Reversible structural change of [Co2Fe2] complexes between diamagnetic hydrogen-bonded 1D chains and paramagnetic complexes within a layered structure of amphiphilic anions.

The combination of amphiphilic ions and metal complexes may enable the construction of assemblies in which the assembly structure and electronic state of the metal complexes change concertedly. In this work, an alternating layered structure of [Co2Fe2] complexes and amphiphilic anions was constructed. In the crystal structure, [Co2Fe2] complexes and water molecules formed a hydrogen-bonded supramolecular one-dimensional (1D) chain in the hydrophilic layer. A reversible structural change between the 1D chain and discrete [Co2Fe2] complexes was found to occur concertedly with an electron transfer-coupled spin transition (ETCST) of the [Co2Fe2] complex and desorption/adsorption of water molecules.

Suppression of KLF5 basal expression in oral carcinoma-derived cells through three intact CREB1-binding sites in the silencer region.

OBJECTIVES: Krüppel-like factor (KLF)5, which is overexpressed in carcinomas such as oral cancer, inhibits epidermal differentiation. KLF5 induces dedifferentiation of carcinoma cells, which effectuates carcinoma progression; nevertheless, the regulatory mechanism affecting the transcription of the KLF5 gene remains ambiguous. METHODS: Transcriptional activity of the KLF5 silencer, specifically the 425-bp region (425-region), was examined using reporter assays. An additional analysis was conducted to assess the impact of the minimal essential region (MER) of KLF5 on its basal expression. The affinity of cAMP responsive element binding protein 1 (CREB1) for three potential CREB1-binding sites in the 425-region was analyzed using DNA pull-down and quantitative chromatin immunoprecipitation assays. Reporter assays employing a human oral squamous carcinoma cell line, HSC2, transfected with small interfering RNA or complementary DNA for CREB1, were performed to investigate the effect of CREB1 binding sites on MER activity. RESULTS: The 425-region exhibited no transcriptional activity and suppressed MER transcriptional activity. This region encodes three putative CREB1-binding sites, and CREB1 demonstrated equal binding affinity for all three sites. The deletion of each of these binding sites reduced CREB1 precipitation and enhanced MER activity. Endogenous CREB1 knockdown and overexpression elevated and reduced MER activity, respectively, at the intact sites. Conversely, site deletion hampered and improved MER activity upon CREB1 knockdown and overexpression, respectively. CONCLUSIONS: Suppression of KLF5 basal expression via CREB1 binding to the 425-region requires all three CREB1-binding sites to remain intact in oral carcinoma cells. Consequently, deletion of the CREB1-binding site relieves suppression of KLF5 basal expression.

Suppression of Krüppel-like factor 5 basal expression by CREB1 binding to far distal element.

BACKGROUND: Krüppel-like factor 5 (KLF5) is a transcription factor regulating the proliferation and differentiation of epithelial cells, and its uncontrolled expression is closely associated with carcinoma progression. Sp3 binding to the minimal essential region (MER) of KLF5 gene is critical for KLF5 basal expression, but the expression control mechanism is unknown. OBJECTIVE: This study aimed to identify a regulatory region for KLF5 basal expression and the binding protein in carcinoma cells by analyzing the promoter upstream region. METHODS: Reporter assays determined the silencer region. The protein binding to the region was identified by database analysis and ChIP assay. The protein mediating the interaction between the region and the MER was confirmed through chromosome conformation capture (3 C) on ChIP assay. The effects of the protein on KLF5 expression were analyzed using qRT-PCR and western blot. RESULTS: Reporter assay localized the 425-region from upstream KLF5 gene as the silencer. Database analysis and ChIP assay found CREB1 binding to the 425-region. CREB1 siRNA or mutation of CREB1-binding site in the 425-region increased luciferase activities and decreased the binding to 425-region. 3 C on ChIP assay showed that CREB1 mediated interaction of the 425-region and the MER. CREB1 overexpression decreased endogenous KLF5 expression and luciferase activity. CONCLUSIONS: The 425-region is the silencer of KLF5 basal expression, and CREB1 binding suppresses the expression.

Formation and Growth of Atomic Scale Seeds of Au Nanoparticle in the Nanospace of an Organic Cage Molecule.

