Luminescent Cyclometalated Iridium(III) Polypyridine Indole Complexes—Synthesis, Photophysics, Electrochemistry, Protein-Binding Properties, Cytotoxicity, and Cellular Uptake

Jason Shing Yip Lau, Pui Kei Lee, Keith Hing Kit Tsang, Cyrus Ho Cheong Ng, Yun Wah Lam, Shuk Han Cheng, Kenneth Kam Wing Lo

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160 Citations (Scopus)

Abstract

A series of luminescent cyclometalated iridium(lll) polypyridine indole complexes, [lr(N-C)2(N-N)](PF6) (HN-C = 2-phenylpyridine (Hppy), N-N = 4-((2-(indol-3-yl)ethyl)aminocarbonyl)-4′-methyl-2,2′- bipyridine (bpy-ind) (1a), N-N = 4-((5-((2-(indol-3-yl)ethyl)aminocarbonyl) pentyl)aminocarbonyl)-4′-methyl-2,2′-bipyridine (bpy-C6-ind) (1b); HN-C = 7,8-benzoquinoline (Hbzq), N-N = bpy-ind (2a), N-N= bpy-C6-ind (2b); and HN-N = 2-phenylquinoline (Hpq), N-N = bpy-ind (3a), N-N = bpy-C6-ind (3b)), have been synthesized, characterized, and their photophysical and electrochemical properties and lipophilicity investigated. Photoexcitation of the complexes in fluid solutions at 298 K and in alcohol glass at 77 K resulted in intense and long-lived luminescence (λem = 540-616 nm, τo = 0.13-5.15 μs). The emission of the complexes has been assigned to a triplet metal-to-ligand charge-transfer (3MLCT) (dπ(lr) → π*(N-N)) excited state, probably with some mixing of triplet intraligand (3IL) (π→π*) (pq) character for complexes 3a,b. Electrochemical measurements revealed that all the complexes showed an irreversible indole oxidation wave at ca. +1.1 V versus SCE, a quasi-reversible iridium(IV/lll) couple at ca. +1.3 V, and a reversible diimine reduction couple at ca. -1.3 V. The interactions of these complexes with an indole-binding protein, bovine serum albumin (BSA), have been studied by emission titrations, and the Ka values are on the order of 10 4 M-1. Additionally, the cytotoxicity of the complexes toward human cervix epithelioid carcinoma (HeLa) cells has been examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC50 values of the complexes ranged from 1.1 to 6.3 μM, which are significantly smaller than that of cisplatin (30.7 μM) under the same experimental conditions. Furthermore, the cellular uptake of the complexes has been investigated by flow cytometry and laser- scanning confocal microscopy. The microscopy images indicated that complex 3a was localized in the perinuclear region upon interiorization. Temperature-dependence experiments suggested that the internalization of the complex was an energy-requiring process such as endocytosis. This has been confirmed by cellular-uptake experiments involving the luminescent conjugates Ir-BSA and Ir-TF (TF = holo-transferrin), which were prepared by conjugation of the proteins with the complex [lr(pq) 2(phen-NCS)](PF6) (phen-NCS = 5-isothiocyanato-1,10- phenanthroline).

Original languageEnglish
Pages (from-to)708-718
Number of pages11
JournalInorganic Chemistry
Volume48
Issue number2
Early online date19 Dec 2008
DOIs
Publication statusPublished - 19 Jan 2009
Externally publishedYes

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