Resolution of 1‐n‐Butyl‐3‐Methyl‐3‐Phospholene 1‐Oxide With TADDOL Derivatives and Calcium Salts of O,O'‐Dibenzoyl‐(2R,3R)‐ or O,O'‐di‐p‐Toluoyl‐(2R,3R)‐tartaric Acid

The resolution methods applying (?)‐(4R,5R)‐4,5‐bis(diphenylhydroxymethyl)‐2,2‐dimethyldioxolane (“TADDOL”), (?)‐(2R,3R)‐α,α,α',α'‐tetraphenyl‐1,4‐dioxaspiro[4.5]decan‐2,3‐dimethanol (“spiro‐TADDOL”), as well as the acidic and neutral Ca²⁺ salts of (?)‐O,O'‐dibenzoyl‐ and (?)‐O,O'‐di‐p‐toluoyl‐(2R,3R)‐tartaric acid were extended for the preparation of 1‐n‐butyl‐3‐methyl‐3‐phospholene 1‐oxide in optically active form. In one case, the intermediate diastereomeric complex could be identified by single‐crystal X‐ray analysis. The absolute P‐configuration of the enantiomers of the phospholene oxide was also determined by comparing the experimentally obtained and calculated CD spectra. Chirality 26:174–182, 2014. © 2014 Wiley Periodicals, Inc.     

High‐Voltage Oxygen‐Redox‐Based Cathode for Rechargeable Sodium‐Ion Batteries

Recently, anionic‐redox‐based materials have shown promising electrochemical performance as cathode materials for sodium‐ion batteries. However, one of the limiting factors in the development of oxygen‐redox‐based electrodes is their low operating voltage. In this study, the operating voltage of oxygen‐redox‐based electrodes is raised by incorporating nickel into P2‐type Na_2/3[Zn_0.3Mn_0.7]O₂ in such a way that the zinc is partially substituted by nickel. As designed, the resulting P2‐type Na_2/3[(Ni_0.5Zn_0.5)_0.3Mn_0.7]O₂ electrode exhibits an average operating voltage of 3.5 V and retains 95% of its initial capacity after 200 cycles in the voltage range of 2.3–4.6 V at 0.1C (26 mA g^?1). Operando X‐ray diffraction analysis reveals the reversible phase transition: P2 to OP4 phase on charge and recovery to the P2 phase on discharge. Moreover, ex situ X‐ray absorption near edge structure and X‐ray photoelectron spectroscopy studies reveal that the capacity is generated by the combination of Ni²⁺/Ni⁴⁺ and O^2?/O^1? redox pairs, which is supported by first‐principles calculations. It is thought that this kind of high voltage redox species combined with oxygen redox could be an interesting approach to further increase energy density of cathode materials for not only sodium‐based rechargeable batteries, but other alkali‐ion battery systems.     

Down‐regulation of c‐fos by shRNA sensitizes adriamycin‐resistant MCF‐7/ADR cells to chemotherapeutic agents via P‐glycoprotein inhibition and apoptosis augmentation

Multidrug resistance (MDR) is a major hurdle in the treatment of cancer. Research indicated that the main mechanisms of most cancers included so‐called “pump” (P‐glycoprotein, P‐gp) and “non‐pump” (apoptosis) resistance. Identification of novel signaling molecules associated with both P‐gp and apoptosis will facilitate the development of more effective strategies to overcome MDR in tumor cells. Since the proto‐oncogene c‐fos has been implicated in cell adaptation to environmental changes, we analyzed its role in mediating “pump” and “non‐pump” resistance in MCF‐7/ADR, an adriamycin (ADR)‐selected human breast cancer cell line with the MDR phenotype. Elevated expression of c‐fos in MCF‐7/ADR cells and induction of c‐fos by ADR in the parental drug‐sensitive MCF‐7 cells suggested a link between c‐fos and MDR phenotype. Down‐regulation of c‐fos expression via shRNA resulted in sensitization of MCF‐7/ADR cells to chemotherapeutic agents, including both P‐gp and non‐P‐gp substrates. Further results proved that c‐fos down‐regulation in MCF‐7/ADR cells resulted in decreased P‐gp expression and activity, enhanced apoptosis, and altered expression of apoptosis‐associated proteins (i.e., Bax, Bcl‐2, p53, and PUMA). All above facts indicate that c‐fos is involved in both P‐gp‐ and anti‐apoptosis‐mediated MDR of MCF‐7/ADR cells. Based on these results, we propose that c‐fos may represent a potential molecular target for resistant cancer therapy, and suppressing c‐fos gene expression may therefore be an effective means to temper breast cancer cell's MDR to cytotoxic chemotherapy. J. Cell. Biochem. 114: 1890–1900, 2013. © 2013 Wiley Periodicals, Inc.     

