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Chelation therapy is a medical procedure for removing toxic metals from human organs and tissues and for the treatment of diseases by using metal-chelating agents. For example, iron chelation therapy is designed not only for the treatment of metal poisoning but also for some diseases that are induced by iron overload, cancer chemotherapy, and related diseases. However, the use of such metal chelators needs to be generally carried out very carefully, because of the side effects possibly due to the non-specific complexation with intracellular metal cations. Herein, we report on the preparation and characterization of some new poly(bpy) ligands (bpy: 2,2′-bipyridyl) that contain one–three bpy ligand moieties and their anticancer activity against Jurkat, MOLT-4, U937, HeLa S3, and A549 cell lines. The results of MTT assays revealed that the tris(bpy) and bis(bpy) ligands exhibit potent activity for inducing the cell death in cancer cells. Mechanistic studies suggest that the main pathway responsible for the cell death by these poly(bpy) ligands is apoptotic cell death. It was also found that the anticancer activity of the poly(bpy) ligands could be controlled by the complexation (anticancer activity is turned OFF) and decomplexation (anticancer activity is turned ON) with biorelevant metal cations. In this paper, these results will be described.

Cytochrome P450 selectively hydroxylates the ω and ω-1 positions of fatty acids. Among synthetic oxidizing catalysts, Suslick’s bis-pocket porphyrin Mn or Fe complex achieved ω oxidation for the first time, but the yield in the preparation of the catalyst was poor due to steric hindrance, and in addition, the catalyst turnover number in the oxidation reaction was low. We have devised a new synthetic strategy involving the introduction of eight bulky aryl groups at the 2,6-positions of the meso-phenyl groups after construction of the porphyrin skeleton. This strategy greatly improved the yield in synthesis of the catalyst, and a number of derivatives of bis-pocket porphyrin and their metal complexes were prepared. These Ru complexes show unique ω-1 selectivity and provide a much higher turnover number in the oxidation of linear alkane with 2,6-dichloropyridine N-oxide, as compared to the reaction catalyzed by conventional Ru porphyrins.Selective direct modification of alkanes is important, but remains challenging. Here, we present a new strategy for efficient synthesis of bis-pocket porphyrins and a wide variety of their derivatives. Furthermore, we show that the Ru porphyrin-pyridine N-oxide system offers unique ω-1 selectivity in alkane oxidation, together with a greatly improved yield of oxidation products compared with a conventional method.

In this manuscript, the regioselective halogenation, nitration, formylation, and acylation of Ir(tpy)3and 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)3using 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 1H 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.

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 1aand 1bwas 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, SRcomplex, was much higher than that of 1a.

A pioneering chemiluminescent molecule reported by Schaap and co-workers, 3-(2′-spiroadamantane)-4-methoxy-4-(3″-hydroxy)phenyl-1,2-dioxetane (AMPD), does not require enzymatic activation but is unsuitable for use under physiological conditions. To overcome this limitation, we have developed a new AMPD derivative that contains an acetamido group at the orthoposition of the hydroxy group as an intramolecular hydrogen-bonding site in order to lower the pKavalue. This compound exhibits a superior chemiluminescence response to AMPD in the physiologically relevant pH range.

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)]217band [Ir(mpiq)(F2ppy)(μ-Br)]227b(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) 21and Ir(mpiq)2(F2ppy) 26, as reported by us. Subsequently, 17band 27bwere converted to the tris-heteroleptic tris-cyclometalated Ir complexes Ir(tpy)(F2ppy)(mpiq) 25consisting 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 25were synthesized and isolated. The second finding is that the different stereoisomers of 25have different stability. Finally, different stereoisomers exhibit different emission spectra. Namely, one of its stereoisomers 25aexhibits a single broad emission from ca. 550 nm to ca. 650 nm (orange emission), while stereoisomer 25cemits dual emission at ca. 509 nm and ca. 600 nm (pale pink emission), as supported by time-dependent density functional theory calculation. To the best of our knowledge, this is the first report of the selective and efficient synthesis of different stereoisomers of tris-heteroleptic tris-cyclometalated Ir(III) complexes that have different stabilities and different photophysical properties.

