Half-substituted fluorocycloparaphenylenes with high symmetry: synthesis, properties and derivatization to densely substituted carbon nanorings.

Fluorinated cycloparaphenylenes (FCPPs) have attracted attention as electron-accepting CPPs as well as strained fluoroarenes. Herein, we report the synthesis and properties of novel FCPPs; F16[8]CPP and F12[6]CPP. Furthermore, the derivatization of F16[8]CPP afforded a new carbon nanoring where sixteen pyrrole rings are densely substituted on the CPP framework.

Noncovalent Modification of Cycloparaphenylene by Catenane Formation Using an Active Metal Template Strategy.

The active metal template (AMT) strategy is a powerful tool for the formation of mechanically interlocked molecules (MIMs) such as rotaxanes and catenanes, allowing the synthesis of a variety of MIMs, including π-conjugated and multicomponent macrocycles. Cycloparaphenylene (CPP) is an emerging molecule characterized by its cyclic π-conjugated structure and unique properties. Therefore, diverse modifications of CPPs are necessary for its wide application. However, most CPP modifications require early stage functionalization and the direct modification of CPPs is very limited. Herein, we report the synthesis of a catenane consisting of [9]CPP and a 2,2'-bipyridine macrocycle as a new CPP analogue that contains a reliable synthetic scaffold enabling diverse and concise post-modification. Following the AMT strategy, the [9]CPP-bipyridine catenane was successfully synthesized through Ni-mediated aryl-aryl coupling. Catalytic C-H borylation/cross-coupling and metal complexation of the bipyridine macrocycle moiety, an effective post-functionalization method, were also demonstrated with the [9]CPP-bipyridine catenane. Single-crystal X-ray structural analysis revealed that the [9]CPP-bipyridine catenane forms a tridentated complex with an Ag ion inside the CPP ring. This interaction significantly enhances the phosphorescence lifetime through improved intermolecular interactions.

Changes in the preoperative ocular surface flora with an increase in patient age: A surveillance analysis of bacterial diversity and resistance to fluoroquinolone.

PURPOSE: This study analyzed the relationship between patient age and the prevalence and fluoroquinolone susceptibility of gram-positive cocci from the ocular surface flora before ophthalmic surgery. METHODS: This surveillance study included scraped samples from the conjunctival sac of 8923 eyes of 5490 patients (70.0 ± 13.7 years) without ocular infection before ophthalmologic surgery between August 2018 and December 2020. A review of microbiological records regarding patient age was used to determine the number of isolates and gram-positive species obtained, as well as their fluoroquinolone susceptibility. Fluoroquinolone susceptibility was determined using the Clinical and Laboratory Standards Institute protocols of broth microdilution. Statistical analysis was performed using a generalized additive model and a log-linear model. RESULTS: In total, 9,894 bacterial isolates obtained from scraped samples from the patients were analyzed. The detected species were Staphylococcus epidermidis (31.0%), Staphylococcus aureus (6.1%), Staphylococcus lugdunensis (3.9%), Enterococcus faecalis (5.8%), Corynebacterium species (31.7%), and Cutibacterium acnes (7.5%) and others. The number of species isolated from the ocular surface was increased at the rate of 1.018 per 10 years of age (p < 0.0001). S. epidermidis, S. lugdunensis, E. faecalis, and Corynebacterium species were isolated more often with an increase in patient age. The levofloxacin resistance ratio of methicillin-sensitive S. epidermidis and Corynebacterium species increased at the rate of 1.204 and 1.087 respectively with a 10-year increase in age (both p < 0.0001). CONCLUSION: Gram-positive bacteria in the ocular surface flora (OSF) exhibited gradual changes in diversity and fluoroquinolone resistance with an increase in patient age. It is important to monitor the OSF of the patients before ophthalmologic surgery to prevent refractory ocular postoperative infection.

Adamantane Annulation to Arenes: A Strategy for Property Modulation of Aromatic π-Systems.

