Mn2+ Complexes Containing Sulfonamide Groups With Ph-Responsive Relaxivity

We present two ligands containing a N-ethyl-4-(trifluoromethyl)benzenesulfonamide group attached to either a 6,6'-(azanediylbis(methylene))dipicolinic acid unit (H(3)DPASAm) or a 2,2'-(1,4,7-triazonane-1,4-diyl)diacetic acid macrocyclic platform (H(3)NO2ASAm). These ligands were designed to provide a pH-dependent relaxivity response upon complexation with Mn2+ in aqueous solution. The protonation constants of the ligands and the stability constants of the Mn2+ 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 K-i(H) = 10.36 and 10.59 for DPASAm(3-) and HNO2ASAm(2-), respectively. These values decrease dramatically to log K-i(H) = 6.43 and 5.42 in the presence of Mn2+, because of the coordination of the negatively charged sulfonamide groups to the metal ion. The higher log K-i(H) 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)(H2O)]center dot 2H(2)O 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 r(1p) = 3.8 mM(-1) s(-1) at pH 9.0 to r(1p) = 8.9 mM(-1) s(-1) at pH 4.0 (10 MHz, 25 degrees C).