Academic Journal
Is Smaller Better? Cu2+/Cu+ Coordination Chemistry and Copper-64 Radiochemical Investigation of a 1,4,7-Triazacyclononane-Based Sulfur-Rich Chelator
| العنوان: | Is Smaller Better? Cu2+/Cu+ Coordination Chemistry and Copper-64 Radiochemical Investigation of a 1,4,7-Triazacyclononane-Based Sulfur-Rich Chelator |
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| المؤلفون: | Tosato M., Franchi S., Isse A. A., Del Vecchio A., Zanoni G., Alker A., Asti M., Gyr T., Di Marco V., Mäcke H. |
| المساهمون: | Tosato, M., Franchi, S., Isse, A. A., Del Vecchio, A., Zanoni, G., Alker, A., Asti, M., Gyr, T., Di Marco, V., Mäcke, H. |
| بيانات النشر: | AMER CHEMICAL SOC |
| سنة النشر: | 2023 |
| المجموعة: | Padua Research Archive (IRIS - Università degli Studi di Padova) |
| الوصف: | The biologically triggered reduction of Cu2+ to Cu+ has been postulated as a possible in vivo decomplexation pathway in 64/67Cu-based radiopharmaceuticals. In an attempt to hinder this phenomenon, we have previously developed a family of S-containing polyazamacrocycles based on 12-, 13-, or 14-membered tetraaza rings able to stabilize both oxidation states. However, despite the high thermodynamic stability of the resulting Cu2+/+ complexes, a marked [64Cu]Cu2+ release was detected in human serum, likely as a result of the partially saturated coordination sphere around the copper center. In the present work, a new hexadentate macrocyclic ligand, 1,4,7-tris[2-(methylsulfanyl)ethyl)]-1,4,7-triazacyclononane (NO3S), was synthe-sized by hypothesizing that a smaller macrocyclic backbone could thwart the observed demetalation by fully encapsulating the copper ion. To unveil the role of the S donors in the metal binding, the corresponding alkyl analogue 1,4,7-tris-n-butyl-1,4,7-triazacyclononane (TACN-n-Bu) was considered as comparison. The acid-base properties of the free ligands and the kinetic, thermodynamic, and structural properties of their Cu2+ and Cu+ complexes were investigated in solution and solid (crystal) states through a combination of spectroscopic and electrochemical techniques. The formation of two stable mononuclear species was detected in aqueous solution for both ligands. The pCu2+ value for NO3S at physiological pH was 6 orders of magnitude higher than that computed for TACN-n-Bu, pointing out the significant stabilizing contribution arising from the Cu2+-S interactions. In both the solid state and solution, Cu2+ was fully embedded in the ligand cleft in a hexacoordinated N3S3 environment. Furthermore, NO3S exhibited a remarkable ability to form a stable complex with Cu+ through the involvement of all of the donors in the coordination sphere. Radiolabeling studies evidenced an excellent affinity of NO3S toward [64Cu]Cu2+, as quantitative incorporation was achieved at high apparent molar activity ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/37115633; info:eu-repo/semantics/altIdentifier/wos/WOS:000985526800001; journal:INORGANIC CHEMISTRY; https://hdl.handle.net/11577/3510757; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85156239914 |
| DOI: | 10.1021/acs.inorgchem.3c00621 |
| الاتاحة: | https://hdl.handle.net/11577/3510757 https://doi.org/10.1021/acs.inorgchem.3c00621 |
| رقم الانضمام: | edsbas.88E276DF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.inorgchem.3c00621 |
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