Structure and Chiroptical Properties of Anthra[1,2-a]anthracene-1-yl Dimers as New Biaryls.

Dimers of anthra[1,2-a]anthracene-1-yl units and its mesityl derivative were synthesized by Ni(0)-mediated coupling of the corresponding chloro derivatives as new biaryls. The X-ray analysis and DFT calculations revealed that two polycyclic aromatic units with nonplanar deformations took a twisted conformation about the single bond as a chiral axis. Enantiomers of the nonsubstituted compound were resolved by chiral HPLC, and the enantiopure samples showed intense Cotton effects at 321 nm in the circular dichroism (CD) spectra and emission bands at 449 nm in the circularly polarized luminescence (CPL) spectra with dissymmetry factor of |glum| 3.6×10-3. The absolute stereochemistry of this biaryl was determined by the theoretical calculation of CD spectrum by the time-dependent DFT method. The barrier to enantiomerization was determined to be 108 kJ mol-1 at 298 K. The dynamic process proceeded via a stepwise mechanism involving the helical inversion of each aromatic unit and the rotation about the biaryl axis as analyzed by the DFT calculations.

Unusually Short H⋠⋠⋠H Contacts in Intramolecularly Cyclized Helically Fused Anthracenes.

The intramolecular coupling of dichloro-substituted helically fused anthracenes using the Yamamoto coupling yielded cyclized products with sterically congested molecular structures. The X-ray analysis and DFT calculations showed that the aromatic framework adopted a nonplanar structure with a twisted conformation about the newly formed single bond, which acts as a chiral axis. Interestingly, the X-ray structure obtained through the Hirshfeld atom refinement revealed short interatomic distances between the inner hydrogen atoms (1.648-1.692 Å), much shorter than the sum of their van der Waals radii. Owing to these unusually short contacts, the 1H NMR spectrum exhibited a significant deshielding (12.5 ppm) and a large nuclear Overhauser effect (44 %). Additionally, the IR spectrum displayed a high-frequency shift of the C-H stretching vibration. These observations, along with the noncovalent interaction plot indicative of a characteristic steric environment, strongly support the presence of steric hindrance. Moreover, dynamic NMR measurement of the mesityl-substituted derivative yielded a barrier to helical inversion of 84 kJ mol-1. The optical properties and crystal packing of the cyclized products are also reported.

Solid-State Self-Assembly: Exclusive Formation and Dynamic Interconversion of Discrete Cyclic Assemblies Based on Molecular Tweezers.

In contrast to self-assembly in solution systems, the construction of well-defined assemblies in the solid state has long been identified as a challenging task. Herein, we report the formation of tweezers-shaped molecules into various assemblies through a solid-state self-assembly strategy. The relatively flexible molecular tweezers undergo exclusive and quantitative assembly into either cyclic hexamers or a porous network through classical recrystallization or the exposure of powders to solvent vapor, despite the fact that they form only dimers in solution. The cyclic hexamers have high thermal stability and exhibit moderate solid-state fluorescence. The formation of heterologous assemblies consisting of different tweezers allows for tuning these solid-state properties of the cyclic hexamer. Furthermore, (trimethylsilyl)ethynyl-substituted tweezers demonstrate solvent-vapor-induced dynamic interconversion between the cyclic hexamer and a pseudocyclic dimer in the solid state. This assembly behavior, which has been studied extensively in solution-based supramolecular chemistry, had not been accomplished in the solid state so far.

Discovery of internal rotation and conformers of 1,2-dichloroethane: the dawn of the concept of conformation.

In 1932, Mizushima and Higasi reported the dependence of the dipole moments of 1,2-dichloroethane on both temperature and solvent in the Proceedings of the Imperial Academy, Japan. This report was followed by their first proposal of the existence of conformers that exchanged by internal rotation about a C-C single bond based on experimental data. Their monumental work marked the beginning of the essential concept of conformation in modern stereochemistry. Their proposal was later confirmed by the direct observation of the anti and gauche conformers of 1,2-dichloroethane by Raman spectroscopy, and further supported by other experimental and theoretical methods. The relative stabilities of the anti and gauche conformers of 1,2-dichloroethane and other 1,2-disubstituted ethanes were discussed in terms of steric, electrostatic, and stereoelectronic effects based on analysis of calculated data. Those studies influenced the development of subsequent research in organic chemistry, such as the conformational analysis of cyclohexane derivatives and the isolation of chiral gauche conformers.

