Chirality influence on the cytotoxic properties of anionic chiral bis(N-heterocyclic carbene)silver complexes

Complexes Na3[Ag(NHCR)2], 2a-e and 2b’-c’, where NHCR is a N-heterocyclic carbene of the 2,2′-(1H-2λ3,3λ4-imidazole-1,3-diyl)dicarboxylate type, were prepared by treatment of compounds HLR, 1a-e and 1b’-c’ (2-(1-(carboxyalkyl)-1H-imidazol-3-ium-3-yl)carboxylate), with silver oxide in the presence of...

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Detalles Bibliográficos
Autores: Carrasco Carrasco, Carlos Jesús, Montilla Ramos, Francisco Javier, Álvarez González, Eleuterio, Calderón Montaño, José Manuel, López Lázaro, Miguel, Galindo del Pozo, Agustín
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/136581
Acceso en línea:https://hdl.handle.net/11441/136581
https://doi.org/10.1016/j.jinorgbio.2022.111924
Access Level:acceso abierto
Palabra clave:Anticancer
Chiral
NHC-dicarboxylate
Silver
X-ray
Descripción
Sumario:Complexes Na3[Ag(NHCR)2], 2a-e and 2b’-c’, where NHCR is a N-heterocyclic carbene of the 2,2′-(1H-2λ3,3λ4-imidazole-1,3-diyl)dicarboxylate type, were prepared by treatment of compounds HLR, 1a-e and 1b’-c’ (2-(1-(carboxyalkyl)-1H-imidazol-3-ium-3-yl)carboxylate), with silver oxide in the presence of aqueous sodium hydroxide. They were characterized by analytical, spectroscopic (infrared, IR, 1H and 13C nuclear magnetic resonance, NMR, and circular dichroism) and X-ray methods (2a). In the solid state, the anionic part of complex 2a, [Ag(NHCH)2]3−, shows a linear disposition of Ccarbene-Ag-Ccarbene atoms and an eclipsed conformation of the two NHC ligands. The proposed bis(NHC) nature of the silver complexes was maintained in solution according to NMR and density functional theory (DFT) calculations. The cytotoxic activity of compounds 2 was evaluated against four cancer cell lines and one non-cancerous cell line and several structure-activity correlations were found for these complexes. For instance, the activity decreased when the bulkiness of the R alkyl group in Na3[Ag(NHCR)2] increased. More interesting is the detected chirality-anticancer relationship, where complexes Na3[Ag{(S,S)-NHCR}2] (R = Me, 2b; iPr, 2c) showed better anticancer activity than those of their enantiomeric derivatives Na3[Ag{(R,R)-NHCR}2] (R = Me, 2b’; iPr, 2c’).