A Peanut-Shaped Polyaromatic Capsule: Solvent-Dependent Transformation and Electronic Properties of a Non-Contacted Fullerene Dimer.

Synthesis of molecular containers capable of incorporating multiple fullerenes remains challenging. Reported here is that room-temperature mixing of metal ions with W-shaped bispyridine ligands featuring polyaromatic panels results in the quantitative formation of a peanut-shaped M2 L4 capsule. The capsule reversibly converts into two molecules of an ML2 double tube in response to changes in the solvent. Notably, the capsule allows the incorporation of two fullerene molecules into the connected two spherical cavities at room temperature. The close proximity yet non-contact of the encapsulated C60 molecules, with a separation of 6.4 Å, was revealed by X-ray crystallographic analysis. The resultant, unusual fullerene dimer undergoes sequential reduction within the capsule to generate (C60 .- )2 , C60 .- ⋅C60 2- , and (C60 2- )2 species. Furthermore, temperature-controlled stepwise incorporation of two C60 molecules into the capsule is demonstrated.

Recognition of Multiple Methyl Groups on Aromatic Rings by a Polyaromatic Cavity.

The methyl group is a small substituent, usually showing relatively weak or no interactions with other functional groups and metal ions. Herein, we present the recognition of the number of methyl groups on synthetic and natural aromatic compounds (i.e., benzene and xanthine derivatives, respectively) by the 1 nm-sized polyaromatic cavity of a coordination capsule in water. Detailed competitive encapsulation experiments as well as X-ray crystallographic analysis revealed that multiple guest-host CH3 -polyaromatic interactions in the confined nanospace are key driving forces for the high selectivity.

Polycationic-Shelled Capsular and Tubular Nanostructures and Their Anionic-Guest Binding Properties.

For the development of novel nanospace with unique electrostatic character, we prepared new capsular and tubular nanostructures by the quantitative assembly of metal ions and bent bisacridinium ligands. The capsule and tube have closed spherical and open cylindrical cavities, respectively, with diameters of around 1 nm surrounded by cationic polyaromatic panels. Thanks to the facile synthetic protocol (three steps), another polycationic capsule with an elliptical nanocavity was also prepared by using an elongated ligand. In spite of the absence of pendant hydrophilic groups, the spherical polyaromatic capsule shows sufficient water solubility due to the polycationic shell. Moreover, the highly cationic cavity (12+) can selectively encapsulate anionic organic compounds in water.

Phthalimide Compounds Containing a Trifluoromethylphenyl Group and Electron-Donating Aryl Groups: Color-Tuning and Enhancement of Triboluminescence.

Trifluoromethylphenyl-substituted phthalimide derivatives favorably form triboluminescence (TL) active noncentrosymmetric crystals. Oligothienyl-, oligophenyl-, and naphthyl-substituted phthalimide derivatives were successfully developed as a series of metal free TL compounds. X-ray crystal structure analyses of bithienyl and naphthyl derivatives revealed noncentrosymmetric layer structures in the same direction. Introduction of suitable electron rich π-units such as thienyl groups enhances their photoluminescence and TL characteristics, and the colors can be also controlled in the visible region. A rigid naphthyl-substituted imide derivative exhibits extremely high TL performance.

Engineering Stacks of V-Shaped Polyaromatic Compounds with Alkyl Chains for Enhanced Emission in the Solid State.

A V-shaped bisanthracene derivative with three butyl groups formed two types of emissive solids that display bluish green and blue fluorescence (ΦF =72 and 32 %, respectively), depending on the preparation conditions. The crystal and powder X-ray analyses reveal that the highly emissive solid adopts a head-to-head arrangement with discrete stacks of the anthracene moieties, whereas the moderately emissive solid adopts a head-to-tail arrangement without the stacks. The obtained molecular arrangements are transformed by thermal stimuli accompanying the change in fluorescence. Furthermore, large enhancements of dye emissions (12-45-fold) through highly efficient host-guest energy transfer were achieved in the solid state by adding minute amounts of various fluorescent dyes (e.g. rubrene and Nile red) to the V-shaped compound.

An M2 L4 Molecular Capsule with a Redox Switchable Polyradical Shell.

Preparation of molecular nanostructures with polyradical frameworks remains a significant challenge because of the limited synthetic accessibility which is entirely different from that of neutral and ionic ones. Herein we report the quantitative formation of a new M2 L4 molecular capsule from metal ions and dihydrophenazine-based ligands. The capsule has a spherical nanocavity (ca. 1 nm in diameter) enclosed by eight redox-active, dihydrophenazine panels. Electrochemical oxidation of the capsule leads to the generation of multiple radical cations on the shell framework. Moreover, a stable tetra(radical cation) capsule can be reversibly obtained by chemical as well as electrochemical oxidation.

