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A Bis‐Chelating O N O ^ / N N ^ Ligand for the Synthesis of Heterobimetallic Platinum(II)/Rhenium(I) Complexes: Tools for the Optimization of a New Class of Platinum(II) Anticancer Agents
Author(s) -
Bertrand Benoît,
Botuha Candice,
Forté Jérémy,
Dossmann Héloïse,
Salmain Michèle
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202001752
Subject(s) - rhenium , ligand (biochemistry) , chemistry , platinum , stereochemistry , pyridine , carbene , chelation , triphenylphosphine , cationic polymerization , medicinal chemistry , combinatorial chemistry , polymer chemistry , inorganic chemistry , organic chemistry , biochemistry , receptor , catalysis
The two independent andN N ^ coordination sites of a newly synthesized bis[2‐(hydroxyphenyl)‐1,2,4‐triazole] platform have been exploited to prepare four monometallic neutral ()Pt II complexes carrying DMSO, pyridine, triphenylphosphine, or N‐heterocyclic carbene as the fourth ligand. Then, the secondN N ^ coordination site was used to introduce an IR‐active rhenium tricarbonyl entity, affording the four corresponding heterobimetallic neutral Pt II /Re I complexes, as well as a cationic Pt II /Re I derivative. X‐ray crystallographic studies showed that distortion of the organic platform occurred to accommodate the coordination geometry of both metal centers. No ligand exchange or transchelation occurred upon incubation of the Pt II complexes in aqueous environment or in the presence of Fe III , respectively. The antiproliferative activity of the ligand and complexes was first screened on the triple‐negative breast cancer cell line MDA‐MB‐231. Then, the IC 50 values of the most active candidates were determined on a wider panel of human cancer cells (MDA‐MB‐231, MCF‐7, and A2780), as well as on a nontumorigenic cell line (MCF‐10A). Low micromolar activities were reached for the complexes carrying a DMSO ligand, making them the first examples of highly active, but hydrolytically stable, Pt II complexes. Finally, the characteristic mid‐IR signature of the {Re(CO) 3 } fragment in the Pt/Re heterobimetallic complexes was used to quantify their uptake in breast cancer cells.