Seed-mediated growth has been widely used to synthesize noble metal nanoparticles with controlled size and shape. Although it is becoming possible to directly observe the nucleation process of metal atoms at the single atom level by using transmission electron microscopy (TEM), it is challenging to control the formation and growth of seeds with only a few metal atoms in homogeneous solution systems. This work reports site-selective formation and growth of atomic scale seeds of the Au nanoparticle in a nanospace of an organic cage molecule. We synthesized a cage molecule with amines and phenols, which were found to both capture and reduce Au(III) ions to spontaneously form the atomic scale seeds containing Au(0) in the nanospace. The growth reaction of the atomic scale seeds afforded Au nanoparticles with an average diameter of 2.0±0.2 nm, which is in good agreement with the inner diameter of the cage molecule.

Structural Conversion of Supramolecular Assembly in Solution by Thermally Induced Intramolecular Electron Transfer of [Co2 Fe2 ] Complex.

Invited for the cover of this issue is the group of Masayuki Nihei at the University of Tsukuba. The image depicts the electron transfer-triggered structural conversion of the supramolecular assembly of a [Co2 Fe2 ] complex between reverse vesicles and entangled one-dimensional chains. Read the full text of the article at 10.1002/chem.202300954.

Structural Conversion of Supramolecular Assembly in Solution by Thermally Induced Intramolecular Electron Transfer of [Co2 Fe2 ] Complex.

Combining metal complexes with amphiphilic molecules leads to a wide variety of functional self-assembled nanostructures. Metal complexes exhibiting spin transitions can be good candidates as the trigger to cause structural conversion of such assembly because they respond to various external stimuli. In this work, we studied a structural conversion of a supramolecular assembly containing a [Co2 Fe2 ] complex through a thermally induced electron transfer-coupled spin transition (ETCST). With an amphiphilic anion, the [Co2 Fe2 ] complex formed reverse vesicles in solution and showed thermal ETCST. In contrast, thermal ETCST in the presence of a bridging hydrogen-bond donor caused structural conversion from the reverse vesicle structure to entangled one-dimensional chains through hydrogen bond formation.

Stacking of a Cofacially Stacked Iron Phthalocyanine Dimer on Graphite Achieved High Catalytic CH4 Oxidation Activity Comparable to That of pMMO.

Numerous biomimetic molecular catalysts inspired by methane monooxygenases (MMOs) that utilize iron or copper-oxo species as key intermediates have been developed. However, the catalytic methane oxidation activities of biomimetic molecule-based catalysts are still much lower than those of MMOs. Herein, we report that the close stacking of a µ-nitrido-bridged iron phthalocyanine dimer onto a graphite surface is effective in achieving high catalytic methane oxidation activity. The activity is almost 50 times higher than that of other potent molecule-based methane oxidation catalysts and comparable to those of certain MMOs, in an aqueous solution containing H2O2. It was demonstrated that the graphite-supported µ-nitrido-bridged iron phthalocyanine dimer oxidized methane, even at room temperature. Electrochemical investigation and density functional theory calculations suggested that the stacking of the catalyst onto graphite induced partial charge transfer from the reactive oxo species of the µ-nitrido-bridged iron phthalocyanine dimer and significantly lowered the singly occupied molecular orbital level, thereby facilitating electron transfer from methane to the catalyst in the proton-coupled electron-transfer process. The cofacially stacked structure is advantageous for stable adhesion of the catalyst molecule on the graphite surface in the oxidative reaction condition and for preventing decreases in the oxo-basicity and generation rate of the terminal iron-oxo species. We also demonstrated that the graphite-supported catalyst exhibited appreciably enhanced activity under photoirradiation owing to the photothermal effect.

Tetranuclear [Cu3Ln] complexes derived from a tetraketone-type ligand.