Structures and Supramolecular Properties of Inclusion Complexes of Anthracene-Triptycene Nanocages with Fullerene Guests and Their Dynamic Motion as Molecular Gyroscopes.

Three derivatives of macrocyclic cage compounds consisting of diarylanthracene and triptycene units were synthesized. These nanocages formed host-guest complexes with C60 and other fullerene guests as confirmed by 1 H NMR and fluorescence spectroscopy. The association constant of the mesityl and 2,4,6-tributoxyphenyl derivatives with C60 was determined to be 2.2 × 104  L mol-1 , which was larger than that of the pentafluorophenyl derivative. Direct experimental evidence of the complexation was obtained by X-ray diffraction analysis: the guest C60 molecule was included in the cavity via multipoint CH⋅⋅⋅π interactions. Dynamic disorders of the included C60 molecule in variable-temperature X-ray analysis indicated uniaxial motion, such as gyroscopic motion. The unique dynamic behavior of the spherical C60 rotor anchored by the cage stator via CH⋅⋅⋅π interactions in the crystal, as well as substituent effects on the association properties, are discussed with the aid of DFT calculations.

Synthesis and Properties of Rubicene-Based Aromatic π-Conjugated Compounds as Five-Membered Ring Embedded Planar Nanographenes.

Polycyclic aromatic hydrocarbons consisting of two or three rubicene substructures were designed as π-conjugated compounds embedding five-membered rings. The target compounds with t-butyl groups were synthesized by the Scholl reaction of precursors consisting of 9,10-diphenylanthracene units, even though a partially precyclized precursor was required for the synthesis of the trimer. These compounds were isolated as stable and dark blue solids. Single-crystal X-ray analysis and DFT calculations revealed the planar aromatic framework of these compounds. In the electronic spectra, the absorption and emission bands were considerably red-shifted compared with those of the reference rubicene compound. In particular, the emission band of the trimer extended to the near-IR region while retaining the emissive property. The narrowed HOMO-LUMO gap with the extension of the π-conjugation was confirmed by cyclic voltammetry and DFT calculations.

Transformation of Highly Hydrophobic Triarylphosphines into Amphiphiles via Staudinger Reaction with Hydrophilic Trichlorophenyl Azide.

Owing to its hydrophobic properties and reactivity, triarylphosphines (PAr3 ) are promising precursors for the development of new amphiphiles. However, an efficient and reliable synthetic method for amphiphiles based on highly hydrophobic PAr3 is still required. Herein, a straightforward transformation of highly hydrophobic PAr3 into amphiphiles via the Staudinger reaction is reported. By simply mixing PAr3 and a hydrophilic trichlorophenyl azide containing two hydrophilic chains, amphiphiles bearing a N=P bond (i. e., an azaylide moiety) were quantitatively formed. The obtained azaylide-based amphiphiles were remarkably water-soluble, enabling their spontaneous self-assembly into 2 nm-sized micelles composed of 4-5 molecules in water with a low critical micelle concentration (up to 0.05 mM or less) due to the effective intermolecular interactions among the hydrophobic surfaces. Although the azaylide moiety is easily hydrolyzed in the presence of water, the azaylide in the amphiphiles displayed notable stability in water even at 60 h, which stems from the LUMO modulation induced by the presence of three electron-withdrawing chloro groups and two twisted alkoxycarbonyl groups, according to DFT calculations. An amphiphile having a large hydrophobic surface solubilized various hydrophobic organic dyes through efficient intermolecular interactions, resulting in the dyes exhibiting either monomer or excimer emissions in water.

Synthesis, Structures, and Properties of Helically Fused Anthraquinones with Unusually Close Carbonyl-Carbonyl Contacts.

