Cyclometalated Iridium(III) Bipyridyl–Phenylenediamine Complexes with Multicolor Phosphorescence: Synthesis, Electrochemistry, Photophysics, and Intracellular Nitric Oxide Sensing

Abstract

We present a new class of phosphorescent cyclometalated iridium(III) bipyridyl-phenylenediamine complexes [Ir(N^C)2 (bpy-DA)](PF6 ) (bpy-DA=4-(N-(2-amino-5-methoxyphenyl)aminomethyl)-4'-methyl-2,2'-bipyridine; HN^C=2-(2,4-difluorophenyl)pyridine (Hdfppy) (1 a), 2-phenylpyridine (Hppy) (2 a), 2-phenylquinoline (Hpq) (3 a), 2-phenylcinchoninic acid methyl ester (Hpqe) (4 a)) and their triazole counterparts [Ir(N^C)2 (bpy-T)](PF6 ) (bpy-T=4-((6-methoxybenzotriazol-1-yl)methyl)-4'-methyl-2,2'-bipyridine; HN^C=Hdfppy (1 b), Hppy (2 b), Hpq (3 b), Hpqe (4 b)). Upon photoexcitation, the diamine complexes exhibited fairly weak green to red phosphorescence under ambient conditions whereas the triazole derivatives emitted strongly. The photophysical properties of complexes 2 a and 2 b have been studied in more detail. Upon protonation, the diamine complex 2 a displayed increased emission intensity, but the emission properties of its triazole counterpart complex 2 b were independent on the pH value of the solution. Also, complex 2 a was found to be readily converted into complex 2 b upon reaction with NO under aerated conditions, resulting in substantial emission enhancement of the solution. The reaction was highly specific toward NO over other reactive oxygen and nitrogen species (RONS) as revealed by spectroscopic analyses. The lipophilicity and cellular uptake efficiency of the diamine complexes have been examined and correlated to their molecular structures. Also, cell-based assays showed that these complexes were noncytotoxic toward human cervix epithelioid carcinoma (HeLa) cells (at 10 μM, 4 h, percentage survival ≈80-95%). Additionally, the diamine complexes have been used to visualize intracellular NO generated both exogenously in HeLa cells and endogenously in RAW 264.7 murine macrophages by laser-scanning confocal microscopy.

Phosphorescent Iridium(III) Complexes for Bioimaging

“…Intracellular NO is difficult to be detected because of its low concentration and short half-life. Since electron-rich diaminoaromatic compounds readily react with NO yielding the triazole derivatives, an iridium(III) complex 73 appended with a diaminoaromatic moiety has been designed as an NO sensor [57]. This complex emits weakly because of the intermolecular reductive quenching of the excited complex by the diamine moiety.…”

“…Complexes containing substrates that bind to membrane transport proteins across the cell membrane in a specific pathway. For example, iridium(III) complex 55 has been used to label reducing sugars including D-glucose, D-galactose, Dlactose, and D-maltose, giving their corresponding conjugates (56)(57)(58)(59)(60) [31]. Interestingly, only the glucose conjugate displays efficient cellular uptake, which has been ascribed to the glucose transporters (GLUTs) in the cell membrane.…”

Theoretical Studies on the Structures and Spectroscopic Properties of Ir Complexes With the Bipyridyl-Phenylenediamine Ligand

“…Recently, Lo and co-workers have prepared a series of (N^C)2Ir(bpy-D) complexes, they found that these complexes show interesting photophysical behavior and modification of these complexes with an ophenylenediamine unit will generate a new class of phosphorescent molecular probes for NO [5]. Although there have been many experimental studies on the photophysical and photochemical properties of these luminescent Ir(III) complexes, there are few corresponding theoretical reports on these complexes.…”

Rhenium(I) Polypyridine Diamine Complexes as Intracellular Phosphorogenic Sensors: Synthesis, Characterization, Emissive Behavior, Biological Properties, and Nitric Oxide Sensing

“…Despite the development of these reagents, the possibility of using phosphorescent transitionmetal diamine complexes as intracellular NO sensors has not been fully explored. [14,15] In the past few years, there has been a fast-growing interest in the cellular-uptake properties of phosphorescent rhenium(I) complexes with a focus on their potential as cellular imaging and therapeutic reagents. [16][17][18][19][20][21] Previously, we have synthesized a series of rhenium(I) and iridium(III) diaminoaromatic complexes as sensors for NO.…”

“…[16][17][18][19][20][21] Previously, we have synthesized a series of rhenium(I) and iridium(III) diaminoaromatic complexes as sensors for NO. [15] Although the rhenium(I) complexes display interesting phosphorogenic properties toward NO, they are unable to react efficiently with NO in living cells, probably due to insufficient reactivity.…”