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

Abstract

In this paper, the synthesis, comprehensive characterization and biological and photocatalytic properties of two series of neutral Ir biscyclometalated complexes of general formula [Ir(C^N) (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) (L1)] (dfppy=2-(4,6-difluorophenyl)pyridinate) [3 a] has been identified as both an efficient photosensitizer for O 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.

Ancillary Ligand Effects on Red‐Emitting Cyclometalated Iridium Complexes

“…Therefore, tuning the emission color and excited‐state dynamics by altering the ancillary ligand structure in heteroleptic iridium complexes with known cyclometalating ligands could be an easier, more efficient, and more expeditious approach. There are several well‐known strategies that use ancillary ligands to tune the emission and/or photochemical properties of cyclometalated iridium complexes over a wide range, including ancillary ligands that are chromophoric and completely change the nature of the excited state or those that have subtler effects on the frontier orbitals and excited states . Our group has recently reported the synthesis and characterization of red‐emitting bis‐cyclometalated Ir III complexes with high efficiency, good device performance, and excellent color purity by using β‐ketoiminate (acNac), β‐diketiminate (NacNac), and smaller bite‐angle N′N ‐diisopropylbenzamidinate (dipba) as the ancillary ligands .…”

“…There are several well-known strategies that use ancillary ligandst o tune the emission and/orp hotochemical properties of cyclometalated iridium complexes over aw ide range, including ancillary ligandst hat are chromophoric and completely change the nature of the excited state or those that have subtler effects on the frontier orbitalsa nd excited states. [20,21,[33][34][35][36] Our group has recently reported the synthesis and characterization of red-emittingb is-cyclometalated Ir III complexes with high efficiency,g ood device performance, and excellent color purity by using b-ketoiminate (acNac), b-diketiminate (NacNac), and smaller bite-angle N'N-diisopropylbenzamidinate (dipba) as the ancillary ligands. [37] We were able to show that the different L^X ligands influence the electronic structures of bis-cyclometalated iridium complexes, in some cases inducing significant redshiftso ft he emission maxima, and in other cases enhancing phosphorescence quantum yields relative to the corresponding acetylacetonate (acac) analogues or the homoleptic tris-cyclometalated complexes featuring the same cyclometalating ligands.…”

Biological activity and photocatalytic properties of a naphthyl-imidazo phenanthroline (HNAIP) ligand and its [Ir(ppy)2(HNAIP)]Cl and [Rh(ppy)2(HNAIP)]Cl complexes

“…Therefore, we can conclude that not only the ligand but also the metal are key for the biological activity. 1), it follows that this species could be adequate for its use in photodynamic therapy (PDT), as occurs with other Ir(III) cyclometallated complexes [41,42]. In view that the absorption bands in both complexes extend from the UV to the Vis region (Fig.…”

Interacción de ARN con doxorrubicina: Influencia del ligando y del metal en la actividad biológica de complejos organometálicos

“…Therefore, it can be concluded that not only the ligand but also the metal is key for the biological activity. As occurs with other Ir(III) cyclometallated complexes [128,183] these species could be adequate for its use in photodynamic therapy (PDT). In view that the absorption spectra in both complexes extend to the Vis region (Figure 1), these were irradiated with UV ( = 365 nm) and Vis ( = 460 nm) light and the IC50 were evaluated.…”