Design, synthesis and biological evaluation of hydantoin derivatives as Mcl-1 selective inhibitors.

As a member of Bcl-2 protein family, myeloid cell leukemia-1 (Mcl-1) plays a critical role in cell apoptosis and has become a promising anti-cancer drug target. Herein, we designed and synthesized a series of hydantoin derivatives as novel Mcl-1 inhibitors based on our previously developed lead compound. Among them, compound M23 and M24 exhibited good binding affinities against Mcl-1 with Ki values of 0.49 µM and 0.33 µM respectively. Especially, compound M23 exhibited good selectivity over Bcl-xL, whereas compound M24 possessed good selectivity over both Bcl-2 and Bcl-xL. Furthermore, we also investigated the effects of these new Mcl-1 inhibitors on cell proliferation, apoptosis and mitochondrial membrane potential, as well as the stability in plasma.

Enhancing Hydrogen Oxidation and Evolution Kinetics by Tuning the Interfacial Hydrogen-Bonding Environment on Functionalized Platinum Surfaces.

Developing efficient catalytic systems for the hydrogen oxidation and evolution reactions (HOR/HER) is essential in the world's transition to renewable energy. There is a growing recognition that the HOR/HER activity depends on properties of the electrochemical interface, rather than just the composition and structure of the catalyst. Herein, we demonstrate that specifically adsorbed organic additives (theophylline derivatives) could enhance the intrinsic HOR/HER activity in base on polycrystalline Pt by up to a factor of 3 via introducing weakly hydrogen-bonded water, as confirmed by in situ surface enhanced infrared and Raman spectroscopies. Optimal HOR/HER activity is achieved on a 7-n-butyltheophylline decorated Pt surface, which sufficiently disrupts the hydrogen bonding network in the double layer without depleting the interfacial water. This work demonstrates the promise of electrochemical interfacial engineering as a strategy to boost electrocatalytic performance.

Design, synthesis and preliminary bioactivity studies of indomethacin derivatives as Bcl-2/Mcl-1 dual inhibitors.

Bcl-2 family proteins, which divides into pro-apoptosis proteins and anti-apoptosis proteins, are involved in cell apoptosis progression. As numerous studies illustrated, targeting Bcl-2 family proteins is more and more attractive and practicable to cancer treatment. In this work, we designed and synthesized a series of indomethacin derivatives as new inhibitors for Bcl-2 family proteins. Our results of binding assay to Bcl-2 proteins, MTT assay and apoptotic assay indicated that some compounds had potent binding affinity to Bcl-2/Mcl-1 but not Bcl-XL. Furthermore, compound 8j showed improved anti-proliferative activity than known Bcl-2 inhibitor WL-276.

Determination of 4-n-butylresorcinol by fluorescence derivatization based on dopamine.

4-n-butylresorcinol (4nBR) is a frequently utilized as whitening ingredients in skincare cosmetics. Compared with other whitening ingredients, it can effectively inhibit tyrosinase with lower toxicity and superior inhibition efficacy. Under alkaline conditions, an induced oxidative coupling reaction can occur between 4nBR and dopamine (DA) to generate strong fluorescent substance azamonardine with an intense emission band centering at 476 nm when excited at 440 nm. This phenomenon can be used to establish a fluorescence analysis method for 4nBR. The results indicated that the linear range of the method was 1.0-24.0 nmol L-1, and the detection limit was as low as 0.25 nmol L-1. The method showed high sensitivity, good selectivity, mild experimental conditions and low cost. The proposed method was successfully used to detect 4nBR in cosmetics, and the results were consistent with those of HPLC. The spiking recoveries were between 98.2% and 108 %.

Alginate-Xylan Biopolymer as a Multifunctional Binder for 5 V High-Voltage LNMO Electrodes.