Unexpected Loss of Stereoselectivity in Ring‐Opening Reaction of 2‐Alkoxy‐2‐Thio‐1,3,2‐Oxathiaphospholanes With a Pyrophosphate Anion

A reaction of DBU promoted ring opening in nucleoside‐3'‐O‐ and nucleoside‐5'‐O‐(2‐thio‐4,4‐pentamethylene‐1,3,2‐oxathiaphospholane) monomers with a pyrophosphate or a methylenediphosphonate anion proceeds with substantial loss of stereoselectivity. Depending on the absolute configuration of the phosphorus atom, so far widely accepted the stereoretentive mechanism of condensation is accompanied by a stereoinvertive one, most likely employing an intramolecular ligand–ligand exchange in an uncharged intermediate. Chirality 27:155–122, 2015. © 2014 Wiley Periodicals, Inc     

Metal–Organophosphine Framework‐Derived N,P‐Codoped Carbon‐Confined Cu3P Nanopaticles for Superb Na‐Ion Storage

Metal–organic framework derived approaches are emerging as a viable way to design carbon‐confined transitional metal phosphides (TMPs@C) for energy storage and conversion. However, their preparation generally involves a phosphorization using a large amount of additional P sources, which inevitably releases flammable, poisonous PH₃. Therefore, developing an efficient strategy for eco‐friendly synthesis of TMPs@C is full of challenges. Here, a metal–organophosphine framework (MOPF) derived strategy is developed to allow an eco‐friendly design of TMPs@C without an additional P source, avoiding release of PH₃. To illustrate this strategy, 1,3,5‐triaza‐7‐phosphaadamantane (PTA) ligands and Cu(NO₃)₂ metal centers are employed to construct Cu/PTA‐MOPFs nanosheets. Cu/PTA‐MOPFs can be directly converted to carbon‐confined Cu₃P nanoparticles by annealing. Benefiting from high heteroatom content in PTA, a high doping content of 3.92 at% N and 8.26 at% P can also be achieved in the carbon matrix. As a proof‐of‐concept application, N,P‐codoped carbon‐confined Cu₃P nanoparticles as anodes for Na‐ion storage exhibit a high initial reversible capacity of 332 mA h g^?1 at 50 mA g^?1, and superb rate and cyclic performance. Due to rich coordination modes of organophosphine, MOPFs are expected to become a promising molecular platform for design of various heteroatom‐doped TMPs@C for energy storage and conversion.     

Front‐Loading Natural‐Product‐Screening Libraries for log P: Background,Development, and Implementation

In the period from January 1981 to December 2010, 1068 small‐molecule new chemical entities (NCEs) were introduced, of which ca. 34% are either a natural product or a close analogue. While this metric reflects the impact natural products have played in delivering new chemical starting points (leads) for the pharmaceutical industry, it does not capture the decline this approach has suffered over the last 20 years as the high‐throughput screening (HTS) of pure compound libraries has become more popular. An impediment to natural‐product drug discovery in the HTS paradigm is the lack of a clear strategy that enables front‐loading of an extract or fraction's chemical constituents so that they are compliant with lead‐ and drug‐like chemical space. To address this imbalance, an approach based on lipophilicity, as measured by clog P has been developed that, together with advances being made in isolation and structural elucidation, can afford natural product leads in timelines compatible with pure compound screening.     