Peripheral structural modifications of arenes are widely used to control or improve the optoelectronic properties, molecular assembly, and stability of aromatic π-materials as well as to explore new functions. However, known modifications are often tedious and complex; therefore, a simple yet powerful modification strategy is needed. We discovered that annulation with a simple adamantane scaffold exerts a significant impact on the properties, alignment, and stability of aromatic π-systems. This unprecedented adamantane annulation was achieved by a two-step transformation of metallated arenes and 4-protoadamantanone, generating a range of adamantane-annulated arenes. Analysis of structural and electronic properties uncovered unique effects of the process, such as high solubility and enhanced conjugation. The oxidation of adamantane-annulated perylenes produced strikingly stable cationic species with emission extended to the near-infrared region. This simple property modulation of aromatic π-systems would not only create potentially ground-breaking π-materials but also novel nanocarbon materials, such as diamond-graphene hybrids.

Methylene-Bridged [6]-, [8]-, and [10]Cycloparaphenylenes: Size-Dependent Properties and Paratropic Belt Currents.

Cycloparaphenylenes (CPPs) and carbon nanobelts (CNBs) represent some of the most iconic cyclic molecular nanocarbons in recent chemistry owing to their unique properties derived from rigid, strained, and cyclic π-conjugated systems. In the last decade, the synthesis of various sizes of CPPs and CNBs has been achieved that allowed not only for investigating their size-dependent properties and strategically using such properties in various applications but also understanding the fundamental features of cyclic π-conjugated systems and molecular nanocarbons in general. Herein, we report on the synthesis, size-dependent properties, and paratropic belt currents of methylene-bridged [n]cycloparaphenylenes ([n]MCPP, n = 6, 8, 10). [8]MCPP and [10]MCPP were synthesized by the same strategy we developed for [6]MCPP synthesis. With readily available ethoxy-substituted pillar[8]arene and pillar[10]arene as precursors, [8]MCPP and [10]MCPP were successfully synthesized in three steps consisting of de-ethylation, triflation, and nickel-mediated aryl-aryl coupling. The structural and electronic properties of MCPPs were investigated by nuclear magnetic resonance analyses, absorption/fluorescence measurements, X-ray crystallographic analyses, and computational studies, revealing their interesting size-dependent properties. The differences in the size dependency between MCPPs and CPPs reflect the belt-form features of MCPPs, namely, methylene-bridging effects on MCPPs. Moreover, an interesting paratropic belt current along the MCPP backbone has been uncovered both experimentally and theoretically. The 1H NMR chemical shifts of MCPPs confirmed the presence of a paratropic belt current, whose strength rapidly decreases with increasing nanobelt size.

N-doped nonalternant aromatic belt via a six-fold annulative double N-arylation.

The design and synthesis of nitrogen (N)-doped molecular nanocarbons are of importance since N-doped nanocarbons have received significant attention in materials science. Herein, we report the synthesis and X-ray crystal structure of a nitrogen-inserted nonalternant aromatic belt. The palladium-catalyzed six-fold annulative double N-arylation provided an aromatic belt bearing six nitrogen atoms in one step from cyclo[6]paraphenylene-Z-ethenylene, the precursor of the (6,6)carbon nanobelt. The C 3i-symmetric structure of the aromatic belt in the solid state was revealed using X-ray crystallography. The multistep (electro)chemical oxidation behavior of the belt, which was facilitated by the six p-methoxyaniline moieties, was studied, and a stable dication species was successfully identified by X-ray crystallography. The present study not only shows the unique structure and properties of the N-doped nonalternant aromatic belt but also expands the scope of accessibility of synthetically difficult belt molecules by the conventional intramolecular contraction pathway.

Synthesis, properties, and material hybridization of bare aromatic polymers enabled by dendrimer support.

