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.

We present two ligands containing a N-ethyl-4-(trifluoromethyl)­benzenesulfonamide group attached to either a 6,6′-(azanediylbis­(methylene))­dipicolinic acid unit (H3DPASAm) or a 2,2′-(1,4,7-triazonane-1,4-diyl)­diacetic acid macrocyclic platform (H3NO2ASAm). These ligands were designed to provide a pH-dependent relaxivity response upon complexation with Mn2+ in aqueous solution. The protonation constants of the ligands and the stability constants of the Mn2+ complexes were determined using potentiometric titrations complemented by spectrophotometric experiments. The deprotonations of the sulfonamide groups of the ligands are characterized by protonation constants of log K i H = 10.36 and 10.59 for DPASAm3– and HNO2ASAm2–, respectively. These values decrease dramatically to log K i H = 6.43 and 5.42 in the presence of Mn2+, because of the coordination of the negatively charged sulfonamide groups to the metal ion. The higher log K i H value in [Mn­(DPASAm)]− is related to the formation of a seven-coordinate complex, while the metal ion in [Mn­(NO2ASAm)]− is six-coordinated. The X-ray crystal structure of Na­[Mn­(DPASAm)­(H2O)]·2H2O confirms the formation of a seven-coordinate complex, where the coordination environment is fulfilled by the donor atoms of the two picolinate groups, the amine N atom, the N atom of the sulfonamide group, and a coordinated water molecule. The lower conditional stability of the [Mn­(NO2ASAm)]− complex and the lower protonation constant of the sulfonamide group results in complex dissociation at relatively high pH (<7.0). However, protonation of the sulfonamide group in [Mn­(DPASAm)]− falls into the physiologically relevant pH window and causes a significant increase in relaxivity from r 1p = 3.8 mM–1 s–1 at pH 9.0 to r 1p = 8.9 mM–1 s–1 at pH 4.0 (10 MHz, 25 °C).

We report a detailed investigation of the potential as magnetic resonance imaging (MRI) contrast agents of Fe(III) complexes with H4EDTA derivatives containing different spacers: trans-cyclohexane-1,2-diamine (t H4CDTA), cis-cyclohexane-1,2-diamine (c H4CDTA),...

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We present a quantitative analysis of the thermodynamic stabilities of Mn(II) complexes, defined by the equilibrium constants (log K MnL values) and the values of pMn obtained as −log[Mn] free for total metal and ligand concentrations of 1 and 10 μM, respectively. We used structural descriptors to analyze the contributions to complex stability of different structural motifs in a quantitative way. The experimental log K MnL and pMn values can be predicted to a good accuracy by adding the contributions of the different motifs present in the ligand structure. This allowed for the identification of features that provide larger contributions to complex stability, which will be very helpful for the design of efficient chelators for Mn(II) complexation. This issue is particularly important to develop Mn(II) complexes for medical applications, for instance, as magnetic resonance imaging (MRI) contrast agents. The analysis performed here also indicates that coordination number eight is more common for Mn(II) than is generally assumed, with the highest log K MnL values generally observed for hepta- and octadentate ligands. The X-ray crystal structure of [Mn 2 (DOTA)(H 2 O) 2 ], in which eight-coordinate [Mn(DOTA)] 2– units are bridged by six-coordinate exocyclic Mn(II) ions, is also reported.