Electron-deficient aromatic ketones consisting of three fused anthraquinone units were synthesized by oxidation of the corresponding fused anthracenes. X-ray analysis revealed that these compounds had nonplanar helical structures with unusual contacts, C=O⋅⋅⋅C=O 2.467 Å, between the inner carbonyl groups. The role of n⋅⋅⋅π* interactions in the short contacts was evaluated using a noncovalent interaction plot and natural bond orbital analysis. The dynamic process involving helical inversion was observed by the variable temperature 1 H NMR measurement of a derivative with 2,4,6-trimethylphenyl groups, and the barrier was estimated to be 77 kJ mol-1 . DFT calculations indicated that the helical inversion proceeded via a multistep mechanism. The characteristic spectroscopic and electrochemical data due to the electron-deficient anthraquinone units and the sterically congested carbonyl groups are discussed with the aid of DFT calculations.

Construction of Helical Structures with Multiple Fused Anthracenes: Structures and Properties of Long Expanded Helicenes.

Invited for the cover of this issue is Shinji Toyota and co-workers at Tokyo Institute of Technology and Okayama University of Science. The image depicts a spirally rising dragon to represent the helical molecular structures in the manuscript. Read the full text of the article at 10.1002/chem.202004720.

Construction of Helical Structures with Multiple Fused Anthracenes: Structures and Properties of Long Expanded Helicenes.

Polycyclic aromatic compounds consisting of four or five fused anthracene units were synthesized by PtCl2 -catalyzed cycloisomerization as novel long expanded helicenes. These compounds have helical structures with significant stacking of the terminal anthracene moieties at 0.33 nm interlayer distance. In the UV-vis and fluorescence spectra, the absorption and emission bands were red-shifted as the number of fused anthracene units was increased. The characteristic broad and long-lived emission bands of the long analogues are explained by the excimer-like stabilization of the excited state. These photophysical data as well as their cyclic voltammetric data are discussed on the basis of the π-conjugation and interlayer π⋅⋅⋅π interactions in the molecular structures and the molecular orbitals. The barrier and mechanism of helical inversion are also reported.

Synthesis, Structures, and Electronic Properties of 2,7-Anthrylene-Based Azacyclophanes Bearing o-, m-, and p-Phenylenediamine Linkers.

A series of novel azacyclophanes consisting of 2,7-anthrylene and phenylene units were designed and synthesized by the Buchwald-Hartwig coupling reaction to investigate their unique electronic properties in multiple oxidized states. Cyclic voltammetry showed that the p-phenylene derivative exhibited three reversible oxidation waves, whereas the o- and m-phenylene derivatives showed two quasi-reversible oxidation waves due to the complicated intramolecular interaction between the oxidized units and neutral units. Moreover, the absorption spectra of the p-phenylene derivative in different oxidation states showed absorption bands at 865 and 1025 nm, which were attributed to intramolecular charge-transfer interactions. The photophysical and electrochemical properties of the p-phenylene analog were also compared with those of the o- and m-phenylene derivatives based on theoretical calculations for further evaluation of the intramolecular electronic interactions.

Synthesis of Azaylide-Based Amphiphiles by the Staudinger Reaction.

Catalyst- and reagent-free reactions are powerful tools creating various functional molecules and materials. However, such chemical bonds are usually hydrolysable or require specific functional groups, which limits their use in aqueous media. Herein, we report the development of new amphiphiles through the Staudinger reaction. Simple mixing of chlorinated aryl azide with a hydrophilic moiety and various triarylphosphines (PAr3) gave rise to azaylide-based amphiphiles NPAr3, rapidly and quantitatively. The obtained NPAr3 formed ca. 2 nm-sized spherical aggregates (NPAr3)n in water. The hydrolysis of NPAr3 was significantly suppressed as compared with those of non-chlorinated amphiphiles nNPAr3. Computational studies revealed that the stability is mainly governed by the decrease in LUMO around the phosphorus atom owing to the o-substituted halogen groups. Furthermore, hydrophobic dyes such as Nile red and BODIPY were encapsulated by the spherical aggregates (NPAr3)n in water.

Exploration of Nano-Saturns: A Spectacular Sphere-Ring Supramolecular System.