A series of tetranuclear [Cu3Ln] complexes, [Cu3Gd(L)3(NO3)2(H2O)3](NO3)·H2O (1), [Cu3Tb(L)3(NO3)2(H2O)3](NO3) (2) and [Cu3Dy(L)3(NO3)3(H2O)2]·1.5(H2O) (3), were synthesized by a one-pot reaction using a simple tetraketone-type ligand (H2L = (3Z,5Z)-4,5-dihydroxy-3,5-octadiene-2,7-dione). X-ray structural analyses revealed that each complex has a planar tetranuclear core of [Cu3Ln] (Ln = Gd, Tb, and Dy), in which the Ln ion is accommodated in the centre of a Cu3O6 metallocycle. A cryomagnetic study revealed that all complexes show intramolecular ferromagnetic interactions between Cu(II) and Ln(III) ions. The [Cu3Gd] complex (1) has an ST = 5 spin ground state and shows a magneto-caloric effect with a maximum magnetic entropy change (-ΔSm) of 16.4 J kg-1 K-1 (5 T, 2.4 K). On the other hand, the [Cu3Tb] complex (2) shows a slow magnetic relaxation behavior under a zero magnetic field. The analysis of an Arrhenius plot reveals that the effective energy barrier of spin reversal is 13.1 K. The [Cu3Dy] complex (3) also shows a slow magnetic relaxation under 1300 Oe dc magnetic field with an effective energy barrier of 6.82 K.

Significant Effect of the Flexibility of Bridging Alkyl Chains on the Proximity of Stacked Porphyrin and Phthalocyanine Conjugated with a Fourfold Rotaxane Linkage.

Invited for the cover of this issue are Kentaro Tanaka at Nagoya University and co-workers. The image depicts the importance of the flexibility of bridging alkyl chains in a molecular conjugate to pack the components closely to generate efficient molecular communication. Read the full text of the article at 10.1002/chem.202200819.

Significant Effect of the Flexibility of Bridging Alkyl Chains on the Proximity of Stacked Porphyrin and Phthalocyanine Conjugated with a Fourfold Rotaxane Linkage.

Spatial distance is an important factor in controlling the functional interactions between molecular units in a conjugate; therefore, the bridging unit has been closely examined. Here, we examined the effect of the flexibility of bridging alkyl chains on the proximity of stacked porphyrin and phthalocyanine conjugated with a fourfold rotaxane linkage. We found that closely stacking two π systems requires bridging alkyl chains above a certain length, and the shorter bridges hinder stacking because of their lower flexibility. The stacking distance between porphyrin and phthalocyanine in the conjugate with decyl (C10 ) chains was estimated to be 4.03 Šand showed a unique physical character arising from short-distance interactions. The longer alkyl chains minimized steric restriction inside the fourfold rotaxane and allowed efficient communication between the porphyrin and phthalocyanine units. This is due to the flexibility of the side chains.

High mobility group AT-hook 2 regulates osteoblast differentiation and facial bone development.

The mutation and deletion of high mobility group AT-hook 2 (Hmga2) gene exhibit skeletal malformation, but almost nothing is known about the mechanism. This study examined morphological anomaly of facial bone in Hmga2-/- mice and osteoblast differentiation of pre-osteoblast MC3T3-E1 cells with Hmga2 gene knockout (A2KO). Hmga2-/- mice showed the size reduction of anterior frontal part of facial bones. Hmga2 protein and mRNA were expressed in mesenchymal cells at ossification area of nasal bone. A2KO cells differentiation into osteoblasts after reaching the proliferation plateau was strongly suppressed by alizarin red and alkaline phosphatase staining analyses. Expression of osteoblast-related genes, especially Osterix, was down-regulated in A2KO cells. These results demonstrate a close association of Hmga2 with osteoblast differentiation of mesenchymal cells and bone growth. Although future studies are needed, the present study suggests an involvement of Hmga2 in osteoblast-genesis and bone growth.

Syntheses, structures, and magnetic properties of a series of Mn-M-Mn trinuclear complexes with different spin configurations.

A series of trinuclear complexes, [MnII2YIII(L)2(HL)2(NO3)3][YIII(NO3)5]·7H2O (1'), [MnII2GdIII(HL)4(NO3)4]2[MnII2GdIII(L)(HL)3(NO3)4][GdIII(NO3)5]4·2(o-Xy)·12H2O (2') and [MnII3(L)(HL)2(NO3)4](NO3)·1.25(p-Xy) (3'), were synthesized using a ß-diketone ligand HL (HL = 1,3-bis(pyridin-2-yl)propane-1,3-dione). X-ray structural analyses revealed that each complex has a trinuclear core with an Mn(II)-M-Mn(II) arrangement (M = YIII (1), GdIII (2), and MnII (3)). In 1' with a diamagnetic Y(III) ion, negligible antiferromagnetic interactions between terminal Mn(II) ions are operative. On the other hand, 2' shows ferromagnetic interactions between Mn(II) and Gd(III) ions, affording a spin ground state of ST = 17/2. The homometallic Mn(II)3 complex of 3' has an ST = 5/2 spin ground state resulting from the antiferromagnetic interactions between neighboring Mn(II) ions. The maximum magnetic entropy change (-ΔSm) of 1'-3' was estimated to be 12.3, 24.8, and 8.0 J kg-1 K-1, respectively.

