The Beneficial Effect of Brazilian Propolis for Liver Damage through Endoplasmic Reticulum Stress.

There is evidence that propolis exhibits anti-inflammatory, anticancer, and antioxidant properties. We assessed the potential beneficial effects of Brazilian propolis on liver injury in nonalcoholic fatty liver disease (NAFLD). Our findings demonstrate that Brazilian propolis suppresses inflammation and fibrosis in the liver of mice with NAFLD by inhibiting the expression of genes involved in endoplasmic reticulum (ER) stress. Additionally, Brazilian propolis also suppressed the expression of ER stress-related genes in HepG2 cells treated with an excess of free fatty acids, leading to cell apoptosis. A deeper analysis revealed that kaempferol, one of the components present in Brazilian propolis, induces cell proliferation through the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and protects against oxidative stress. In conclusion, Brazilian propolis exhibits hepatoprotective properties against oxidative stress by inhibiting ER stress in NAFLD-induced model mice.

Achiral 2-pyridone and 4-aminopyridine act as chiral inducers of asymmetric autocatalysis with amplification of enantiomeric excess via the formation of chiral crystals.

Enantiomorphous crystals of achiral 2-pyridone and 4-aminopyridine served as sources of chirality, to induce the asymmetric autocatalysis of 5-pyrimidyl alkanol during the asymmetric addition of diisopropylzinc to the corresponding pyrimidine-5-carbaldehyde, that is, the Soai reaction. Following a significant amplification of enantiomeric excess through asymmetric autocatalysis, highly enantioenriched 5-pyrimidyl alkanol could be synthesized with their corresponding absolute configurations to those of chiral crystals of 2-pyridone and 4-aminopyridine.

Better Covalent Connection in a Molecular Triad Enables More Efficient Photochemical Energy Storage.

Numerous studies have explored the kinetics of light-induced charge separation and thermal charge recombination in donor-acceptor compounds, but quantum efficiencies have rarely been investigated. Here, we report on two essentially isomeric molecular triads, both comprising a π-extended tetrathiafulvalene (ExTTF) donor, a ruthenium(II)-based photosensitizer, and a naphthalene diimide (NDI) acceptor. The key difference between the two triads is how the NDI acceptor is connected. Linkage at the NDI core provides stronger electronic coupling to the other molecular components than connection via the nitrogen atoms of NDI. This change in molecular connectivity is expected to accelerate both energy-storing charge separation and energy-wasting charge recombination processes, but it is not a priori clear how this will affect the triad's ability to store photochemical energy; any gain resulting from faster charge separation could potentially be (over)compensated by losses through accelerated charge recombination. The new key insight emerging from our study is that the quantum yield for the formation of a long-lived charge-separated state increases by a factor of 5 when going from nitrogen- to core-connected NDI, providing the important proof of concept that better molecular connectivity indeed enables more efficient photochemical energy storage. The physical origin of this behavior seems to root in different orbital connectivity pathways for charge separation and charge recombination, as well as in differences in the relevant orbital interactions depending on NDI connection. Our work provides guidelines for how to discriminate between energy-storing and energy-wasting electron transfer reactions in order to improve the quantum yields for photochemical energy storage and solar energy conversion.

Association Between the Development of Thrombosis and Worsening of Disease Severity in Patients With Moderate COVID-19 on Admission　- From the CLOT-COVID Study.

BACKGROUND: The worsening of coronavirus disease 2019 (COVID-19) severity is a critical issue in current clinical settings and may be associated with the development of thrombosis.Methods and Results: This study used patient data obtained in the CLOT-COVID study, a retrospective multicenter cohort study. The demographics of patients with moderate COVID-19 on admission with and without worsened severity during hospitalization were compared and predictors were identified. Of 927 patients with moderate COVID-19 on admission, 182 (19.6%) had worsened severity during hospitalization. Patients with worsening of severity were older, more likely to have hypertension, diabetes, heart disease, and active cancer, and more likely to use pharmacological thromboprophylaxis. Patients with worsening of severity had higher D-dimer levels on admission and were more likely to develop thrombosis and major bleeding during hospitalization than those without worsening. Increased age (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.03, P=0.005), diabetes (OR: 1.63, 95% CI: 1.11-2.33, P=0.012), D-dimer levels >1.0 µg/mL on admission (OR: 2.10, 95% CI: 1.45-3.03, P<0.001), and thrombosis (OR: 6.28, 95% CI: 2.72-14.53, P<0.001) were independently associated with worsening of COVID-19 severity. CONCLUSIONS: Approximately 20% of patients with moderate COVID-19 had worsened severity during hospitalization. Increased age, diabetes, D-dimer levels >1.0 µg/mL on admission, and the development of thrombosis during hospitalization were significantly associated with worsened COVID-19 severity.

