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DFT calculations were used to study the performance of Na2ZrO3 and Y-doped Na2ZrO3 as cathode materials for sodium ion batteries, including the stability of desodiated structures, desodiation energy, redox mechanism, and diffusion of Na ion.

Energy transfer plays a special role in photocatalysis by utilizing the potential energy of the excited state through indirect excitation, in which a photosensitizer determines the thermodynamic feasibility of the reaction. Bioinspired by the energy-transfer ability of natural product cercosporin, here we developed a green and highly efficient organic photosensitizer HiBRCP (hexaisobutyryl reduced cercosporin) through structural modification of cercosporin. After structural manipulation, its triplet energy was greatly improved, and then, it could markedly promote the efficient geometrical isomerization of alkenes from the E-isomer to the Z-isomer. Moreover, it was also effective for energy-transfer-mediated organometallic catalysis, which allowed realization of the cross-coupling of aryl bromides and carboxylic acids through efficient energy transfer from HiBRCP to nickel complexes. Thus, the study on the relationship between structural manipulation and their photophysical properties provided guidance for further modification of cercosporin, which could be applied to more meaningful and challenging energy-transfer reactions.

Objective: To determine whether sodium-glucose co-transporter 2 (SGLT2) inhibitors, compared with glucagon-like peptide-receptor agonists (GLP-1RAs) or dipeptidyl peptidase-4 (DPP4) inhibitors are associated with an increased risk of early bladder cancer events. Research Design & Methods: We conducted a multi-site, population-based, new-user active comparator cohort study using the United Kingdom Clinical Practice Research Datalink, Medicare fee-for-service, Optum© Clinformatics® Data Mart, and MarketScan Health from January 2013 through December 2020. We assembled two cohorts of adults with type 2 diabetes initiating (1) SGLT2 inhibitors or GLP-1RAs, and (2) SGLT2 inhibitors or DPP4 inhibitors. Cox proportional hazards models were fit to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident bladder cancer. The models were weighted using propensity score fine stratification. Site-specific HRs were pooled using random-effects models. Results: SGLT2 inhibitor (n=453,560) and GLP-1RA (n=375,997) users had a median follow-up ranging from 1.5-2.2 years. Overall, SGLT2 inhibitors were not associated with an increased risk of bladder cancer, compared with GLP-1RAs (HR=0.90; 95% CI: 0.81-1.00). Similarly, when compared with DPP-4 inhibitors (n=853,186), SGLT2 inhibitors (n=347,059) were not associated with an increased risk of bladder cancer (HR: 0.99, 95% CI: 0.91-1.09) over a median follow-up ranging from 1.6-2.6 years. Results were consistent across sensitivity analyses. Conclusions: Contrary to previous randomized controlled trials, these findings indicate that the use of SGLT2 inhibitors is not associated with an increased risk of bladder cancer when compared with GLP-1RAs or DPP4 inhibitors. This should provide reassurance on the short-term effects of SGLT2 inhibitors on bladder cancer incidence.

To develop a photocatalyst with catalytical activity for substrates with low reactivities is always highly desired. Herein, based on the principle of structure–property relationships, we rationally designed the natural product cercosporin, the naturally occurring perylenequinonoid pigment, to develop a novel organic perylenephotoreductant, hexacetyl reduced cercosporin (HARCP), through structural manipulation. Compared with cercosporin, HARCP shows prominent electrochemical and photophysical characteristics with greatly improved photoreductive activity, fluorescence lifetime and fluorescence quantum yield. These properties allowed HARCP as a powerful photoreductant to efficiently realize a series of benchmark reactions, including photoreduction, alkoxylation and hydroxylation to construct C–H and C–O bonds using aryl halides as substrates under mild conditions, all of which have never been achieved by the same photocatalyst. Thus, this study well supports the notion that the principle between structural manipulation and photocatalytic activity is of great significance to design customized photocatalysts for photoredox chemistry.

Amphichoterpenoids A–C (1–3), unprecedented picoline-derived meroterpenoids possessing a pyrano[3,2-c]pyridinyl-γ-pyranone scaffold, were characterized from the ascidian-derived fungus Amphichorda felina SYSU-MS7908. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway was proposed. The isolated compounds displayed moderate inhibitory activity against acetylcholinesterase with 50% inhibiting concentration (IC50) values of 18.8–53.2 μmol/L.

The adsorptions of iron(II) phthalocyanine (FePc) on graphene and defective graphene were investigated systematically using density functional theory. Three types of graphene defects covering stone-wales (SW), single vacancy (SV), and double vacancy (DV) were taken into account, in which DV defects included DV(5-8-5), DV(555-777), and DV(5555-6-7777). The calculations of formation energies of defects showed that the SW defect has the lowest formation energy, and it was easier for DV defects to form compared with the SV defect. It is more difficult to rotate or move FePc on the surface of defective graphenes than on the surface of graphene due to bigger energy differences at different sites. Although the charge analysis indicated the charge transfers from graphene or defective graphene to FePc for all studied systems, the electron distributions of FePc on various defective graphenes were different. Especially for FePc@SV, the d

First-principles calculations based on density functional theory were utilized to study the performance of Na

The natural abundance of potassium in the earth’s crust is 1000 times higher than that of lithium, so energy technologies built on potassium are more sustainable. Potassium-ion batteries have attra...

