Understanding the Effect of the Electron Spin Relaxation on the Relaxivities of Mn(II) Complexes with Triazacyclononane Derivatives

[Image: see text] Investigating the relaxation of water (1)H nuclei induced by paramagnetic Mn(II) complexes is important to understand the mechanisms that control the efficiency of contrast agents used in diagnostic magnetic resonance imaging (MRI). Herein, a series of potentially hexadentate triazacyclononane (TACN) derivatives containing different pendant arms were designed to explore the relaxation of the electron spin in the corresponding Mn(II) complexes by using a combination of (1)H NMR relaxometry and theoretical calculations. These ligands include 1,4,7-triazacyclononane-1,4,7-triacetic acid (H(3)NOTA) and three derivatives in which an acetate group is replaced by sulfonamide (H(3)NO2ASAm), amide (H(2)NO2AM), or pyridyl (H(2)NO2APy) pendants. The analogue of H(3)NOTA containing three propionate pendant arms (H(3)NOTPrA) was also investigated. The X-ray structure of the derivative containing two acetate groups and a sulfonamide pendant arm [Mn(NO2ASAm)](−) evidenced six-coordination of the ligand to the metal ion, with the coordination polyhedron being close to a trigonal prism. The relaxivities of all complexes at 20 MHz and 25 °C (1.1–1.3 mM(–1) s(–1)) are typical of systems that lack water molecules coordinated to the metal ion. The nuclear magnetic relaxation profiles evidence significant differences in the relaxivities of the complexes at low fields (<1 MHz), which are associated with different spin relaxation rates. The zero field splitting (ZFS) parameters calculated by using DFT and CASSCF methods show that electronic relaxation is relatively insensitive to the nature of the donor atoms. However, the twist angle of the two tripodal faces that delineate the coordination polyhedron, defined by the N atoms of the TACN unit (lower face) and the donor atoms of the pendant arms (upper face), has an important effect in the ZFS parameters. A twist angle close to the ideal value for an octahedral coordination (60°), such as that in [Mn(NOTPrA)](−), leads to a small ZFS energy, whereas this value increases as the coordination polyhedron approaches to a trigonal prism.