Mn2+ Complexes with Pyridine-Containing 15-Membered Macrocycles: Thermodynamic, Kinetic, Crystallographic, and 1H/17O Relaxation Studies

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• 作者：Bohuslav Draho ; Jan Kotek ; Petr Hermann ; Ivan Luke ; va Tth
• 刊名：Inorganic Chemistry
• 出版年：2010
• 出版时间：April 5, 2010
• 年：2010
• 卷：49
• 期：7
• 页码：3224-3238
• 全文大小：1115K
• 年卷期：v.49,no.7(April 5, 2010)
• ISSN：1520-510X

文摘

Given its five unpaired d-electrons, long electronic relaxation time, and fast water exchange, Mn²⁺ is a potential candidate for contrast agent application in medical magnetic resonance imaging. Nevertheless, the design of chelators that ensure stable Mn²⁺ complexation and optimal relaxation properties remains a coordination chemistry challenge. Here, we report the synthesis of two pyridine-containing ligands L1 and L2, with 15-membered triaza-dioxa-crown and pentaaza-crown ether macrocycles, respectively, and the characterization of their Mn²⁺ complexes. Protonation constants of the ligands and stability constants of various metal complexes were determined by potentiometry. The presence of the pyridine in the macrocyclic ring induces rigidity of the complexes which results in a greater thermodynamic stability with respect to the nonpyridine analogues. Solid-state structures of MnL1 and MnL2 confirmed seven-coordination of Mn²⁺ with Cl⁻ and H₂O in axial positions. The dissociation kinetics of MnL2 in the presence of Zn²⁺ were followed by relaxometric measurements. They proved the prime importance of the proton-assisted dissociation while the zinc(II)-assisted pathway is not important at physiological pH. For MnL1, the dissociation was too fast to be studied by conventional relaxivity measurements under pH 6. A combined ¹⁷O NMR and ¹H NMRD study on MnL1 and MnL2 yielded the parameters that govern the relaxivity of these complexes. The water exchange rate for MnL1, k_ex²⁹⁸ = 0.38 × 10⁷ s⁻¹, is the lowest value ever reported for a Mn²⁺ complex, while a considerably higher value was obtained for MnL2 (k_ex²⁹⁸ = 6.9 × 10⁷ s⁻¹). Anion binding was studied by relaxometric titrations. They revealed weak interactions between MnL2 and phosphate or citrate, leading to the formation of monohydrated species. Overall, the incorporation of a pyridine into a polyaza macrocycle scaffold has several beneficial effects on the Mn²⁺ chelates with respect to potential MRI contrast agent applications: (i) The thermodynamic and the kinetic stability of the complexes is increased. (ii) The rigidified ligand backbone results in higher coordination numbers of the metal ion, allowing for two inner-sphere water molecules in aqueous solution.