LiNi0.5Mn1.5O4 (LNMO) with a spinel structure is one of the most promising cathode materials choices for Li-ion batteries (LIBs). However, at a high operating voltages, the decomposition of organic electrolytes and the dissolution of transition metals, especially Mn(II) ions, cause unsatisfactory cycle stability. The initial application of a sodium alginate (SA)-xylan biopolymer as an aqueous binder aims to address the aforementioned problems. The SX28-LNMO electrode has a sizable discharge capacity, exceptional rate capability, and long-term cyclability with a capacity retention of 99.8% after 450 cycles at 1C and a remarkable rate capability of 121 mAh g-1 even at 10C. A more thorough investigation illustrated that SX28 binder provides a substantial adhesion property and generates a uniform (CEI) layer on the LNMO surface, suppressing electrolytes' oxidative decomposition upon cycling and improving LIB performances. This work highlights the potential of hemicellulose as an aqueous binder for 5.0 V high-voltage cathodes.

In Situ Preparation of High-Performance Silicon-Based Integrated Electrodes Using Cross-Linked Cyclodextrins.

The strategy of material modification for improving the stability of silicon electrodes is laborious and costly, while the conventional binders cannot withstand the repeated massive volume variability of silicon-based materials. Hence, there is a demand to settle the silicon-based materials' problems with green and straightforward solutions. This paper presents a high-performance silicon anode with a binder obtained by in situ thermal cross-linking of citric acid (CA) and ß-cyclodextrin (ß-CD) during the electrode preparation process. The Si electrode with a binder synthesized by the one-pot method shows excellent cycling performance. It maintains a specific capacity of 1696 mAh·g-1 after 200 cycles at a high current of 0.5 C. Furthermore, the carbonylation of ß-CD to carbonyl-ß-CD (c-ß-CD) introduced better water solubility, and the c-ß-CD can generate multidimensional connections with CA and Si, which significantly enhances the specific capacity to 1941 mAh·g-1 at 0.5 C. The results demonstrate that the prepared integrated electrode facilitates the formation of a stable and controllable solid electrolyte interface layer of Si and accommodates Si's repeated giant volume variations.

Development of QSRR model for hydroxamic acids using PCA-GA-BP algorithm incorporated with molecular interaction-based features.

As a potent zinc chelator, hydroxamic acid has been applied in the design of inhibitors of zinc metalloenzyme, such as histone deacetylases (HDACs). A series of hydroxamic acids with HDAC inhibitory activities were subjected to the QSRR (Quantitative Structure-Retention Relationships) study. Experimental data in combination with calculated molecular descriptors were used for the development of the QSRR model. Specially, we employed PCA (principal component analysis) to accomplish dimension reduction of descriptors and utilized the principal components of compounds (16 training compounds, 4 validation compounds and 7 test compounds) to execute GA (genetic algorithm)-BP (error backpropagation) algorithm. We performed double cross-validation approach for obtaining a more convincing model. Moreover, we introduced molecular interaction-based features (molecular docking scores) as a new type of molecular descriptor to represent the interactions between analytes and the mobile phase. Our results indicated that the incorporation of molecular interaction-based features significantly improved the accuracy of the QSRR model, (R2 value is 0.842, RMSEP value is 0.440, and MAE value is 0.573). Our study not only developed QSRR model for the prediction of the retention time of hydroxamic acid in HPLC but also proved the feasibility of using molecular interaction-based features as molecular descriptors.

Cross-linked ß-CD-CMC as an effective aqueous binder for silicon-based anodes in rechargeable lithium-ion batteries.

As a non-active material component, the binder can effectively maintain the integrity of battery electrodes. In this work, based on the inspired structure of fishing nets, a three-dimensional mesh adhesive using widely sourced raw materials CMC and ß-CD was designed. These cross-linked cyclodextrins have the advantage of dispersing the stress at the anchor point and moderating the significant volume changes of the Si anode. The Si/ß-CD-CMC electrode maintains a reversible capacity of 1702 mA h g-1 even after 200 cycles at a high current of 0.5C. This work represents a significant step forward in Si anode binders and enables the cross-linked cyclodextrins to have potential applications in energy storage systems.