Temperature Control of the Self-Assembly Process of 4-Aminoquinoline Amphiphile: Selective Construction of Perforated Vesicles and Nanofibers, and Structural Restoration Capability.

The construction of diverse and distinctive self-assembled structures in water, based on the control of the self-assembly processes of artificial small molecules, has received considerable attention in supramolecular chemistry. Cage-like perforated vesicles are distinctive and interesting self-assembled structures. However, the development of self-assembling molecules that can easily form perforated vesicles remains challenging. This paper reports a lower critical solution temperature (LCST) behavior-triggered self-assembly property of a 4-aminoquinoline (4-AQ)-based amphiphile with a tetra(ethylene glycol) chain, in HEPES buffer (pH 7.4). This property allows to form perforated vesicles after heating at 80 °C (> LCST). The self-assembly process of the 4-AQ amphiphile can be controlled by heating at 80 °C (> LCST) or 60 °C (< LCST). After cooling to room temperature, the selective construction of the perforated vesicles and nanofibers was achieved from the same 4-AQ amphiphile. Furthermore, the perforated vesicles exhibited slow morphological transformation into intertwined-like nanofibers but were easily restored by brief heating above the LCST.

Temperature Control of the Self-Assembly Process of 4-Aminoquinoline Amphiphile: Selective Construction of Perforated Vesicles and Nanofibers, and Structural Restoration Capability.

Invited for the cover of this issue is the group of Yosuke Hisamatsu, Naoki Umezawa, and co-workers at Nagoya City University and Nagoya Institute of Technology. The image depicts the selective construction of perforated vesicles and nanofibers, influenced by the heating temperatures during the self-assembly process of the 4-aminoquinoline amphiphile. Read the full text of the article at 10.1002/chem.202400134.

Design and Synthesis of Poly(2,2'-Bipyridyl) Ligands for Induction of Cell Death in Cancer Cells: Control of Anticancer Activity by Complexation/Decomplexation with Biorelevant Metal Cations.

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.

Fluorescence Response and Self-Assembly of a Tweezer-Type Synthetic Receptor Triggered by Complexation with Heme and Its Catabolites.

There is increasing interest in the development and applications of synthetic receptors that recognize target biomolecules in aqueous media. We have developed a new tweezer-type synthetic receptor that gives a significant fluorescence response upon complexation with heme in aqueous solution at pH 7.4. The synthetic receptor consists of a tweezer-type heme recognition site and sulfo-Cy5 as a hydrophilic fluorophore. The receptor-heme complex exhibits a supramolecular amphiphilic character that facilitates the formation of self-assembled aggregates, and both the tweezer moiety and the sulfo-Cy5 moiety are important for this property. The synthetic receptor also exhibits significant fluorescence responses to biliverdin and bilirubin, but shows very weak fluorescence responses to flavin mononucleotide, folic acid, and nicotinamide adenine dinucleotide, which contain smaller π-scaffolds.

Stable Iron Porphyrin Intramolecularly Coordinated by Alcoholate Anion: Synthesis and Evaluation of Axial Ligand Effect of Alcoholate on Spectroscopy and Catalytic Activity.

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.

Stereospecific Synthesis of Tris-heteroleptic Tris-cyclometalated Iridium(III) Complexes via Different Heteroleptic Halogen-Bridged Iridium(III) Dimers and Their Photophysical Properties.

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 synthesized and isolated. The second finding is that the different stereoisomers of 25 have different stability. Finally, different stereoisomers exhibit different emission spectra. Namely, one of its stereoisomers 25a exhibits a single broad emission from ca. 550 nm to ca. 650 nm (orange emission), while stereoisomer 25c emits 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.

Design and synthesis of a luminescent iridium complex-peptide hybrid (IPH) that detects cancer cells and induces their apoptosis.

Tumor necrosis factor related apoptosis inducing ligand (TRAIL) triggers the cell-extrinsic apoptosis pathway by complexation with its signaling receptors such as death receptors (DR4 and DR5). TRAIL is a C3-symmetric type II transmembrane protein, consists of three monomeric units. Cyclometalated iridium(III) complexes such as fac-Ir(tpy)3 (tpy = 2-(4-tolyl)pyridine) also possess a C3-symmetric structure and are known to have excellent luminescence properties. In this study, we report on the design and synthesis of a C3-symmetric and luminescent Ir complex-peptide hybrid (IPH), which contains a cyclic peptide that had been reported to bind to death receptor (DR5). The results of MTT assay of Jurkat, K562 and Molt-4 cells with IPH and co-staining experiments with IPH and an anti-DR5 antibody indicate that IPH binds to DR5 and induces apoptosis in a manner parallel to the DR5 expression level. Mechanistic studies of cell death suggest that apoptosis and necrosis-like cell death are differentiated by the position of the hydrophilic part that connects Ir complex and the peptide units. These findings suggest that IPHs could be a promising tool for controlling apoptosis and necrosis by activation of the extra-and intracellular cell death pathway and to develop new anticancer drugs that detect cancer cells and induce their cell death.

