Tris-Azo Triangular Paraphenylenes: Synthesis and Reversible Interconversion into Radial π-Conjugated Macrocycles.

We report the synthesis of cycloparaphenylene derivatives featuring tris-azo groups. The smaller derivative, [3]cycloazobenzene, adopts a triangular all-cis form and exhibits thermally and photochemically stable characteristics due to significant ring strain as well as symmetric Kagome-patterned crystal packing. In contrast, the as-synthesized [3]cycloazobenzene with three biphenylene bridges adopts a triangular all-cis form, which undergoes photoinduced isomerization, leading to a photostationary state. Interestingly, the addition of an excess of acid selectively leads to the formation of an all-trans form. DFT calculations reveal that the interconversion from a triangular to a circular shape correlates with an increase in HOMO and a decrease in LUMO, characteristics intrinsic to radial π-conjugated systems.

High-Intensity Circular Dichroism of Head-To-Tail Regioregular Poly(1,4-Phenylene)s in the Aggregated State.

Circular dichroism (CD) studies on poly(1,4-phenylene)s bearing a chiral side chain in the aggregated conditions were carried out. Little CD was observed in a solution form, while addition of a poor solvent into the polyphenylene solution induced aggregation and a strong CD was observed, accordingly. Applying the controlled degree of polymerization (DP) of poly(1,4-phenylene) in the use of bidentate diphosphine Chiraphos as a ligand for the nickel catalyst, the relationship of DP with CD strength was studied to reveal to show the highest CD at the DP=84 (gabs=ca. 2×10-2). It was also found that the related aggregation was observed in good solvent 1,2-dichloroethane upon standing the solution at 4 °C for 3-23 days to observe gabs=ca. 10-1. Studies on the substituent effect of poly(1,4-phenylene) suggested that CD behaviors were dependent on the type of non-chiral substituent on the aromatic ring as well as the side-chain chirality.

A Ni0(cod)(dq) (COD: 1,5-cycloctadiene; DQ: duroquinone) complex as a catalyst precursor for oligothiophene and polythiophene synthesis.

Nickel-catalyzed syntheses of oligothiophene and polythiophene were carried out with Ni(cod)(dq) (COD: 1,5-cycloctadiene; DQ: duroquinone) as a catalyst precursor. Studies on the ligand exchange of Ni(cod)(dq) revealed that a high temperature was necessary to replace COD and DQ with PPh3 and N-heterocyclic carbene IPr. A coupling reaction of a metalated 3-hexylthiophene with 2-chloro-3-hexylthiophene employing Ni(cod)(dq) with IPr proceeded with a remarkably reduced amount of homocoupling byproduct. Polymerization of 2-chloro-3-hexylthiophene with Ni(cod)(dq)/DPPP also resulted in the reduction of the regioregularity defect.

Photosalience and Thermal Phase Transitions of Azobenzene- and Crown Ether-Based Complexes in Polymorphic Crystals.

Stimuli-responsive molecular crystals have attracted considerable attention as promising smart materials with applications in various fields such as sensing, actuation, and optoelectronics. Understanding the structure-mechanical property relationships, however, remains largely unexplored when it comes to functionalizing these organic crystals. Here, we report three polymorphic crystals (Forms A, B, and C) formed by the non-threaded complexation of a dibenzo[18]crown-6 (DB18C6) ether ring and an azobenzene-based ammonium cation, each exhibiting distinct thermal phase transitions, photoinduced deformations, and mechanical behavior. Structural changes on going from Form A to Form B and from Form C to Form B during heating and cooling, respectively, are observed by single-crystal X-ray crystallography. Form A shows photoinduced reversible bending, whereas Form B exhibits isotropic expansion. Form C displays uniaxial negative expansion with a remarkable increase of 44% in thickness under photoirradiation. Force measurements and nanoindentation reveal that the soft crystals of Form A with a low elastic modulus demonstrate a significant photoresponse, attributed to the non-threaded molecular structure, which permits flexibility of the azobenzene unit. This work represents a significant advance in the understanding of the correlation between structure-thermomechanical and structure-photomechanical properties necessary for the development of multi-stimulus-responsive materials with tailored properties.

Ferrocene-Containing Pseudorotaxanes in Crystals: Aromatic Interactions with Hammett Correlation.