Aromatic polymers are the first-choice platform for current organic materials due to their distinct optical, electronic, and mechanical properties as well as their biocompatibility. However, bare aromatic polymer backbones tend to strongly aggregate, rendering them essentially insoluble in organic solvent. While the typical solution is to install many solubilizing substituents on the backbones, this often provokes undesired property changes. Herein, we report the synthesis of bare aromatic polymers enabled by a dendrimer support. An initiator arene containing a diterpenoid-based dendrimer undergoes Pd-catalyzed polymerization with monomers bearing no solubilizing substituents to furnish bare aromatic polymers such as polythiophenes and poly(para-phenylene)s. The high solubility of dendrimer-ligated polymers allows not only the unveiling of the properties of unsubstituted π-conjugated backbone, but also mild release of dendrimer-free aromatic polymers and even transfer of aromatic polymers to other materials, such as silica gel and protein, which may accelerate the creation of hybrid materials nowadays challenging to access.

Perfluorocycloparaphenylenes.

Perfluorinated aromatic compounds, the so-called perfluoroarenes, are widely used in materials science owing to their high electron affinity and characteristic intermolecular interactions. However, methods to synthesize highly strained perfluoroarenes are limited, which greatly limits their structural diversity. Herein, we report the synthesis and isolation of perfluorocycloparaphenylenes (PFCPPs) as a class of ring-shaped perfluoroarenes. Using macrocyclic nickel complexes, we succeeded in synthesizing PF[n]CPPs (n = 10, 12, 14, 16) in one-pot without noble metals. The molecular structures of PF[n]CPPs (n = 10, 12, 14) were determined by X-ray crystallography to confirm their tubular alignment. Photophysical and electrochemical measurements revealed that PF[n]CPPs (n = 10, 12, 14) exhibited wide HOMO-LUMO gaps, high reduction potentials, and strong phosphorescence at low temperature. PFCPPs are not only useful as electron-accepting organic materials but can also be used for accelerating the creation of topologically unique molecular nanocarbon materials.

Age factor in the fluoroquinolone susceptibility of gram-positive cocci isolates from bacterial keratitis cases between 2008 and 2016.

PURPOSE: To determine the relationship between fluoroquinolone susceptibility of gram-positive cocci (GPC) isolated from patients with bacterial keratitis and the age of the patients or the date of onset. METHODS: Bacterial isolates were obtained from corneal lesions of patients with infectious keratitis treated between January 2008 and December 2016. The fluoroquinolone susceptibility of GPC was assessed, and a retrospective review of microbiological records was performed. Fluoroquinolone susceptibility was measured through broth microdilution in accordance with protocols of the Clinical and Laboratory Standards Institute. Statistical analysis was performed using a generalized estimating equation and cubic spline to determine the association between fluoroquinolone susceptibility of GPC isolated from corneal lesions and patient age. RESULTS: Of the 1200 bacterial isolates, 471 GPC were identified. They included Staphylococcus epidermidis (45.6%), other coagulase-negative Staphylococcus sp. (17.8%), and Staphylococcus aureus (18.3%). Levofloxacin susceptibility of GPC exhibited a negative relationship with age and had an odds ratio of 0.893 (95% confidence interval, 0.825-0.967) for every 10 years of age. A non-adjusted cubic spline curve was well correlated with year-adjusted data in a generalized additive model, and the levofloxacin susceptibility of GPC was initially stable but gradually declined after 40 years of age, before re-stabilizing again after 70 years of age. CONCLUSION: The fluoroquinolone susceptibility of GPC isolated from corneal lesions of infectious keratitis is high in children under 15 years of age and declines with an increase in age of patients using a generalized estimating equation and cubic spline.

Development of potent inhibitors for strigolactone receptor DWARF 14.

Strigolactones (SLs) are plant hormones that suppress shoot branching through perception by their receptor protein DWARF 14 (D14). The artificial regulation of SL signaling has been considered a potent agricultural technique because plant architecture is strongly related to crop yield. In this communication, we describe the development of a small-molecule D14 inhibitor that functions at sub-micromolar levels. This potent inhibitor may be a lead compound for a first-in-class plant growth regulator.

Changes in drinking behavior among evacuees after the Fukushima Daiichi Nuclear Power Plant accident:the Fukushima Health Management Survey.

