Search

We previously reported the design and synthesis of amphiphilic Ir complex–cationic peptide hybrids (2a–2f), which contain basic peptide sequences such as KKGG (K = lysine, G = glycine) at the 5′-positions (para position with respect to the C–Ir bond) of three 2-(4′-tolyl)pyridine (tpy) ligands. Among them, 2c–2e induced the necrosis-like cell death of Jurkat cells through a calcium-dependent pathway, possibly involving a Ca2+–calmodulin (CaM) complex. Herein, we report the synthesis of amphiphilic Ir(ppy)3 complexes (ppy = 2-phenylpyridine) containing the KKGG sequence at the 4′-position of the ppy moiety (4a–4d) to examine the effect of the position of the cationic peptide sequence on the cytotoxicities of the complexes against Jurkat cells. The results of 3-(4,5-dimethly-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays and a mechanistic study indicate that 4b and 4c, which contain C6 and C8 linkers, induce cell death through a calcium-dependent pathway accompanied by membrane disruption in a manner similar to that of 2c–2e but with smaller half-maximal effective concentration (EC50) values than those of 2c–2e. The results of the photoaffinity labeling of Jurkat cells with 5b containing a photoreactive 3-trifluoromethyl-3-phenyldiazirine (TFPD) unit and co-staining experiments with specific probes for intracellular organelles suggest that 4b and 4c bind to Ca2+–CaM and are localized in the mitochondria during cell death.

In previous work, we reported on that Ir complex-cationic peptide hybrids (IPHs) that contain three KKGG or KKKGG sequences (K: lysine, G: glycine) induce cell death in cancer cells by an intracellular Ca2+-dependent pathway and function as luminescent detectors in dead cells. To identify the target biomolecules by photoaffinity labeling, we designed and synthesized IPH that contains a photoreactive and hydrophobic 4-[3-(trifluotomethyl)-3H-diazirine-3-yl]benzoyl (TFDB) group and found that it has more potent cytotoxicity against Jurkat cells than the previously prepared compounds. Herein, we report on the preparation of some new IPHs that contain hydrophobic acyl groups at the N-terminus of the peptide portions of the molecules. Among them, an IPH containing a n-dodecanoyl group was found to have much more potent cancer cell death activity and superior selectivity for cancer cells (Jurkat cells) over normal cells. The results of mechanistic studies suggest that the cell death of Jurkat cells is induced via different pathway from that induced by the previously synthesized IPHs. The results of this study are described herein.

We synthesized intramolecularly aliphatic alcoholate-coordinated iron porphyrins (1a, 1b) that retain their axial coordination in the presence of another ligand or oxidant. The electron-donative character of alcoholate was less than that of thiolate, and the coordination ability of a sixth ligand to 1a and 1b was very much lower than in the case of the thiolate-coordinated compounds. Density functional theory calculations indicated that the marked difference in coordination ability could be explained in terms of thermodynamic and steric factors. The catalytic oxidizing ability of the thiolate-coordinated compound, SR complex, was much higher than that of 1a.

In this article we report on the successful synthesis and isolation of cyclometalated Ir complexes having three different nonsymmetric ligands based on ligand-selective electrophilic reactions via interligand HOMO (highest occupied molecular orbital) hopping phenomena. It was hypothesized that the electrophilic substitution reactions of bis-heteroleptic Ir complexes having 8-benzenesulfonamidoquinoline as an ancillary ligand, 5a and 7, would proceed at the 5 position of the quinoline ring of these Ir complexes to afford 18 and 19, because their HOMOs are localized on the quinoline rings, as predicted by density functional theory (DFT) calculations. In these products, the HOMO is transferred to one of two ppy ligands, in which the phenyl group is trans to the Ir-N (1 position of quinoline) bond, and hence, the iodination or formylation of 18 and 19 occurs at the 5' position of the ppy ligand to provide 20a, 23, and 24. Furthermore, we carried out the functionalization of 20a using cross-coupling reactions to obtain tris-heteroleptic Ir complexes containing three different ligands in good yields with negligible diastereomer formation. Photochemical properties, especially dual emission, and response to pH change, of new dual-emissive tris-heteroleptic cyclometalated Ir complexes, 21-24, are also reported.