Due to the small weight and large flexibility, membrane structures are prone to vibration under external excitation. Furthermore, it may affect the normal function of membrane structures. In view of the limitation of traditional perturbation method and small deflection theory in solving strongly nonlinear vibration problem of membranes. an improved multi-scale method is proposed in this paper to investigate the characteristics of strongly nonlinear vibration of membrane. Firstly, based on the large deflection theory of membrane and the improved multi-scale method, the strongly nonlinear damped vibration control equation of membrane with consideration of geometrical non-linearity is solved. Then, the analytical expressions of the frequency and displacement functions of the strongly nonlinear vibration of membranes are obtained, which are compared with the numerical results. Furthermore, the vibration characteristics of the membrane under the initial displacement are explained together with the experimental results. The results show that the improved multi-scale method is more suitable for solving the strongly nonlinear vibration of membranes than the traditional perturbation method, since the accuracy is higher. Therefore, such a discovery exhibit exposes a more accurate theoretical method for the vibration control and design of membranes.

First-principles computations were performed to investigate the performance of KTiOPO4 (KTP) as a cathode material for potassium-ion batteries (PIBs), including the stability and electronic properties of depotassiated structures and mechanisms of K deintercalation and diffusion. As depotassiation proceeds, oxygen hole polarons are produced, and there are not peroxides or superoxides formed after deep depotassiation. The anionic oxygen redox in KTP provides a voltage vs K/K+ over 4 V by the PBE+U method and over 5 V with the more reliable HSE06 hybrid functional. When all K in KTP is removed, the calculated volume compression is only 1.528%. The AIMD simulations at 300 K for TiOPO4 verify its thermal stability. The PBE+U calculations predict a low ion diffusion barrier of 0.29 eV in bulk KTP, indicating a good charge-discharge rate for KTP as a cathode for PIBs. All of the calculated results indicate that KTP can be a promising cathode material for PIBs.

Bimetallic oxide NiCo2O4 and its composites hold promising applications for supercapacitors owing to their theoretical capacity, inexpensiveness, and ease of synthesis. In this work, novel CuO/Cu2O/NiCo2O4 (CCNC) open-structured three-dimensional (3D) composites were synthesized. The multiple components and open structure of the composite provide many open channels for ion diffusion, thus, promoting good rate performance during the electrochemical reaction. The optimized sample (CCNC3–6) shows good electrochemical performance, with a high specific capacitance of 1614 F g−1 at a current density of 1 A g−1, and good rate performance by maintaining a capacitance of 1383 F g−1 for increasing current density to 20 A g−1 (with a merely 14% capacitance loss, as compared with that at 1 A g−1). The composite also shows enhanced cycle stability than pure NiCo2O4, with 81% remaining capacitance after 3000 cycles. The CCNC 3D nanocomposites are demonstrated to be promising for high-performance supercapacitor applications.

Ascidian-derived microorganisms are a significant source of pharmacologically active metabolites with interesting structural properties. When discovering bioactive molecules from ascidian-derived fungi, two new phenols, roussoelins A (1) and B (2), and ten known polyketides (3–12) were isolated from the ascidian-derived fungus Roussoella siamensis SYSU-MS4723. The planar structure of compounds 1 and 2 was established by analysis of HR-ESIMS and NMR data. The conformational analysis of the new compounds was assigned according to coupling constants and selective gradient NOESY experiments, and absolute configurations were completed by the modified Mosher’s method. Among the isolated compounds, 1, 2, and 9 showed moderate antioxidant capacity. Graphical abstract

Ru(II) complexes were synthesized with π-expanding (phenyl, fluorenyl, phenanthrenyl, naphthalen-1-yl, naphthalene-2-yl, anthryl, and pyrenyl groups) attached at a 1H-imidazo[4,5-f][1,10]phenanthroline ligand and 4,4′-dimethyl-2,2′-bipyridine (4,4′-dmb) co-ligands. These Ru(II) complexes were characterized by 1D and 2D NMR, and mass spectroscopy, and studied for visible-light and dark toxicity to human malignant melanoma SK-MEL-28 cells. In the SKMEL-28 cells, the Ru(II) complexes are highly phototoxic (EC(50) = 0.2–0.5 μM), and have low dark toxicity (EC(50) = 58–230 μM). The highest phototherapeutic index (PI) of the series was found with the Ru(II) complex bearing the 2-(pyren-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline ligand. This high PI is in part attributed to the π-rich character added by the pyrenyl group, and a possible low-lying and longer-lived (3)IL state due to equilibration with the (3)MLCT state. While this pyrenyl Ru(II) complex possessed a relatively high quantum yield for singlet oxygen formation (Φ(Δ) = 0.84), contributions from type-I processes (oxygen radicals and radical ions) are competitive with the type-II ((1)O(2)) process based on effects of added sodium azide and solvent deuteration.

