Sodium and Manganese Stoichiometry of P2-Type Na2/3 MnO2.

To realize a reversible solid-state Mn(III/IV) redox couple in layered oxides, co-operative Jahn-Teller distortion (CJTD) of six-coordinate Mn(III) (t2g (3) -eg (1) ) is a key factor in terms of structural and physical properties. We develop a single-phase synthesis route for two polymorphs, namely distorted and undistorted P2-type Na2/3 MnO2 having different Mn stoichiometry, and investigate how the structural and stoichiometric difference influences electrochemical reaction. The distorted Na2/3 MnO2 delivers 216 mAh g(-1) as a 3 V class positive electrode, reaching 590 Wh (kg oxide)(-1) with excellent cycle stability in a non-aqueous Na cell and demonstrates better electrochemical behavior compared to undistorted Na2/3 MnO2 . Furthermore, reversible phase transitions correlated with CJTD are found upon (de)sodiation for distorted Na2/3 MnO2 , providing a new insight into utilization of the Mn(III/IV) redox couple for positive electrodes of Na-ion batteries.

Reversal of P-glycoprotein-mediated paclitaxel resistance by new synthetic isoprenoids in human bladder cancer cell line.

We isolated a paclitaxel-resistant cell line (KK47/TX30) from a human bladder cancer cell line (KK47/WT) in order to investigate the mechanism of and reversal agents for paclitaxel resistance. KK47/TX30 cells exhibited 700-fold resistance to paclitaxel and cross-resistance to vinca alkaloids and topoisomerase II inhibitors. Tubulin polymerization assay showed no significant difference in the ratio of polymerized alpha- and beta-tubulin between KK47/WT and KK47/TX30 cells. Western blot analysis demonstrated overexpression of P-glycoprotein (P-gp) and lung resistance-related protein (LRP) in KK47/TX30 cells. Drug accumulation and efflux studies showed that the decreased paclitaxel accumulation in KK47/TX30 cells was due to enhanced paclitaxel efflux. Cell survival assay revealed that verapamil and cepharanthine, conventional P-gp modulators, could completely overcome paclitaxel resistance. To investigate whether new synthetic isoprenoids could overcome paclitaxel resistance, we synthesized 31 isoprenoids based on the structure of N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine (SDB), which could reverse multidrug resistance (MDR), as shown previously. Among those examined, trans-N,N'-bis(3,4-dimethoxybenzyl)-N-solanesyl-1,2-diaminocyclohexane (N-5228) could completely reverse paclitaxel resistance in KK47/TX30 cells. N-5228 inhibited photoaffinity labeling of P-gp by [(3)H]azidopine, suggesting that N-5228 could bind to P-gp directly and could be a substrate of P-gp. Next, we investigated structural features of these 31 isoprenoids in order to determine the structural requirements for the reversal of P-gp-mediated paclitaxel resistance, suggesting that the following structural features are important for overcoming paclitaxel resistance: (1) a basic structure of 8 to 10 isoprene units, (2) a cyclohexane ring or benzene ring within the framework, (3) two cationic sites in close proximity to each other, and (4) a benzyl group with 3,4-dimethoxy functionalities, which have moderate electron-donating ability. These findings may provide valuable information for the development of P-gp-mediated MDR-reversing agents.