Preparation of Highly Fluorescent Host-Guest Complexes with Tunable Color upon Encapsulation.

Unlike previous coordinative host-guest systems, highly emissive host-guest complexes (up to Φ(F) = 0.5) were successfully prepared upon encapsulation of various fluorescent dyes (e.g., BODIPY and coumarin derivatives) by a Pt(II)-linked coordination capsule in water. Picosecond time-resolved spectroscopy elucidates the photophysical behaviors of the obtained complexes. Notably, the emission color of the fluorescent guest within the capsule can be readily modulated upon pairwise encapsulation with planar aromatic molecules.

Anisotropic expansion of an M2L4 coordination capsule: host capability and frame rearrangement.

Anisotropic expansion of a spherical M2L4 coordination capsule through the elongation of the ligand led to a new M2L'4 capsule. The expanded capsule provides an elliptical cavity encircled by polyaromatic frameworks with large openings and thereby can encapsulate elliptical fullerene C70 and monofunctionalized fullerene C60 in high yields. In addition, selective formation of a new M2L2L'2 capsule occurs by mixing the original M2L4 and expanded M2L'4 capsules in a 1:1 ratio upon addition of C60 or monofunctionalized C60 as a template molecule.

Wide-ranging host capability of a Pd(II)-linked M2L4 molecular capsule with an anthracene shell.

This article reports that an M2L4 molecular capsule is capable of encapsulating various neutral molecules in quantitative yields. The capsule was obtained as a single product by mixing a small number of components; two Pd(II) ions and four bent bispyridine ligands containing two anthracene panels. Detailed studies of the host capability of the Pd(II)-linked capsule revealed that spherical (e.g., paracyclophane, adamantanes, and fullerene C60), planar (e.g., pyrenes and triphenylene), and bowl-shaped molecules (e.g., corannulene) were encapsulated in the large spherical cavity, giving rise to 1:1 and 1:2 host-guest complexes, respectively. The volume of the encapsulated guest molecules ranged from 190 to 490 Å(3). Within the capsule, the planar guests adopt a stacked-dimer structure and the bowl-shaped guests formed an unprecedented concave-to-concave capsular structure, which are fully shielded by the anthracene shell. Competitive binding experiments of the capsule with a set of the planar guests established a preferential binding series for pyrenes≈phenanthrene>triphenylene. Furthermore, the capsule showed the selective formation of an unusual ternary complex in the case of triphenylene and corannulene.

Vegfrecine, an inhibitor of VEGF receptor tyrosine kinases isolated from the culture broth of Streptomyces sp.

A new inhibitor of VEGF receptor tyrosine kinases, vegfrecine (1), was isolated from the culture broth of Streptomyces sp. MK931-CF8. The molecular structure of 1 was determined by NMR and MS analysis combined with synthesis. Compound 1 showed potent inhibitory activity against vascular endothelial growth factor receptor (VEGFR) tyrosine kinases in in vitro enzyme assays, but platelet-derived growth factor receptors (PDGFRs), fibroblast growth factor receptor (FGFR), and epidermal growth factor receptor (EGFR) responded only weakly. Compound 1 is a promising new selective VEGFR inhibitor for investigating new treatments of cancer and inflammatory diseases.

Doubly activated supramolecular reaction: transesterification of acyclic oligoether esters with metal alkoxides.

Transesterification reactions of acyclic oligoether esters E3-E10 with metal alkoxides were accelerated upon noncovalent complexation of the esters with metal ions. In the reaction of monovalent alkaline metal alkoxides, CH(3)ONa and CH(3)OK, plots of the observed rate constants k(obs) with respect to the chain length of E3-E10 showed selective acceleration of the transesterification. Compared with the shortest E3, which can hardly bind metal ion, 4.3- and 6.6-fold accelerations in the maxima were achieved in the combinations of E5/CH(3)ONa and E6/CH(3)OK, respectively. Supramolecular intermediate complex could be spectrometrically visualized by ESI-FT-ICR-MS in the course of reaction. Kinetic experiments, together with structural analyses by means of NMR, mass spectrometry, and DFT calculations of the intermediate complexes, indicate that a size-fit complex of host substitute with alkali metal ion allows strong electron withdrawing due to the close contact of the carbonyl oxygen to the metal ion, resulting in the selective rate enhancement of the reaction, while in the reaction of E3-E10 with a divalent alkaline earth metal alkoxide, (CH(3)CH(2)O)(2)Ba, the k(obs) values increased stepwise with elongation of the side arm to attain an dramatic large acceleration. In comparison with the k(obs) of E3, 4610-fold acceleration was achieved in the reaction of E10. The double activation of the host substrate and guest counter nucleophile at once brings about this extraordinary rate acceleration. The strong wrapping complexation of long oligoether ester with barium ethoxide allows for the effective electron withdrawal from the ester carbonyl group (host activation) as well as separation of the accompanying guest alkoxide anions (guest activation).

