Luminescent Re(I)/Au(I) Species As Selective Anticancer Agents for HeLa Cells

Luengo, A. ; Redrado, M. ; Marzo, I. (Universidad de Zaragoza) ; Fernández-Moreira, V. (Universidad de Zaragoza) ; Gimeno, M.C. (Universidad de Zaragoza)

Resumen: A series of neutral and cationic heterotrimetallic complexes of the type fac-[Re(CO)3(bipy(CC)2-(AuL)2)X]n, where bipy(CC)2 is 4, 4'-alkynyl-2, 2'-bipyridine; L is either triphenylphosphine (PPh3), [1, 3-bis(2, 6-diisopropylphenyl)-imidazol-2-ylidene] (IPr), or tert-butyl isocyanide (CNtBu); and X is a chloride (n = 0) or acetonitrile (n = 1), were synthesized and characterized together with their Re(I) precursors, i.e., fac-[Re(CO)3(bipy(CC)2)X]n. X-ray diffraction of complexes 1, 3, and 6 corroborated the expected octahedral and linear distribution of the ligands along the Re(I) and Au(I) centers, respectively. Luminescent studies showed that all the complexes displayed a broad emission band centered between 565 and 680 nm, corresponding to a 3MLCT from the Re(I) to the diimine derivative. The presence of the gold fragment coordinated to the diimine ligand shifted in all cases the emission maxima toward higher energies. Such an emission difference could be potentially used for assessing the precise moment of interaction of the probe with the biological target if the gold fragment is implicated. Antiproliferative studies in cancer cells, A549 (lung cancer) and HeLa (cervix cancer), showed a generalized selectivity toward HeLa cells for those heterotrimetallic species incubated at longer times (72 vs 24 h). ICP-MS spectrometry revealed the greater cell internalization of cationic vs neutral species. Preliminary fluorescence microscopy experiments showed a different behavior of the complexes in HeLa and A549 cell lines. Whereas the complexes in A549 were randomly distributed in the outside of the cell, those incubated with HeLa cells were located close to the cellular membrane, suggesting some type of interaction, and possibly explaining their cellular selectivity when it comes to the antiproliferative activity displayed in the different cell lines.

Idioma: Inglés

DOI: 10.1021/acs.inorgchem.0c00813

Año: 2020

Publicado en: Inorganic Chemistry 59, 13 (2020), 8960–8970
ISSN: 0020-1669

Factor impacto JCR: 5.165 (2020)

Categ. JCR: CHEMISTRY, INORGANIC & NUCLEAR rank: 5 / 45 = 0.111 (2020) - Q1 - T1

Factor impacto SCIMAGO: 1.348 - Chemistry (miscellaneous) (Q1) - Physical and Theoretical Chemistry (Q1) - Inorganic Chemistry (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/E07-20R
Financiación: info:eu-repo/grantAgreement/ES/MCIU/RED2018-102471-T
Financiación: info:eu-repo/grantAgreement/ES/MCIU/RTI2018-097836-J-I00
Financiación: info:eu-repo/grantAgreement/ES/MINECO-FEDER/CTQ2016-75816-C2-1-P

Tipo y forma: Article (PostPrint)

Área (Departamento): Área Química Inorgánica (Dpto. Química Inorgánica)
Área (Departamento): Área Biología Celular (Dpto. Bioq.Biolog.Mol. Celular)