When the membrane material in the air field vibrates, it will drive the movement of the surrounding air. The aerodynamic force generated by the moving air will act on the membrane material in turn, resulting in the change of dynamic characteristics such as membrane vibration frequency. In this paper, the additional air mass produced by membrane vibration in air is studied. Firstly, under the assumption that the incoming flow is uniform and incompressible ideal potential flow, the additional air mass acting on the surface is derived by using the thin airfoil theory and potential flow theory respectively. Then, according to the first law of thermodynamics and the principle of aeroelasticity, the analytical expression of the additional air mass is derived. Finally, through a specific example, the variation of the additional air mass with the membrane material parameters and pretension, as well as the influence of the aerodynamic force on the vibration frequency and amplitude of the membrane is obtained.

A new family of ten dinuclear Ru(II) complexes based on the bis[pyrrolyl Ru(II)] triad scaffold, where two Ru(bpy)2 centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and in vitro photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(II)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients (e) ≥ 104 at 600–620 nm and longer. Phosphorescence quantum yields (Φp) were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields (ΦΔ) ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC50 values in the range of 10–100 μM and phototherapeutic indices (PIs) as large as 5400 and 260 with broadband visible (28 J cm−2, 7.8 mW cm−2) and 625 nm red (100 J cm−2, 42 mW cm−2) light, respectively. The bis[pyrrolyl Ru(II)] triad with a pyrenyl linker (5h) was especially potent, with an EC50 value of 1 nM and PI > 27 000 with visible light and subnanomolar activity with 625 nm light (100 J cm−2, 28 mW cm−2). The lead compound 5h was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxicity in this more resistant model (EC50 = 60 nM and PI > 1200 with 625 nm light) despite a lower dark cytotoxicity. The in vitro PDT effects of 5h extended to bacteria, where submicromolar EC50 values and PIs >300 against S. mutans and S. aureus were obtained with visible light. This activity was attenuated with 625 nm red light, but PIs were still near 50. The ligand-localized 3ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.

Forest productivity (increment of above-ground biomass) is determined by biodiversity but also by stand structure attributes. However, the relative strengths of these drivers in determining productivity remain controversial in subtropical forests. In this study, we analyzed a tree growth data from 500 plots with in a 20 ha mature subtropical forest in eastern China. We used spatial simultaneous autoregressive error models to examine the effects of diversity variables (species richness, evenness, and composition), stand structural attributes (stand density, tree size range and diversity), environmental factors (topography and soil), and initial above-ground biomass (AGB) on productivity. We also applied structural equation models to quantify the relative importance of diversity, stand structure, environmental factors, and initial AGB in determining forest productivity. Our results showed that stand structure together with diversity and initial AGB governed forest productivity. Tree size diversity (DBH Shannon’s diversity index) had the largest positive effect on forest productivity. These results provide new evidence that structural explanatory variables have greater contributions to productivity for mature subtropical forests, strongly supporting the niche complementarity hypothesis. Our work highlights the importance of tree size diversity in promoting high forest productivity, and suggests that regulating and conserving complexity of forest stand structure should be among the most important goals in subtropical forest management.

A series of cationic heteroleptic iridium(III) complexes bearing tris-diimine ligands [Ir(phen)2(R-phen)]3+ (R-phen = phenanthroline (1), 3,8-diphenylphenanthroline (2), 3,8-dipyrenylphenanthroline (3), 3-phenylphenanthroline (4), 3-pyrenylphenanthroline (5), and 3,8-diphenylethynylphenanthroline (6)) were synthesized and characterized. These complexes possessed phen ligand-localized 1π,π* transitions below 300 nm, and charge transfer (1CT) and/or 1π,π* transitions between 300 and 520 nm. In 1, 2, 4, and 6, the low-energy bands were mixed 1CT/1π,π*. However, the increased π-donating ability of the pyrenyl substituent(s) in 3 and 5 split the low-energy bands into a pyrene-based 1π,π* transition at 300–380 nm and an intraligand charge transfer (1ILCT) transition at 380–520 nm. All complexes were emissive at room temperature in CH3CN, but the parentage of the emitting state varied depending on the R substituent(s). Complex 1 exhibited predominantly phen ligand-localized 3π,π* emission mixed with metal-to-lig...

In the context of the COVID-19 global pandemic, promoting influenza knowledge and vaccine helps reduce the risk of dual pandemics and relieve the pressure on healthcare systems. Due to the low rate of influenza vaccination in China, we conducted a cross-sectional survey to investigate whether a knowledge gap regarding influenza and influenza vaccine exists between Chinese groups of different socioeconomic statuses and then explore the possible factors influencing knowledge level. A total of 951 valid questionnaires were collected online in this study. Variance analysis shows a knowledge gap regarding influenza and influenza vaccination between different socioeconomic status groups. Correlation analysis shows that internet media, social media, public communication, and interpersonal communication are positively associated with the knowledge level. Multilevel regression analysis shows a significant interaction between internet media and educational level. This study finds that internet media use helps narrow the knowledge gap between groups with different education levels. This article recommends a multi-channel promotion of influenza and vaccine knowledge and better pertinence between contents and readers.

