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

Abstract

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.

Design Principles for the Development of Gd(III) Polarizing Agents for Magic Angle Spinning Dynamic Nuclear Polarization

“… 51 Indeed, a similar twist angle has been linked to lower ZFS in six-coordinated Mn(II) complexes. 52 …”

“…Nevertheless, the fact that the distortion from an ideal prism is the lowest for Gd­(tpatcn) is probably why it also has the lowest ZFS . Indeed, a similar twist angle has been linked to lower ZFS in six-coordinated Mn­(II) complexes …”

“…51 Indeed, a similar twist angle has been linked to lower ZFS in six-coordinated Mn(II) complexes. 52 Figure 3 shows the negative lobe of the 1 H DNP Zeeman field profiles for MAS DNP experiments at 9.4 T of 4 mM solutions of the new complexes in glycerol-d 8 /D 2 O/H 2 O (6:3:1) solutions. A fixed concentration (4 mM) was chosen here as this was found to be optimal previously.…”

Thermodynamic Stability of Mn(II) Complexes with Aminocarboxylate Ligands Analyzed Using Structural Descriptors

“… 42 However, complexes with 1,4,7-triazacyclononane derivatives such as H 3 NOTA and related ligands generally form six-coordinate complexes in solution. 43 − 45…”

“…Heptacoordinated metal complexes are relatively rare within the first-row transition-metal series but are more abundant for Mn­(II) than for any other metal ion within the series. , Typical seven-coordinate Mn­(II) complexes are those with EDTA 4– ( L4 , Chart ) and its derivatives, in which a coordinated water molecule completes the metal coordination sphere. − A remarkable example of this class is H 3 PyC3A ( L10 , Chart ), which forms a very stable Mn­(II) complex that generates excellent MRI contrast. , Seven coordination is also favored by 15-membered macrocyclic ligands containing five donor atoms, which generally provide pentagonal bipyramidal coordination in which the equatorial positions are occupied by the donor atoms of the macrocyclic unit. , The Mn­(II) complex with the triethyl ester derivative of the 12-membered macrocycle H 3 PCTA ( L37 , Chart ) was also found to be seven-coordinated in the solid state . However, complexes with 1,4,7-triazacyclononane derivatives such as H 3 NOTA and related ligands generally form six-coordinate complexes in solution. − …”