Saturn-like systems consisting of nanoscale rings and spheres are fascinating motifs in supramolecular chemistry. Several ring molecules are known to include spherical molecules at the center of the cavity via noncovalent attractive interactions. In this Minireview, we generalize the molecular design, the structural features, and the supramolecular chemistry of such "nano-Saturns", which consist of monocyclic rings and fullerene spheres (mainly C60 ), on the basis of previous experimental and theoretical studies. Ring molecules are classified into three types (loop, belt, and disk) according to their shapes and possible interactions. Whereas typical belt-shaped rings tend to form tight complexes due to the wide contact area via π-π interactions, flat disk-shaped rings generally form weak complexes due to the narrow contact area mainly via CH-π interactions. In spite of the small association energies, disk-shaped rings are attractive because such rings can mimic the planet Saturn precisely as exemplified by an anthracene cyclic hexamer-C60 complex.

Phase II study of adjuvant chemotherapy with paclitaxel and nedaplatin for uterine cervical cancer with lymph node metastasis.

The purpose of this phase II trial was to assess the efficacy and toxicity of paclitaxel and nedaplatin (TN) as the initial postoperative adjuvant chemotherapy for uterine cervical cancer with lymph node metastases (LNM). Patients with FIGO stage IB1-IIA2 squamous cell carcinoma of the uterine cervix were enrolled. Histological confirmation of LNM was mandatory. Intravenous paclitaxel at 175 mg/m2 and nedaplatin at 80 mg/m2 were administered every 28-day cycle, of which there were 5 cycles after radical hysterectomy. Sixty-two patients were enrolled in the study from November 2011 to July 2015. Their median age was 48.5 years (range 28-64). The median tumor diameter was 37 mm (5-64). Overall, 30 patients (48.4%) had 1 metastatic lymph node, 11 (17.7%) had 2, 3 (4.8%) had 3, 5 (8.1%) had 4, and 13 (21.0%) had 5 or more. With a median follow-up of 45.7 months (range 23.4-69.5), the 2-year relapse-free survival and 2-year overall survival rates were 79.0% (90% CI, 69.0%-86.2%) and 93.5% (95% CI, 83.7%-97.5%), respectively. Almost all adverse events were relatively mild. Grade 3-4 adverse events (NCI-CTC ver. 4.0) that occurred in 5% or more of patients were neutropenia (60.7%) and infection (6.6%). The proportion of patients who completed 5 cycles of treatment was 90.3%. Postoperative adjuvant chemotherapy with TN for cervical cancer with LNM was demonstrated to be an effective and feasible treatment. A phase III trial is warranted to compare this with concurrent chemoradiotherapy.

Donor-Donor'-Acceptor Triads Based on [3.3]Paracyclophane with a 1,4-Dithiafulvene Donor and a Cyanomethylene Acceptor: Synthesis, Structure, and Electrochemical and Photophysical Properties.

Donor-donor'-acceptor triads (1, 2), based on [3.3]paracyclophane ([3.3]PCP) as a bridge, with electron-donating properties (D') using 1,4-dithiafulvene (DTF; TTF half unit) as a donor and dicyanomethylene (DCM; TCNE half unit) or an ethoxycarbonyl-cyanomethylene (ECM) as an acceptor were designed and synthesized. The pulse radiolysis study of 1 a in 1,2-dichloroethane allowed the clear assignment of the absorption bands of the DTF radical cation (1 a.+ ), whereas the absorption bands due to the DCM radical anion could not be observed by γ-ray radiolysis in 2-methyltetrahydrofuran rigid glass at 77 K. Electrochemical oxidation of 1 a first generates the DTF radical cation (1 a.+ ), the absorption bands of which are in agreement with those observed by a pulse radiolysis study, followed by dication (1 a2+ ). The ESR spectrum of 1 a.+ showed a symmetrical signal with fine structure and an ESR simulation predicted that the spin of 1 a.+ is delocalized over S and C atoms of the DTF moiety and the central C atom of the trimethylene bridge bearing the DTF moiety. Pulse radiolysis, ESR, and electrochemical studies indicate that the DTF radical cation of 1 a.+ is more stable than that of 6.+ , and the latter shows a strong tendency to dimerize. This result indicates that the [3.3]PCP moiety as a bridge can stabilize the DTF radical cation more than the 1,3-diphenylpropane moiety because of kinetic stability due to its rigid structure and the weak electronic interaction of DTF and DCM moieties through [3.3]PCP.