First-principles computations were performed to investigate the performance of KTiOPO

A new family of ten dinuclear Ru(II) complexes based on the bis[pyrrolyl Ru(II)] triad scaffold, where two Ru(bpy)2 centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and in vitro photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(II)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients (e) ≥104 at 600–620 nm and longer. Phosphorescence quantum yields were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC50 values in the range of 10–100 µM and phototherapeutic indices (PIs) as large as 5,400 and 260 with broadband visible (28 J cm-2, 7.8 mW cm-2) and 625-nm red (100 J cm-2, 42 mW cm-2) light, respectively. The bis[pyrrolyl Ru(II)] triad with a pyrenyl linker (5h) was especially potent, with an EC50 value of 1 nM and PI >27,000 with visible light and subnanomolar activity with 625-nm light (100 J cm-2, 28 mW cm-2). The lead compound 5h was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxcicity in this more resistant model (EC50=60 nM and PI>1,200 with 625-nm light) despite a lower dark cytotoxicity. The in vitro PDT effects of 5h extended to bacteria, where submicromolar EC50 values and PIs >300 against S. mutans and S. aureus were obtained with visible light. This activity was attenuated with 625-nm red light, but PIs were still near 50. The ligand-localized 3ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.

Ca

// Jing Zhang 1, * , Nan Luo 1, * , Yu Tian 2, * , Jiazhi Li 3 , Xiaozhou Yang 1 , Huimin Yin 1 , Congshu Xiao 1 , Jie Sheng 4 , Yang Li 1 , Bo Tang 1 , Rongkuan Li 1 1 Department of Infection, The Second Hospital of Dalian Medical University, Dalian, Liaoning, P.R. China 2 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, P.R. China 3 Department of Pathology, Dalian Medical University, Dalian, Liaoning, P.R. China 4 Department of Urology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, P.R. China * These authors contributed equally to this work Correspondence to: Bo Tang, email: dytangbo @163.com Rongkuan Li, email: dalianlrk@126.com Yang Li, email: 805707550@qq.com Keywords: USP22, liver neoplasms, chemoresistance, Smad4, Akt Received: May 17, 2016 Accepted: February 13, 2017 Published: March 01, 2017 ABSTRACT USP22, a member of the deubiquitinases (DUBs) family, is known to be a key subunit of the human Spt-Ada-Gcn5 acetyltransferase (hSAGA) transcriptional cofactor complex. Within hSAGA, USP22 removes ubiquitin from histone proteins, thus regulating the transcription and expression of downstream genes. USP22 plays important roles in many cancers; however, its effect and the mechanism underlying HCC chemoresistance remain unclear. In the present study, we found that USP22 was highly expressed in chemoresistant HCC tissues and cells and was correlated with the prognosis of HCC patients who received chemotherapy. Silencing USP22 in chemoresistant HCC Bel/Fu cells dramatically inhibited proliferation, migration, invasion and epithelial-mesenchymal transition in vitro ; suppressed tumorigenic and metastatic capacities in vivo ; and inhibited drug resistance-related proteins (MDR1, LRP, MRP1). Mechanistically, we found that USP22 knockdown exerts its function through down-regulating PI3K and activating Smad4, which inhibited phosphorylation of Akt. Silencing Smad4 blocked USP22 knockdown-induced Akt inhibition in Bel/Fu cells. Our results, for the first time, provide evidence that USP22 plays a critical role in the development of chemoresistant HCC cells and that high USP22 expression serves as a molecular marker for the prognosis of HCC patients who undergo chemotherapy.

Facile synthesis of a thin tubular CAU-1 membrane was carried by simple in-situ solvothermal growth method through the use of the asymmetric α-Al2O3 tube support with the same metal centre as the CAU-1 framework. The solvent ratio, reactant concentration and support property were found significant for the formation of a dense and continuous pure CAU-1 membrane with highly permeable and selective CO2 towards N2 and CH4. A high CO2 permeance of 0.80×10−6 mol m−2 s−1 Pa−1 with separation factor of 14.8 was achieved for the M3 for 1:1 CO2/N2 binary mixtures at room temperature. Both the increase of ethanol in the solvent mixture and reactant concentration were favourable for the formation of a dense and well intergrown pure CAU-1 membrane while their excessive increase led to impure NH2-MIL-53 formation. The composition and pore size of the support contributed to high permeance and selectivity of CAU-1 membrane for CO2/N2 separation.

