Stability, Relaxometric And Computational Studies On Mn2+ Complexes With Ligands Containing A Cyclobutane Scaffold

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 degrees C, 0.1 M KCl). The stability constant of the complex with a hexadentate ligand containing four acetate groups (L1(4-), log K-MnL = 10.26) is improved upon replacing one (L2(4-), log K-MnL = 14.71) or two (L3(4-), 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 H-1 NMRD studies and O-17 chemical shifts and transverse relaxation rates. The H-1 relaxivities determined at 60 MHz (3.3 and 2.4 mM(-1) s(-1) at 25 and 37 degrees C, respectively) are comparable to those of monohydrated complexes such as [Mn(edta)](2-). The exchange rate of the inner-sphere water molecule (k298ex = 248 x 10(6) s(-1)) is slightly lower than that of the edta(4-) 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 O-17 hyperfine coupling constant A/PLANCK CONSTANT OVER TWO PI 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.