Synthesis, Characterization, and Biological Evaluation of Novel [M(η<sup>6</sup>-arene)<sub>2</sub>]<sup>+</sup> (M = Re, <sup>99m</sup>Tc) Hosted Terpyridines and Copper Complexes Thereof
We report the synthesis, characterization, and in vitro biological activities of [Re(η<sup>6</sup>-arene)<sub>2</sub>]<sup>+</sup>-terpyridine conjugates and their Cu<sup>II</sup> complexes. The terpyridine (terpy) chelators were attached to the [Re(η<sup>6</sup>-arene)<sub>2</sub>]<sup>+</sup> scaffold via secondary amine linkers allowing for heteroleptic mono- and homoleptic bis-terpyridine-substituted chelators. Complexation with CuCl<sub>2</sub> afforded the respective square pyramidal [Cu(terpy)Cl<sub>2</sub>] complexes hosted on the [Re(η<sup>6</sup>-arene)<sub>2</sub>]<sup>+</sup> scaffold. The chelator conjugates and their respective complexes were found to be remarkably cytotoxic against malignant HT29 and A549 human cancer cell lines in vitro with IC<sub>50</sub> values in the low micromolar range. Mitochondrial respiration disruption was identified as a possible mode of action of these novel drug candidates. Crucially, the [Re(η<sup>6</sup>-arene)<sub>2</sub>]<sup>+</sup> hosts delivered water solubility of the otherwise insoluble [Cu(terpy)Cl<sub>2</sub>] motif. Importantly, the homoleptic [<sup>99m</sup>Tc(η<sup>6</sup>-arene)<sub>2</sub>]<sup>+</sup>-terpyridine conjugate is available in a single step, which enables the presented system to be used as a theranostic approach to modern medicinal inorganic chemistry.
Authors
- Matthieu Scarpi‐Luttenauer (ORCID: https://orcid.org/0000-0001-8003-9527)
- Olivier Blacque (ORCID: https://orcid.org/0000-0001-9857-4042)
- Samia Hidalgo
- Gilles Gasser (ORCID: https://orcid.org/0000-0002-4244-5097)
- Roger Alberto (ORCID: https://orcid.org/0000-0001-5978-3394)
- Joshua Csucker (ORCID: https://orcid.org/0000-0001-9141-0918)
- Pierre Mesdom (ORCID: https://orcid.org/0000-0003-1069-2138)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Institut de physique du globe de Paris (FR)
- Chimie ParisTech - PSL (FR)
- University of Zurich (CH)
- Université Paris Cité (FR)
- Université Paris Sciences et Lettres (FR)
Publication Details
- Journal
- Inorganic Chemistry
- Published
- 2024-09-16
- DOI
- https://doi.org/10.1021/acs.inorgchem.4c03018
- Citations
- 1
- Primary Topic
- Radiopharmaceutical Chemistry and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.40
Funders
- Agence Nationale de la Recherche
- Fondation ARC pour la Recherche sur le Cancer
- Universität Zürich
- European Research Council