Five heteroleptic cationic iridium complexes with a π-expansive cyclometalating 2,3-diphenylbenzo[g]quinoxaline (dpbq) ligand (C^N ligand) and different diimine ligands (N^N ligands) (i.e. 2,2′-bipyridine (bpy, 1), phenanthroline (phen, 2), 2-(2-pyridinyl)quinoline (pqu, 3), 2,2′-bisquinoline (bqu, 4), and 2-(quinolin-2-yl)quinoxaline (quqo, 5)) were synthesized and characterized. The lowest-energy singlet electronic transitions (S1 states) were mainly dpbq ligand-centred 1ILCT (intraligand charge transfer)/1MLCT (metal to ligand charge transfer) transitions mixed with some 1π,π* transitions for complexes 1–4 with increased contributions from 1LLCT (ligand to ligand charge transfer) in 3 and 4. For complex 5, the S1 state was switched to the 1LLCT/1MLCT transitions. All five complexes displayed weak near-infrared (NIR) phosphorescence, with maximal emission output spanning 700–1400 nm and quantum yields being on the order of 10−3. The triplet state absorptions of 1–4 all resembled that of the [Ir(dpbq)2Cl]2 dimer with lifetimes of ca. 400 ns, while the TA spectrum of 5 possessed the characteristics of both the quqo ligand and the [Ir(dpbq)2Cl]2 dimer with a bi-exponential decay of ca. 5 μs and 400 ns. While the photophysics of these complexes differ slightly, their theranostic photodynamic therapy (PDT) effects varied drastically. All of the complexes were biologically active toward melanoma cells. Complexes 2 and 3 were the most cytotoxic, with 230–340 nM activity and selectivity factors for melanoma cells over normal skin fibroblasts of 34 to 40 fold. Complexes 2, 3, and 5 became very potent cytotoxins with light activation, with EC50 values as low as 12–18 nM. This potent nanomolar light-triggered activity combined with a lower dark toxicity resulted in 5 having a phototherapeutic index (PI) margin of almost 275. The bpy coligand led to the least amount of dark toxicity of 1, while phen and pqu produced cytotoxic but selective complexes 2 and 3. The quqo coligand produced the most potent complex 5 for in vitro PDT, both in terms of photocytotoxicity and PI. All Ir(III) complexes exhibited very bright NIR phosphorescence in melanoma cells. The wide range of cytotoxicity and photocytotoxicity effects within a relatively small class of complexes highlights the importance of the identity of the coligand in the biological activity of the π-expansive biscyclometalated Ir(III) complexes, and their bright NIR emission in live cells demonstrates their potential as theranostic PDT agents.

A new family of cyclometalated ruthenium(II) complexes [Ru(N^N)(2) (C^N)](+) derived from the π-extended benzo[h]imidazo[4,5-f]quinolone ligand appended with thienyl groups (n=1–4, compounds 1–4) was prepared and characterized for their chemical, photophysical, and photobiological properties. The lipophilicities of 1–4, determined as octanol-water partition coefficients (log P(o/w)), were positive and increased with the number of thienyl units. The absorption and emission bands of the C^N compounds were red-shifted by up to 200 nm relative to the analogous Ru(II) diimine systems. All of the complexes exhibited dual emission, with the intraligand fluorescence ((1)IL, C^N-based) shifting to lower energies with increasing n and the metal-to-ligand charge transfer phosphorescence ((3)MLCT, N^N-based) remaining unchanged. Compounds 1–3 exhibited excited state absorption (ESA) profiles consistent with lowest-lying (3)MLCT states when probed by nanosecond transient absorption (TA) spectroscopy with 532-nm excitation, and had contributions from (1)IL(C^N) states with 355-nm excitation. These assignments were supported by the lifetimes observed (300 µM); 1–3 were cytotoxic and yielded EC(50) values between 1–20 µM. The photocytotoxicites with visible light ranged from 87 nM with a phototherapeutic index (PI) of 13 for 1 to approximately 1 µM (PI = >267) for 4. With red light, EC(50) values varied from 270 nM (PI=21) for 3 to 12 µM for 4 (PI = >25). The larger PIs for 4, especially with visible light, were attributed to the much lower dark cytotoxicity for this compound. Since the dark cytotoxicity contributes substantially to the observed photocytotoxicity for 1–3, it was not possible to assess whether the (3)IL state of 4 led to a much more potent phototoxic mechanism in the absence of dark toxicity. There was no stark contrast in cellular uptake and accumulation by laser scanning confocal and differential interference contrast (DIC) microscopy to explain the large differences in dark toxicities between 1–3 and 4. Nevertheless, the study highlights a new family of Ru(II) C^N complexes where π-conjugation beyond a certain point results in low dark cytotoxicity with high photocytotoxicity, opposing the notion that cyclometalated Ru(II) systems are too toxic to be phototherapeutic agents.

This study investigates the correlation between photocytotoxicity and the prolonged excited state lifetimes exhibited by certain Ru(II) polypyridyl photosensitizers comprised of π-expansive ligands. The eight metal complexes selected for this study differ markedly in their triplet state configurations and lifetimes. Human melanoma SKMEL28 and human leukemia HL60 cells were used as in vitro models to test photocytotoxicity induced by the compounds when activated by either broadband visible or monochromatic red light. The photocytotoxicities of the metal complexes investigated varied over two orders of magnitude and were positively correlated with their excited state lifetimes. The complexes with the longest excited state lifetimes, contributed by low-lying (3)IL states, were the most phototoxic toward cancer cells under all conditions.