Introduction Traumatic experiences and disordered sleep are strongly associated with drinking problems. We examined the effects of experiencing the Great East Japan Earthquake and subsequent nuclear power plant accident, and of sleep problems, on behavioral changes observed in non-drinkers.Methods This study examined cross-sectional data from the Mental Health and Lifestyle Survey conducted among residents in restricted areas of Fukushima in 2012. Participants were 21,454 evacuees aged 20 years or older at the time of disaster. People who did not drink before the disaster but became drinkers afterwards were compared with the rest of the cohort. We analyzed the association between behavioral changes in non-drinkers and potentially predictive variables, using logistic regression.Results The behavioral change of non-drinkers becoming drinkers (n=2,148) was significantly related to being male (OR=1.93, 95% CI:1.74-2.15), being younger (21-49 yrs, OR=1.85, 95% CI: 1.60-2.13), having less educational attainment (up to high school graduate, OR=1.21, 95% CI:1.09-1.35), smoking (OR=1.22, 95% CI:1.08-1.38), losing family or relatives (OR=1.21, 95% CI:1.07-1.37), change in employment (OR=1.19, 95% CI:1.07-1.32), having severe sleep problems as measured by a Japanese version of the Athens Insomnia Scale (3-8, OR=1.45, 95% CI:1.30-1.62), and severity of traumatic symptoms as measured by the PTSD Checklist Stressor-Specific (PCL-S) score (<44, OR=1.33, 95% CI:1.17-1.51).Conclusion Having sleep problems and having more severe traumatic symptoms are significantly related to non-drinkers becoming drinkers.

Benzalkonium Chloride Resistance in Staphylococcus epidermidis on the Ocular Surface of Glaucoma Patients Under Long-Term Administration of Eye Drops.

Purpose: We previously reported the presence of multidrug-resistant staphylococci on the ocular surface of glaucoma patients using prostaglandin analog drops for more than 1 year. Here, we investigated the effect of benzalkonium chloride (BAC) on these multidrug-resistant staphylococci. Methods: Staphylococcus epidermidis was isolated from the conjunctival sacs of 32 eyes of 32 patients comprised of 13 eyes treated with 0.005% latanoprost (Xalatan; Xa group) and 19 eyes treated with 0.004% travoprost (Travatan Z; Tz group). The minimum inhibitory concentrations (MICs) of prostaglandin analogs and BAC were measured. The presence of efflux pump genes was analyzed using polymerase chain reaction. Results: No difference was found in the MIC values of prostaglandin analogs. In contrast, the MIC values of BAC were significantly higher for the isolates from the Xa group than for those from the Tz group (2.02 vs. 1.02 µg/mL; P = 0.001). One proton-motive efflux gene, qacC/smr, was detected more frequently in the Xa isolates than in the Tz isolates (P < 0.001). The prevalence of methicillin resistance was correlated with the presence of qacC/smr (P = 0.010), and the MIC of BAC was significantly correlated with the detection of qacA/B and qacC/smr sequences (P = 0.03 and P < 0.001, respectively). Conclusions: The long-term use of eye drops containing BAC might select BAC-resistant S. epidermidis harboring qacC/smr. Translational Relevance: These findings suggest that the long-term use of eye drops containing BAC might be inappropriate in terms of avoiding antimicrobial resistance.

A Nonalternant Aromatic Belt: Methylene-Bridged [6]Cycloparaphenylene Synthesized from Pillar[6]arene.

The synthesis, structure, and properties of methylene-bridged [6]cycloparaphenylene ([6]CPP), a nonalternant aromatic belt, are described. This belt-shaped methylene-bridged [6]CPP, in which each phenylene unit is tethered to its neighbors by methylene bridges, was constructed through 6-fold intramolecular nickel-mediated aryl-aryl coupling of triflate-functionalized pillar[6]arene in 18% isolated yield. As compared to the analogous [6]CPP, the methylene bridges coplanarize neighboring paraphenylene units and enhance the degree of π-conjugation, which results in a significant decrease in energy gap. Moreover, the incorporation of small molecules in the defined pocket of methylene-bridged [6]CPP makes it an attractive supramolecular architecture. Methylene-bridged [6]CPP is characterized by high internal strain energy reaching 110.2 kcal mol-1, attributed to its restricted structure. This work not only exhibits an efficient strategy to construct a new family of aromatic belt, but also showcases their properties, which combine the merits of CPPs and pillararenes.

