Synthesis, structure and superoxide dismutase activity of a novel tetranuclear copper(II) complex Na2[Cu4Na2(TACNTA)4(H2O)6]·(H2O)26

Li, Qingxiang; Li, Qiao; Cheng, Gang; Yang, Xiangliang; Zhou, Jing-Yan; Xu, Heng

doi:10.1016/j.inoche.2010.07.019

Cited by 7 publications

(5 citation statements)

References 27 publications

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“…H 3 nota was the first macrocyclic polyamino-polycarboxylate ligand synthesized. , Since then, this ligand has been thoroughly investigated, mostly in complexes with trivalent metal ions , because the relatively small and preorganized ligand cavity of H 3 nota is perfectly suited for transition-metal ions requiring octahedral or twisted-trigonal-prismatic arrangements. H 3 nota hexacoordination has been observed in solid-state complexes with divalent metal ions, including Fe(II), Ni(II), Cu(II), − and Zn(II) . Furthermore, the H 3 nota ligand is pentadentate in the [Cu(Cl)(H 2 nota)] complex, wherein two carboxylate groups are protonated and one of the groups remains uncoordinated …”

Section: Introductionmentioning

confidence: 99%

NOTA Complexes with Copper(II) and Divalent Metal Ions: Kinetic and Thermodynamic Studies

et al. 2018

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Hnota derivatives are among the most studied macrocyclic ligands and are widely used for metal ion binding in biology and medicine. Despite more than 40 years of chemical research on Hnota, the comprehensive study of its solution chemistry has been overlooked. Thus, the coordination behavior of Hnota with several divalent metal ions was studied in detail with respect to its application as a chelator for copper radioisotopes in medical imaging and therapy. In the solid-state structure of the free ligand in zwitterionic form, one proton is bound in the macrocyclic cavity through a strong intramolecular hydrogen-bond system supporting the high basicity of the ring amine groups (log K = 13.17). The high stability of the [Cu(nota)] complex (log K = 23.33) results in quantitative complex formation, even at pH <1.5. The ligand is moderately selective for Cu(II) over other metal ions (e.g., log K(Zn) = 22.32 and log K(Ni) = 19.24). This ligand forms a more stable complex with Mg(II) than with Ca(II) and forms surprisingly stable complexes with alkali-metal ions (stability order Li(I) > Na(I) > K(I)). Thus, Hnota shows high selectivity for small metal ions. The [Cu(nota)] complex is hexacoordinated at neutral pH, and the equatorial NO interaction is strengthened by complex protonation. Detailed kinetic studies showed that the Cu(II) complex is formed quickly (millisecond time scale at c ≈ 0.1 mM) through an out-of-cage intermediate. Conversely, conductivity measurements revealed that the Zn(II) complex is formed much more slowly than the Cu(II) complex. The Cu(II) complex has medium kinetic inertness (τ 46 s; pH 0, 25 °C) and is less resistant to acid-assisted decomplexation than Cu(II) complexes with Hdota and Hteta. Surprisingly, [Cu(nota)] decomplexation is decelerated in the presence of Zn(II) ions due to the formation of a stable dinuclear complex. In conclusion, Hnota is a good carrier of copper radionuclides because the [Cu(nota)] complex is predominantly formed over complexes with common impurities in radiochemical formulations, Zn(II) and Ni(II), for thermodynamic and, primarily, for kinetic reasons. Furthermore, the in vivo stability of the [Cu(nota)] complex may be increased due to the formation of dinuclear complexes when it interacts with biometals.

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Section: Introductionmentioning

confidence: 99%

NOTA Complexes with Copper(II) and Divalent Metal Ions: Kinetic and Thermodynamic Studies

et al. 2018

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“…Distortion of the octahedral geometry is best reflected by the bond angle (∠O(3)–Cu(1)–N(3): 156.0° vs 180.0°) and the elongated apical distances (Cu(1)–O(3): 2.3160(13) Å, Cu(1)–N(3): 2.6111(15) Å). The observed deviations from an ideal octahedral environment arise both from the expected Jahn–Teller distortion, − as well as the distinct macrocyclic conformational constraint induced upon quaternization of N(4) compared to that of another N 3 O 3 macrocycle, [Cu II (NOTA)] − . − With our model complex in hand, we turned our attention to the solution structure of Cu II (DO3A C4H8 ) and Cu II (HDO3A) at variable pH.…”