A series of cationic heteroleptic iridium(III) complexes bearing tris-diimine ligands [Ir(phen)(2)(R-phen)](3+) (R-phen = phenanthroline (1), 3,8-diphenylphenanthroline (2), 3,8-dipyrenylphenanthroline (3), 3-phenylphenanthroline (4), 3-pyrenylphenanthroline (5), and 3,8-diphenylethynylphenanthroline (6)) were synthesized and characterized. These complexes possessed phen ligand-localized (1)π,π* transitions below 300 nm, and charge transfer ((1)CT) and/or (1)π,π* transitions between 300 and 520 nm. In 1, 2, 4, and 6, the low-energy bands were mixed (1)CT/(1)π,π*. However, the increased π-donating ability of the pyrenyl substituent(s) in 3 and 5 split the low-energy bands into a pyrene-based (1)π,π* transition at 300-380 nm and an intraligand charge transfer ((1)ILCT) transition at 380-520 nm. All complexes were emissive at room temperature in CH(3)CN, but the parentage of the emitting state varied depending on the R substituent(s). Complex 1 exhibited predominantly phen ligand-localized (3)π,π* emission mixed with metal-to-ligand charge transfer ((3)MLCT) character, while the emission of 2, 4, and 6 was predominantly from the excited-state with (3)π,π*/(3)ILCT/(3)MLCT character. The emission from 3 and 5 was dominated by pyrene-based (3)π,π* states mixed with (3)ILCT character. The different natures of the lowest triplet excited states were also reflected by the different spectral features and lifetimes of the triplet transient absorption of these complexes. Complexes 3 and 5 had singlet oxygen quantum yields as high as 81 and 72%, respectively. Both gave submicromolar phototoxicities toward cancer cells (SK-MEL-28 human melanoma) and bacteria (S. aureus and S. mutans) with visible light activation (and marginal to no photobiological activity with red light). Their visible-light phototherapeutic indices (PIs) toward SK-MEL-28 cells were 248 for 3 and >435 for 5; PIs were lower in bacteria (≤62) due to their inherent antimicrobial activities. Both complexes were shown to produce substantial amounts of intracellular reactive oxygen species (ROS), which may account for their photobiological activities.

Cu

Three strained Ru(II) metal-organic dyads were prepared and characterized by NMR, mass spectrometry, and analytical HPLC to probe whether these constructs could act as multifunctional photochemotherapy (PCT) agents. The compounds incorporated the crowded 6,6'-dimethyl-2,2'-bipyridine (6,6'-dmb) ligand to impart stoichiometric photocisplatin activity, and imidazo[4,5-f] [1,10]phenanthroline (IP) appended with n thiophene units (nT; n=1-3) to add capacity for singlet oxygen sensitization. With visible light activation, each complex of the series underwent rapid and selective photoejection of 6,6'-dmb in less than 10min, with half-lives (t1/2) as short as 46.3s for [Ru(6,6'-dmb)2(IP-1T)](2+). Photo-triggered ligand loss slowed with increasing n, and was slowest for [Ru(6,6'-dmb)2(IP-3T)](2+) (t1/2=273s). This trend also held for photoadduct formation with DNA; [Ru(6,6'-dmb)2(IP-1T)](2+) produced relaxed circular DNA at the lowest concentrations. Singlet oxygen yields (ΦΔ) increased with n, whereby ΦΔ for [Ru(6,6'-dmb)2(IP-1T)](2+) was only 3%, but increased to 42% on going to [Ru(6,6'-dmb)2(IP-3T)](2+). This photosensitization process was reflected by single-strand breaks in the gel-mobility shift assays of [Ru(6,6'-dmb)2(IP-3T)](2+), but was not discernible for the other compounds. Despite different photochemical and photophysical reactivities, all of the compounds were potent phototoxic agents toward cancer cells (EC50=1-2μM) with relatively short compound-to-light intervals and moderate visible light doses. [Ru(6,6'-dmb)2(IP-3T)](2+) was exceptionally photoactive toward cancer cells at longer intervals (EC50=200nM, PI=750). Phototherapeutic margins increased with n due to decreased dark cytotoxicity for the more π-expansive complexes, making metal-organic dyad [Ru(6,6'-dmb)2(IP-3T)](2+) the best multifunctional PCT agent.