Six-fold C-H borylation of hexa-peri-hexabenzocoronene.

Hexa-peri-hexabenzocoronene (HBC) is known to be a poorly soluble polycyclic aromatic hydrocarbon for which direct functionalization methods have been very limited. Herein, the synthesis of hexaborylated HBC from unsubstituted HBC is described. Iridium-catalyzed six-fold C-H borylation of HBC was successfully achieved by screening solvents. The crystal structure of hexaborylated HBC was confirmed via X-ray crystallography. Optoelectronic properties of the thus-obtained hexaborylated HBC were analyzed with the support of density functional theory calculations. The spectra revealed a bathochromic shift of absorption bands compared with unsubstituted HBC under the effect of the σ-donation of boryl groups.

Synthesis of Highly Twisted, Nonplanar Aromatic Macrocycles Enabled by an Axially Chiral 4,5-Diphenylphenanthrene Building Block.

The synthesis, structures, and properties of highly twisted, nonplanar aromatic macrocycles are described. These macrocycles with an approximately 90° twist angle were synthesized by an effective synthetic approach through a quadruple Suzuki-Miyaura coupling of 4,5-bisarylphenanthrene, a novel axially chiral nonplanar building block. By varying the cross-coupling partner as the spacer, a family of twisted macrocycles was synthesized, allowing for a systematic study of the effect of the spacer on macrocycle shape and photophysical properties. For example, a unique macrocyclic aggregation-induced emission (AIE) emitter with double tetraphenylethylene units as the spacers was readily synthesized. Furthermore, attributed to its conformationally restricted twisted structure, a 3,6-disubstituted-1,8-naphthalimide-incorporated macrocycle showed remarkable solvatofluorochromism with high fluorescence quantum yields. The excellent conformational stability of these macrocycles further enabled complete enantiomeric resolution and characterization. The racemization barrier of macrocycle was determined experimentally and supported by DFT calculations.

Programmable synthesis of multiply arylated cubanes through C-H metalation and arylation.

Cubane (C8H8), a cubic alkane, has long attracted attention owing to its unique 3D structure. In order to utilize the cubane scaffold widely in science and technology, a powerful method for synthesizing diverse cubane derivatives is required. Herein, we report the synthesis of mono-, di-, tri-, and tetra-arylated cubanes. Directed ortho-metalation with lithium base/alkyl zinc and subsequent palladium-catalyzed arylation enabled C-H metalation and arylation of cubane. This reaction allows the late-stage and regioselective installation of a wide range of aryl groups, realizing the first programmable synthesis of diverse multiply arylated cubanes.

Ni-Catalyzed α-Selective C-H Borylations of Naphthalene-Based Aromatic Compounds.

The ability of α-borylated naphthalene-based aromatic compounds is important because it provides ready access to interesting novel extended π-systems. In this report, we disclose the Ni-catalyzed α-selective C-H borylations of naphthalene-based aromatic compounds. The reaction proceeds with peri-xanthenoxanthene and other aromatic compounds to regioselectively afford the α-borylated products without directing groups. The selectivities of these transformations are different from those of Ir-catalyzed C-H borylation reactions and can be used in a complementary manner.

Synthesis of sterically hindered 4,5-diarylphenanthrenes via acid-catalyzed bisannulation of benzenediacetaldehydes with alkynes.