A fluorescent calix[4]arene with naphthalene units at the upper rim exhibits long fluorescence emission lifetime without fluorescence quenching.

We synthesised a new compound with four naphthyl groups in the upper rims of calix[4]arene (1). Compared to the monomer unit, compound 1 has redshifted absorption and fluorescence, together with high fluorescence quantum yield and long fluorescence lifetime, which is extremely rare because long fluorescence lifetime emission tends to reduce the quantum yield. Single-crystal X-ray analysis and quantum calculations in the S1 state revealed π-π through-space interactions between naphthalene rings.

Cyclic monoterpenes trapped in a polyaromatic capsule: unusual selectivity, isomerization, and volatility suppression.

Cyclic monoterpenes (CMTs) are intractable natural products with high volatility and strong odors so that there has been no molecular receptor capable of selectively and tightly trapping CMTs in both solution and the solid state. We herein report that a polyaromatic capsule acts as a functional nanoflask for CMTs with the following five features: (i) the capsule can selectively bind menthone from mixtures with other saturated CMTs in water. In contrast, (ii) treatment of the capsule with mixtures of menthone and π-conjugated CMTs gives rise to ternary host-guest complexes with high pair-selectivity. Notably, (iii) the encapsulated menthone displays unusual isomerization from a typical chair conformer to otherwise unstable conformers upon heating. (iv) The selective binding of volatilized CMTs is demonstrated by the capsule even in the solid state at atmospheric pressure. Furthermore, (v) the volatilities of CMTs are significantly suppressed at elevated temperatures by the capsule upon encapsulation in solution as well as in the solid state.

Environment-sensitive emission of anionic hydrogen-bonded urea-derivative-acetate-ion complexes and their aggregation-induced emission enhancement.

Anions often quench fluorescence (FL). However, strong ionic hydrogen bonding between fluorescent dyes and anion molecules has the potential to control the electronic state of FL dyes, creating new functions via non-covalent interactions. Here, we propose an approach, utilising ionic hydrogen bonding between urea groups and anions, to control the electronic states of fluorophores and develop an aggregation-induced emission enhancement (AIEE) system. The AIEE ionic hydrogen-bonded complex (IHBC) formed between 1,8-diphenylnaphthalene (p-2Urea), with aryl urea groups at the para-positions on the peri-phenyl rings, and acetate ions exhibits high environmental sensitivities in solution phases, and the FL quantum yield (QY) in ion-pair assemblies of the IHBC and tetrabutylammonium cations is more than five times higher than that of the IHBC in solution. Our versatile and simple approach for the design of AIEE dye facilitates the future development of environment-sensitive probes and solid-state emitting materials.

Ring rotation of ferrocene in interlocked molecules in single crystals.

This work describes unique molecular motions of ferrocene-containing interlocked molecules observed by single-crystal X-ray crystallography. The rotational flexibility of ferrocene is achieved using combinations of ferrocene-tethered ammonium and 30-membered ring dibenzo-crown ether. By contrast, ferrocene was locked in the complex with an 18-membered ring dibenzo-crown ether and CH2Cl2. When the complex was heated at 358 K, CH2Cl2 was removed from the complex, which led to drastic structural changes, including a semieclipsed-to-disordered transition of ferrocene and flipping of the dibenzo-crown ether.

Structural basis for the kexin-like serine protease from Aeromonas sobria as sepsis-causing factor.

The anaerobic bacterium Aeromonas sobria is known to cause potentially lethal septic shock. We recently proposed that A. sobria serine protease (ASP) is a sepsis-related factor that induces vascular leakage, reductions in blood pressure via kinin release, and clotting via activation of prothrombin. ASP preferentially cleaves peptide bonds that follow dibasic amino acid residues, as do Kex2 (Saccharomyces cerevisiae serine protease) and furin, which are representative kexin family proteases. Here, we revealed the crystal structure of ASP at 1.65 A resolution using the multiple isomorphous replacement method with anomalous scattering. Although the overall structure of ASP resembles that of Kex2, it has a unique extra occluding region close to its active site. Moreover, we found that a nicked ASP variant is cleaved within the occluding region. Nicked ASP shows a greater ability to cleave small peptide substrates than the native enzyme. On the other hand, the cleavage pattern for prekallikrein differs from that of ASP, suggesting the occluding region is important for substrate recognition. The extra occluding region of ASP is unique and could serve as a useful target to facilitate development of novel antisepsis drugs.

The oxidation of 8-oxo-7,8-dihydroguanine by iodine.