As promising and environmentally friendly catalysts, tungsten-containing heteropoly acids combined with supported noble metals were used for one-pot hydrothermal conversion of cellulose into polyols in the presence of pressurized hydrogen. The microcrystalline cellulose was completely converted over a mixed catalyst consisting of a low concentration of phosphotungstic acid (PTA) (0.03 wt%) and Ru/activated carbon (Ru/AC) via an one-pot hydrothermal reaction, with an ethylene glycol (EG) yield of up to 53.1% under optimal conditions. The catalytic activity of the mixed catalyst gradually decreased with increasing reaction runs, which could be mainly ascribed to the aggregation of Ru/AC particles, and to the coverage of the active sites of Ru due to the deposition of organic materials. Cellobiose was used as a model feedstock for a comparative study on the reaction pathways of the conversion of cellulose, and the results revealed that catalytic conversion of cellobiose consisted of at least three important parallel reactions under the present hydrothermal conditions, which were also most likely involved during the catalytic conversion of cellulose for EG production. Effective control of these reactions would be helpful to further maximize the EG yield during the catalytic conversion of cellulose.

The synthesis, photophysics, reverse saturable absorption, and photodynamic therapeutic effect of six cationic biscyclometalated Ir(III) complexes (1–6) with extended π-conjugation on the diimine ligand and/or the cyclometalating ligands are reported in this paper. All complexes possess ligand-localized 1π,π* absorption bands below 400 nm and charge-transfer absorption bands above 400 nm. They are all emissive in the 500–800 nm range in deoxygenated solutions at room temperature. All complexes exhibit strong and broad triplet excited-state absorption at 430–800 nm, and thus strong reverse saturable absorption for ns laser pulses at 532 nm. Complexes 1–4 are strong reverse saturable absorbers at 532 nm, while complex 6 could be a good candidate as a broadband reverse saturable absorber at 500–850 nm. The degree of π-conjugation of the diimine ligand mainly influences the 1π,π* transitions in their UV-vis absorption spectra, while the degree of π-conjugation of the cyclometalating ligand primarily affects the nature and energies of the lowest singlet and emitting triplet excited states. However, the lowest-energy triplet excited states for complexes 3–6 that contain the same benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine (dppn) diimine ligand but different cyclometalating ligands remain the same as the dppn ligand-localized 3π,π* state, which gives rise to the long-lived, strong excited-state absorption in the visible to the near-IR region. All of the complexes exhibit a photodynamic therapeutic effect upon visible or red light activation, with complex 6 possessing the largest phototherapeutic index reported to date (>400) for an Ir(III) complex. Interactions with biological targets such as DNA suggest that a novel mechanism of action may be at play for the photosensitizing effect. These Ir(III) complexes also produce strong intracellular luminescence that highlights their potential as theranostic agents.

Transition metal complexes are of increasing interest as photosensitizers in photodynamic therapy (PDT) and, more recently, for photochemotherapy (PCT). In recent years, Ru (II) polypyridyl complexes have emerged as the most widely studied systems for both PDT and PCT. Their rich photochemical and photophysical properties derive from a variety of excited-state electronic configurations accessible with visible and near-infrared light, and these properties can be exploited for both energy- and electron-transfer processes that can yield highly potent oxygen-dependent and/or oxygen-independent photobiological activity. Selected examples highlight the use of rational design in coordination chemistry to control the lowest-energy triplet excited state configurations for eliciting a particular type of photoreactivity for PDT and/or PCT effects. These principles are also discussed in the context of the development of TLD1433, the first Ru(II)-based photosensitizer for PDT to enter a human clinical trial. The design of TLD1433 arose from a tumor-centered approach, as part of a complete PDT package that included the light component and the protocol for treating nonmuscle invasive bladder cancer. Briefly, this review summarizes the challenges to bringing PDT into mainstream cancer therapy. It considers the chemical and photophysical solutions that transition metal complexes offer, and it puts into context the multidisciplinary effort needed to bring a new drug to clinical trial.

A series of cationic dinuclear iridium(III) complexes (Ir1 - Ir5) bearing terpyridine-capped fluorenyl bridging ligand and different polypyridyl or cyclometalating terminal tridentate ligands were synthesized, characterized, and evaluated for their photophysical and photobiological activities. The influence of the bridging and terminal ligands on the photophysical properties of the complexes was investigated by UV-vis absorption, emission, and transient absorption spectroscopy, and simulated by TDDFT calculations. All of the complexes displayed strong bridging-ligand localized visible (1)π,π* absorption and red- or near-infrared (NIR) phosphorescence as well as broad triplet excited-state absorption across both visible and NIR wavelengths. These triplet states were assigned as predominantly (3)π,π* for Ir1 (τ = 3.1 μs) and Ir4 (τ = 48 μs), and predominantly (3)CT (charge transfer) for Ir2, Ir3 and Ir5 (τ = 1.7–2.7 μs). Complexes Ir1 – Ir5 acted as in vitro photodynamic therapy (PDT) agents toward human SK-MEL-28 melanoma cells when activated with visible light, with submicromolar photocytotoxicity and phototherapeutic indices (PIs) ranging from 20 to almost 300. The in vitro PDT effects with visible light did not correlate with singlet oxygen ((1)O(2)) quantum yields or DNA photocleaving capacity probed under cell-free conditions. All of the Ir(III) complexes phosphoresced brightly when associated with compromised cells (with or without a light treatment) and exhibited photoactivated cellular uptake, highlighting the theranostic potential of this new class of Ir(III) complex photosensitizers.