P‐bodies and their functions during mRNA cell cycle: Mini‐review

P‐bodies (processing bodies) are observed in different organisms such as yeast, Caenorhabditis elegans and mammals. A typical eukaryotic cell contains several types of spatially formed granules, such as P‐bodies, stress granules and a variety of ribonucleoprotein bodies. These microdomains play important role in mRNA processing, including RNA interference, repression of translation and mRNA decay. The P‐bodies components as well as stress granules may play an important role in host defense against viral infection. The complete set of P‐bodies protein elements is still poor known. They contain conserved protein core limited to different organisms or to stress status of the cell. P‐bodies are related also to some neuronal mRNA granules as well as to maternal RNA granules or male germ cell granules. In this mini‐review, we focus on the structure of P‐bodies and their function in the mRNA utilization and processing because of the high mRNA's dynamics between different cellular compartments and its key role in modulation of gene expression. Copyright © 2012 John Wiley & Sons, Ltd.     

High‐Efficiency CsPbI2Br Perovskite Solar Cells with Dopant‐Free Poly(3‐hexylthiophene) Hole Transporting Layers

CsPbI₂Br is emerging as a promising all‐inorganic material for perovskite solar cells (PSCs) due to its more stable lattice structure and moisture resistance compared to CsPbI₃, although its device performance is still much behind this counterpart. Herein, a preannealing process is developed and systematically investigated to achieve high‐quality CsPbI₂Br films by regulating the nucleation and crystallization of perovskite. The preannealing temperature and time are specifically optimized for a dopant‐free poly(3‐hexylthiophene) (P3HT)‐based device to target dopant‐induced drastic performance degradation for spiro‐OMeTAD‐based devices. The resulting P3HT‐based device exhibits comparable power conversion efficiency (PCE) to spiro‐OMeTAD‐based devices but much enhanced ambient stability with over 95% PCE after 1300 h. A diphenylamine derivative is introduced as a buffer layer to improve the energy‐level mismatch between CsPbI₂Br and P3HT. A record‐high PCE of 15.50% for dopant‐free P3HT‐based CsPbI₂Br PSCs is achieved by alleviating the open‐circuit voltage loss with the buffer layer. These results demonstrate that the preannealing processing together with a suitable buffer layer are applicable strategies for developing dopant‐free P3HT PSCs with high efficiency and stability.     

Nanofiber‐Based Bulk‐Heterojunction Organic Solar Cells Using Coaxial Electrospinning

Nanofibers consisting of the bulk heterojunction organic photovoltaic (BHJ–OPV) electron donor–electron acceptor pair poly(3‐hexylthiophene):phenyl‐C₆₁‐butyric acid methyl ester (P3HT:PCBM) are produced through a coaxial electrospinning process. While P3HT:PCBM blends are not directly electrospinnable, P3HT:PCBM‐containing fibers are produced in a coaxial fashion by utilizing polycaprolactone (PCL) as an electrospinnable sheath material. Pure P3HT:PCBM fibers are easily obtained after electrospinning by selectively removing the PCL sheath with cyclopentanone (average diameter 120 ± 30 nm). These fibers are then incorporated into the active layer of a BHJ–OPV device, which results in improved short‐circuit current densities, fill factors, and power‐conversion efficiencies (PCE) as compared to thin‐film devices of identical chemical composition. The best‐performing fiber‐based devices exhibit a PCE of 4.0%, while the best thin‐film devices have a PCE of 3.2%. This increase in device performance is attributed to the increased in‐plane alignment of P3HT polymer chains on the nanoscale, caused by the electrospun fibers, which leads to increased optical absorption and subsequent exciton generation. This methodology for improving device performance of BHJ–OPVs could also be implemented for other electron donor–electron acceptor systems, as nanofiber formation is largely independent of the PV material.     