Mortality-associated Risk Factors in Hospitalized COVID-19 Patients in Japan: Findings of the CLOT-COVID Study.

BACKGROUND: Reports of mortality-associated risk factors in patients with the novel coronavirus disease 2019 (COVID-19) are limited. METHODS: We evaluated the clinical features that were associated with mortality among patients who died during hospitalization (n = 158) and those who were alive at discharge (n = 2,736) from the large-scale, multicenter, retrospective, observational cohort CLOT-COVID study, which enrolled consecutively hospitalized COVID-19 patients from 16 centers in Japan from April to September 2021. Data from 2,894 hospitalized COVID-19 participants of the CLOT-COVID study were analyzed in this study. RESULTS: Patients who died were older (71.1 years vs 51.6 years, P < 0.001), had higher median D-dimer values on admission (1.7 µg/mL vs 0.8 µg/mL, P < 0.001), and had more comorbidities. On admission, the patients who died had more severe COVID-19 than did those who survived (mild: 16% vs 63%, moderate: 47% vs 31%, and severe: 37% vs 6.2%, P < 0.001). In patients who died, the incidence of thrombosis and major bleeding during hospitalization was significantly higher than that in those who survived (thrombosis: 8.2% vs 1.5%, P < 0.001; major bleeding: 12.7% vs 1.4%, P < 0.001). Multivariable logistic regression analysis revealed that age >70 years, high D-dimer values on admission, heart disease, active cancer, higher COVID-19 severity on admission, and development of major bleeding during hospitalization were independently associated with a higher mortality risk. CONCLUSION: This large-scale observational study in Japan identified several independent risk factors for mortality in hospitalized patients with COVID-19 that could facilitate appropriate risk stratification of patients with COVID-19.

Nickel(II) Analogues of Phosphorescent Platinum(II) Complexes with Picosecond Excited-State Decay.

Square-planar NiII complexes are interesting as cheaper and more sustainable alternatives to PtII luminophores widely used in lighting and photocatalysis. We investigated the excited-state behavior of two NiII complexes, which are isostructural with two luminescent PtII complexes. The initially excited singlet metal-to-ligand charge transfer (1 MLCT) excited states in the NiII complexes decay to metal-centered (3 MC) excited states within less than 1 picosecond, followed by non-radiative relaxation of the 3 MC states to the electronic ground state within 9-21 ps. This contrasts with the population of an emissive triplet ligand-centered (3 LC) excited state upon excitation of the PtII analogues. Structural distortions of the NiII complexes are responsible for this discrepant behavior and lead to dark 3 MC states far lower in energy than the luminescent 3 LC states of PtII compounds. Our findings suggest that if these structural distortions could be restricted by more rigid coordination environments and stronger ligand fields, the excited-state relaxation in four-coordinate NiII complexes could be decelerated such that luminescent 3 LC or 3 MLCT excited states become accessible. These insights are relevant to make NiII fit for photophysical and photochemical applications that relied on PtII until now.

Molecular Design Principles to Elongate the Metal-to-Ligand Charge Transfer Excited-State Lifetimes of Square-Planar Nickel(II) Complexes.