The photophysical and photobiological properties of a new class of cyclometalated ruthenium(II) compounds incorporating π-extended benzo[h]imidazo[4,5-f]quinoline (IBQ) cyclometalating ligands (C^N) bearing thienyl rings (n=1–4, compounds 1–4) were investigated. Their octanol-water partition coefficients (log P(o/w)) were positive, and increased with n. Their absorption and emission energies were red-shifted substantially compared to the analogous Ru(II) diimine (N^N) complexes. They displayed C^N-based intraligand (IL) fluorescence and triplet excited-state absorption that shifted to longer wavelengths with increasing n, and N^N-based metal-to-ligand charge transfer (MLCT) phosphorescence that was independent of n. Their photoluminescence lifetimes (τ(em)) ranged from 4–10 ns for (1)IL states and 12–18 ns for (3)MLCT states. Transient absorption lifetimes (τ(TA)) were 5–8 μs with 355-nm excitation, ascribed to (3)IL states that became inaccessible for 1–3 with 532-nm excitation (1–3, τ(TA)=16–17 ns); the (3)IL of 4 only was accessible by lower energy excitation, τ(TA)=3.8 μs. Complex 4 was nontoxic (EC(50) >300 μM) to SK-MEL-28 melanoma cells and CCD1064-Sk normal skin fibroblasts in the dark, while 3 was selectively cytotoxic to melanoma (EC(50)= 5.1 μM) only. Compounds 1 and 2 were selective for melanoma cells in the dark, with submicromolar potencies (EC(50)=350–500 nM) and selectivity factors (SFs) around 50. The photocytotoxicities of compounds 1–4 toward melanoma cells were similar, but only compounds 3 and 4 displayed significant phototherapeutic indices (PIs) (3, 43; 4, >1,100). The larger cytotoxicities for compounds 1 and 2 were attributed to increased cellular uptake and nuclear accumulation, and possibly related to the DNA-aggregating properties of all four compounds as demonstrated by cell-free gel mobility-shift assays. Together, these results demonstrate a new class of thiophene-containing Ru(II) cyclometalated compounds that contain both highly selective chemotherapeutic agents and extremely potent photocytotoxic agents.

Ce3+, Nd3+ codoped (Sr0.6Ca0.4)3(Al0.6Si0.4)O4.4F0.6 phosphors were synthesized through the high-temperature solid-state reaction method. Luminescence spectra, absorption spectra, and decay lifetimes of these samples have been measured to prove the energy-transfer process from Ce3+ to Nd3+. Under UV and blue light excitation, (Sr0.6Ca0.4)3(Al0.6Si0.4)O4.4F0.6:Ce3+,Nd3+ phosphors exhibit near-infrared (NIR) emission, mainly peaking at 1093 nm and secondarily at 916 nm. The NIR emission matches well with the band gap of c-Si. Results of this work suggest that the (Sr0.6Ca0.4)3(Al0.6Si0.4)O4.4F0.6:Ce3+, Nd3+ phosphors have potential application as down-shifting luminescent convertor for enhancing the photoelectric conversion efficiency of c-Si solar cell.

Streptomyces venezuelae ISP5230 was grown in the presence of phenylalanine analogues to observe whether they could be incorporated into novel jadomycin structures. It was found that the bacteria successfully produced jadomycins incorporating 4-aminophenylalanine enantiomers. Upon isolation and characterization of jadomycin 4-amino-l-phenylalanine (1), it was synthetically derivatized, using activated succinimidyl esters, to yield a small jadomycin amide library. These are the first examples of oxazolone-ring-containing jadomycins that have incorporated an amino functionality subsequently used for derivatization.

Ru(II) dyads derived from organic units that impart low-lying 3IL excited states combine the most attractive features of organic photosensitizers with those of coordination complexes. The result is a bichromophoric system with excited-state lifetimes that are significantly longer than those associated with traditional 3MLCT states. Incorporation of α-oligothiophenes as the organic chromophore leads to systems that act as dual Type I/II photosensitizers, opening up the possibility of treating hypoxic tumors with photodynamic therapy (PDT) and overcoming problems with in vivo dosimetry. These photosensitizers, particularly those that consist of three thiophene units and higher, are remarkable DNA binders and photocleavers when exposed to light, exhibiting no interference with DNA structural integrity in the absence of a light-trigger. Such light-responsive agents localize in the nuclei of cells without the need for a carrier and produce a potent PDT response with minimal dark toxicity. This phototherapeutic effect translates directly to animals and is superior to the clinical agent Photofrin® in this model. These Ru(II) dyads can be activated with light in the PDT window, despite very low molar extinction coefficients in this region, and this phenomenon can be attributed to the efficiency with which these agents operate. The ability to activate these prodrugs with ultraviolet to near-infrared light marks an unprecedented versatility that can be exploited to match treatment depth to tumor invasion depth without compromising potency, giving rise to photosensitizers for multiwavelength PDT.