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, 5aand 7, would proceed at the 5 position of the quinoline ring of these Ir complexes to afford 18and 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 transto the Ir–N (1 position of quinoline) bond, and hence, the iodination or formylation of 18and 19occurs at the 5′ position of the ppy ligand to provide 20a, 23, and 24. Furthermore, we carried out the functionalization of 20ausing 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 Brønsted 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 CF3moieties 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-12with ZnBr2gave the heteroleptic μ-complex [{Ir(tpy)(F2ppy)(μ-Br)}2] 27bas a major product, resulting from the selective elimination of the tpy ligand of mer-12, and treatment of 27bwith acetylacetone (acacH) afforded the corresponding tris-heteroleptic Ir complex Ir(tpy)(F2ppy)(acac)18. In addition, another tris-heteroleptic Ir complex 35ahaving 8-benzenesulfonylamidoquinoline (8BSQ) ligand was synthesized. Mechanistic studies of this degradation reaction and the photochemical properties, especially a dual emission, of these newly synthesized tris-heteroleptic Ir complexes are also reported.

Cyclometalated iridium(III) (Ir(III)) complexes exhibit excellent photophysical properties that include large Stokes shift, high emission quantum yields, and microsecond-order emission lifetimes, due to low-lying metal-to-ligand charge transfer (spin-forbidden singlet–triplet (3MLCT) transition). As a result, analogs have been applied for research not only in the material sciences, such as the development of organic light-emitting diodes (OLEDs), but also for photocatalysts, bioimaging probes, and anticancer reagents. Although a variety of methods for the synthesis and the applications of functionalized cyclometalated iridium complexes have been reported, functional groups are generally introduced to the ligands prior to the complexation with Ir salts. Therefore, it is difficult to introduce thermally unstable functional groups such as peptides and sugars due to the harsh reaction conditions such as the high temperatures used in the complexation with Ir salts. In this review, the functionalization of Ir complexes after the formation of cyclometalated Ir complexes and their biological and material applications are described. These methods are referred to as “post-complexation functionalization (PCF).” In this review, applications of PCF to the design and synthesis of Ir(III) complexes that exhibit blue –red and white color emissions, luminescence pH probes, luminescent probes of cancer cells, compounds that induce cell death in cancer cells, and luminescent complexes that have long emission lifetimes are summarized.

A series of tris‐cyclometalated IrIIIcomplexes 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.

A new structure for an adenine‐selective host molecule, featuring the pertinent link of five‐six‐five‐membered heteroaromatic rings and two carbamoyl NH sites, was developed. This structure provides a correctly oriented array of complementary hydrogen bonding sites for the adenine nucleobase, which exploits both Watson–Crick and Hoogsteen‐type interactions. The complexation with adenine nucleobases by multiple hydrogen bonding was supported by 1H NMR spectroscopy. This type of host displayed high selectivity in complexation, with an accompanying fluorescent response to lipophilized adenosine in CHCl3. Furthermore, a remarkably selective potentiometric response was attained for adenosine 5′‐monophosphate over 5′‐GMP, 5′‐CMP, and 5′‐UMP by using an ion‐selective electrode with a PVC‐supported solvent polymeric membrane. This indicates recognition of water‐soluble nucleotide guests through the membrane–water interface. These findings are expected to form a reliable basis for the development of artificial sensing systems for mononucleotides in biological systems.

Peptides are attractive drug candidates, but their utility is greatly limited by their inherent susceptibility to proteolytic degradation and their inability to pass through the cell membrane. Here, we employ a strategy of temporary cyclization to develop a cell-active lysine-specific demethylase 1 (LSD1/KDM1A) inhibitor peptide. We first identified a highly potent LSD1-inhibitory linear peptide, with the assistance of X-ray crystal structure data of inhibitor peptide-bound LSD1·CoREST. The peptide was converted to a redox-activatable cyclic peptide incorporating cell-penetrating peptide (CPP), expecting selective activation under intracellular reducing conditions. The cyclic peptide moiety exhibited enhanced stability to protease and was converted to the linear, unmodified LSD1 inhibitor peptide under reducing conditions. The cyclic peptide with CPP inhibited the proliferation of human acute myeloid leukemia cells (HL-60) in the low micromolar concentration range.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.