Square-planar NiII complexes and their electronically excited states play key roles in cross-coupling catalysis and could offer new opportunities to complement well-known isoelectronic PtII luminophores. Metal-to-ligand charge transfer (MLCT) excited states and their deactivation pathways are particularly relevant in these contexts. We sought to extend the lifetimes of 3MLCT states in square-planar NiII complexes by creating coordination environments that seemed particularly well adapted to the 3d8 valence electron configuration. Using a rigid tridentate chelate ligand, in which a central cyclometalated phenyl unit is flanked by two coordinating N-heterocyclic carbenes, along with a monodentate isocyanide ligand, a very strong ligand field is created. Bulky substituents at the isocyanide backbone furthermore protect the NiII center from nucleophilic attack in the axial directions. UV-Vis transient absorption spectroscopies reveal that upon excitation into 1MLCT absorption bands and ultrafast intersystem crossing to the 3MLCT excited state, the latter relaxes onward into a metal-centered triplet state (3MC). A torsional motion of the tridentate ligand and a NiII-carbon bond elongation facilitate 3MLCT relaxation to the 3MC state. The 3MLCT lifetime gets longer with increasing ligand field strength and improved steric protection, thereby revealing clear design guidelines for square-planar NiII complexes with enhanced photophysical properties. The longest 3MLCT lifetime reached in solution at room temperature is 48 ps, which is longer by a factor of 5-10 compared to previously investigated square-planar NiII complexes. Our study contributes to making first-row transition metal complexes with partially filled d-orbitals more amenable to applications in photophysics and photochemistry.

Therapeutic-Dose vs. Prophylactic-Dose Anticoagulation Therapy for Critically Ill Patients With COVID-19 in a Practice-Based Observational Study.

BACKGROUND: The potential benefit of therapeutic-dose anticoagulation for critically ill patients with coronavirus disease 2019 (COVID-19) is still controversial.Methods and Results: In the CLOT-COVID study, 225 patients with severe COVID-19 on admission requiring mechanical ventilation or extracorporeal membrane oxygenation were divided into patients with therapeutic-dose anticoagulation (N=110) and those with prophylactic-dose anticoagulation (N=115). There was no significant difference in the incidence of thrombosis between the groups (9.1% vs. 7.8%, P=0.73). CONCLUSIONS: Among a cohort of critically ill patients with COVID-19, approximately half received therapeutic-dose anticoagulation, although it did not show a potential benefit compared with prophylactic-dose anticoagulation.

Incidence, risk factors, and clinical impact of major bleeding in hospitalized patients with COVID-19: a sub-analysis of the CLOT-COVID Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) causes extensive coagulopathy and a potential benefit of anticoagulation therapy has been documented for prevention of thromboembolic events. Bleeding events has also been reported as a notable complication; whereas, the incidence, risks, and clinical impact of bleeding remain unclear. METHOD: The CLOT-COVID Study was a nationwide, retrospective, multicenter cohort study on consecutive hospitalized patients with COVID-19 in Japan between April 2021 and September 2021. In this sub-analysis, we compared the characteristics of patients with and without major bleeding; moreover, we examined the risk factors for and clinical impact of bleeding events. RESULTS: Among 2882 patients with COVID-19, 57 (2.0%) had major bleeding. The incidence of major bleeding increased with COVID-19 severity as follows: 0.5%, 2.3%, and 12.3% in patients with mild, moderate, and severe COVID-19, respectively. COVID-19 severity, history of major bleeding, and anticoagulant type/dose were independently and additively associated with the bleeding incidence. Compared with patients without major bleeding, those with major bleeding exhibited a longer duration of hospitalization (9 [6-14] vs 28 [19-43] days, P < 0.001) and higher mortality during hospitalization (4.9% vs. 35.1%, P < 0.001). CONCLUSIONS: In the real-world clinical practice, the incidence of major bleeding was not uncommon, especially in patients with severe COVID-19. Independent risk factors for major bleeding included history of major bleeding, COVID-19 severity, and anticoagulant use, which could be associated with poor clinical outcomes including higher mortality. Precise recognition of the risks for bleeding may be helpful for an optimal use of anticoagulants and for better outcomes in patients with COVID-19.

Development of Capsular Fibrosis Beneath the Liver Surface in Humans and Mice.

