A Bisamide Derivative of [Mn(1,4-DO2A)] - Solution Thermodynamic, Kinetic, and NMR Relaxometric Studies

A new 1,4-DO2A-bisamide [1,4-DO2AM; 1,4-DO2A = 2,2′-(1,4,7,10-tetraazacyclododecane-1,4-diyl)diacetic acid] ligand was synthesized, and its Mn^II complex was prepared and investigated in detail by solution thermodynamic, kinetic, and ¹H and ¹⁷O NMR relaxometric measurements. Although the stability constant of [Mn(1,4-DO2AM)]²⁺ (log K_MnL = 12.64) is 2.5 log K units lower than that of [Mn(1,4-DO2A)], its kinetic inertness, investigated through its transmetallation reactions with Zn²⁺ ions, is much higher. In particular, the dissociation half-life (t_1/2) of [Mn(1,4-DO2AM)]²⁺ is ten times higher than that of [Mn(1,4-DO2A)] (t_1/2 = 556 vs. 49 h, pH 7.4). The longer rotational correlation time (τ_R = 53 ps) for [Mn(1,4-DO2AM)]²⁺ is mainly responsible for the slightly higher (+20 %) relaxivity (r₁ = 2.5 mM^-1 s^-1, 20 MHz, 25 °C) with respect to that of [Mn(1,4-DO2A)]. Notably, the water exchange rate of the coordinated water molecule is one order of magnitude slower than that of [Mn(1,4-DO2A)] (²⁹⁸k_ex = 115 ± 6 × 10⁶ s^-1). Finally, the dynamic properties of [Zn(1,4-DO2AM)] were investigated by NMR spectroscopy, and the decoordination and arm-rotation processes of the acetamide pendant arms were followed.