ABSTRACT:The melt intercalation method was employed to prepare poly(butylene terephthalate) (PBT)/montmorillonite (MMT) nanocomposites, and the microstructures were characterized with X-ray diffraction and transmission electron microscopy. Then, the nonisothermal crystallization behavior of the nanocomposites was studied with differential scanning calorimetry (DSC). The DSC results showed that the exothermic peaks for the nanocomposites distinctly shifted to lower temperatures at various cooling rates in comparison with that for pure PBT, and with increasing MMT content, the peak crystallization temperature of the PBT/MMT hybrids declined gradually. The nonisothermal crystallization kinetics were analyzed by the Avrami, Jeziorny, Ozawa, and Mo methods on the basis of the DSC data. The results revealed that very small amounts of clay (1 wt %) could accelerate the crystallization process, whereas higher clay loadings reduced the rate of crystallization. In addition, the activation energy for the transport of the macromolecular segments to the growing surface was determined by the Kissinger method. The results clearly indicated that the hybrids with small amounts of clay presented lower activation energy than PBT, whereas those with higher clay loadings showed higher activation energy. The MMT content and the crystallization conditions as well as the nature of the matrix itself affected the crystallization behavior of the hybrids.

Reactions between 4'-phenyl-terpyridine (L) and several Cu(II) salts (p-toluenesulfonate, benzoate and o-, m- or p-hydroxybenzoate) led to the formation of [Cu(p-SO3C6H4CH3)L(H2O)2](p-SO3C6H4CH3) (1), [Cu(OCOPh)2L] (2), [Cu(o-OCOC6H4OH)2L] (3), [Cu(m-OCOC6H4OH)2L]4·MeOH (·MeOH) and [Cu(p-OCOC6H4OH)2L]5·2H2O (·2H2O), which were characterized by elemental and TG-DTA analyses, ESI-MS, IR spectroscopy and single crystal X-ray diffraction, as well as by conductivimetry. In all structures the Cu atoms present N3O3 octahedral coordination geometries, which, in 2-5, are highly distorted as a result of the chelating-bidentate mode of one of the carboxylate ligands. Intermolecular π···π stacking interactions could also be found in 2-5 (in the 3.569-3.651 Å range and involving solely the pyridyl rings). Medium-strong hydrogen bond interactions lead to infinite 1D chains (in 1 and 4) and to an infinite 2D network (in 5). Compounds 1 and 4 show high in vitro cytotoxicity towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma cell lines. The antiproliferative potential of compound 1 is due to an increase of the apoptotic process that was confirmed by Hoechst staining, flow cytometry and RT-qPCR. All compounds able to non-covalently intercalate the DNA helix and induce in vitro pDNA double-strand breaks in the absence of H2O2. Concerning compound 1, the hydroxyl radical and singlet oxygen do not appear to be involved in the pDNA cleavage process and the fact that this cleavage also occurs in the absence of molecular oxygen points to a hydrolytic mechanism of cleavage.

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Potent and selective small-molecule inhibitors of the p53-MDM2 interaction intended for the treatment of p53 wild-type tumors have been designed and optimized in a number of chemical series. This review details recent disclosures of compounds in advanced optimization and features key series that have given rise to clinical trial candidates. The structure-activity relationships for inhibitor classes are discussed with reference to x-ray structures, and common structural features are identified.

Inhibition of murine double minute 2 (MDM2)-p53 protein−protein interaction with small molecules has been shown to reactivate p53 and inhibit tumor growth. Here, we describe rational, structure-guided, design of novel isoindolinone-based MDM2 inhibitors. MDM2 X-ray crystallography, quantum mechanics ligand-based design, and metabolite identification all contributed toward the discovery of potent in vitro and in vivo inhibitors of the MDM2-p53 interaction with representative compounds inducing cytostasis in an SJSA-1 osteosarcoma xenograft model following once-daily oral administration.