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

Cieslik, Patrick; Comba, Peter; Dittmar, Benedikt; Ndiaye, Daouda; Tóth, Éva; Velmurugan, Gunasekaran; Wadepohl, Hubert

doi:10.1002/anie.202115580

Cited by 32 publications

(61 citation statements)

References 67 publications

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“…Indeed, the most stable macrocyclic complex with one inner-sphere water molecule [Mn(PC2A-EA)] + 15 (Scheme 1) has log K MnL = 19.01 and pM = 9.27, and an exceptionally high log K MnL = 24.3 and pM = 12.73 have been recently reported for the Mn 2+ complex of a bispidine ligand containing five pyridine units, which forms a peculiar, eight-coordinate structure with one water molecule in the first coordination sphere. 46 Kinetic Inertness. In general, Mn 2+ complexes are known as particularly labile, though examples of higher inertness have been reported both with linear ligands (transCDTA and derivatives) 12 and azamacrocycles (DOTA and PC2A derivatives).…”

Section: Protonation Constants Of the Ligands And Thermodynamic Stabi...mentioning

confidence: 99%

^55/52Mn²⁺ Complexes with a Bispidine-Phosphonate Ligand: High Kinetic Inertness for Imaging Applications

Ndiaye

Silva

et al. 2022

Inorg. Chem.

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Bispidine (3,nonane) provides a rigid and preorganized scaffold that is particularly interesting for the stable and inert complexation of metal ions, especially for their application in medical imaging. In this study, we present the synthesis of two bispidine ligands with N-methanephosphonate (H 4 L 1 ) and N-methanecarboxylate (H 3 L 2 ) substituents as well as the physico-chemical properties of the corresponding Mn 2+ and Zn 2+ complexes. The two complexes [Mn(L 1 )] 2− and [Mn(L 2 )] − have relatively moderate thermodynamic stability constants according to potentiometric titration data. However, they both display an exceptional kinetic inertness, as assessed by transmetallation experiments in the presence of 50 equiv excess of Zn 2+ , showing only ∼40 and 20% of dissociation for [Mn(L 1 )] 2− and [Mn(L 2 )] − , respectively, after 150 days at pH 6 and 37 °C. Proton relaxivities amount to r 1 = 4.31 mM −1 s −1 ([Mn(L 1 )] 2− ) and 3.64 mM −1 s −1 ([Mn(L 2 )] − ) at 20 MHz, 25 °C, and are remarkable for Mn 2+ complexes with one inner-sphere water molecule (q = 1); they are comparable to that of the commercial contrast agent [Gd(DOTA)(H 2 O)] − . The presence of one inner-sphere water molecule and an associative water exchange mechanism was confirmed by temperature-dependent transverse 17 O relaxation rate measurements, which yielded k ex 298 = 0.12 × 10 7 and 5.5 × 10 7 s −1 for the water exchange rate of the phosphonate and the carboxylate complex, respectively. In addition, radiolabeling experiments with 52 Mn were also performed with H 2 (L 1 ) 2− showing excellent radiolabeling properties and quantitative complexation at pH 7 in 15 min at room temperature as well as excellent stability of the complex in various biological media over 24 h.

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Section: Protonation Constants Of the Ligands And Thermodynamic Stabi...mentioning

confidence: 99%

^55/52Mn²⁺ Complexes with a Bispidine-Phosphonate Ligand: High Kinetic Inertness for Imaging Applications

Ndiaye

Silva

et al. 2022

Inorg. Chem.

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“…Manganese(II) ions prefer to exist in ix coordinate complexes. However, these Mn(II) complexes are often unstable and easily interact with other molecules/ligands which can modify their coordination spheres, with consequences to their interaction modes with specific enzymes [ 72 , 73 , 74 ].…”

Section: History and Applications Of Metallodrugsmentioning

confidence: 99%

NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments

Santos

Monteiro

Gomes

et al. 2022

IJMS

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After the serendipitous discovery of cisplatin, a platinum-based drug with chemotherapeutic effects, an incredible amount of research in the area of coordination chemistry has been produced. Other transition metal compounds were studied, and several new relevant metallodrugs have been synthetized in the past few years. This review is focused on coordination compounds with first-row transition metals, namely, copper, cobalt, nickel or manganese, or with zinc, which have potential or effective pharmacological properties. It is known that metal complexes, once bound to organic drugs, can enhance the drugs’ biological activities, such as anticancer, antimicrobial or anti-inflammatory ones. NSAIDs are a class of compounds with anti-inflammatory properties used to treat pain or fever. NSAIDs’ properties can be strongly improved when included in complexes using their compositional N and O donor atoms, which facilitate their coordination to metal ions. This review focuses on the research on this topic and on the promising or effective results that complexes of first-row transition metals and NSAIDs can exhibit.

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“…Eight-coordinate Mn(II) complexes are rare. , Eight-coordinate bispidine derivatives providing exceptionally high thermodynamic stabilities (log K MnL > 24) have been reported recently . Remarkable examples in the context of MRI contrast agents are the cyclen derivatives [Mn(DOTAM)] 2+ (DOTAM = L36 , Chart ) and the analogue containing four 2-pyridyl pendants, which were both found to exhibit eight-coordinate metal ions in the solid state. , However, it is not clear whether eight coordination is favored for these complexes by the presence of charge-neutral pendant arms.…”

Section: Resultsmentioning

confidence: 99%

“…As such, it does not anticipate novel chelators like bispidines. 27 , 48 However, these types of ligands can be added to the model once stability constant data are collected for a few examples.…”

Section: Discussionmentioning

confidence: 99%

“…The reemergence of Mn(II) complexes as MRI contrast agents has stimulated a great amount of work to determine their thermodynamic stabilities. ,, Compared to Gd(III)-based MRI contrast agents, the stability constants of Mn(II) complexes are typically lower. High-spin Mn(II) has no ligand field stabilization energy (LFSE), is generally kinetically labile, and forms less stable complexes than biologically important divalent cations like Fe(II), Zn(II), and Cu(II).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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

Cited by 32 publications

References 67 publications

^55/52Mn²⁺ Complexes with a Bispidine-Phosphonate Ligand: High Kinetic Inertness for Imaging Applications

^55/52Mn²⁺ Complexes with a Bispidine-Phosphonate Ligand: High Kinetic Inertness for Imaging Applications

NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments

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

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

Cited by 32 publications

References 67 publications

55/52Mn2+ Complexes with a Bispidine-Phosphonate Ligand: High Kinetic Inertness for Imaging Applications

55/52Mn2+ Complexes with a Bispidine-Phosphonate Ligand: High Kinetic Inertness for Imaging Applications

NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments

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

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^55/52Mn²⁺ Complexes with a Bispidine-Phosphonate Ligand: High Kinetic Inertness for Imaging Applications

^55/52Mn²⁺ Complexes with a Bispidine-Phosphonate Ligand: High Kinetic Inertness for Imaging Applications