Mn²⁺ complexes of open-chain ligands with a pyridine backbone: less donor atoms lead to higher kinetic inertness

Abstract

The loss of a coordinating donor atom in the ligand leads to lower thermodynamic stability, but higher kinetic inertness of Mn2+ complexes.

Gadolinium Complexes of Highly Rigid, Open-Chain Ligands Containing a Cyclobutane Ring in the Backbone: Decreasing Ligand Denticity Might Enhance Kinetic Inertness

“…One can simply conclude that, in this case, the addition of a second picolinate function is detrimental for the kinetic inertness (as experimentally assessed at pH 6 and 4). We note that a decrease in kinetic inertness upon increasing the ligand denticity has been already reported for linear Mn 2+ complexes . In general, such a situation can occur when the additional donor atoms of the ligand (i) contribute to more efficient proton-assisted dissociated pathways, since they provide more protonation sites and/or (ii) allow for the formation of dinuclear species, which would not be possible without those donor atoms.…”

Inertness of Superoxide Dismutase Mimics Mn(II) Complexes Based on an Open-Chain Ligand, Bioactivity, and Detection in Intestinal Epithelial Cells

“…For EnPI2C and EnPI2CP, a cyclohexyl group was added between the two amino groups in order to introduce rigidity into the ligand skeleton and consequently reduce the kinetic lability. As previously shown, the Mn complex [Mn(CDTA)] 2+ or [Mn(PyC3A)] 2+ studied, respectively, by Kálmán and Tircsó, Gale et al, and Laine et al, contains a similar diaminocyclohexane motif (Figure S1) and displayed remarkably slow dissociation rate, possibly due to a weaker ability to reach open conformation [49,56,57]. EnPI2-derived ligands were synthetized using a protocol similar to that used for EnPI2, previously reported by Cisnetti et al [42] but with racemic (±)-(trans)-1,2-diaminocyclohexane instead of 1,2diaminoethane as a reagent.…”

“…This behavior was explained by the formation of a preorganized and more rigid coordination cavity that encapsulates the manganese ion. Other open-chain ligands for Mn coordination were described, but they did not reach as good kinetic inertness as Mn-CDTA [57]. Mn-CDTA complex is hence considered as the gold standard for rigid and inert Mn 2+ complex involving an open-chain ligand.…”

Manganese(II)-Based Responsive Contrast Agent Detects Glucose-Stimulated Zinc Secretion from the Mouse Pancreas and Prostate by MRI

“…Both types vary in i) thermodynamic stability, ii) kinetic inertness, iii) number of inner-sphere water molecules (q), iv) water exchange rates (kex), v) binding interactions with plasma proteins, vi) oxidation (Mn 2+ /Mn 3+ ) and vii) general versatility. [28][29][30][31]20,[32][33][34][35][36] Among the most promising Mn 2+ chelates reported so far are those having picolinate-based coordinating groups attached to either a macrocyclic or acyclic amine. 37,38 This is the case for the recently reported [Mn(PyC3A)(H2O)] − with a r1 relaxivity value comparable to commercially available GBCA, rapid hepatobiliary/renal clearance in vivo, and low toxicity.…”

“…However, a renewed interest in Mn 2+ has led to the development of newer types of ligands for optimal chelation, some derived from macrocyclic ligands and others from acyclic ligands. Both types vary in (i) thermodynamic stability, (ii) kinetic inertness, (iii) number of inner-sphere water molecules ( q ), (iv) water exchange rates ( k ex ), (v) binding interactions with plasma proteins, (vi) oxidation (Mn 2+ /Mn 3+ ), and (vii) general versatility. ,− Among the most promising Mn 2+ chelates reported so far are those bearing picolyl coordinating groups attached to either a macrocyclic or acyclic amine. , This is the case for Mn­( N -picolyl- N , N ′, N ′-trans-l,2-cyclohexylenediaminetriacetate hydrate, [MnPyC3A·(H 2 O) − ], a recently reported complex having a r 1 relaxivity comparable to commercially available GBCA that also displays rapid hepatobiliary/renal clearance in vivo and low toxicity . A peptide-conjugated version of this agent has also been used to target fibrin filaments in cardiac thrombus. , …”