Cationic Amphiphilic Tris-Cyclometalated Iridium(III) Complexes Induce Cancer Cell Death via Interaction with Ca2+-Calmodulin Complex.

In our previous paper, we reported on the preparation of some cationic amphiphilic Ir complexes (2c, 2d) containing KKGG peptides that induce and detect cell death of Jurkat cells. Mechanistic studies suggest that 2c interacts with anionic molecules and/or membrane receptors on the cell surface to trigger an intracellular Ca2+ response, resulting in the induction of cell death, accompanied by membrane disruption. We have continued the studies of cell death of Jurkat cells induced by 2c and found that xestospongin C, a selective inhibitor of an inositol 1,4,5-trisphosphate receptor located on the endoplasmic reticulum (ER), reduces the cytotoxicity of 2c, suggesting that 2c triggers the release of Ca2+ from the ER, leading to an increase in the concentration of cytosolic Ca2+, thus inducing cell death. Moreover, we synthesized a series of new amphiphilic cationic Ir complexes 5a-c containing photoreactive 3-trifluoromethyl-3-phenyldiazirine (TFPD) groups, in an attempt to identify the target molecules of 2c. Interestingly, it was discovered that a TFPD group functions as a triplet quencher of Ir complexes. It was also found that 5b is useful as a turn-on phosphorescent probe of acidic proteins such as bovine serum albumin (BSA) (pI = 4.7) and their complexation was confirmed by luminescence titrations and SDS-PAGE of photochemical products between them. These successful results allowed us to carry out photoaffinity labeling of the target biomolecules of 5b (2c and analogues thereof) in Jurkat cells. A proteomic analysis of the products obtained by the photoirradiation of 5b with Jurkat cells suggests that the Ca2+-binding protein "calmodulin (CaM)" is one of target proteins of the Ir complexes. Indeed, 5b was found to interact with the Ca2+-CaM complex, as evidenced by luminescence titrations and the results of photochemical reactions of 5b with CaM in the presence of Ca2+ (SDS-PAGE). A plausible mechanism for cell death induced by a cationic amphiphilic Ir complex is discussed on the basis of our results.

Design and Synthesis of Tris-Heteroleptic Cyclometalated Iridium(III) Complexes Consisting of Three Different Nonsymmetric Ligands Based on Ligand-Selective Electrophilic Reactions via Interligand HOMO Hopping Phenomena.

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.

Efficient Synthesis of Tris-Heteroleptic Iridium(III) Complexes Based on the Zn2+-Promoted Degradation of Tris-Cyclometalated Iridium(III) Complexes and Their Photophysical Properties.

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 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, and treatment of 27b with acetylacetone (acacH) afforded the corresponding tris-heteroleptic Ir complex Ir(tpy)(F2ppy)(acac)18. In addition, another tris-heteroleptic Ir complex 35a having 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.

Design and Synthesis of Heteroleptic Cyclometalated Iridium(III) Complexes Containing Quinoline-Type Ligands that Exhibit Dual Phosphorescence.

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.

Supramolecular Complexes Formed by the Self-assembly of Hydrophobic Bis(Zn(2+)-cyclen) Complexes, Copper, and Di- or Triimide Units for the Hydrolysis of Phosphate Mono- and Diesters in Two-Phase Solvent Systems (Cyclen=1,4,7,10-Tetraazacyclododecane).

We previously reported on supramolecular complexes 4 and 5, formed by the 4 : 4 : 4 or 2 : 2 : 2 assembly of a dimeric zinc(II) complex (Zn2L(1)) having 2,2'-bipyridyl linker, dianion of cyanuric acid (CA) or 5,5-diethylbarbituric acid (Bar), and copper(II) ion (Cu(2+)) in an aqueous solution. The supermolecule 4 possesses Cu2(µ-OH)2 centers and catalyzes hydrolysis of phosphate monoester dianion, mono(4-nitrophenyl)phosphate (MNP), at neutral pH. In this manuscript, we report on design and synthesis of hydrophobic supermolecules 9 and 10 by 4 : 4 : 4 and 2 : 2 : 2 self-assembly of hydrophobic Zn2L(2) and Zn2L(3) containing long alkyl chains, CA or Bar, and Cu(2+) and their phosphatase activity for the hydrolysis of MNP and bis(4-nitrophenyl)phosphate (BNP) in two-phase solvent systems. We assumed that the Cu2(µ-OH)2 active sites of 9 and 10 would be more stable in organic solvent than in aqueous solution and that product inhibition of the supermolecules might be avoided by the release of HPO4(2-) into the aqueous layer. The findings indicate that 9 and 10 exhibit phosphatase activity in the two-phase solvent system, although catalytic turnover was not observed. Furthermore, the hydrolysis of BNP catalyzed by the hydrophobic 2 : 2 : 2 supermolecules in the two-phase solvent system is described.

