Exceptional Manganese(II) Stability and Manganese(II)/Zinc(II) Selectivity with Rigid Polydentate Ligands**

Abstract

While MnII complexes meet increasing interest in biomedical applications, ligands are lacking that enable high MnII complex stability and selectivity vs. ZnII, the most relevant biological competitor. We report here two new bispidine derivatives, which provide rigid and large coordination cavities that perfectly match the size of MnII, yielding eight‐coordinate MnII complexes with record stabilities. In contrast, the smaller ZnII ion cannot accommodate all ligand donors, resulting in highly strained and less stable six‐coordinate complexes. Combined theoretical and experimental data (X‐ray crystallography, potentiometry, relaxometry and 1H NMR spectroscopy) demonstrate unprecedented selectivity for MnII vs. ZnII (KMnL/KZnL of 108–1010), in sharp contrast to the usual Irving–Williams behavior, and record MnII complex stabilities and inertness with logKMnL close to 25.

Against the Norm: Non Irving–Williams Transmetalation in Transition Metal Dimers

“…The ferromagnetic exchange observed is unexpected based on previous magneto−structural correlations of O-bridged Cu II dimers, which consider only the Cu−O−Cu angles. 38−42 The Cu1−O−Cu2 angles in CuCu are 106.01(10)°and 105.22 (10)°and would be expected to promote strong antiferromagnetic interactions based on this model, as shown by similar Schiff base-derived Cu II dimers. 43−46 Thus, as discussed by Ruiz and coworkers, 47 other structural factors in CuCu including complex asymmetry, metal ion geometry, O− Cu−O−Cu torsion angles, the out-of-plane shift of the phenolato units, and the seven-coordinate Cu II ion should be considered.…”

“…9 The trend can be loosely extended to include all first row transition metal based complexes, but is only definitive for mononuclear octahedral complexes with numerous exceptions known for other geometries. 10,11 A large proportion of complexes found in the literature have ligand frameworks derived from salen type Schiff bases, as not only do they have simple preparations but they also commonly have preformed multidentate coordination pockets, providing a driving force for the coordination and formation of a stable complex. 12,13 One of the downfalls of Schiff base ligands, however, is the ease at which they undergo cleavage in acidic conditions.…”

Toward Personalized Medicine: One Chelator for Imaging and Therapy with Lutetium-177 and Actinium-225

“…This is expected from the rigidity of the bispidine backbone and is also found in other bispidine complexes. 29,35,49 Continuous shape analyses for the determination of the coordination geometries further emphasize the similarities between the metal complex structures: 56 The smallest continuous shape measure value (the CShM values are dimensionless with 0 < CShM <100, where CShM = 0 indicates a perfect polyhedron and CShM = 100 indicates no accordance to the polyhedron) is in all the three cases found for a slightly distorted spherically capped square antiprism (see the Supporting Information for more details). 45 The protonation constants of L1 and the thermodynamic stabilities of its In III , Lu III , and La III complexes were accessible via potentiometric titration and are listed in Table 3, together with the values of the octadentate bispidine bispa 2 , 41 as well as DOTA and DTPA.…”

“…19,20 This was addressed by the development of a large variety of picolinic acid and hydroxyquinoline-based ligands such as octapa, py4pa, octox, macropa, and py-macrodipa (Scheme 1), and some of the radiochemical results are promising. 21−27 Bispidine (3,7-diazabicyclo[3.3.1]nonane)-based ligands are adamantane derived with very rigid structures, ideal for the complexation of large metal ions such as Mn II , 28,29 Bi III , 30 Pd II , 31 and Ln III . 32 These ligands, first described by Mannich and Mohs, 33 are highly modular and allow for a large variety of denticities and donor group combinations.…”

“…Bispidine (3,7-diazabicyclo[3.3.1]­nonane)-based ligands are adamantane derived with very rigid structures, ideal for the complexation of large metal ions such as Mn II , , Bi III , Pd II , and Ln III . These ligands, first described by Mannich and Mohs, are highly modular and allow for a large variety of denticities and donor group combinations .…”