Synthesis and Electronic Properties of Length-Defined 9,10-Anthrylene-Butadiynylene Oligomers.

Linear π-conjugated oligomers consisting of anthracene and diacetylene units were readily synthesized by a one-pot process that involved desilylation and oxidative coupling from appropriate building units. We were able to isolate length-defined oligomers ranging from 2-mer to 6-mer as stable and soluble solids. The bathochromic shifts in the UV-vis spectra suggested that the π-conjugation was extended with elongation of the linear chain. Cyclic voltammetric measurements showed characteristic reversible oxidation waves that were dependent on the number of anthracene units.

Nano-Saturn: Experimental Evidence of Complex Formation of an Anthracene Cyclic Ring with C60.

An anthracene cyclic hexamer was synthesized by the coupling reaction as a macrocyclic hydrocarbon host. This disk-shaped host included a C60 guest in 1:1 ratio to form a Saturn-type supramolecular complex in solution and in crystals. X-ray analysis unambiguously revealed that the guest molecule was accommodated in the middle of the host cavity with several CH⋅⋅⋅π contacts. The association constant Ka determined by NMR titration measurements was 2.3×103  L mol-1 at 298 K in toluene. The structural features and the role of CH⋅⋅⋅π interactions are discussed with the aid of DFT calculations.

Oxidation State-Dependent Intramolecular Electronic Interaction of Carbazole-Based Azacyclophanes with 9,10-Anthrylene Units.

We designed an azacyclophane comprising 3,6-substituted carbazole and 9,10-anthrylene units to investigate the unique electronic properties of the oxidation states arising from the presence of multiple oxidizable azacyclophane. This compound and its analogue containing 1,4-phenylene in substitution of 9,10-anthrylene units were synthesized by Buchwald-Hartwig coupling reactions. Cyclic voltammograms of both the 9,10-anthrylene and 1,4-phenylene derivatives exhibited four quasi-reversible oxidation processes. The absorption spectra of the oxidation states of the 9,10-anthrylene derivative exhibited broad absorption bands in the near-infrared region arising from charge-resonance and intramolecular charge-transfer interactions. The photophysical and electrochemical properties of the 9,10-anthrylene derivative were compared with those of the corresponding 1,4-phenylene derivative on the basis of theoretical calculations to evaluate the intramolecular electronic interactions.

Intramolecular Charge-Transfer Interaction of Donor-Acceptor-Donor Arrays Based on Anthracene Bisimide.

We designed anthracene bisimide (ABI) derivatives having two triphenylamine (TPA) groups as donor units at the 9,10-positions to form a novel π-conjugated donor-acceptor system. These compounds and their analogues with ethynylene linkers were synthesized by Suzuki-Miyaura and Sonogashira coupling reactions, respectively. In UV-vis spectra, the linker-free derivatives showed broad absorption bands arising from intramolecular charge-transfer interactions. Introducing ethynylene linkers resulted in a considerable red shift of the absorption bands. In fluorescence spectra, the ethynylene derivatives showed intense emission bands at 600-650 nm. Their photophysical and electrochemical properties were compared with those of the corresponding mono TPA derivatives on the basis of theoretical calculations and cyclic voltammetry to evaluate the intramolecular electronic interactions between the donor and acceptor units.

Chemistry of anthracene-acetylene oligomers XXV: on-surface chirality of a self-assembled molecular network of a fan-blade-shaped anthracene-acetylene macrocycle with a long alkyl chain.

An anthracene cyclic dimer with two different linkers and a dodecyl group was synthesized by means of coupling reactions. The calculated structure had a planar macrocyclic π core and a linear alkyl chain. Scanning tunneling microscopy observations at the 1-phenyloctane/graphite interface revealed that the molecules formed a self-assembled monolayer that consisted of linear striped bright and dark bands. In each domain, the molecular network consisted of either Re or Si molecules that differed in the two-dimensional chirality about the macrocyclic faces, which led to a unique conglomerate-type self-assembly. The molecular packing mode and the conformation of the alkyl chains are discussed in terms of the intermolecular interactions and the interactions between the molecules and the graphite surface with the aid of MM3 simulations of a model system.