000168652 001__ 168652
000168652 005__ 20260212205631.0
000168652 0247_ $$2doi$$a10.1039/d5dt02366a
000168652 0248_ $$2sideral$$a148046
000168652 037__ $$aART-2025-148046
000168652 041__ $$aeng
000168652 100__ $$aMorales-Pioz, Eva$$uUniversidad de Zaragoza
000168652 245__ $$aStructure–activity insights into benzimidazole-based Ir(iii) cyclometallated complexes for cancer therapy
000168652 260__ $$c2025
000168652 5060_ $$aAccess copy available to the general public$$fUnrestricted
000168652 5203_ $$aA family of cyclometallated Ir(III) complexes incorporating benzimidazole-based C^N ligands and ancillary diimines with distinct functionalities, 2-(pyridin-2-yl)-1H-benzo[d]imidazole (L1), 4-(1H-benzo[d]imidazol-2-yl)thiazole (L2), di(pyridin-2-yl)amine (L3), [2,2′-bipyridine]-4,4′-dicarboxylic acid (L4), and dibutyl[2,2′-bipyridine]-4,4′-dicarboxylate (L5), has been synthesised. All complexes display oxygen-sensitive emission in the 477–695 nm range; however, singlet oxygen (1O2) generation, detected by fluorescence spectroscopy, was only observed for complexes 1, 4, and 5, which exhibit non-structured emission bands associated with 3MLCT and 3LLCT transitions. In contrast, complexes 2 and 3 show structured emission profiles consistent with predominant 3LC character. The complexes exhibit distinct antitumour activity in A549 cells depending on the nature of the ancillary ligand. Complex 3, bearing an exocyclic amine donor, displayed efficient cellular uptake and significant dark cytotoxicity. Complexes 1 and 2, featuring endocyclic benzimidazole donors, showed lower cellular accumulation and no activity in the dark. A similar trend was observed for complex 4, while complex 5, its esterified analogue, showed remarkable chemotherapeutic activity and high cell uptake. The different pKa values of 2, 3 and 4 further correlate with their internalization capacity. Upon light irradiation, complexes 2, 3, and 5 exhibited enhanced antiproliferative effects and induced apoptotic cell death, probably through reactive oxygen species (ROS) generation as indicated by flow cytometry. Nevertheless, only complex 2 retained phototherapeutic potential due to its low dark toxicity. Mechanistic studies revealed that complex 2 is capable of oxidising NADH under irradiation and generating H2O2. Overall, these results reveal clear structure–activity relationships and highlight complex 2 as a promising candidate for photodynamic therapy (PDT), while complexes 3 and 5 act predominantly as chemotherapeutic-like agents.
000168652 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E07-23R$$9info:eu-repo/grantAgreement/ES/MICINN/RED2022-134074-T$$9info:eu-repo/grantAgreement/ES/MICIU AEI/PID2022-136861NB-I00$$9info:eu-repo/grantAgreement/ES/MICIU AEI/PID2022-137862NB-I00
000168652 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttps://creativecommons.org/licenses/by-nc/4.0/deed.es
000168652 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000168652 700__ $$aMartínez, Mónica
000168652 700__ $$aBenedi, Andrea
000168652 700__ $$aTejera-Ruiz, María
000168652 700__ $$aMarzo, Isabel
000168652 700__ $$0(orcid)0000-0003-0553-0695$$aGimeno, M. Concepción
000168652 700__ $$aVázquez-López, Ezequiel M.
000168652 700__ $$aGarcía-Fontán, Soledad
000168652 700__ $$0(orcid)0000-0002-1218-7218$$aFernández-Moreira, Vanesa
000168652 7102_ $$12010$$2760$$aUniversidad de Zaragoza$$bDpto. Química Inorgánica$$cÁrea Química Inorgánica
000168652 773__ $$g55, 2 (2025), 643-652$$pDalton Trans.$$tDalton Transactions$$x1477-9226
000168652 8564_ $$s1448142$$uhttps://zaguan.unizar.es/record/168652/files/texto_completo.pdf$$yVersión publicada
000168652 8564_ $$s2657020$$uhttps://zaguan.unizar.es/record/168652/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000168652 909CO $$ooai:zaguan.unizar.es:168652$$particulos$$pdriver
000168652 951__ $$a2026-02-12-20:38:47
000168652 980__ $$aARTICLE