Single crystals of pseudorotaxanes, [(FcCH2NH2CH2Ar)(DB24C8)][PF6] (DB24C8 = dibenzo[24]crown-8, Fc = Fe(C5H4)(C5H5), Ar = -C6H3-3,4-Cl2, -C6H3-3,4-F2, -C6H4-4-F, -C6H4-4-Cl, -C6H4-4-Br, -C6H3-3-F-4-Me, -C6H4-4-I) and [(FcCH2NH2CH2C6H4-4-Me)(DB24C8)][Ni(dmit)2] (dmit = 1,3-dithiole-2,4,5-dithiolate), were obtained from solutions containing DB24C8 and ferrocenylmethyl(arylmethyl)ammonium. X-ray crystallographic analyses of the pseudorotaxanes revealed that the aryl ring of the axle moiety and the catechol ring of the macrocyclic component were at close centroid distances and parallel or tilted orientation. The structures with parallel aromatic rings showed correlation of the distances between the centroids to Hammett substituent constants of the aryl groups.

Multiple and early hyperbaric oxygen treatments enhance muscle healing after muscle contusion injury: a pilot study.

BACKGROUND: The optimal timing of hyperbaric oxygen (HBO2) treatments for the best recovery following muscle injury has yet to be determined. Thus, the optimal number and timing of HBO2 treatments for maximal muscle regeneration were explored. METHODS: The HBO2 treatment protocol consisted of 2.5 ATA 100% oxygen for 120 minutes. Muscle-injured rats were randomized to one of 10 groups: single HBO2 treatment immediately after injury (HBO 1T day 0), one day (HBO 1T day 1), three days (HBO 1T day 3) and five days (HBO 1T day 5) after injury; three HBO2 treatments from immediately after injury to two days after injury (HBO 3T day 0-2), from one to three days after injury (HBO 3T day 1-3), from three to five days after injury (HBO 3T day 3-5), from five to seven days after injury (HBO 3T day 5-7); five daily HBO2 treatments (HBO 5T); and no treatment (NT). RESULTS: HBO 5T and HBO 3T day 0-2, days 1-3 and days 3-5 significantly promoted CD206-positive cell infiltration, satellite cell differentiation and muscle regeneration compared to the NT group. CONCLUSION: Five HBO2 treatments and three HBO2 treatments within three days of injury promote muscle regeneration.

Formal preparation of regioregular and alternating thiophene-thiophene copolymers bearing different substituents.

Differently substituted thiophene-thiophene-alternating copolymers were formally synthesized employing a halo-bithiophene as a monomer. Nickel-catalyzed polymerization of bithiophene with substituents at the 3-position, including alkyl-, fluoroalkyl-, or oligosiloxane-containing groups, afforded the corresponding copolymers in good to excellent yield. The solubility test in organic solvents was performed to reveal that several copolymers showed a superior solubility. X-ray diffraction analysis of the thin film of the alternating copolymers composed of methyl and branched oligosiloxane substituents was also performed, and the results suggested the formation of a dual-layered film structure.

Reversible Laser-Induced Bending of Pseudorotaxane Crystals.

This study investigated the dynamic photoresponse of pseudorotaxane crystals with azobenzene and ferrocenyl groups in the axle component. X-ray crystallography showed pseudorotaxanes with a methylazobenzene group and a dibromophenylene ring in the cyclic component to exhibit twisting of the trans-azobenzene groups at torsion angles of 17° and 38°, respectively. Repeated alternating laser irradiation of the crystals at 360 and 445 nm produced bending of 20-30° in opposite directions, with no evidence of decay. Under 445 nm irradiation, bending took place within 0.3 s. A crystal of nonsubstituted pseudorotaxane showed bending of only 2° under 360 nm irradiation due to multiple π-π interactions between the planar trans-azobenzene groups. The pseudorotaxane crystals have two chromophores, bent rapidly and reversibly on irradiation at rates depending on the molecular structure.

The facilitatory effects of hyperbaric oxygen treatment on membrane bone wound healing in a rat calvarial defect model.

