Origin of the Isomer Stability of Polymethylated DOTA Chelates Complexed with Ln<sup>3+</sup> Ions

Lee, Yong‐Sok; Mou, Zhongyu; Opina, Ana Christina L.; Vasalatiy, Olga

doi:10.1002/ejic.202100019

Cited by 5 publications

(5 citation statements)

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“…287 The relative conformational stabilities of SAP and TSAP conformations of DOTA-type cyclen-Lu(III) complexes with different chiralities of methylated cyclen and carboxylate pendants has recently been rationalized computationally. 302 Another recent approach used a photocatalyzed reaction to conjugate a vinyl probe to proteins. 303 Using 2,2-dimethoxy-2phenylacetophenone (DPAP) as a photoactivated radical initiator, the ligation rate of the vinylpicolinic acid modified probe 111 (Figure 9) with GB1 T53C was greatly accelerated, but the Δχ tensors obtained were small.…”

Section: Chemicalmentioning

confidence: 99%

“…Notably, a second conformational species has also been reported for DOTA-M8 , although this probe contains four additional stereocenters in the cyclen ring . The relative conformational stabilities of SAP and TSAP conformations of DOTA-type cyclen-Lu(III) complexes with different chiralities of methylated cyclen and carboxylate pendants has recently been rationalized computationally …”

Section: General Overview Of Natural and Chemically Generated Paramag...mentioning

confidence: 99%

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Paramagnetic Chemical Probes for Studying Biological Macromolecules

et al. 2022

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Paramagnetic chemical probes have been used in electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) spectroscopy for more than four decades. Recent years witnessed a great increase in the variety of probes for the study of biological macromolecules (proteins, nucleic acids, and oligosaccharides). This Review aims to provide a comprehensive overview of the existing paramagnetic chemical probes, including chemical synthetic approaches, functional properties, and selected applications. Recent developments have seen, in particular, a rapid expansion of the range of lanthanoid probes with anisotropic magnetic susceptibilities for the generation of structural restraints based on residual dipolar couplings and pseudocontact shifts in solution and solid state NMR spectroscopy, mostly for protein studies. Also many new isotropic paramagnetic probes, suitable for NMR measurements of paramagnetic relaxation enhancements, as well as EPR spectroscopic studies (in particular double resonance techniques) have been developed and employed to investigate biological macromolecules. Notwithstanding the large number of reported probes, only few have found broad application and further development of probes for dedicated applications is foreseen.

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Section: Chemicalmentioning

confidence: 99%

Section: General Overview Of Natural and Chemically Generated Paramag...mentioning

confidence: 99%

Paramagnetic Chemical Probes for Studying Biological Macromolecules

et al. 2022

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“…The structural modifications of the Bn-DOTA skeleton avoiding the N 3 O 3 configuration upon Ga complexation may constitute a way. 36 …”

Section: Discussionmentioning

confidence: 99%

“…A bifunctional Bn-DOTA providing a single Ga complex with high in vivo stability is needed. The structural modifications of the Bn-DOTA skeleton avoiding the N 3 O 3 configuration upon Ga complexation may constitute a way …”

Section: Discussionmentioning

confidence: 99%

Stability Estimation of Gallium Complexes of DOTA Derivatives for Radiotheranostic Applications