Crystal structure of the cataract‐causing P23T γD‐crystallin mutant

Up to now, efforts to crystallize the cataract‐associated P23T mutant of human γD‐crystallin have not been successful. Therefore, insights into the light scattering mechanism of this mutant have been exclusively obtained from solution work. Here we present the first crystal structure of the P23T mutant at 2.5 Å resolution. The protein exhibits essentially the same overall structure as seen for the wild‐type protein. Based on our structural data, we confirm that no major conformational changes are caused by the mutation, and that solution phase properties of the mutant appear exclusively associated with cataract formation. Proteins 2013. © 2013 Wiley Periodicals, Inc.     

Burn‐in Free Nonfullerene‐Based Organic Solar Cells

Organic solar cells that are free of burn‐in, the commonly observed rapid performance loss under light, are presented. The solar cells are based on poly(3‐hexylthiophene) (P3HT) with varying molecular weights and a nonfullerene acceptor (rhodanine‐benzothiadiazole‐coupled indacenodithiophene, IDTBR) and are fabricated in air. P3HT:IDTBR solar cells light‐soaked over the course of 2000 h lose about 5% of power conversion efficiency (PCE), in stark contrast to [6,6]‐Phenyl C61 butyric acid methyl ester (PCBM)‐based solar cells whose PCE shows a burn‐in that extends over several hundreds of hours and levels off at a loss of ≈34%. Replacing PCBM with IDTBR prevents short‐circuit current losses due to fullerene dimerization and inhibits disorder‐induced open‐circuit voltage losses, indicating a very robust device operation that is insensitive to defect states. Small losses in fill factor over time are proposed to originate from polymer or interface defects. Finally, the combination of enhanced efficiency and stability in P3HT:IDTBR increases the lifetime energy yield by more than a factor of 10 when compared with the same type of devices using a fullerene‐based acceptor instead.     

Design of novel artemisinin‐like derivatives with cytotoxic and anti‐angiogenic properties

Artemisinins are plant products with a wide range of medicinal applications. Most prominently, artesunate is a well tolerated and effective drug for treating malaria, but is also active against several protozoal and schistosomal infections, and additionally exhibits anti‐angiogenic, anti‐tumorigenic and anti‐viral properties. The array of activities of the artemisinins, and the recent emergence of malaria resistance to artesunate, prompted us to synthesize and evaluate several novel artemisinin‐like derivatives. Sixteen distinct derivatives were therefore synthesized and the in vitro cytotoxic effects of each were tested with different cell lines. The in vivo anti‐angiogenic properties were evaluated using a zebrafish embryo model. We herein report the identification of several novel artemisinin‐like compounds that are easily synthesized, stable at room temperature, may overcome drug‐resistance pathways and are more active in vitro and in vivo than the commonly used artesunate. These promising findings raise the hopes of identifying safer and more effective strategies to treat a range of infections and cancer.     

Inhibition of P‐Glycoprotein‐Induced Multidrug Resistance by a Clerodane‐Type Diterpenoid from Sindora sumatrana

The aim of the present study was to investigate the effects of di‐ and sesquiterpenoids isolated from the pods of Sindora sumatrana Miq. (Leguminosae) on P‐glycoprotein (P‐gp) function in an adriamycin‐resistant human breast cancer cell line, MCF‐7/ADR. Over‐expression of P‐gp is known to be one of the mechanisms involved in multidrug resistance (MDR), which is a major obstacle in clinical cancer treatment. Among six di‐ and sesquiterpenoids extracted from S. sumatrana, (+)‐7β‐acetoxy‐15,16‐epoxycleroda‐3,13(16),14‐trien‐18‐oic acid ( 1 ) showed a strong P‐gp inhibitory effect, as great as that of verapamil, a representative P‐gp inhibitor. Compound 1 enhanced daunomycin accumulation more than fourfold and significantly decreased daunomycin efflux compared with control, resulting in a decrease in the IC₅₀ value for daunomycin. These results suggest that compound 1 inhibits the functioning of P‐gp and, therefore, can be developed as an MDR‐reversing agent.