We report on the efficient synthesis of tris-heteroleptic iridium (Ir) complexes based on the degradation of tris-cyclometalated Ir complexes (IrL3, L: cyclometalating ligand) in the presence of Bronsted and Lewis acids such as HCl (in 1,4-dioxane), AlCl3, TMSCl, and ZnX2 (X = Br or Cl), which affords the corresponding halogen-bridged Ir dimers (μ-complexes). Tris-cyclometalated Ir complexes containing electron-withdrawing groups such as fluorine, nitro, or CF3 moieties on the ligands were less reactive. This different reactivity was applied to the selective degradation of heteroleptic Ir complexes such as fac-Ir(tpy)2(F2ppy) (fac-12) (tpy: 2-(4′-tolyl)pyridine and F2ppy: 2-(4′,6′-difluorophenyl)pyridine), mer-Ir(tpy)2(F2ppy) (mer-12), and mer-Ir(mpiq)2(F2ppy) (mer-15) (mpiq: 1-(4′-methylphenyl)isoquinoline). For example, the reaction of mer-12 with ZnBr2 gave the heteroleptic μ-complex [{Ir(tpy)(F2ppy)(μ-Br)}2] 27b as a major product, resulting from the selective elimination of the tpy ligand of mer-12, ...

Herein, we report on the stereospecific synthesis of two single isomers of tris-heteroleptic tris-cyclometalated iridium(III) (Ir(III)) complexes composed of three different nonsymmetric cyclometalating ligands via heteroleptic halogen-bridged Ir dimers [Ir(tpy)(F2ppy)(μ-Br)]2 17b and [Ir(mpiq)(F2ppy)(μ-Br)]2 27b (tpyH: (2-(4′-tolyl)pyridine) and F2ppyH: (2-(4′,6′-difluorophenyl)pyridine), and mpiqH: (1-(4′-methylphenyl)isoquinoline)) prepared by Zn2+-promoted degradation of Ir(tpy)2(F2ppy) 21 and Ir(mpiq)2(F2ppy) 26, as reported by us. Subsequently, 17b and 27b were converted to the tris-heteroleptic tris-cyclometalated Ir complexes Ir(tpy)(F2ppy)(mpiq) 25 consisting of tpy, F2ppy, and mpiq, as confirmed by spectroscopic data and X-ray crystal structure analysis. The first important point in this work is the selective synthesis of specific isomers among eight possible stereoisomers of Ir complexes having the same combination of three cyclometalating ligands. Namely, two meridional forms of 25 were synthe...

The design and synthesis of some cyclometalated iridium(III) complexes containing quinoline-type ligands as ancillary ligands are reported. The emission spectra of Ir(III) complexes containing a quinolinolate (6, 8, 10) moiety exhibit a single emission peak at ca. 590 nm, resulting in a red colored emission. However, Ir(III) complexes containing 8-sulfonamidoquinoline ligands (11, 13–21) exhibit two different emission peaks (dual emission) at ca. 500 nm and ca. 600 nm upon excitation at 366 nm, resulting in a red-colored emission for 11 and a pale yellow-colored emission for 14–18 at 298 K. Especially, a white emission was observed for 19 at 298 and 77 K in dimethyl sulfoxide. The mechanistic studies based on time-dependent density functional theory calculations and time-resolved emission spectroscopy suggest that this dual emission originates from two independent emission states.

A series of tris-cyclometalated IrIII complexes were prepared by regioselective substitution reactions (formylation, thiocyanation, and iodination) and subsequent conversions (cyanation, cross-coupling reaction, reduction, and oxidation) on a 2-(4′-methoxyphenyl)pyridine (mppy) ligand of fac-[Ir(mppy)3]. The introduction of electron-withdrawing groups such as CHO, CN, and sulfonyl groups (SO2Me, SO2Ar) at the 5′-position of the phenyl ring of the mppy portion induces a considerable blueshift in luminescence emission (from 495 nm to approximately 465 nm) in degassed organic solvents.

In this manuscript, the regioselective halogenation, nitration, formylation, and acylation of Ir(tpy)(3) and Ir(ppy)(3) (tpy = 2-(4'-tolyl)pyridine and ppy = 2-phenylpyridine) and the subsequent conversions are described. During attempted bromination of the three methyl groups in fac-Ir(tpy)(3) using N-bromosuccinimide (NBS) and benzoyl peroxide (BPO), three protons at the 5'-position (p-position with respect to the C-Ir bond) of phenyl rings in tpy units were substituted by Br, as confirmed by (1)H NMR spectra, mass spectra, and X-ray crystal structure analysis. It is suggested that such substitution reactions of Ir complexes proceed via an ionic mechanism rather than a radical mechanism. UV-vis and luminescence spectra of the substituted Ir(III) complexes are reported. The introduction of electron-withdrawing groups such as CN and CHO groups at the 5'-position of tpy induces a blue shift of luminescence emission to about 480 nm, and the introduction of electron-donating groups such as an amino group results in a red shift to about 600 nm. A reversible change of emission for the 5'-amino derivative of Ir(tpy)(3), Ir(atpy)(3), between red and green occurs upon protonation and deprotonation.