We examined the effect of hyperbaric oxygen (HBO2) treatment on bone wound healing in a rat calvarial defect. Critical-sized defects were created in the calvaria of adult Wistar rats. The animals were divided into four groups--HBO2, normobaric oxygen, hyperbaric air, and no treatment. Treatments were performed five days a week, for two weeks. Micro-computerized tomography and histological analysis were used to evaluate the bone defects. Regenerated bone areas were calculated as the percentage of new bone in the cross-sectional area of defect. The new bone cross-sectional area was significantly greater in the HBO2 group than in the other groups. There were no significant differences in the numbers of nucleated cells in the new bone areas. Although new bone volume per defect volume was significantly greater in the HBO2 group than in the other groups, no significant differences in bone mineral density in the new bone area were observed. These findings indicate the facilitatory role of HBO2 treatment on bone wound healing in the rat calvarial bone defect, and it does not appear to have any negative effects on bone maturity. We propose that HBO2 treatment would be useful in promoting bone regeneration following injury in the orofacial region.

Effects of hyperbaric oxygen on muscle fatigue after maximal intermittent plantar flexion exercise.

The purpose of this study was to investigate the effects of hyperbaric oxygen (HBO) treatment on muscle fatigue after maximal intermittent plantar flexion exercise. Twenty healthy male volunteers (aged from 21 to 24 years) were randomly assigned to either HBO or normoxic group and were blinded to their treatment and group assignment. The HBO group breathed 100% oxygen under 2.5 atmosphere absolute (ATA) for 60 minutes, whereas the normoxic group breathed room air under 1.2 ATA for 70 minutes. The subjects performed a fatigue test, which consisted of 50 maximal unilateral isometric plantar flexions, before and after intervention. Surface electromyography was recorded from triceps surae muscle. Subjects performed maximal voluntary contractions of isometric plantar flexions, and voluntary activation and twitch contractile properties were evaluated with cutaneous tibial nerve stimuli before and after intervention. Compared with initial values during repetitions 4-10, the plantar flexion torque during repetitions 41-50 decreased to 88.5 and 83.2% after HBO and normoxic treatment, respectively. A smaller decrease in muscle force was observed in the HBO group compared with the normoxic group. No differences in function between treatment groups were observed after nerve stimulation. These results suggest that HBO contributes to sustained force production due to suppressing the muscle fatigue progression. In practice, HBO can contribute to the prevention of excess fatigue of agonist muscles for specific exercises involving repeated jumping.

Designing 2D stripe winding network through crown-ether intermediate Ullmann coupling on Cu(111) surface.

Chemical synthesis typically yields the most thermodynamically stable ordered arrangement, a principle also governing surface synthesis on an atomically level two-dimensional (2D) surface, fostering the creation of structured 2D formations. The linear connection arising from energetically stable chemical bonding precludes the generation of a 2D random network comprised of one-dimensional (1D) convoluted stripes through on-surface synthesis. Nonetheless, we underscored that on-surface synthesis possesses the capability not solely to fashion a 2D ordered linear network but also to fabricate a winding 2D network employing a precursor with a soft ring and intermediate state bonding within the Ullmann reaction. Here, on-surface synthesis was exhibited on Cu(111) employing a 2D self-assembled monolayer array of 4,4',5,5'-tetrabromodibenzo[18]crown-6 ether (BrCR) precursors. These precursors were purposefully structured, with a crown ether ring at the core and Br atoms positioned at the head and tail ends, facilitating preferential connections along the elongated axis to foster a 1D stripe configuration. We illustrate how adjustments in the quantities of the intermediate state, serving as a primary linkage, can yield a labyrinthine, convoluted winding 2D network of stripes. The progression of growth, underlying mechanisms, and electronic structures were scrutinized using an ultrahigh vacuum low-temperature scanning tunneling microscopy and spectroscopy (STM/STS) setup combined with density functional theory (DFT) calculations. This experimental evidence opens a novel functionality in leveraging on-surface synthesis for the formation of a 2D random network. This discovery holds promise as a pioneering constituent in the construction of a ring host supramolecule, augmenting its capability to ensnare guest atoms, molecules, or ions.

Facile Photoresponsive Actuators Based on Ferrocene-Doped Poly(butyl methacrylate).

This paper presents facile photoresponsive actuators comprising ferrocene as a guest chromophore and poly(butyl methacrylate) (PBMA) as a host matrix. The ferrocene-doped PBMA film exhibits mechanical expansion and contraction when a 445 nm laser is turned on and off, respectively. The photoresponsive film is attached by a commercially available acetylcellulose adhesive tape, which exhibits a bending motion that is controlled by turning the laser on and off. Thereafter, the double-layer film is employed to fabricate a table-shaped lifting machine (0.7 mg) that lifts a 10.5 mg object up and down by turning the laser on and off, respectively, and the mechanical force offered by the double-layer film is recorded. Additionally, the film is coated with gold and applied to an electric circuit that serves as a reversible photoresponsive switch. This film preparation technique is applied to other chromophores (e.g., Coumarin 343, Rhodamine 6G, Sudan Blue II, and Solvent Green 3) to independently control the motions of the films with 445, 520, and 655 nm lasers. The ferrocene-containing films also exhibit photoinduced healing from mechanical damage. Finally, the photoirradiation-accompanied morphological changes in the film are observed via small-angle X-ray scattering.

