Mn²⁺ Complexes Containing Sulfonamide Groups with pH-Responsive Relaxivity

We present two ligands containing a <i>N</i>-ethyl-4-(trifluoromethyl)­benzenesulfonamide group attached to either a 6,6′-(azanediylbis­(methylene))­dipicolinic acid unit (H₃DPASAm) or a 2,2′-(1,4,7-triazonane-1,4-diyl)­diacetic acid macrocyclic platform (H₃NO2ASAm). 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 <i>K</i>_i^H = 10.36 and 10.59 for DPASAm^3– and HNO2ASAm^2–, respectively. These values decrease dramatically to log <i>K</i>_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 <i>K</i>_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)]<b>·</b>2H₂O 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 <i>r</i>_1p = 3.8 mM^–1 s^–1 at pH 9.0 to <i>r</i>_1p = 8.9 mM^–1 s^–1 at pH 4.0 (10 MHz, 25 °C).