Photochemical Properties of Red-Emitting Tris(cyclometalated) Iridium(III) Complexes Having Basic and Nitro Groups and Application to pH Sensing and Photoinduced Cell Death

Abstract

Cyclometalated iridium(III) complexes, because of their photophysical properties, have the potential for use as luminescent probes for cellular imaging. We previously reported on a pH-activatable iridium complex that contains three N,N-diethylamino groups, namely, fac-Ir(deatpy)3 5, which was synthesized via a regioselective aromatic substitution reaction at the 5'-position with tolylpyridine groups of fac-Ir(tpy)3 2. It was found that 5 shows a considerable enhancement in emission intensity in the pH range from neutral to slightly acidic (pH 6.5-7.4) in aqueous solution and selectively stains lysosome in HeLa-S3 cells, due to the protonation of the diethylamino groups. In addition, 5 functions as a pH-dependent singlet oxygen ((1)O2) generator and induces necrosis-like cell death. However, observing the green emission of 5 is often hampered by autofluorescence emanating from nearby tissues. To overcome this problem, we designed and synthesized a series of new pH-activatable Ir(III) complexes that contain diethylamino, guanidyl, and iminoimidazolidinyl groups on the mpiq ligand of Ir(mpiq)3 7 and the tfpiq ligand of Ir(tfpiq)3 8, which exhibit a red emission, namely, Ir(deampiq)3 13, Ir(gmpiq)3 14, Ir(imzmpiq)3 15, and Ir(imztfpiq)3 16. The emission intensity of these Ir complexes is enhanced substantially by protonation of their basic groups, and they induce the necrosis-like cell death of HeLa-S3 cells by photoirradiation at 465 nm. A strong orange-red emission of Ir(mpiq-NO2)3 9 and Ir(tfpiq-NO2)3 10 is also reported.

Design, Synthesis, and Anticancer Activities of Cyclometalated Tris(2‐phenylpyridine)iridium(III) Complexes with Cationic Peptides at the 4′‐Position of the 2‐Phenylpyridine Ligand

“…Previously, we reported that the Ir complexes function as photosensitizers for the production of singlet oxygen ( 1 O 2 ) from triplet oxygen ( 3 O 2 ) to induce the death of HeLa cells, an adhesive cancer cell line . Thus, we checked the effect of the photoirradiation of the Ir complexes on the cell viability of Jurkat cells and found that Jurkat cells undergo cell death after photoirradiation ( λ = 465 nm) for 10 min even in the absence of the Ir complexes; therefore, the Jurkat cells are somewhat sensitive to photoirradiation.…”

“…First, 2‐(4′‐methoxycarbonylphenyl)pyridine ( 8 ) was synthesized from 4‐(methoxycarbonyl)phenylboronic acid ( 6 ) and 2‐bromopyridine ( 7 ) in the presence of Pd(OAc) 2 and K 3 PO 4 in i PrOH/H 2 O (1:1) . The complexation of 8 with IrCl 3 was performed as described in our previous paper to give 9 , the methyl ester of which was hydrolyzed by treatment with aqueous NaOH and EtOH in freshly distilled tetrahydrofuran (THF) to obtain 10 . The condensation of 10 with mono‐Boc‐protected (Boc = tert ‐butyloxycarbonyl) diamine derivatives ( n = 2, 6, 8, 16) afforded 11 – 14 , and the subsequent removal of the Boc‐protecting group, gave 15 – 18 .…”

“…We previously reported the synthesis of cationic amphiphilic Ir complexes such as 2 (Scheme ) through regioselective formylation at the 5′‐position of the tpy moiety ( para position with respect to the C–Ir bond) and successive conversions . The Ir complexes 2c and 2d , which contain the KKGG and KKKGG sequences (K = lysine, G = glycine) connected through appropriate alkyl (C 6 and C 8 ) linkers between the Ir core and the peptide and have net charges of +9 to +12, have considerable cytotoxicities [half‐maximal effective concentration (EC 50 ) values of 7–16 µ m ] against Jurkat cells (a human T‐lymphoma cell line) , .…”

Selective Photooxidation of Sulfides Catalyzed by Bis‐cyclometalated IrIII Photosensitizers Bearing 2,2′‐Dipyridylamine‐Based Ligands

“…Additional experiments were performed to determine the actual oxidant and formulate a plausible mechanism. In particular, the addition of NaN 3 ( 1 O 2 quencher, entry 4 in Table ) drastically suppressed the photooxidation of the substrate, and this suggested that the process is essentially mediated by 1 O 2 in an ET process . Other additives, such as 1,4‐benzoquinone (quencher of O 2 .− ) and 1,4‐dimethoxybenzene (scavenger of sulfide radical cations, R 2 S .+ ) (entries 5 and 6 in Table ) were also used as indirect probes for O 2 .− and R 2 S .+ .…”

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

“…In general, phosphorescent biscyclometalatedi ridium(III) complexes display very interesting emission properties, for example,h igh quantum yields, large Stokes shifts, long-lived phosphorescence, modular color-tuningp ossibilities, and good photostability.A saresult, they are being studied in the development of solid-state lighting devices,s uch as organic lightemitting diodes( OLEDs) [14] and light-emitting electrochemical cells (LECs), [15,16] as biological imaging agents, [17] and as analytical probes. [18] In addition, they work as efficient PSsi ns inglet oxygen production and can be used as O 2 probes, [19,20] as photodynamic anticancer agents, [21][22][23][24][25][26][27][28][29][30][31][32][33][34] and as catalysts in photooxidation reactions. [35] Previous reports have shown that biscyclometalated Ir III complexes with 2-(2-hydroxyphenyl)oxazolebased N^O ancillary ligands, similart ot hose used in this work, exhibit highly efficient phosphorescence.…”