Strong Influence of the Ancillary Ligand over the Photodynamic Anticancer Properties of Neutral Biscyclometalated IrIII Complexes Bearing 2‐Benzoazole‐Phenolates

• Published in: Chemistry : a European journal 2018-11, Vol.24 (66), p.17523-17537
• Main Authors: Martínez‐Alonso, Marta, Busto, Natalia, Aguirre, Larry Danilo, Berlanga, Leticia, Carrión, M. Carmen, Cuevas, José V., Rodríguez, Ana M., Carbayo, Arancha, Manzano, Blanca R., Ortí, Enrique, Jalón, Félix A., García, Begoña, Espino, Gustavo
• Format: Article
• Language: English
• Subjects: 2-arylazoles; Adenocarcinoma; anticancer complexes; Anticancer properties; Biological properties; Catalysis; Catalytic activity; Chemistry; Colon; Colon cancer; Cytotoxicity; Derivatives; heteroleptic neutral iridium(III) complexes; Internalization; Iridium; Irradiation; Ligands; phosphorescent complexes; Photodynamic therapy; Photoluminescence; Photons; Photooxidation; Photosensitization; Selectivity; Thioanisole; Toxicity; Ultraviolet radiation
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201803784

In this paper, the synthesis, comprehensive characterization and biological and photocatalytic properties of two series of neutral IrIII biscyclometalated complexes of general formula [Ir(C^N)2(N^O)], where the N^O ligands are 2‐(benzimidazolyl)phenolate‐N,O (L1, series a) and 2‐(benzothiazolyl)phenolate‐N,O (L2, series b), and the C^N ligands are 2‐(phenyl)pyridinate or its derivatives, are described,. Complexes of types a and b exhibit dissimilar photophysical and biological properties. In vitro cytotoxicity tests conclusively prove that derivatives of series a are harmless in the dark against SW480 cancer cells (colon adenocarcinoma), but express enhanced cytotoxicity versus the same cells after stimulation with UV or blue light. In contrast, complexes of type b show a very high cytotoxic activity in the dark, but low photosensitizing ability. Thus, the ancillary N^O ligand is the main factor in terms of cytotoxic activity both in the dark and upon irradiation. However, the C^N ligands play a key role regarding cellular uptake. In particular, the complex of formula [Ir(dfppy)2(L1)] (dfppy=2‐(4,6‐difluorophenyl)pyridinate) [3 a] has been identified as both an efficient photosensitizer for 1O2 generation and a potential agent for photodynamic therapy. These capabilities are probably related to a combination of its notable cellular internalization, remarkable photostability, high photoluminescence quantum yield, and long triplet excited‐state lifetime. Both types of complexes exhibit notable catalytic activity in the photooxidation of thioanisole and S‐containing aminoacids with full selectivity. Phototherapy: Influence of the ancillary ligand on the PDT properties of IrIII complexes—two series of IrIII complexes with 2‐benzoazole‐phenolates are described, and their anticancer activity both in the dark and under irradiation are evaluated.