The synthesis of sterically hindered phenanthrenes via acid-catalyzed bisannulation reaction is described. Treatment of 1,4-benzenediacetaldehyde with terminal aryl alkynes in the presence of B(C6F5)3 provides 4,5-diarylphenanthrenes in good yields with excellent regioselectivity. The use of internal alkyne substrates enabled the synthesis of sterically hindered 3,4,5,6-tetrasubstituted phenanthrenes displaying augmented backbone helicity. Furthermore, 1,5-disubstituted, 1,8-disubstituted, 1,2,5,6-tetrasubstituted, and 1,2,7,8-tetrasubstituted phenanthrenes can be obtained through the reaction of alkynes with 1,3-benzenediacetaldehyde or 1,2-benzenediacetaldehyde disilyl acetal.

Psychometric evaluation of the simplified Japanese version of the Athens Insomnia Scale: The Fukushima Health Management Survey.

We investigated the psychometric properties of the simplified Japanese version of the Athens Insomnia Scale (AIS-SJ) using baseline data from the Fukushima Health Management Survey. Data from 22 878 men and 27 669 women aged 16 years and older were analysed (Mage  = 52.9 ± 18.6). Participants lived in the Fukushima evacuation zone and experienced the Great East Japan Earthquake. The AIS-SJ was used to assess participants' insomnia symptoms, and its validity was examined by administering the Kessler 6-item Psychological Distress Scale (K6) and assessing education, self-rated health and disaster-related experiences. A confirmatory factor analysis revealed that the two-factor model was a better fit than the one-factor model. The AIS-SJ and its subscales had acceptable reliability (Cronbach's alpha, 0.81). Test of measurement invariance confirmed strict invariance across groups for the participants' characteristics of gender and mental illness history, but not for participants' age. AIS-SJ scores exhibited a near-normal distribution (skewness, 0.45; kurtosis, -0.89). There were significant age differences only among women, and gender differences in AIS-SJ scores with small effect sizes. The AIS-SJ scores had weak-to-moderate correlations with mental illness history, bereavement, experiencing the tsunami, experiencing the nuclear power plant incident, housing damage and losing one's job (polyserial correlations, 0.36, 0.17, 0.13, 0.18, 0.13, and 0.15, respectively), and strong correlations with self-rated health (polyserial correlation, 0.51), psychological distress (rs , 0.60) and post-traumatic stress disorder (rs , 0.60). The AIS-SJ is a useful instrument for assessing community dwellers' insomnia symptoms.

Additive intraocular pressure-lowering effects of the Rho kinase inhibitor ripasudil in Japanese patients with various subtypes of glaucoma.

PURPOSE: The present study aimed to investigate the effectiveness of adjunctive therapy involving the Rho-associated, coiled-coil-containing protein kinase (ROCK) inhibitor ripasudil in lowering intraocular pressure (IOP) in patients with different subtypes of glaucoma, on the basis of the time of IOP measurement STUDY DESIGN: Retrospective study METHODS: In total, 58 patients who underwent adjunctive therapy with ripasudil at a single institution were included. They were classified into a primary open-angle glaucoma (POAG) group, an exfoliation glaucoma (XFG) group, and a secondary glaucoma associated with uveitis, or steroid glaucoma (SG), group. The average IOPs within 6 months before (pre-IOP) and after (post-IOP) the addition of ripasudil were compared among the 3 groups. The IOP values of the morning-visit and afternoon-visit groups were also compared to reflect the peak effectiveness of ripasudil. RESULTS: The IOP reductions in the POAG (n = 38), XFG (n = 6), and SG (n = 14) groups were -1.1, +0.5, and +0.5 mmHg, respectively. Significant reductions in IOP were observed in the POAG group (P = .014). The IOP reductions in the POAG morning-visit and afternoon-visit groups were -1.9 and +0.5 mmHg, respectively. IOP was significantly reduced in the morning-visit POAG group after treatment with ripasudil (P = .002). The IOP values measured during morning visits were lower than those measured during afternoon visits (IOP reduction: -1.3 mmHg; P = .011). CONCLUSIONS: The findings of the present study indicate that ripasudil is effective as an adjunctive therapy for lowering IOP in patients with POAG; these reductions are more significant when measured closer to the time of peak effectiveness.