TY - JOUR
T1 - Luminescent Cyclometalated Iridium(III) Polypyridine Indole Complexes—Synthesis, Photophysics, Electrochemistry, Protein-Binding Properties, Cytotoxicity, and Cellular Uptake
AU - Lau, Jason Shing Yip
AU - Lee, Pui Kei
AU - Tsang, Keith Hing Kit
AU - Ng, Cyrus Ho Cheong
AU - Lam, Yun Wah
AU - Cheng, Shuk Han
AU - Lo, Kenneth Kam Wing
PY - 2009/1/19
Y1 - 2009/1/19
N2 - 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).
AB - 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).
KW - Hela Cells
KW - Humans
KW - animal
UR - http://www.scopus.com/inward/record.url?scp=60849099645&partnerID=8YFLogxK
U2 - 10.1021/ic801818x
DO - 10.1021/ic801818x
M3 - Article
C2 - 19099443
AN - SCOPUS:60849099645
VL - 48
SP - 708
EP - 718
JO - Inorganic Chemistry
JF - Inorganic Chemistry
SN - 0020-1669
IS - 2
ER -