Different Modes of Anion Response Cause Circulatory Phase Transfer of a Coordination Cage with Controlled Directionality.

Controlled directional transport of molecules is essential to complex natural systems, from cellular transport up to organismal circulatory systems. In contrast to these natural systems, synthetic systems that enable transport of molecules between several spatial locations on the macroscopic scale, when external stimuli are applied, remain to be explored. Now, the transfer of a supramolecular cage is reported with controlled directionality between three phases, based on a cage that responds reversibly in two distinct ways to different anions. Notably, circulatory phase transfer of the cage was demonstrated based on a system where the three layers of solvent are arranged within a circular track. The direction of circulation between solvent phases depended upon the order of addition of anions.

Site-Selective Supramolecular Complexation Activates Catalytic Ethane Oxidation by a Nitrido-Bridged Iron Porphyrinoid Dimer.

Development of supramolecular methods to further activate a highly reactive intermediate is a fascinating strategy to create novel potent catalysts for activation of inert chemicals. Herein, a supramolecular approach to enhance the oxidizing ability of a high-valent oxo species of a nitrido-bridged iron porphyrinoid dimer that is a known potent molecular catalyst for light alkane oxidation is reported. For this purpose, a nitrido-bridged dinuclear iron complex of porphyrin-phthalocyanine heterodimer 35+ , which is connected through a fourfold rotaxane, was prepared. Heterodimer 35+ catalyzed ethane oxidation in the presence of H2 O2 at a relatively low temperature. The site-selective complexation of 35+ with an additional anionic porphyrin (TPPS4- ) through π-π stacking and electrostatic interactions afforded a stable 1:1 complex. It was demonstrated that the supramolecular post-synthetic modification of 35+ enhances its catalytic activity efficiently. Moreover, supramolecular conjugates achieved higher catalytic ethane oxidation activity than nitrido-bridged iron phthalocyanine dimer, which is the most potent iron-oxo-based molecular catalyst for light-alkane oxidation reported so far. Electrochemical measurements proved that the electronic perturbation from TPPS4- to 35+ enhanced the catalytic activity.

Programmable arrangement of metal ions in a cofacially stacked assembly of porphyrinoids toward molecular tags.

Cofacial assemblies of metalloporphyrinoids represent a fascinating platform for the fabrication of novel functional molecular assemblies based on π-π, d-d, and d-π interactions between components. In this paper, we present a novel synthetic strategy for the programmable arrangement of different metal ions inside a cofacially stacked trimer of porphyrinoids. A combination of two different assemblies was utilized for our purpose: a tetracationic fourfold rotaxane heterodimer between a porphyrin with four alkylammonium chains and a phthalocyanine bearing four peripheral crown ethers, and a stacked assembly between the fourfold rotaxane heterodimer and an additional tetraanionic porphyrin. Three metal ions, namely Cu(ii), Ag(ii), and Au(iii), were arranged inside the cofacially stacked assembly of three porphyrinoids. Moreover, paramagnetic Cu(ii) ions were arranged inside a cofacially stacked heterotrimer of porphyrinoids and were precisely programmed, affording the desired spin-spin communications as readable information. These results indicated that the developed strategy is effective for arranging various metal ions in cofacially stacked assemblies of porphyrinoids toward the creation of molecular tags or bar codes.

Oxygen Reduction to Water by a Cofacial Dimer of Iron(III)-Porphyrin and Iron(III)-Phthalocyanine Linked through a Highly Flexible Fourfold Rotaxane.