Glisson's capsule is the connective tissue present in the portal triad as well as beneath the liver surface. Little is known about how Glisson's capsule changes its structure in capsular fibrosis (CF), which is characterized by fibrogenesis beneath the liver surface. In this study, we found that the human liver surface exhibits multilayered capsular fibroblasts and that the bile duct is present beneath the mesothelium, whereas capsular fibroblasts are scarce and no bile ducts are present beneath the mouse liver surface. Patients with cirrhosis caused by alcohol abuse or hepatitis C virus infection show development of massive CF. To examine the effect of alcohol on CF in mice, we first injected chlorhexidine gluconate (CG) intraperitoneally and then fed alcohol for 1 month. The CG injection induces CF consisting of myofibroblasts beneath the mesothelium. One month after CG injection, the fibrotic area returns to the normal structure. In contrast, additional alcohol feeding sustains the presence of myofibroblasts in CF. Cell lineage tracing revealed that mesothelial cells give rise to myofibroblasts in CF, but these myofibroblasts disappear 1 month after recovery with or without alcohol feeding. Capsular fibroblasts isolated from the mouse liver spontaneously differentiated into myofibroblasts and their differentiation was induced by transforming growth factor beta 1 (TGF-ß1) or acetaldehyde in culture. In alcohol-fed mice, infiltrating CD11b+ Ly-6CLow/- monocytes had reduced mRNA expression of matrix metalloproteinase 13 and matrix metalloproteinase 9 and increased expression of tissue inhibitor of matrix metalloproteinase 1, Tgfb1, and interleukin-10 during resolution of CF. Conclusion: The present study revealed that the structure of Glisson's capsule is different between human and mouse livers and that alcohol impairs the resolution of CF by changing the phenotype of Ly-6CLow/- monocytes.

Lubiprostone Induces Claudin-1 and Protects Intestinal Barrier Function.

INTRODUCTION: Lubiprostone, a chloride channel activator, is said to reduce epithelial permeability. However, whether lubiprostone has a direct effect on the epithelial barrier function and how it modulates the intestinal barrier function remain unknown. Therefore, the effects of lubiprostone on intestinal barrier function were evaluated in vitro. METHODS: Caco-2 cells were used to assess the intestinal barrier function. To examine the expression of claudins, immunoblotting was performed with specific antibodies. The effects of lubiprostone on cytokines (IFNγ, IL-6, and IL-1ß) and aspirin-induced epithelial barrier disruption were assessed by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability. RESULTS: IFNγ, IL-6, IL-1ß, and aspirin significantly decreased TEER and increased epithelial permeability. Lubiprostone significantly improved the IFNγ-induced decrease in TEER in a dose-dependent manner. Lubiprostone significantly reduced the IFNγ-induced increase in FITC labeled-dextran permeability. The changes induced by IL-6, IL-1ß, and aspirin were not affected by lubiprostone. The expression of claudin-1, but not claudin-3, claudin-4, occludin, and ZO-1 was significantly increased by lubiprostone. CONCLUSION: Lubiprostone significantly improved the IFNγ-induced decrease in TEER and increase in FITC labeled-dextran permeability. Lubiprostone increased the expression of claudin-1, and this increase may be related to the effect of lubiprostone on the epithelial barrier function.

A New Dimension for Coordination Polymers and Metal-Organic Frameworks: Towards Functional Glasses and Liquids.

There are two categories of coordination polymers (CPs): inorganic CPs (i-CPs) and organic ligand bridged CPs (o-CPs). Based on the successful crystal engineering of CPs, we here propose noncrystalline states and functionalities as a new research direction for CPs. Control over the liquid or glassy states in materials is essential to obtain specific properties and functions. Several studies suggest the feasibility of obtaining liquid/glassy states in o-CPs by design principles. The combination of metal ions and organic bridging ligands, together with the liquid/glass phase transformation, offer the possibility to transform o-CPs into ionic liquids and other ionic soft materials. Synchrotron measurements and computational approaches contribute to elucidating the structures and dynamics of the liquid/glassy states of o-CPs. This offers the opportunity to tune the porosity, conductivity, transparency, and other material properties. The unique energy landscape of liquid/glass o-CPs offers opportunities for properties and functions that are complementary to those of the crystalline state.

Intense Red-Blue Luminescence Based on Superfine Control of Metal-Metal Interactions for Self-Assembled Platinum(II) Complexes.