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.

In our previous publication, it was reported that fac-Ir(atpy)3 3 (atpy = 2-(5'-amino-4'-tolyl)pyridine), which contains three amino groups at the 5'-position of the atpy ligands, exhibits a pH-dependent change in the color of the emitted radiation. Aqueous solution of 3 shows a weak red emission (at around 613 nm) under neutral or basic conditions, but the emission color changes to green (at around 530 nm) under acidic conditions, where the NH2 group is protonated to become an electron-withdrawing (NH3)(+) group. In this manuscript, we report on the preparation of some new pH-responsive Ir(III) complexes; fac-Ir(4Pyppy)3 5 and fac-Ir(3Pyppy)3 6 that contain three pyridyl groups at the 5'-position of the 2-phenylpyridine (ppy) ligand, and Ir(4Pyppym)3 7 and Ir(3Pyppym)3 8 that contain a pyridyl group at the same position of the 2-phenylpyrimidine (ppym) ligand. The introduction of three pyridyl groups on iodinated Ir(ppy)3 and Ir(ppym)3 was achieved via Suzuki-Miyaura cross-coupling reaction assisted by microwave irradiation. Solutions of the acid-free Ir(III) complexes 5, 6, 7, and 8 showed a strong green emission (at around 500 nm) in dimethylsulfoxide (DMSO). Protonation of three pyridyl groups of 5 and 7 causes a significant red-shift in the emission wavelength (at around 600 nm) with a decrease in emission intensity. The pH-dependent emission change of these complexes is also discussed. The generation of singlet oxygen ((1)O2) by the photoirradiation of the Ir complexes 5 and 6 was evidenced by the decomposition of 1,3-diphenylisobenzofuran (DPBF), the oxidation of thioanisole, and the oxidation of 2,2,5,5-tetramethyl-3-pyrroline-3-carboxamide (TPC). The induction of necrosis-like cell death of HeLa-S3 cells upon photoirradiation of 5 at 465 nm is also reported.

Cyclometalated iridium(III) complexes have received considerable attention and are important candidates for use as luminescent probes for cellular imaging because of their potential photophysical properties. We previously reported that fac-Ir(atpy)(3)4 (atpy = 2-(5'-amino-4'-tolyl)pyridine) containing three amino groups at the 5'-position of the atpy ligand shows a maximum red emission (at around 600 nm) under neutral and basic conditions and a green emission (at 531 nm) at acidic pH (pH 3-4). In this Article, we report on the design and synthesis of a new pH-sensitive cyclometalated Ir(III) complex containing a 2-(5'-N,N-diethylamino-4'-tolyl)pyridine (deatpy) ligand, fac-Ir(deatpy)(3)5. The complex exhibits a considerable change in emission intensity between neutral and slightly acidic pH (pH 6.5-7.4). Luminescence microscopic studies using HeLa-S3 cells indicate that 5 can be used to selectively stain lysosome, an acidic organelle in cells. Moreover, complex 5 is capable of generating singlet oxygen in a pH-dependent manner and inducing the death of HeLa-S3 cells upon photoirradiation at 377 or 470 nm.

In Nature, organized nanoscale structures such as proteins and enzymes are formed in aqueous media via intermolecular interactions between multicomponents. Supramolecular and self-assembling strategies provide versatile methods for the construction of artificial chemical architectures for controlling reaction rates and the specificities of chemical reactions, but most are designed in hydrophobic environments. The preparation of artificial catalysts that have potential in aqueous media mimicking natural enzymes such as hydrolases remains a great challenge in the fields of supramolecular chemistry. Herein, we describe that a dimeric Zn(2+) complex having a 2,2'-bipyridyl linker, cyanuric acid, and a Cu(2+) ion automatically assembles in an aqueous solution to form a 4:4:4 complex, which is stabilized by metal-ligand coordination bonds, π-π-stacking interactions, and hydrogen bonding and contains μ-Cu(2)(OH)(2) cores analogous to the catalytic centers of phosphatase, a dinuclear metalloenzyme. The 4:4:4 complex selectively accelerates the hydrolysis of a phosphate monoester, mono(4-nitrophenyl)phosphate, at neutral pH.

N,N'-Di-4-triazolylurea (DTU) has developed as a new ADDA module and DTU forms a stable ADDA*DAAD heterocomplex with 2,7-diamido-1,8-naphthyridine (DAN) (K(s) = 2.6 x 10(5) M(-1) in CHCl(3)). The K(s) value of the complex between DTU and DAN is 100-fold greater than that of the complex between N,N'-di-2-pyridylurea and DAN due to replacement of a pyridine ring with a 1,2,3-triazole ring.