et al. 2022

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Tetraazacyclododecane-1,4,7-triacetic acid (DO3A) has been used to prepare 68 Ga-labeled probes for the diagnostic counterpart of radiotheranostic applications. While DO3A provides stable complexes with therapeutic radionuclides such as 90 Y, 177 Lu, and 225 Ac, further improvement of the in vivo stability of the Ga-DO3A complex is required. Considering the high stability of an intact Ga-DOTA complex, the stability of Ga complexes of DOTA and DO3A derivatives, including benzyl-DOTA (Bn-DOTA), was evaluated to gain fundamental knowledge for developing the next-generation radiotheranostic probes using 68 Ga as a diagnostic counterpart. Following the complexation reaction to prepare 67 Ga-labeled DOTA and DO3A derivatives, the stability of the resulting 67 Ga-labeled compounds was evaluated in murine plasma and apo-transferrin challenge. [ 67 Ga]Ga-Bn-DOTA produced two isomers, and one of the isomers exhibited the highest stability among the tested complexes. The X-ray crystallography showed that the less stable isomer of Ga-Bn-DOTA suggested an N 3 O 3 coordination geometry, while Ga-DOTA and Ga-Bn-DO3A show N 4 O 2 coordination. To further evaluate the stability, a synthetic somatostatin analogue, [Tyr 3 ]octreotide (TOC), was used as a model peptide, and p-COOH-Bn-DOTA and DO3A were conjugated with TOC to prepare DOTA-Bn-TOC and DOTATOC.[ 67 Ga]Ga-DOTA-Bn-TOC also yielded two isomers with varying stability, and one isomer exhibited significantly higher stability than [ 67 Ga]Ga-DOTATOC both in vitro and in vivo. These findings indicate that para-substituted Bn-DOTA would constitute a suitable chelating agent for developing next-generation radiotheranostic probes, although high-performance liquid chromatography purification is needed. Thus, further chemical modification on the Bn-DOTA molecule is also needed to avoid the formation of a Ga complex with the N 3 O 3 configuration.

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“…In solution, Gd‐DOTA‐complexes are present as two conformers of a quadratic antiprismatic coordination polyhedron: a compact square antiprismatic (SAP) and an elongated twisted square antiprismatic (TSAP) modification [9] . Steric crowding, for example through α‐substituted pendant arms favor the TSAP conformer in DOTA‐complexes [7b,8b,10] . To compensate the steric demand, the coordination polyhedron undergoes a distortion along the longitudinal axis (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Solution Structure and Relaxivity of Ln‐DOTXAZA Derivatives

et al. 2022

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Herein we report the synthesis and structural analysis of tunable 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)derivatives bearing azidoethyl side chains. According to the number of azidoethyl side chains, the compounds are termed DOTXAZA (with X = 1-4). All derivatives retain the wellapproved DOTA scaffold for metal complexation with 8 coordinating functionalities and are applicable to Cu-catalyzed alkyne-azide cycloaddition (CuAAC). They may thus be used to assemble new Gd-based contrast agents (GBCAs) with tailored pharmacokinetic or MRI properties retaining the high stability of clinically used DOTA-derived GBCAs. The complex geometry of all DOTXAZA derivatives was investigated in solution with NMR-spectroscopy of the corresponding Eu-complexes. A correlation of complex geometry with the longitudinal relaxivity of corresponding Gd-complexes revealed an increase in relaxivity with increasing substitution number in the DOTXAZA series. Moreover, CuAAC-modified DOTAZA-derivatives with neutral, charged, and zwitterionic groups were prepared. Although of similar molecular mass, the corresponding Gdcomplexes revealed pronounced differences in relaxivities from r 1 = 3.9-7.9 mm À 1 s À 1 in water at 1.5 T and 37 °C. Relaxivities of these complexes were found to be strongly dependent on side chain charge and are most likely determined by second-sphere water effects.

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Origin of the Isomer Stability of Polymethylated DOTA Chelates Complexed with Ln³⁺ Ions

Cited by 5 publications

References 45 publications

Paramagnetic Chemical Probes for Studying Biological Macromolecules

Paramagnetic Chemical Probes for Studying Biological Macromolecules

Stability Estimation of Gallium Complexes of DOTA Derivatives for Radiotheranostic Applications

Solution Structure and Relaxivity of Ln‐DOTXAZA Derivatives

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Origin of the Isomer Stability of Polymethylated DOTA Chelates Complexed with Ln3+ Ions

Cited by 5 publications

References 45 publications

Paramagnetic Chemical Probes for Studying Biological Macromolecules

Paramagnetic Chemical Probes for Studying Biological Macromolecules

Stability Estimation of Gallium Complexes of DOTA Derivatives for Radiotheranostic Applications

Solution Structure and Relaxivity of Ln‐DOTXAZA Derivatives

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Origin of the Isomer Stability of Polymethylated DOTA Chelates Complexed with Ln³⁺ Ions