentiometric titrations complemented by spectrophotometric experiments. The deprotonations of the sulfonamide groups of the ligands are characterized by protonation constants of log = 10.36 and 10.59 for DPASAm and HNO2ASAm, respectively. These values decrease dramatically to log = 6.43 and 5.42 in the presence of Mn, because of the coordination of the negatively charged sulfonamide groups to the metal ion. The higher log value in [Mn(DPASAm)] is related to the formation of a seven-coordinate complex, while the metal ion in [Mn(NO2ASAm)] is six-coordinated. The X-ray crystal structure of Na[Mn(DPASAm)(HO)]2HO confirms the formation of a seven-coordinate complex, where the coordination environment is fulfilled by the donor atoms of the two picolinate groups, the amine N atom, the N atom of the sulfonamide group, and a coordinated water molecule. The lower conditional stability of the [Mn(NO2ASAm)] complex and the lower protonation constant of the sulfonamide group results in complex dissociation at relatively high pH (<7.0). However, protonation of the sulfonamide group in [Mn(DPASAm)] falls into the physiologically relevant pH window and causes a significant increase in relaxivity from = 3.8 mM s at pH 9.0 to = 8.9 mM s at pH 4.0 (10 MHz, 25 °C).