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Chitosan-functionalized pyridine-based thiosemicarbazones and their copper(II) complexes have been found to own a substantial antiproliferative activity against the tumorigenic Madin Darby canine kidney (MDCK) and MCF-7 cancer cell lines. In the current study, chitosan oligosaccharide (CS) (87% DDA, M

The formation of amyloid fibrils and oligomers is a hallmark of several neurodegenerative disorders, including Alzheimer's disease (AD), and contributes to the disease pathway. To progress our understanding of these diseases at a molecular level, it is crucial to determine the mechanisms and rates of amyloid formation and replication. In the context of AD, the self-replication of aggregates of the Aβ42 peptide by secondary nucleation, leading to the formation of new aggregates on the surfaces of existing ones, is a major source of both new fibrils and smaller toxic oligomeric species. However, the core mechanistic determinants, including the presence of intermediates, as well as the role of heterogeneities in the fibril population, are challenging to determine from bulk aggregation measurements. Here, we obtain such information by monitoring directly the time evolution of individual fibrils by TIRF microscopy. Crucially, essentially all aggregates have the ability to self-replicate via secondary nucleation, and the amplification of the aggregate concentration cannot be explained by a small fraction of "superspreader" fibrils. We observe that secondary nucleation is a catalytic multistep process involving the attachment of soluble species to the fibril surface, followed by conversion/detachment to yield a new fibril in solution. Furthermore, we find that fibrils formed by secondary nucleation resemble the parent fibril population. This detailed level of mechanistic insights into aggregate self-replication is key in the rational design of potential inhibitors of this process.

An efficient protocol for the synthesis of biologically essential pyrroloquinolinones has been developed under Cp*CoIII catalysis, which involves a cascade reaction of C(7)-H alkenylation with alkynes followed by nucleophilic addition. A wide variety of internal alkynes including enyne, diyne, and ynamide and more challenging terminal alkynes were successfully employed for the annulation in good to excellent yield with high regioselectivity.

A class of rotaxane is created, not by encapsulating a conventional linear thread, but rather by wrapping a large cucurbit[10]uril macrocycle about a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate as the axle. The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch points to the helicate strands that form the surface of the cylinder (like branches and roots on a tree trunk). The supramolecular cylinder that forms the axle is itself a member of a unique and remarkable class of helicate metallo-drugs that bind Y-shaped DNA junction structures and induce cell death. While pseudo-rotaxanation does not modify the DNA-binding properties, proper, mechanically-interlocked rotaxanation transforms the DNA-binding and biological activity of the cylinder. The ability of the cylinder to de-thread from the rotaxane (and thus to bind DNA junction structures) is controlled by the extent of branching: fully-branched cylinders are locked inside the cucurbit[10]uril macrocycle, while cylinders with incomplete branch points can de-thread from the rotaxane in response to competitor guests. The number of branch points can thus afford kinetic control over the drug de-threading and release.

The compound 4,4′-dinitro-2,2′,6,6′-tetracarboxybiphenyl (H4A) was shown to produce cocrystals and salts with various N-heterocycles such as 4,4′-bipyridylethylene, 4,4′-bipyridine, 4,4′-bipyridyle...

Large-scale commercial synthesis of bulk-heterojunction (BHJ) solar cell materials is very challenging and both time and energy consuming. Synthesis of π-conjugated polymers (CPs) with uniform batch-to-batch molecular weight and low dispersity is a key requirement for better reproducibility of high-efficiency polymer solar cells. Herein, a conjugated polymer (CP) PTB7-Th, well known for its high performance, has been synthesized with high molecular weight and low dispersity in a closed microwave reactor. The microwave reaction procedure is known to be more controlled and consumes less energy. The precursors were strategically reacted for different reaction time durations to obtain the optimum molecular weight. All different CPs were well characterized using 1H NMR, gel permeation chromatography (GPC), UV–vis, photoluminescence (PL), electron spin resonance (ESR), and Raman spectroscopy, whereas the film morphology was extensively studied via atomic force microscopy (AFM) and grazing incidence X-ray diffraction (GIXRD) techniques. The effect of molecular weight on a conventional BHJ solar cell with PC71BM acceptor was investigated to derive systematic structure–property relationships. The CP obtained after 35 min of reaction time and integrated into BHJ devices under ambient conditions provided the best performance with a power conversion efficiency (PCE) of 8.09%, which was quite similar to the results of CPs synthesized via a thermal route. An enhanced PCE of 8.47% was obtained for the optimized polymer (35 min microwave reaction product) when device fabrication was carried out inside a glovebox. The organic thin-film transistor (OTFT) device with the microwave-synthesized CP displayed better hole mobility (0.137 cm2 V–1 s–1) as compared to that with the thermally synthesized CP. This study also proved that the device stability and reproducibility of the microwave-synthesized CP were much better and more consistent than those of the thermally developed CP.

The ruthenium(II) complexes [RuCl(L1)(L3)]Cl (1), [RuCl(L1)(L4)]Cl (2), [RuCl(L2)(L4)]Cl (3), [RuCl(L1)(L5)]Cl (4), and [RuCl(L2)(L5)]Cl (5) of NNN-donor dipicolylamine (dpa) bases (L4, L5) having BODIPY (boron-dipyrromethene) moieties, NN-donor phenanthroline derivatives (L1, L2), and benzyldipicolylamine (bzdpa, L3) were prepared and characterized by spectroscopic techniques and their cellular localization/uptake and photocytotoxicity studied. Complex 1, as its PF6 salt (1a), has been structurally characterized with help of a single-crystal X-ray diffraction technique. It has a RuN5Cl core with the Cl bonded trans to the amine nitrogen atom of bzdpa. The complexes showed intense absorption spectral bands near 500 nm (e ≈ 58000 M-1 cm-1) in 2 and 3 and 654 nm (e ≈ 80000 M-1 cm-1) in 4 and 5 in 1/1 DMSO/DPBS (v/v). Complex 5 having biotin and PEGylated-disteryl BODIPY gave a singlet oxygen quantum yield (ΦΔ) of ∼0.65 in DMSO. Complex 5 exhibited remarkable PDT (photodynamic therapy) activity (IC50 ≈ 0.02 μM) with a photocytotoxicity index (PI) value of >5000 in red light of 600-720 nm in A549 cancer cells. The biotin-conjugated complexes showed better photocytotoxicity in comparison to nonbiotinylated analogues in A549 cells. The complexes displayed less toxicity in HPL1D normal cells in comparison to A549 cancer cells. The emissive BODIPY complexes 3 and 5 (ΦF ≈ 0.07 in DMSO) showed significant mitochondrial localization.