ClickZip lanthanide chelates as robust building blocks for multimetallic compounds and probes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00639647" target="_blank" >RIV/61388963:_____/25:00639647 - isvavai.cz</a>

Result on the web

<a href="https://hdl.handle.net/11104/0370112" target="_blank" >https://hdl.handle.net/11104/0370112</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

ClickZip lanthanide chelates as robust building blocks for multimetallic compounds and probes

Original language description

Lanthanide chelates are indispensable in biomedical applications but since the introduction of chelator DOTA there has been limited progress on improving their thermodynamic stability and kinetic inertness. Recently reported ClickZip chelates improve the inertness up to a million-fold relative to DOTA, opening new possibilities for applications [1]. Here, we report ClickZip chelates modified to serve as building blocks and demonstrate their robustness and versatility in construction of higher-order multimetallic molecular architectures. ClickZip chelates have been synthesized according to published procedures [1] modified to add functional groups at various positions of the chelator. These included but were not limited to one carboxylic and one amino group, so that the chelates can serve as amino acid building blocks. Multimetallic oligomers were synthesized by linear concatenation of the ClickZip building blocks via standard peptide coupling chemistry in solution (PyAOP in DMSO). Dimers and trimers were synthesized with nearly quantitative yields and purified by preparative HPLC. The identity of the compounds was confirmed by high-resolution MS spectra and ICP-MS analysis to quantify the metal content. Five different positions on the original ClickZip chelates can be relatively easily modified with various functional groups, leading to a range of chemically diverse building blocks (Figure 1). Each building block can be individually loaded with selected lanthanide ion before further controlled synthetic assembly of the building blocks into higher-order architectures. This synthetic approach provides access to a practically limitless number of compounds containing multiple (different) lanthanide units in well-defined positions. With emphasis on synthetic ease, the use of peptide coupling for concatenation of amino-acid building blocks into linear peptide-like oligomers was explored in particular. Trimers containig three different lanthanide ClickZip units were successfully prepared (Figure 2). Ultra-stable ClickZip lanthanide chelates are amenable to chemical modifications that significantly expand our ability to create stable multi-metallic compounds with well-defined structures. Such advanced constructs may serve as multi-color MRI probes [2], luminescent probes [3] and multi-modal probes [4]. Novel ClickZip ultra-stable chelates are presented as building blocks leading to a new class of multi-metallic compounds with a range of applications. The work presents new chemical tools that significantly advance our synthetic capabilities to construct imaging probes with advantageous properties.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/LX22NPO5104" target="_blank" >LX22NPO5104: National Institute for Research of Metabolic and Cardiovascular Diseases</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů