Luminescent cyclometalated platinum compounds with N, P, and O^O ligands: Density-functional theory studies and analysis of the anticancer potential

Luminescent platinum cyclometalated complexes are species of interest mainly due to their applications in the optoelectronic and biological fields, especially with regard to their anticancer activity. Given this level of interest, a series of cyclometalated (2-[2′-thienyl]pyridinate, thpy and 2-[2,4...

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Detalles Bibliográficos
Autores: Leal, Jorge, Durá, Gema, Jalón, Félix A., Zafon, Elisenda, Massaguer i Vall-llovera, Anna, Cuevas-Vicario, José Vicente, Santos Peinado, Lucía, Rodríguez, Ana María Blanco, Manzano, Blanca R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/27495
Acceso en línea:http://hdl.handle.net/10256/27495
Access Level:acceso abierto
Palabra clave:Patí -- Ús terapèutic
Platinum -- Therapeutic use
Fotoquimioteràpia
Photochemotherapy
Càncer -- Tractament
Cancer -- Treatment
Descripción
Sumario:Luminescent platinum cyclometalated complexes are species of interest mainly due to their applications in the optoelectronic and biological fields, especially with regard to their anticancer activity. Given this level of interest, a series of cyclometalated (2-[2′-thienyl]pyridinate, thpy and 2-[2,4-difluorophenyl]pyridinate, dfppy) platinum complexes with N-donor, PTA (1,3,5-triaza-7-phosphaadamantane) or chrysin-derived ligands (incorporating piperidine, HL1, or morpholine, HL2, fragments) were synthesized. The complexes are luminescent with tunable emission wavelengths. Aggregation in solution was observed for [Pt(dfppy)L1], 5. Density-functional theory (DFT) studies provided descriptions of the highest occupied molecular orbital (HOMO) and least unoccupied molecular orbital (LUMO) characteristics and their influence on the photophysical properties. The orbitals of 5–6 were different in nature to those of 1–4. Time-dependent DFT (TD-DFT) calculations showed that for 1–4 the excited states S<inf>1</inf> and T<inf>1</inf> reflect metal-to-ligand charge transfer (MLCT) and ligand-centered (LC) (C^N) contributions while for 5–6 these states are an LC transition centered on L1 or L2. The speciation in DMSO and DMSO/H<inf>2</inf>O was evaluated. Biological studies showed that [Pt(thpy)Cl(Hthpy)], 1, [Pt(dfppy)Cl(Hdfppy)], 2, and 5 exert significant cytotoxic activity against human cervical (HeLa) and lung (A549) carcinoma cells. The cytotoxicity of 1 increased 2.84-fold upon irradiation (blue). Microscopy assays on 5 showed that this compound accumulates in cytoplasmic organelles, preferentially in mitochondria. Mitochondrial metabolism was disrupted by the activity of the complexes, leading to a decline in the adenosine triphosphate (ATP) cellular content. Overall, the results show an alternative anticancer activity for complexes 1, 2, and 5, which could be of great interest for the treatment of tumors with acquired resistance to conventional DNA-targeted anticancer drugs