8-Oxo-7,8-dihydroguanine was specifically oxidized by iodine with aqueous KI. Under acidic conditions, the major product was dehydro-guanidinohydantoin. Under basic conditions, two diastereoisomers of spirohydantoin were chiefly obtained. In addition, unstable diimine was detected for the first time.

Anti-influenza activity of phenethylphenylphthalimide analogs derived from thalidomide.

Swine-origin influenza A virus has caused pandemics throughout the world and influenza A is regarded as a serious global health issue. Hence, novel drugs that will target these viruses are very desirable. Influenza A expresses an RNA polymerase essential for its transcription and replication which comprises PA, PB1, and PB2 subunits. We identified potential novel anti-influenza agents from a screen of 34 synthesized phenethylphenylphthalimide analogs derived from thalidomide (PPT analogs). For this screen we used a PA endonuclease inhibition assay, a PB2 pathogenicity-determinant domain-binding assay, and an anti-influenza A virus assay. Three PPT analogs, PPT-65, PPT-66, and PPT-67, were found to both inhibit PA endonuclease activity and retard the growth of influenza A, suggesting a correlation between their activities. PPT-28 was also found to inhibit the growth of influenza A. These four analogs have a 3,4-dihydroxyphenethyl group in common. We also discuss the possibility that 3,4-dihydroxyphenethyl group flexibility may play an important functional role in PA endonuclease inhibition. Another analog harboring a dimethoxyphenethyl group, PPT-62, showed PB2 pathogenicity-determinant domain-binding activity, but did not inhibit the growth of the virus. Our present results indicate the utility of the PA endonuclease assay in the screening of anti-influenza drugs and are therefore useful for future strategies to develop novel anti-influenza A drugs and for mapping the function of the influenza A RNA polymerase subunits.

Cavitand-Based Pd-Pyridyl Coordination Capsules: Guest-Induced Homo- or Heterocapsule Selection and Applications of Homocapsules to the Protection of a Photosensitive Guest and Chiral Capsule Formation.

A 2 : 4 mixture of tetrakis[4-(4-pyridyl)phenyl]cavitand (1) or tetrakis[4-(4-pyridyl)phenylethynyl]cavitand (2) and Pd(dppp)(OTf)2 self-assembles into a homocapsule {12 ⋅ [Pd(dppp)]4 }8+ ⋅ (TfO- )8 (C1) or {22 ⋅ [Pd(dppp)]4 }8+ ⋅ (TfO- )8 (C2), respectively, through Pd-Npy coordination bonds. A 1 : 1 : 4 mixture of 1, 2, and Pd(dppp)(OTf)2 produced a mixture of homocapsules C1, C2, and a heterocapsule {1 ⋅ 2 ⋅ [Pd(dppp)]4 }8+ ⋅ (TfO- )8 (C3) in a 1 : 1 : 0.98 mole ratio. Selective formation (self-sorting) of homocapsules C1 and C2 or heterocapsule C3 was controlled by guest-induced encapsulation under thermodynamic control. Applications of Pd-Npy coordination capsules with the use of 1 were demonstrated. Capsule C1 serves as a guard nanocontainer for trans-4,4'-diacetoxyazobenzene to protect against the trans-to-cis photoisomerization by encapsulation. A chiral capsule {12 ⋅ [Pd((R)-BINAP)]4 }8+ ⋅ (TfO- )8 (C5) was also constructed. Capsule C5 induces supramolecular chirality with respect to prochiral 2,2'-bis(alkoxycarbonyl)-4,4'-bis(1-propynyl)biphenyls by diastereomeric encapsulation through the asymmetric suppression of rotation around the axis of the prochiral biphenyl moiety.

Photoinduced Mechanical Motions of Pseudorotaxane Crystals Composed of Azobenzene and Ferrocenyl Groups on an Axle and a Crown Ether Ring.

This work describes the design and characterization of photoresponsive dynamic pseudorotaxane crystals composed of azobenzene and ferrocenyl groups in an ammonium cation axle component threaded through dibenzo[24]crown-8 ether rings. Pseudorotaxanes provide flexibility for cis and trans isomerization of azobenzene groups in a crystal state, enabling reversible bending motions under alternating 360 and 445 nm laser irradiation. For such bending motions, strained azobenzene structures were essential; these motifs were obtained by increasing the bulkiness of the substituents on the axle and ring molecules. In addition, the crystals showed photosalient effects, such as jumping motions, under 445 nm laser irradiation. These motions were assisted by the photoabsorption of the ferrocenyl group, which converted 445 nm laser light into heat. The maximum lifting weight accompanied by the photoinduced mechanical motion of a particular crystal was estimated to be 9600 times the crystal weight. These pseudorotaxane crystals exhibit promising features for applications in micro-nanometer-sized miniature mechanical devices.