Thermally-induced phase transition of pseudorotaxane crystals: changes in conformation and interaction of the molecules and optical properties of the crystals.

This paper presents a pseudorotaxane that acts as a thermally driven molecular switch in the single-crystal state. Crystals of the cationic pseudorotaxane consisting of dibenzo[24]crown-8 (DB24C8) and N-(xylylammonium)-methylferrocene as the cyclic and axle component molecules, respectively, undergo crystalline-phase transition at 128 °C with heating and 116 °C with cooling, according to differential-scanning-calorimetry measurements. X-ray crystallographic analyses revealed that the phase transition was accompanied by rotation of the 4-methylphenyl group of the axle component molecule and a simultaneous shift in the position of the PF(6)(-) counteranion. Crystalline phase transition changes the conformation and position of the DB24C8 molecule relative to the ammonium cation partially; the interaction between the cyclic component and the PF(6)(-) anion in the crystal changes to a greater extent. Moreover, there are changes in the vibration angle (θ) and birefringence (Δn) on the (001) face of the crystal transitionally; θ is rotated by +12°, and Δn is decreased from 0.070 to 0.059 upon heating across the phase transition temperature. The phase transition and accompanying change in the optical properties of the crystal occur reversibly and repeatedly upon heating and cooling processes. The switching rotation of the aromatic plane of the molecule induces a change in the optical anisotropy of the crystal, which is regarded as a demonstration of a new type of optical crystal. Partial replacement of the PF(6)(-) anion with the bulkier AsF(6)(-) anion forms crystals with similar crystallographic parameters. An increase in the AsF(6)(-) content decreases the reversible-phase-transition temperature gradually down to 99 °C (T(end)) and 68 °C (T(exo)) ([AsF(6)(-)]:[PF(6)(-)] = 0.4:0.6).

Pd-catalysed direct arylation polymerisation for synthesis of low-bandgap conjugated polymers and photovoltaic performance.

Low-bandgap conjugated copolymers based on a donor-acceptor structure have been synthesised via palladium-complex catalysed direct arylation polymerisation. Initially, we report the optimisation of the synthesis of poly(cyclopentadithiophene-alt-benzothiadiazole) (PCPDTBT) formed between cyclopentadithiophene and dibromobenzothiadiazole units. The polymerisation condition has been optimised, which affords high-molecular-weight polymers of up to M(n) = 70 k using N-methylpyrrolidone as a solvent. The polymers are used to fabricate organic photovoltaic devices and the best performing PCPDTBT device exhibits a moderate improvement over devices fabricated using the related polymer via Suzuki coupling. Similar polymerisation conditions have also been applied for other monomer units.

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.

Hydrophobic and Hydrophilic Conjugated Polymer Dots as Binary Photocatalysts for Enhanced Visible-Light-Driven Hydrogen Evolution through Förster Resonance Energy Transfer.

Organic semiconducting polymers exhibited promising photocatalytic behavior for hydrogen (H2) evolution, especially when prepared in the form of polymer dots (Pdots). However, the Pdot structures were formed using common nonconjugated amphiphilic polymers, which have a negative effect on charge transfer between photocatalysts and reactants and are unable to participate in the photocatalytic reaction. This study presents a new strategy for constructing binary Pdot photocatalysts by replacing the nonconjugated amphiphilic polymer typically employed in the preparation of polymer nanoparticles (Pdots) with a low-molecular-weight conjugated polyelectrolyte. The as-prepared polyelectrolyte/hydrophobic polymer-based binary Pdots truly enhance the electron transfer between the Pt cocatalyst and the polymer photocatalyst with good water dispersibility. Moreover, unlike the nonconjugated amphiphilic polymer, the photophysics and mechanism of this photocatalytic system through time-correlated single-photon counting (TCSPC) and transient absorption (TA) measurements confirmed the Förster resonance energy transfer (FRET) between the polyelectrolyte as a donor and the hydrophobic polymer as an acceptor. As a result, the designated binary Pdot photocatalysts significantly enhanced the hydrogen evolution rate (HER) of 43 900 µmol g-1 h-1 (63.5 µmol h-1, at 420 nm) for PTTPA/PFTBTA Pdots under visible-light irradiation.

