A Novel Dialkylamino-Functionalized Chalcone,DML6, Inhibits Cervical Cancer Cell Proliferation,In Vitro,via Induction of Oxidative Stress,Intrinsic Apoptosis and Mitotic Catastrophe

In this study, we designed, synthesized and evaluated, in vitro, novel chalcone analogs containing dialkylamino pharmacophores in the cervical cancer cell line, OV2008. The compound, DML6 was selective and significantly decreased the proliferation of OV2008 and HeLa cells in sub-micromolar concentrations, compared to prostate, lung, colon, breast or human embryonic kidney cell line (HEK293). DML6, at 5 μM, arrested the OV2008 cells in the G2 phase. Furthermore, DML6, at 5 μM, increased the levels of reactive oxygen species and induced a collapse in the mitochondrial membrane potential, compared to OV2008 cells incubated with a vehicle. DML6, at 5 μM, induced intrinsic apoptosis by significantly (1) increasing the levels of the pro-apoptotic proteins, Bak and Bax, and (2) decreasing the levels of l the anti-apoptotic protein, Bcl-2, compared to cell incubated with a vehicle. Furthermore, DML6, at 5 and 20 μM, induced the cleavage of caspase-9, followed by subsequent cleavage of the executioner caspases, caspase-3 and caspase-7, which produced OV2008 cell death. Overall, our data suggest that DML6 is an apoptosis-inducing compound that should undergo further evaluation as a potential treatment for cervical cancer.     

Catalytic asymmetric dihydroxylation of olefins using polysulfone-based novel microencapsulated osmium tetroxide

A polysulfone based novel polymer-supported osmium catalyst has been developed. The catalyst was prepared from commercially available polysulfone, based on a microencapsulation technique and was employed in the asymmetric dihydroxylation of various olefins using (DHQD)₂PHAL as the chiral ligand and NMO as the co-oxidant in H₂O-acetone-CH₃CN (1:1:1). The catalyst was recovered by simple filtration and was reused to obtain excellent yields with good enantioselectivity up to five times.     

A mild and efficient method for the chemoselective deprotection of acetonides with lanthanum(III) nitrate hexahydrate

Acetonides are hydrolyzed selectively and efficiently with lanthanum(III) nitrate hexahydrate in acetonitrile. The method has good compatibility with other sensitive hydroxyl protecting groups such as trityl, TBDMS, THP, OAc, OBz and OBn.     

Nonlinear vibration analysis of vortex-induced vibrations in overhead power lines with nonlinear vibration absorbers

Nonlinear Dynamics - Vortex-induced vibrations are one of the major factors in fatigue failure of power transmission lines and can be mitigated using vibration absorbers in the form of Stockbridge...     

Phototriggered Release of a Transmembrane Chloride Carrier from an o‐Nitrobenzyl‐Linked Procarrier

While there have been many studies on synthetic chloride carriers and a recent application for apoptotic cell death, so far, the proposed huge potential of these systems in targeting cancer has not been realized due to their cytotoxicity to healthy cells. Herein, we describe the development of an indole‐2‐carboxamide receptor as an efficient membrane chloride carrier while the corresponding o‐nitrobenzyl‐linked derivative is a procarrier of the ion. Photoirradiation of the procarrier in liposomes results in release of the active carrier with up to 90 % transport efficiency. Such photorelease of the carrier also works within cancer cells, resulting in efficient cell killing. Such photocleavable procarriers have great potential as a photodynamic therapy to combat various types of cancers.     

Metal-like Ductility in Organic Plastic Crystals: Role of Molecular Shape and Dihydrogen Bonding Interactions in Aminoboranes

Ductility is a common phenomenon in many metals but is difficult to achieve in molecular crystals. Organic crystals bend plastically on one or two face-specific directions but fracture when stressed in any other arbitrary directions. An exceptional metal-like ductility and malleability in the isomorphous crystals of two globular molecules, BH₃NMe₃ and BF₃NMe₃, is reported, with characteristic tensile stretching, compression, twisting, and thinning. The mechanically deformed samples, which transition to lower symmetry phases, retain good long-range order amenable to structure determination by single-crystal X-ray diffraction. Molecules in these high-symmetry crystals interact through electrostatic forces (B⁻−N⁺) to form columnar structures with multiple slip planes and weak dispersive forces between columns. On the other hand, the limited number of facile slip planes and strong dihydrogen bonding in BH₃NHMe₂ negates ductility. Our study has implications for the design of soft ferroelectrics, solid electrolytes, barocalorics, and soft robotics.     

Esterase-Activatable Synthetic M+/Cl− Channel Induces Apoptosis and Disrupts Autophagy in Cancer Cells

The formation of a supramolecular synthetic M⁺/Cl⁻ channel in the membrane phospholipid bilayer has been reported upon activation of a methyl pivalate-linked N¹,N³-dialkyl-2-hydroxyisophthalamide by esterases. The channel formation induces apoptosis in cancer cells via the intrinsic pathway. Interestingly, the supramolecular channel was also shown to disrupt autophagy in cancer cells by causing alkalization of lysosomes – a feature that has been confirmed at the cellular and protein level.     

Sorting of polymorphs based on mechanical properties. Trimorphs of 6-chloro-2,4-dinitroaniline

Mechanical shearing of crystals of a polymorph with a layered structure may be used to separate them from harder crystals of a visually indistinguishable polymorph that resist such shearing.