A series of assembled PtII complexes comprising N-heterocyclic carbene and cyanide ligands was constructed using different substituent groups, [Pt(CN)2 (R-impy)] (R-impyH+ =1-alkyl-3-(2-pyridyl)-1H-imidazolium, R=Me (Pt-Me), Et (Pt-Et), i Pr (Pt-i Pr), and t Bu (Pt-t Bu)). All the complexes exhibited highly efficient photoluminescence with an emission quantum yield of 0.51-0.81 in the solid state at room temperature, originating from the triplet metal-metal-to-ligand charge transfer (3 MMLCT) state. Their emission colors cover the entire visible region from red for Pt-Me to blue for Pt-t Bu. Importantly, Pt-t Bu is the first example that exhibits blue 3 MMLCT emission. The 3 MMLCT emission was proved and characterized based on the temperature dependences of the crystal structures and emission properties. The wide-range color tuning of luminescence using the 3 MMLCT emission presents a new strategy of superfine control of the emission color.

Effects of cigarette smoke on barrier function and tight junction proteins in the bronchial epithelium: protective role of cathelicidin LL-37.

BACKGROUND: Airway epithelial barrier function is maintained by the formation of tight junctions (TJs) and adherens junctions (AJs). Inhalation of cigarette smoke causes airway epithelial barrier dysfunction and may contribute to the pathogenesis of chronic lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). We assessed the effects of cigarette smoke on barrier function and expression of multiple TJ and AJ proteins in the bronchial epithelium. We also examined whether treatment with glucocorticosteroids (GCSs), long-acting ß2-agonists (LABAs), and human cathelicidin LL-37 can protect against cigarette smoke extract (CSE)-induced barrier dysfunction. METHODS: Calu-3 cells cultured at the air-liquid interface were pretreated with or without GCSs, LABAs, GCSs plus LABAs, or LL-37, and subsequently exposed to CSE. Barrier function was assessed by transepithelial electronic resistance (TEER) measurements. Gene and protein expression levels of TJ and AJ proteins were analyzed by quantitative PCR and western blotting, respectively. Immunofluorescence staining of TJ and AJ proteins was performed. RESULTS: CSE decreased TEER and increased permeability in a concentration-dependent manner. CSE suppressed gene expression of claudin-1, claudin-3, claudin-4, claudin-7, claudin-15, occludin, E-cadherin, junctional adhesion molecule-A (JAM-A) and zonula occludens-1 (ZO-1) within 12 h post-CSE exposure, while suppressed protein expression levels of occludin at 12 h. CSE-treated cells exhibited discontinuous or attenuated immunostaining for claudin-1, claudin-3, claudin-4, occludin, ZO-1, and E-cadherin compared with untreated cells. GCS treatment partially restored CSE-induced TEER reduction, while LABA treatment had no effect. GCS and LABA combination treatment had no additive effect on CSE-induced TEER reduction and gene suppression of TJ and AJ proteins. Human cathelicidin LL-37 counteracted CSE-induced TEER reduction and prevented disruption of occludin and ZO-1. LL-37 also attenuated CSE-induced decreases in gene and protein expression levels of occludin. CONCLUSIONS: CSE caused airway epithelial barrier dysfunction and simultaneously downregulated multiple TJ and AJ proteins. GCS and LABA combination treatment had no additive effect on CSE-induced TEER reduction. LL-37 counteracted CSE-induced TEER reduction and prevented disruption of occludin and ZO-1. Use of LL-37 to counteract airway epithelial barrier dysfunction may have significant benefits for respiratory diseases such as asthma and COPD.

Chenodeoxycholic Acid Releases Proinflammatory Cytokines from Small Intestinal Epithelial Cells Through the Farnesoid X Receptor.

