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

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 (t_1/2 = 1134 hours vs. 12 hours; pH 7.4). ¹⁷O NMR confirmed one inner sphere water in MnL2 and fast exchange (k_ex 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.