Mn2+ Complex of a Fluorinated CDTA-Derivative: Stability, Inertness, and Paramagnetic 1H, 17O, and 19F Relaxation Properties.

L2 is a bisamide derivative of cyclohexyl-diamine tetraacetate (CDTA) containing one trifluoromethyl-piperidine- and one dimethyl-amide. While the amide functions are stable at pH 7, at pH 4.35 hydrolysis occurs after 1 day, and it is faster for the amide involving the piperidine. pH potentiometry showed lower basicity for L2 than for CDTA, and similar stability for the two complexes (pMn  =  8.28 vs. 8.68 for MnL2 and MnCDTA, respectively). The replacement of carboxylates by amides results in two orders of magnitude higher kinetic inertness for MnL2 (t1/2 = 1134 hours vs. 12 hours; pH 7.4). 17O NMR confirmed one inner sphere water in MnL2 and fast exchange (kex 298  =  2.8 × 107 s-1). Its proton relaxivity is remarkable for a small Mn2+ chelate (r1  =  4.59 mM-1s-1, 25 °C, 20 MHz). In the complex, 19F relaxation is strongly accelerated with respect to free L2, with more important effect on longitudinal (130-fold), than on transverse relaxation (25-70-fold). A Mn─F distance of ∼8 Å was estimated from the 19F relaxation rates. MnL2 provides good signal-to-noise ratios on 19F phantom UTE MR images. These data show that fluorinated, monohydrated Mn2+ complexes can offer both 1H and 19F MRI detection.