BACKGROUND/AIMS: Bile acids have recently been associated with the pathogenesis of irritable bowel syndrome (IBS). We therefore evaluated the expression of bile acid receptors in the intestinal mucosa of IBS patients as well as the effects of bile acids on small intestinal epithelial cells. METHODS: Intestinal biopsy specimens were obtained from 15 IBS patients and 15 healthy controls. The effects of bile acid stimulation on trans-epithelial electrical resistance (TEER) and permeability in differentiated Caco-2 cells were measured. Proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. mRNA levels of bile acid receptors, including farnesoid X receptor (FXR), and cytokines were determined by real-time reverse transcription-PCR. Caco-2 cells were pre-incubated with the FXR antagonist guggulsterone. RESULTS: FXR mRNA expression at the terminal ileum was increased in IBS patients. Chenodeoxycholic acid (CDCA) significantly decreased TEER, increased permeability, and increased interleukin-8 (IL-8) release from Caco-2 cells. Pre-incubation with guggulsterone blocked CDCA-mediated IL-8 release; however, the decrease in TEER was not reversed. CDCA-induced IL-6 and IL-8 mRNA levels were blocked by guggulsterone. CDCA increased IL-6, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor release, whereas guggulsterone significantly blocked IL-6 and TNF-α release. CONCLUSIONS: FXR expression was elevated at the terminal ileum in IBS patients. CDCA increased proinflammatory cytokines, while guggulsterone blocked these increases.

Isolation of a unique hepatic stellate cell population expressing integrin α8 from embryonic mouse livers.

BACKGROUND: Hepatic stellate cells (HSCs) play an important role in liver fibrogenesis. However, little is known about their phenotype and role in liver development. The aim of this study is to identify specific markers for embryonic HSCs. RESULTS: Using antibodies against ALCAM and PDPN, we separated mesothelial cells (MCs) and HSCs from developing livers and identified integrin α8 (ITGA8) as a marker for embryonic desmin+ HSCs that are preferentially localized near the developing liver surface and α-smooth muscle actin+ perivascular mesenchymal cells around the vein. A cell lineage-tracing study revealed that upon differentiation, MC-derived HSCs or perivascular mesenchymal cells express ITGA8 during liver development. Using anti-ITGA8 antibodies, we succeeded in isolating MC-derived HSCs and perivascular mesenchymal cells from embryonic livers. In direct co-culture, ITGA8+ mesenchymal cells promoted the expression of hepatocyte and cholangiocyte markers in hepatoblasts. In the normal adult liver, expression of ITGA8 was restricted to portal fibroblasts in the portal triad. Upon liver injury, myofibroblasts increased the expression of ITGA8. CONCLUSIONS: ITGA8 is a specific cell surface marker of MC-derived HSCs and perivascular mesenchymal cells in the developing liver. Our data suggest that ITGA8+ mesenchymal cells maintain the phenotype of hepatoblast in liver development. Developmental Dynamics 247:867-881, 2018. © 2018 Wiley Periodicals, Inc.

Chemical synthesis of an indomethacin ester prodrug and its metabolic activation by human carboxylesterase 1.

It is necessary to consider the affinity of prodrugs for metabolic enzymes for efficient activation of the prodrugs in the body. Although many prodrugs have been synthesized with consideration of these chemical properties, there has been little study on the design of a structure with consideration of biological properties such as substrate recognition ability of metabolic enzymes. In this report, chemical synthesis and evaluation of indomethacin prodrugs metabolically activated by human carboxylesterase 1 (hCES1) are described. The synthesized prodrugs were subjected to hydrolysis reactions in solutions of human liver microsomes (HLM), human intestine microsomes (HIM) and hCES1, and the hydrolytic parameters were investigated to evaluate the hydrolytic rates of these prodrugs and to elucidate the substrate recognition ability of hCES1. It was found that the hydrolytic rates greatly change depending on the steric hindrance and stereochemistry of the ester in HLM, HIM and hCES1 solutions. Furthermore, in a hydrolysis reaction catalyzed by hCES1, the Vmax value of n-butyl thioester with chemically high reactivity was significantly lower than that of n-butyl ester.

Phosphorescence Properties of Discrete Platinum(II) Complex Anions Bearing N-Heterocyclic Carbenes in the Solid State.

