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Core-shell phosphorescent nanoparticles were used to detect intracellular ClO– via ratiometric and photoluminescence lifetime imaging.

Biothiols, such as cysteine (Cys) and homocysteine (Hcy), play very crucial roles in biological systems. Abnormal levels of these biothiols are often associated with many types of diseases. Therefore, the detection of Cys (or Hcy) is of great importance. In this work, we have synthesized an excellent "OFF-ON" phosphorescent chemodosimeter 1 for sensing Cys and Hcy with high selectivity and naked-eye detection based on an Ir(III) complex containing a 2,4-dinitrobenzenesulfonyl (DNBS) group within its ligand. The "OFF-ON" phosphorescent response can be assigned to the electron-transfer process from Ir(III) center and C^N ligands to the DNBS group as the strong electron-acceptor, which can quench the phosphorescence of probe 1 completely. The DNBS group can be cleaved by thiols of Cys or Hcy, and both the (3)MLCT and (3)LC states are responsible for the excited-state properties of the reaction product of probe 1 and Cys (or Hcy). Thus, the phosphorescence is switched on. Based on these results, a general principle for designing "OFF-ON" phosphorescent chemodosimeters based on heavy-metal complexes has been provided. Importantly, utilizing the long emission-lifetime of phosphorescence signal, the time-resolved luminescent assay of 1 in sensing Cys was realized successfully, which can eliminate the interference from the short-lived background fluorescence and improve the signal-to-noise ratio. As far as we know, this is the first report about the time-resolved luminescent detection of biothiols. Finally, probe 1 has been used successfully for bioimaging the changes of Cys/Hcy concentration in living cells.

Three novel sesquinlignans, tatanans A (1), B (2), and C (3), have been isolated from the rhizomes of Acorus tatarinowii Schott. Their structures were established by spectroscopic techniques and single-crystal X-ray analysis. Tatanans A-C potently increase GK enzymatic activity with EC(1.5) values in the range of 0.16-1.85 μM. The potent GK activity and unique structural features of tatanans make them promising leads for therapeutic development of antihyperglycemic drugs.

A novel class of phthalimides functionalized with privileged scaffolds was designed, synthesized and evaluated as potential inhibitors of plasmepsin 2 (Ki: 0.99 ± 0.1 μM for 6u) and plasmepsin 4 (Ki: 3.3 ± 0.3 μM for 6t), enzymes found in the digestive vacuole of the plasmodium parasite and considered as crucial drug targets. Three compounds were identified as potential candidates for further development. The listed compounds were also assayed for their antimalarial efficacy against chloroquine (CQ) sensitive strain (3D7) of Plasmodium falciparum. Assay of twenty seven hydroxyethylamine derivatives revealed four (5e, 6j, 6o and 6s) as strongly active, which were further evaluated against CQ resistant strain (7GB) of P. falciparum. Compound 5e possessing the piperidinopiperidine moiety exhibited promising antimalarial activity with an IC50 of 1.16 ± 0.04 μM. Further, compounds 5e, 6j, 6o and 6s exhibited low cytotoxic effect on MCF-7 cell line. Compound 6s possessing C 2 symmetry was identified as the least cytotoxic with significant antimalarial activity (IC50: 1.30 ± 0.03 μM). The combined presence of hydroxyethylamine and cyclic amines (piperazines and piperidines) was observed as crucial for the activity. The current studies suggest that hydroxyethylamine based molecules act as potent antimalarial agent and may be helpful in drug development.

HIV drug resistance continues to emerge; consequently, there is an urgent need to develop next generation antiretroviral therapeutics.1 Here we report on the structural and kinetic effects of an HIV protease drug resistant variant with the double mutations Gly48Thr and Leu89Met (PRG48T/L89M), without the stabilizing mutations Gln7Lys, Leu33Ile, and Leu63Ile. Kinetic analyses reveal that PRG48T/L89M and PRWT share nearly identical Michaelis–Menten parameters; however, PRG48T/L89M exhibits weaker binding for IDV (41-fold), SQV (18-fold), APV (15-fold), and NFV (9-fold) relative to PRWT. A 1.9 Å resolution crystal structure was solved for PRG48T/L89M bound with saquinavir (PRG48T/L89M-SQV) and compared to the crystal structure of PRWT bound with saquinavir (PRWT-SQV). PRG48T/L89M-SQV has an enlarged active site resulting in the loss of a hydrogen bond in the S3 subsite from Gly48 to P3 of SQV, as well as less favorable hydrophobic packing interactions between P1 Phe of SQV and the S1 subsite. PRG48T/L89M-SQV assumes a more open conformation relative to PRWT-SQV, as illustrated by the downward displacement of the fulcrum and elbows and weaker interatomic flap interactions. We also show that the Leu89Met mutation disrupts the hydrophobic sliding mechanism by causing a redistribution of van der Waals interactions in the hydrophobic core in PRG48T/L89M-SQV. Our mechanism for PRG48T/L89M-SQV drug resistance proposes that a defective hydrophobic sliding mechanism results in modified conformational dynamics of the protease. As a consequence, the protease is unable to achieve a fully closed conformation that results in an expanded active site and weaker inhibitor binding.

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In this work, ethylene/1‐hexene copolymerization with a novel SiO2‐supported inorganic and organic hybrid chromium‐based catalyst was investigated. This catalyst was prepared using the residual surface hydroxyl groups in Phillips catalyst to support bis(triphenylsilyl) chromate (BC) in order to get the merits from two important chromium‐based catalysts namely inorganic Phillips and organic S‐2 catalysts. The influences of addition amount of 1‐hexene and BC were systematically investigated. With increasing 1‐hexene from 0 to 7 vol%, the activity of HCat‐2 catalyst showed a decreasing tendency. Its copolymer also showed the better short chain branches distribution through the temperature rising elution fractionation cross successive self‐nucleation and annealing characterization.