VEGF and bFGF induction by nitric oxide is associated with hyperbaric oxygen-induced angiogenesis and muscle regeneration.

Hyperbaric oxygen (HBO) treatment promotes early recovery from muscle injury. Reactive oxygen species (ROS) upregulation is a key mechanism of HBO, which produces high O2 content in tissues through increased dissolution of oxygen at high pressure. Nitric oxide (NO), a type of ROS, generally stabilizes hypoxia-inducible factor (HIF) 1α and stimulates secretion of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) from endothelial cells and macrophages, which then induces angiogenesis. The purpose of the present study was to investigate whether HBO could promote angiogenesis via induction of NO and induce muscle regeneration in contused rat skeletal muscles. The HBO protocol consisted of 2.5 atmospheres absolute (ATA) 100% oxygen for 120 minutes, once a day for 5 consecutive days. We also evaluated the effects of a ROS inhibitor (NAC) or NOS-specific inhibitor (L-NAME) on HBO. HBO significantly increased NO3-, VEGF, and bFGF levels and stabilized HIF1α within 1 day. HBO promoted blood vessel formation at 3-7 days and muscle healing at 5-7 days after contusion. Administration of both NAC and L-NAME before HBO suppressed angiogenesis and muscle regeneration even after HBO. HBO thus promoted angiogenesis and muscle regeneration mainly through generation of NO in the early phase after muscle contusion injury.

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.

Skipping Breakfast for 6 Days Delayed the Circadian Rhythm of the Body Temperature without Altering Clock Gene Expression in Human Leukocytes.

Breakfast is often described as "the most important meal of the day" and human studies have revealed that post-prandial responses are dependent on meal timing, but little is known of the effects of meal timing per se on human circadian rhythms. We evaluated the effects of skipping breakfast for 6 days on core body temperature, dim light melatonin onset, heart rate variability, and clock gene expression in 10 healthy young men, with a repeated-measures design. Subjects were provided an isocaloric diet three times daily (3M) or two times daily (2M, i.e., breakfast skipping condition) over 6 days. Compared with the 3M condition, the diurnal rhythm of the core body temperature in the 2M condition was delayed by 42.0 ± 16.2 min (p = 0.038). On the other hand, dim light melatonin onset, heart rate variability, and clock gene expression were not affected in the 2M condition. Skipping breakfast for 6 days caused a phase delay in the core body temperature in healthy young men, even though the sleep-wake cycle remained unchanged. Chronic effects of skipping breakfast on circadian rhythms remain to be studied.

Antitumor effects of 2-oxoglutarate through inhibition of angiogenesis in a murine tumor model.

Hypoxia-inducible factor 1 (HIF-1) plays essential roles in tumor angiogenesis and growth by regulating the transcription of several key genes in response to hypoxic stress and growth factors. HIF-1 is a heterodimeric transcriptional activator consisting of inducible alpha and constitutive beta subunits. In oxygenated cells, proteins containing the prolyl hydroxylase domain (PHD) directly sense intracellular oxygen concentrations. PHDs tag HIF-1alpha subunits for polyubiquitination and proteasomal degradation by prolyl hydroxylation using 2-oxoglutarate (2-OX) and dioxygen. Our recent studies showed that 2-OX reduces HIF-1alpha, erythropoietin, and vascular endothelial growth factor (VEGF) expression in the hepatoma cell line Hep3B when under hypoxic conditions in vitro. Here, we report that similar results were obtained in Lewis lung cancer (LLC) cells in in vitro studies. Furthermore, 2-OX showed potent antitumor effects in a mouse dorsal air sac assay and a murine tumor xenograft model. In the dorsal air sac assay, 2-OX reduced the numbers of newly formed vessels induced by LLC cells. In a murine tumor xenograft model, intraperitoneal injection of 2-OX significantly inhibited tumor growth and angiogenesis in tumor tissues. Moreover, 5-fluorouracil combined with 2-OX significantly inhibited tumor growth in this model, which was accompanied by reduction of Vegf gene expression and inhibited angiogenesis in tumor tissues. These results suggest that 2-OX is a promising anti-angiogenic therapeutic agent.