Effect of metal complexation on the radiolytic stability of DOTA

Mahti, Ilyes; Guillaumont, Dominique; Berthon, Claude; Saint-Louis, Georges; Hérès, Xavier; Berthon, Laurence

doi:10.1039/d3dt00977g

Cited by 4 publications

(2 citation statements)

References 92 publications

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“…Atom C5 is in the vicinity of two electronegative atoms, and a change in electron density during protonation and deprotonation affects its NBO charge. The proposed methodology can be applied to predicting the reactive sites in newly obtained ligands [42]. A molecular electrostatic potential (MEP) map is a way to predict reactive sites for noncovalent interactions [43,44].…”

Section: Theoretical Structural and Reactivity Analysis Of Plagmentioning

confidence: 99%

Synthesis, Structural Characterization, Cytotoxicity, and Protein/DNA Binding Properties of Pyridoxylidene-Aminoguanidine-Metal (Fe, Co, Zn, Cu) Complexes

Jevtovic,

Alhar,

Milenković

et al. 2023

IJMS

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Pyridoxylidene-aminoguanidine (PLAG) and its transition metal complexes are biologically active compounds with interesting properties. In this contribution, three new metal-PLAG complexes, Zn(PLAG)(SO4)(H2O)].∙H2O (Zn-PLAG), [Co(PLAG)2]SO4∙2H2O (Co-PLAG), and [Fe(PLAG)2]SO4∙2H2O) (Fe-PLAG), were synthetized and characterized by the X-ray crystallography. The intermolecular interactions governing the stability of crystal structure were compared to those of Cu(PLAG)(NCS)2 (Cu-PLAG) within Hirshfeld surface analysis. The structures were optimized at B3LYP/6-31+G(d,p)(H,C,N,O,S)/LanL2DZ (Fe,Co,Zn,Cu), and stability was assessed through Natural Bond Orbital Theory and Quantum Theory of Atoms in Molecules. Special emphasis was put on investigating the ligand’s stability and reactivity. The binding of these compounds to Bovine and Human serum albumin was investigated by spectrofluorometric titration. The importance of complex geometry and various ligands for protein binding was shown. These results were complemented by the molecular docking study to elucidate the most important interactions. The thermodynamic parameters of the binding process were determined. The binding to DNA, as one of the main pathways in the cell death cycle, was analyzed by molecular docking. The cytotoxicity was determined towards HCT116, A375, MCF-7, and A2780 cell lines. The most active compound was Cu-PLAG due to the presence of PLAG and two thiocyanate ligands.

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Section: Theoretical Structural and Reactivity Analysis Of Plagmentioning

confidence: 99%

Synthesis, Structural Characterization, Cytotoxicity, and Protein/DNA Binding Properties of Pyridoxylidene-Aminoguanidine-Metal (Fe, Co, Zn, Cu) Complexes

Jevtovic,

Alhar,

Milenković

et al. 2023

IJMS

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“…We designed a novel trifunctional chelating agent composed of a 1,4,7,10-tetr aazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) derivative as a chelator to coordinate a radiometal, a CTSB substrate to conjugate with CTSB, and an azide group to be introduced into mAb, that is, azide-DOTA-CTSB substrate (ADCS) (Figure 1A). DOTA is a suitable chelator for application to RICs with long biological half-lives in blood, as there have been reports on the stable coordination of DOTA with radionuclides with long halflives, such as 111 In (2.8 days) and 89 Zr (3.3 days) for diagnosis and 177 Lu (6.6 days) and 225 Ac (9.9 days) for therapy [14][15][16][17]. A DOTA derivative with one carboxy group and one amino group was reported as a favorable chelator to introduce functional units [18].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of a Cathepsin B–Recognizing Trifunctional Chelating Agent to Improve Tumor Retention of Radioimmunoconjugates

Jinda,

Nakashima,

Watanabe

et al. 2024

Labelled Comp Radiopharmac

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Cathepsin B (CTSB) is a lysosomal protease that is overexpressed in tumor cells. Radioimmunoconjugates (RICs) composed of CTSB‐recognizing chelating agents are expected to increase the molecular weights of their radiometabolites by forming conjugates with CTSB in cells, resulting in their improved retention in tumor cells. We designed a novel CTSB‐recognizing trifunctional chelating agent, azide‐[111In]In‐DOTA‐CTSB‐substrate ([111In]In‐ADCS), to synthesize a RIC, trastuzumab‐[111In]In‐ADCS ([111In]In‐TADCS), and evaluated its utility to improve tumor retention of the RIC. [111In]In‐ADCS and [111In]In‐TADCS were synthesized with satisfactory yield and purity. [111In]In‐ADCS was markedly stable in murine plasma until 96 h postincubation. [111In]In‐ADCS showed binding to CTSB in vitro, and the conjugation was blocked by the addition of CTSB inhibitor. In the internalization assay, [111In]In‐TADCS exhibited high‐level retention in SK‐OV‐3 cells, indicating the in vitro utility of the CTSB‐recognizing unit. In the biodistribution assay, [111In]In‐TADCS showed high‐level tumor accumulation, but the retention was hardly improved. In the first attempt to combine a CTSB‐recognizing unit and RIC, these findings show the fundamental properties of the CTSB‐recognizing trifunctional chelating agent to improve tumor retention of RICs.

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Effect of Europium Complexation on N,N,N′,N′-Tetraoctyldiglycolamide Degradation Against Gamma Radiation

Sánchez-García,

Galán

2023

Arab J Sci Eng

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Diglycolamide extractants (DGAs) are playing an important role for many of aqueous separation processes under development for the advanced nuclear fuel cycle. This family of ligands exhibits excellent extracting and resistant properties, with TODGA (N,N,N′,N′-tetraoctyldiglycolamide) being a particularly successful extractant studied intensively in recent decades. Nowadays, the main issues for TODGA-based solvents are related to the understanding and simulation of the radiolytic degradation under realistic conditions, which is limiting aspect for the development of an advanced aqueous nuclear separation process. In that sense, in this work, TODGA ligand stability, solvent composition and performance were evaluated considering the effect of metal complexation under gamma radiation. For that, the irradiation of a TODGA solvent in the presence of Eu metal was carried out, varying the ligand/metal ratio. The goal was to not only study TODGA degradation using HPLC–MS technique but also to identify and quantify its degradation compound under these experimental conditions. The results revealed a protection of TODGA molecules due to metal ion complexation, with no observed changes in the degradation pathway, as confirmed by the quantification of formed degradation compounds.

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Effect of metal complexation on the radiolytic stability of DOTA

Abstract: Radiometals are increasingly used in nuclear medicine for both, diagnostic and therapeutic purposes. DOTA ligand (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) is widely used as a chelating agent for various radionuclides, including 89Zr, with...

Cited by 4 publications

References 92 publications

Synthesis, Structural Characterization, Cytotoxicity, and Protein/DNA Binding Properties of Pyridoxylidene-Aminoguanidine-Metal (Fe, Co, Zn, Cu) Complexes

Synthesis, Structural Characterization, Cytotoxicity, and Protein/DNA Binding Properties of Pyridoxylidene-Aminoguanidine-Metal (Fe, Co, Zn, Cu) Complexes

Synthesis and Evaluation of a Cathepsin B–Recognizing Trifunctional Chelating Agent to Improve Tumor Retention of Radioimmunoconjugates

Effect of Europium Complexation on N,N,N′,N′-Tetraoctyldiglycolamide Degradation Against Gamma Radiation

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