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

Abstract

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.

Endeavor toward Redox-Responsive Transition Metal Contrast Agents Based on the Cross-Bridge Cyclam Platform

“…The dissociation of the Mn­(II) complex implies that the thermodynamic stability of the complex is low, which together with the high basicity of cross-bridge derivatives causes complex dissociation in water at neutral pH. The stability constant of the complex can be estimated using the structural descriptors published recently . Assuming a contribution of Δlog K = 4.1 for cyclam and a contribution of Δlog K = 2.7 for a carboxylate, we estimate a stability constant of log K = 6.8.…”

A seven-coordinate Mn(ii) complex with a pyridine-based 15-membered macrocyclic ligand containing one acetate pendant arm: structure, stability and relaxation properties

“…Recently, an empirical approach, based on various structural descriptors, has been proposed to estimate stability constants for Mn( ii ) complexes. 42 Considering the stabilization effect of the additional acetate in comparison with the parent 15-pyN 3 O 2 , this method predicts log K ML = 9.64 for MnL1 , ca. 1.4 units lower than the experimental value.…”

Divalent Manganese Complexes as Potential Replacements for Gadolinium-Based Contrast Agents

“…If one of those coordination sites is occupied by a water ligand, then this leaves 5 or 6 sites to be bonded by the chelator. The lower charge of Mn 2+ versus Gd 3+ and the lower denticity of the appropriate chelator result in lower thermodynamic stability constants for Mn 2+ complexes when compared with Gd 3+ 37,38 . The coordination number of Mn 2+ cannot be reliably predicted.…”

“…The lower charge of Mn 2+ versus Gd 3+ and the lower denticity of the appropriate chelator result in lower thermodynamic stability constants for Mn 2+ complexes when compared with Gd 3+ . 37,38 The coordination number of Mn 2+ cannot be reliably predicted. As a result, some hexadentate chelators such as the macrocycle NOTA (Fig.…”