Design and Synthesis of Amphiphilic and Luminescent Tris-Cyclometalated Iridium(III) Complexes Containing Cationic Peptides as Inducers and Detectors of Cell Death via a Calcium-Dependent Pathway.

Cationic amphiphilic peptides have the potential to function as agents for the treatment of microbial infections and cancer therapy. The cationic and hydrophobic parts of these molecules allow them to associate strongly with negatively charged bacterial or cancer cell membranes, thus exerting antimicrobial and anticancer activities through membrane disruption. Meanwhile, cyclometalated iridium(III) complexes such as fac-Ir(ppy)3 (ppy = 2-phenylpyridine) and fac-Ir(tpy)3 (tpy = 2-(4'-tolyl)pyridine) possess C3-symmetric structures and excellent photophysical properties as phosphorescence materials, which make them important candidates for use in biological applications such as chemosensors, biolabeling, living cell staining, in vivo tumor imaging, and anticancer agents. We recently reported on some regioselective substitution reactions of Ir(tpy)3 and Ir(ppy)3 at the 5'-position (p-position with respect to the C-Ir bond) on the 2-phenylpyridine ligands and their subsequent conversions to a variety of functional groups. We report here on the design and synthesis of amphiphilic and luminescent tris-cyclometalated Ir complexes in which cationic peptides are attached through alkyl chain linkers that work as inducers and detectors of cell death. Ir complexes containing cationic peptides such as a KKGG sequence and alkyl chain linkers of adequate length (C6 and C8) exhibit considerable cytotoxicity against cancer cells such as Jurkat, Molt-4, HeLa-S3, and A549 cells, and that dead cells are well stained with these Ir complexes. Furthermore, an Ir complex in which the KKGG peptide is attached through a C6 linker displayed lower cytotoxicity against normal mouse lymphocytes. Mechanistic studies suggest that Ir complexes containing the KKGG peptide interact with anionic molecules on the cell surface and/or membrane receptors to trigger the Ca(2+) dependent pathway and intracellular Ca(2+) response, resulting in necrosis accompanied by membrane disruption.

Photochemical Properties of Red-Emitting Tris(cyclometalated) Iridium(III) Complexes Having Basic and Nitro Groups and Application to pH Sensing and Photoinduced Cell Death.

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.

Synthesis and photochemical properties of pH responsive tris-cyclometalated iridium(III) complexes that contain a pyridine ring on the 2-phenylpyridine ligand.

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.

Control of the stepwise self-assembly process of a pH-responsive amphiphilic 4-aminoquinoline-tetraphenylethene conjugate.

Controlling the kinetic processes of self-assembly and switching their kinetic properties according to the changes in external environments are crucial concepts in the field of supramolecular polymers in water for biological and biomedical applications. Here we report a new self-assembling amphiphilic 4-aminoquinoline (4-AQ)-tetraphenylethene (TPE) conjugate that exhibits kinetically controllable stepwise self-assembly and has the ability of switching its kinetic nature in response to pH. The self-assembly process of the 4-AQ amphiphile comprises the formation of sphere-like nanoparticles, a transition to short nanofibers, and their growth to long nanofibers with ∼1 µm length scale at room temperature (RT). The timescale of the self-assembly process differs according to the pH-responsivity of the 4-AQ moiety in a weakly acidic to neutral pH range. Therefore, after aging for 24 h at RT, the 4-AQ amphiphile forms metastable short nanofibers at pH 5.5, while it forms thermodynamically favored long nanofibers at pH 7.4. Moreover, the modulation of nanofiber growth proceeding spontaneously at RT was achieved by switching the kinetic pathway through changing the pH between 7.4 and 5.5.

Design and synthesis of a luminescent cyclometalated iridium(III) complex having N,N-diethylamino group that stains acidic intracellular organelles and induces cell death by photoirradiation.

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.

Post-complexation Functionalization of Cyclometalated Iridium(III) Complexes and Applications to Biomedical and Material Sciences.

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.

Selective hydrolysis of phosphate monoester by a supramolecular phosphatase formed by the self-assembly of a bis(Zn(2+)-cyclen) complex, cyanuric acid, and copper in an aqueous solution (cyclen = 1,4,7,10-tetraazacyclododecane).

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.