Section: Results and Discussionmentioning

confidence: 99%

N,N-Alkylation Clarifies the Role of N- and O-Protonated Intermediates in Cyclen-Based ⁶⁴Cu Radiopharmaceuticals

et al. 2022

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Radioisotopes of Cu, such as 64Cu and 67Cu, are alluring targets for imaging (e.g., positron emission tomography, PET) and radiotherapeutic applications. Cyclen-based macrocyclic polyaminocarboxylates are one of the most frequently examined bifunctional chelators in vitro and in vivo, including the FDA-approved 64Cu radiopharmaceutical, Cu(DOTATATE) (Detectnet); however, connections between the structure of plausible reactive intermediates and their stability under physiologically relevant conditions remain to be established. In this study, we share the synthesis of a cyclen-based, N,N-alkylated spirocyclic chelate, H2DO3AC4H8 , which serves as a model for N-protonation. Our combined experimental (in vitro and in vivo) and computational studies unravel complex pH-dependent speciation and enable side-by-side comparison of N- and O-protonated species of relevant 64Cu radiopharmaceuticals. Our studies suggest that N-protonated species are not inherently unstable species under physiological conditions and demonstrate the potential of N,N-alkylation as a tool for the rational design of future radiopharmaceuticals.

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“…The comparison of solid-state structures of Cu II À H 3 nota complexes [36][37][38][39] (Table S5) shows that each structure has a different distortion of the (mostly) octahedral coordination sphere. [Cu(L 1 )] has the aforementioned 4 + 2 character, and [Cu(L 2 )] has an elongated tetragonally-pyramidal geometry, whereas the geometry of Cu II -H 3 nota complexes ranges from an elongated tetragonal bipyramid to a twisted trigonal prism.…”

Section: Crystal Structuresmentioning

confidence: 99%

Complexes of NOTA‐Monoamides with Cu^II Ions: Structural, Equilibrium, and Kinetic Study

et al. 2022

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NOTA monoamides are commonly and widely used chelators for the complexation of copper radioisotopes applied in molecular imaging and targeted nuclear therapy. However, information about their coordination behavior remains scarce. In this study, two NOTA‐monoamides, N‐ethyl (H2L1) and N,N‐diethyl (H2L2), were synthesized as model ligands and tested to probe differences in their coordination behavior between the secondary and tertiary amide pendant arms for potential applications as copper radioisotope carriers. Our results demonstrated that the solid [Cu(L1)] and [Cu(L2)] complex have a distorted octahedral arrangement, similar to structure of the [Cu(Hnota)] complex. As shown by equilibrium data, the ligands have a slightly lower basicity, and thus complexes with divalent metal ions and LiI have slightly lower stability constants than those of the parent ligand, H3nota. The dissociation constants of the CuII, ZnII and NiII complexes with H2L1 also indicate deprotonation and N‐coordination of the secondary amide group at pH>9. Complexation of CuII ions with the title ligands is slower than that with H3nota but still very fast (quantitative binding in <1 s, pH 2, millimolar concentrations), and CuII complexes of both monoamide ligands are more resistant to acid‐assisted decomplexation than the CuII‐H3nota complex. Therefore, our coordination data highlight that NOTA‐monoamides are suitable chelators for molecular imaging and nuclear medicine.

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Synthesis, structure and superoxide dismutase activity of a novel tetranuclear copper(II) complex Na2[Cu4Na2(TACNTA)4(H2O)6]·(H2O)26

Cited by 7 publications

References 27 publications

NOTA Complexes with Copper(II) and Divalent Metal Ions: Kinetic and Thermodynamic Studies

NOTA Complexes with Copper(II) and Divalent Metal Ions: Kinetic and Thermodynamic Studies

N,N-Alkylation Clarifies the Role of N- and O-Protonated Intermediates in Cyclen-Based ⁶⁴Cu Radiopharmaceuticals

Complexes of NOTA‐Monoamides with Cu^II Ions: Structural, Equilibrium, and Kinetic Study

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Synthesis, structure and superoxide dismutase activity of a novel tetranuclear copper(II) complex Na2[Cu4Na2(TACNTA)4(H2O)6]·(H2O)26

Cited by 7 publications

References 27 publications

NOTA Complexes with Copper(II) and Divalent Metal Ions: Kinetic and Thermodynamic Studies

NOTA Complexes with Copper(II) and Divalent Metal Ions: Kinetic and Thermodynamic Studies

N,N-Alkylation Clarifies the Role of N- and O-Protonated Intermediates in Cyclen-Based 64Cu Radiopharmaceuticals

Complexes of NOTA‐Monoamides with CuII Ions: Structural, Equilibrium, and Kinetic Study

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Product

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N,N-Alkylation Clarifies the Role of N- and O-Protonated Intermediates in Cyclen-Based ⁶⁴Cu Radiopharmaceuticals

Complexes of NOTA‐Monoamides with Cu^II Ions: Structural, Equilibrium, and Kinetic Study