A µ-oxo-dinuclear iron complex of a supramolecular porphyrin-phthalocyanine conjugate was synthesized and its catalytic electrochemical oxygen reduction properties were investigated. In the conjugate, porphyrin and phthalocyanine units were connected to form a cofacial dimeric structure through a flexible fourfold rotaxane linkage, which was advantageous for accommodating small substrates between the iron centers. The conjugate showed efficient catalytic properties, at more positive potentials than those of other reported dinuclear porphyrinoid iron complexes, to selectively afford water through a four-electron reduction process.

Electronic perturbation of supramolecular conjugates of porphyrins and phthalocyanines.

The redox potential of a supramolecular porphyrin-phthalocyanine heterodimer was perturbed by the stacking of an extra metalloporphyrin to the phthalocyanine. This stacking gave rise to π-π and electrostatic interactions between the tetracationic dimer and the tetraanionic metalloporphyrin, with a Au(iii) metalloporphyrin exhibiting a larger effect than Cu(ii) and Pd(ii) complexes among square planar complexes.

Minimal essential region for krüppel-like factor 5 expression and the regulation by specificity protein 3-GC box binding.

Krüppel-like factor 5 (KLF5) transcriptionally controls the proliferation-differentiation balance of epithelium and is overexpressed in carcinomas. Although genomic region modifying KLF5 expression is widespread in different types of cells, the region that commonly regulates basal expression of the genes across cell-types is uncertain. In this study we determined the minimal essential region for the expression and its regulatory transcription factors using oral carcinoma cells. A reporter assay defined a 186bp region downstream of the transcription start site and a cluster of six GC boxes (GC1-GC6) as the minimal essential region. Mutation in the GC1 or GC6 regions but not other GC boxes significantly decreased the reporter expression. The decrease by the GC1 mutation was reproduced in the 2kbp full-length promoter, but not by the GC6 mutation. Additionally, specificity proteins (Sp) that can be expressed in epithelial cells and bind GC box, Sp3 co-localized with KLF5 in oral epithelium and carcinomas and chromatin immunoprecipitation analyses showed Sp3 as the prime GC1-binding protein. Inhibition of Sp-GC box binding by mithramycin A and knockdown of Sp3 by the short interfering RNA decreased expression of the reporter gene and endogenous KLF5. These data demonstrate that a 186bp region is the minimal essential region and that Sp3-GC1 binding is essential to the basal expression of KLF5.

Krüppel-like factors 4 and 5 expression and their involvement in differentiation of oral carcinomas.

Proliferation-differentiation balance of epithelial cells is regulated by Krüppel-like factors (KLF) 4 and 5, and the unbalanced expression relates to carcinoma progression. However, little is known about the expression and role in oral carcinomas. This study examined expression of KLF4 and KLF 5 in the carcinomas by immunohistochemistry (n = 67) and the involvement in proliferation and differentiation of carcinoma cells. KLF4 was detected in keratinizing carcinoma cells and KLF5 in non-keratinizing cells. KLF4 staining declined in the patient with lymph node metastasis (P < 0.05) and in parallel with the histological dedifferentiation (P = 0.09). Exogenous overexpression of KLF4 arranged cells in a cobble-like structure with desmosomes and KLF5 elongated cells like fibroblasts without desmosomes. KLF4 suppressed fibronectin expression, and KLF5 down-regulated and degraded E-cadherin. The proliferation was not affected by KLFs. Thus, down-regulation of KLF4 and up-regulation of KLF5 may stimulate oral carcinoma progression through the dedifferentiation of carcinoma cells.

Triply stacked heterogeneous array of porphyrins and phthalocyanine through stepwise formation of a fourfold rotaxane and an ionic complex.

We report the preparation and crystal structure of a triply stacked metal complex array in which a Cu-phthalocyanine is sandwiched between different Cu-porphyrins. The discrete heterogeneous assembly was prepared through formation of a fourfold rotaxane from a tetradactyl porphyrin with alkylammonium moieties and a phthalocyanine bearing four crown ethers and the subsequent formation of an ionic complex between the fourfold rotaxane and a tetraanionic porphyrin. The tetraanionic porphyrin, Cu-TPPS(4-), is selectively bound to the fourfold rotaxane through cooperative π-π and ionic interactions. The crystal structure revealed the columnar stacked array of the three planar building components in a precise order and spatial arrangement that promote intermolecular electronic communication.