The synthesis, crystal structures, and photophysical properties of four anionic platinum complexes bearing N-heterocyclic carbenes (NHCs), n-Bu4N[Pt(CN)2(NHC)] (H2NHC+ = 1-methyl-3-phenyl-1 H-imidazolium (1), 1-methyl-3-phenyl-1 H-benzimidazolium (2), 1-methyl-3-(naphthalen-2-yl)-1 H-imidazolium (3), 1-methyl-3-(naphthalen-1-yl)-1 H-imidazolium (4)), are reported. The tetra- n-butylammonium salts afforded discrete Pt(II) complexes surrounded by the bulky cations in the crystalline states with no Pt-Pt, π-π, or solute-solvent interactions. As a result, the crystals exhibited strong phosphorescence with quantum yields of 0.24-0.72 at 298 K. The three isomeric complexes 2-4 with π-extended structures of 1 exhibited luminescence with different colors depending on the π-extension site. These complexes in a discrete and restricted space enabled the comparative investigation of the luminescent states and regioselective benzannulation effect using computational methods and luminescence spectroscopy. Blue-emissive 1 and 2 exhibited lifetime changes at temperatures of 77-298 K, suggesting the influence of dark states located 2000-3000 cm-1 above the emissive state. In contrast, yellow- and orange-emissive 3 and 4 showed no thermal deactivation effect at ambient temperature. The temperature dependence of the emission lifetimes in the low-temperature region of 4-77 K showed that blue-emissive 1 and 2 had a relatively large zero-field splittings (ZFSs) of 35 and 28 cm-1, respectively, indicating the significant contribution of triplet metal-to-ligand charge transfer character to the 3π-π* emission. On the other hand, the ZFS of 4 was less than 2 cm-1, suggesting purer 3π-π* character.

Effect of Water Coordination on Luminescent Properties of Pyrazine-Bridged Dinuclear Cu(I) Complexes.

Two luminescent pyrazine-bridged dinuclear Cu(I) complexes, namely, [{Cu(PPh3)2(H2O)}(µ-MeOpyz){Cu(PPh3)2(CH3CN)}](BF4)2 and [{Cu(PPh3)2(H2O)}(µ-MeOpyz){Cu(PPh3)2(H2O)}](BF4)2 (H2O-Cu2-AN and H2O-Cu2-H2O; PPh3 = triphenylphosphine, MeOpyz = 2-methoxypyrazine), were successfully synthesized and characterized by single-crystal X-ray diffraction and luminescence measurements. X-ray analysis revealed that the water molecules are coordinated to both Cu(I) ions to form almost the same P2N1O1 coordination structure in H2O-Cu2-H2O, whereas one of the two Cu ions in H2O-Cu2-AN was coordinated by acetonitrile instead of water to form a different P2N2 coordination environment. The asymmetric H2O-Cu2-AN exhibits very bright yellow-green emission with a high emission quantum yield (λem = 550 nm, Φ = 0.70) at room temperature in the solid state in spite of the coordination of water molecule, which usually tends to deactivate the emissive state through O-H vibration. The intense emission at room temperature is a result of thermally activated delayed fluorescence, and the remarkable temperature dependence of emission lifetimes indicates the existence of unique multiple emission states for the asymmetric dinuclear complex. In contrast, the emission of H2O-Cu2-H2O was observed at longer wavelengths with remarkably a lower quantum yield (λem = 580 nm, Φ = 0.05). Time-dependent density functional theory calculations suggested that the emission could result from the metal-to-ligand charge-transfer transition state. However, it could be rapidly deactivated by the structural distortion around the Cu ion with a less-bulky coordination environment in H2O-Cu2-H2O.

Using a flexible shaft agitator to enhance the rheology of a complex fungal fermentation culture.

The rheology behavior of biological fluids particularly when the viscosity is high and rheology is complex, is an important issue to understand, particularly for studies in mass-transfer and for solving technical problems with mixing in stirred bioreactors. In this paper, the use of a Swingstir(®) impeller during the fermentation of Aspergillus oryzae resulted in decreases from the parameters of a power-law model, in viscosity and in the thixotropic behavior of a cultivation broth. The results showed that both the K L a and the alpha amylase activity were improved when using the Swingstir(®) in comparison with Fullzone(®) impeller (FZ) at the same level of energy consumption. Increasing the pellet porosity during mixing via the Swingstir(®) resulted in increases in oxygen mass transfer and the average shear stress.