High Thermal Stability of Copper-Based Perovskite Scintillators for High-Temperature X-ray Detection.

High-temperature scintillation detectors play a significant role in oil exploration. However, traditional scintillators have limited ability to meet the requirements of practical applications owing to their low thermal stability. In this study, we designed and developed a one-dimensional (1D) Cs5Cu3Cl6I2 scintillator with high thermal stability. In addition, by preparing Cs5Cu3Cl7I, we proved that the Cs5Cu3Cl6I2 scintillator exhibits high thermal stability because the bridges linking the structural units in the 1D chain structure are only formed by I- ions, which improve their structural rigidity. The scintillator has a high steady-state light yield (59,700 photons MeV-1) and exhibits the highest spatial resolution for powder-based scintillation screens (18 lp mm-1) after cyclic treatment within the temperature range of 298-423 K. The Cs5Cu3Cl6I2 scintillator allows the visualization of alloy melting, indicating that it has significant potential for application in high-temperature environments. This study provides a new perspective toward the design of scintillators with high thermal stability.

Visualization of X-rays with an Ultralow Detection Limit via Zero-Dimensional Perovskite Scintillators.

X-rays play an extremely significant role in medical diagnosis, safety testing, scientific research, and other practical applications. However, as the main sources of radioactive pollution, the hazard of X-rays to human health and the environment has been a major concern. Herein, the explored perovskite scintillator of Cs2Zr1-xPbxCl6 in this work exhibits an ultrahigh radioluminescence intensity owing to the enhanced X-ray absorption for the introduction of Pb2+ ions. The Cs2Zr1-xPbxCl6 crystals are demonstrated as efficient scintillators with a self-trapped exciton emission and extremely high steady-state light yield (∼101,944 photons meV-1). This fascinating scintillator provides a convenient visual tool for X-ray detection even for an indoor lighting environment, reaching a low detection limit of ∼14.2 nGy·s-1, which is about 1/387 of the typical medical imaging dose (5.5 µGy·s-1). Moreover, X-ray imaging with a high resolution of 16.6 lp·mm-1 is achieved with the as-explored Cs2Zr1-xPbxCl6 scintillator film. Herein, the Cs2Zr1-xPbxCl6 scintillator provides a feasible strategy for X-ray monitoring in the field of biomedicine, high-energy physics, national security, and other applications.

Design, synthesis and biological evaluation of novel zanamivir derivatives as potent neuraminidase inhibitors.

Neuraminidase (NA) is an important antiviral drug target. Zanamivir is one of the most potent NA inhibitors. In this paper, a series of zanamivir derivatives as potential NA inhibitors were studied by combination of molecular modeling techniques including 3D-QSAR, molecular docking, and molecular dynamics (MD) simulation. The results show that the best CoMFA (comparative molecular field analysis) model has q2 = 0.728 and r2 = 0.988, and the best CoMSIA (comparative molecular similarity indices analysis) model has q2 = 0.750 and r2 = 0.981, respectively. The built 3D-QSAR models show significant statistical quality and excellent predictive ability. Seven new NA inhibitors were designed and predicted. 20 ns of MD simulations were carried out and their binding free energies were calculated. Two designed compounds were selected to be synthesized and biologically evaluated by NA inhibition and virus inhibition assays. One compound (IC50 = 0.670 µM, SI > 149) exhibits excellent antiviral activity against A/WSN/33 H1N1, which is superior to the reference drug zanamivir (IC50 = 0.873 µM, SI > 115). The theoretical and experimental results may provide reference for development of new anti-influenza drugs.

Molecular modeling study, synthesis and biological evaluation of combretastatin A-4 analogues as anticancer agents and tubulin inhibitors.

As the major structural component of microtubules, tubulin is an interesting target for the development of anticancer agents. In this study, 64 tubulin polymerization inhibitors of five-membered heterocycle-based combretastatin A-4 analogues were studied by a combination of molecular modeling techniques including 3D-QSAR, molecular docking, and molecular dynamics (MD) simulation. The CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) models were established with desirable statistical parameters and excellent predictive ability. 20 ns MD simulations were successfully performed to confirm the detailed binding mode and validate the rationality of docking results. Combining the binding free energy calculations and 3D-QSAR results, some new heterocycle-based combretastatin A-4 analogues were designed. Three of them were synthesized and biologically evaluated. Compound 13a displayed potent antiproliferative activity (IC50 value of 1.31 µM against HepG2 cells, IC50 value of 1.37 µM against A549 cells) and inhibition of tubulin polymerization activity (IC50 value of 0.86 µM). Compound 13b also presented good activity against HepG2 cells (IC50 value of 4.75 µM). The experimental results demonstrated that the built models were effective for the development of novel anticancer agents and tubulin inhibitors.

Molecular modeling study of CP-690550 derivatives as JAK3 kinase inhibitors through combined 3D-QSAR, molecular docking, and dynamics simulation techniques.

To develop more potent JAK3 kinase inhibitors, a series of CP-690550 derivatives were investigated using combined molecular modeling techniques, such as 3D-QSAR, molecular docking and molecular dynamics (MD). The leave-one-out correlation (q2) and non-cross-validated correlation coefficient (r2) of the best CoMFA model are 0.715 and 0.992, respectively. The q2 and r2 values of the best CoMSIA model are 0.739 and 0.995, respectively. The steric, electrostatic, and hydrophobic fields played important roles in determining the inhibitory activity of CP-690550 derivatives. Some new JAK3 kinase inhibitors were designed. Some of them have better inhibitory activity than the most potent Tofacitinib (CP-690550). Molecular docking was used to identify some key amino acid residues at the active site of JAK3 protein. 10ns MD simulations were successfully performed to confirm the detailed binding mode and validate the rationality of docking results. The calculation of the binding free energies by MMPBSA method gives a good correlation with the predicted biological activity. To our knowledge, this is the first report on MD simulations and free energy calculations for this series of compounds. The combination results of this study will be valuable for the development of potent and novel JAK3 kinase inhibitors.