In this manuscript, the inorganic perovskite CsPbIBr is investigated as a photovoltaic material that offers higher stability than the organic-inorganic hybrid perovskite materials. It is demonstrated that CsPbIBr does not irreversibly degrade to its component salts as in the case of methylammonium lead iodide but instead is induced (by water vapor) to transform from its metastable brown cubic (1.92 eV band gap) phase to a yellow phase having a higher band gap (2.85 eV). This is easily reversed by heating to 350 °C in a dry environment. Similarly, exposure of unencapsulated photovoltaic devices to water vapor causes current (J) loss as the absorber transforms to its more transparent (yellow) form, but this is also reversible by moderate heating, with over 100% recovery of the original device performance. NMR and thermal analysis show that the high band gap yellow phase does not contain detectable levels of water, implying that water induces the transformation but is not incorporated as a major component. Performances of devices with best efficiencies of 9.08% (V = 1.05 V, J = 12.7 mA cm and FF = 68.4%) using a device structure comprising glass/ITO/c-TiO/CsPbIBr/Spiro-OMeTAD/Au are presented, and further results demonstrating the dependence of the performance on the preparation temperature of the solution processed CsPbIBr films are shown. We conclude that encapsulation of CsPbIBr to exclude water vapor should be sufficient to stabilize the cubic brown phase, making the material of interest for use in practical PV devices.

Camptothecin (CPT), a natural product and its synthetic derivatives exert potent anticancer activity by selectively targeting DNA Topoisomerase I (Top1) enzyme. CPT and its clinically approved derivatives are used as Top1 poisons for cancer therapy suffer from many limitations related to stability and toxicity. In order to envisage structurally diverse novel chemical entity as Top1 poison with better efficacy, Ligand-based-pharmacophore model was developed using 3D QSAR pharmacophore generation ( HypoGen algorithm) methodology in Discovery studio 4.1 clients. The chemical features of 29 CPT derivatives were taken as the training set. The selected pharmacophore model Hypo1 was further validated by 33 test set molecules and used as a query model for further screening of 1,087,724 drug-like molecules from ZINC databases. These molecules were subjected to several assessments such as Lipinski rule of 5, SMART filtration and activity filtration. The molecule obtained after filtration was further scrutinized by molecular docking analysis on the active site of Top1 crystal structure (PDB ID: 1T8I ). Six potential inhibitory molecules have been selected by analyzing the binding interaction and Ligand-Pharmacophore mapping with the validated pharmacophore model. Toxicity assessment TOPKAT program provided three potential inhibitory ‘hit molecules’ ZINC68997780, ZINC15018994 and ZINC38550809. MD simulation of these three molecules proved that the ligand binding into the protein-DNA cleavage complex is stable and the protein-ligands conformation remains unchanged. These three hit molecules can be utilized for designing future class of potential topoisomerase I inhibitor.

To overcome chemical limitations of camptothecin (CPT), we report design, synthesis, and validation of a quinoline-based novel class of topoisomerase 1 (Top1) inhibitors and establish that compound 28 (N-(3-(1H-imidazol-1-yl)­propyl)-6-(4-methoxyphenyl)-3-(1,3,4-oxadiazol-2-yl)­quinolin-4-amine) exhibits the highest potency in inhibiting human Top1 activity with an IC50 value of 29 ± 0.04 nM. Compound 28 traps Top1–DNA cleavage complexes (Top1ccs) both in the in vitro cleavage assays and in live cells. Point mutation of Top1-N722S fails to trap compound 28-induced Top1cc because of its inability to form a hydrogen bond with compound 28. Unlike CPT, compound 28 shows excellent plasma serum stability and is not a substrate of P-glycoprotein 1 (permeability glycoprotein) advancing its potential anticancer activity. Finally, we provide evidence that compound 28 overcomes the chemical instability of CPT in human breast adenocarcinoma cells through generation of persistent and less reversible Top1cc-induced DNA double-strand breaks as detected by γH2AX foci immunostaining after 5 h of drug removal.

Steady-state access to intraband transitions in colloidal quantum dots (CQDs), via doping, permits exploitation of the electromagnetic spectrum at energies below the band gap. CQD intraband optoelectronics allows envisaging cheap mid-and long-wavelength infrared photodetectors and light-emitting devices, which today employ epitaxial materials. As intraband devices start to emerge, thorough studies of the basic properties of intraband transitions in different CQD materials are needed to guide technological research. In this work, we investigate the size and temperature dependence of the intraband transition in heavily n-doped PbS quantum dot (QD) films. In the studied QD size range (5−8 nm), the intraband energy spans from 209 to 151 meV. We measure the intraband absorption coefficient of heavily doped PbS QD films to be around 2 × 10 4 cm −1 , proving that intraband absorption is as strong as interband absorption. We demonstrate a negative dependence of the intraband energy with temperature, in contrast to the positive dependence of the interband transition. Also opposite to the interband case, the temperature dependence of the intraband energy increases with decreasing size, going from −29 μeV/K to −49 μeV/K in the studied size range.

Toll-like receptor 7 (TLR7) is an established therapeutic target in myriad autoimmune disorders, but no TLR7 antagonist is available for clinical use to date. Herein, we report a purine scaffold TLR7 antagonist, first-of-its-kind to our knowledge, which was developed by rationally dissecting the structural requirements for TLR7-targeted activity for a purine scaffold. Specifically, we identified a singular chemical switch at C-2 that could make a potent purine scaffold TLR7 agonist to lose agonism and acquire antagonist activity, which could further be potentiated by the introduction of an additional basic center at C-6. We ended up developing a clinically relevant TLR7 antagonist with favorable pharmacokinetics and 70.8% oral bioavailability in mice. Moreover, the TLR7 antagonists depicted excellent selectivity against TLR8. To further validate the in vivo applicability of this novel TLR7 antagonist, we demonstrated its excellent efficacy in preventing TLR7-induced pathology in a preclinical murine model of psoriasis.