Stability, relaxometric and computational studies on Mn2+ complexes with ligands containing a cyclobutane scaffold

Abstract

The stability constants of Mn²⁺ complexes with ligands containing a trans-1,2-cyclobutanediamine spacer functionalized with picolinate and/or carboxylate functions were determined using potentiometric titrations (25 °C, 0.1 M KCl). The stability constant of the complex with a hexadentate ligand containing four acetate groups (L1⁴⁻, log K_MnL = 10.26) is improved upon replacing one (L2⁴⁻, log K_MnL = 14.71) or two (L3⁴⁻, log K_MnL = 15.81) carboxylate groups with picolinates. The [Mn(L1)]²⁻ complex contains a water molecule coordinated to the metal ion in aqueous solutions, as evidenced by ¹H NMRD studies and ¹⁷O chemical shifts and transverse relaxation rates. The ¹H relaxivities determined at 60 MHz (3.3 and 2.4 mM⁻¹ s⁻¹ at 25 and 37 °C, respectively) are comparable to those of monohydrated complexes such as [Mn(edta)]²⁻. The exchange rate of the inner-sphere water molecule (k²⁹⁸_ex = 248 × 10⁶ s⁻¹) is slightly lower than that of the edta⁴⁻ analogue. DFT calculations (M11/def2-TZVP) suggest that the water exchange reaction follows a dissociatively activated mechanism, providing activation parameters in reasonably good agreement with the experimental data. DFT calculations also show that the ¹⁷O hyperfine coupling constant A/ℏ is affected slightly by changes in the Mn–O_water distance and the orientation of the water molecule with respect to the Mn–O vector.