Correlation of structure and phase behaviour for a series of modular,chiral liquid crystal diacrylates based on lactic acid

The mesogenic properties of a family of chiral liquid crystal (LC) diacrylates based on a 4-[4-(1R-methyl-2-hydroxyethoxy)phenyl]phenyl 4-hydroxybenzoate core were studied as a function of different tail lengths. In general, this family of LCs was found to exhibit a strong preference for adopting the chiral smectic A phase. Systematic variation of the alkyl spacer lengths on either side of the chiral core revealed that the onset of smectic A behaviour is highly sensitive to the length of the tail adjacent to the chiral unit. However, no correlation between phase transition temperatures and the length of the spacer on the other side of the core was observed. With a fixed spacer length on the chiral side of the core, systematic changes in the length of the other tail resulted in the formation of a monotropic smectic B phase and an increased tendency to supercool.     

Synthesis and Preclinical Evaluation of QS-21 Variants Leading to Simplified Vaccine Adjuvants and Mechanistic Probes

QS-21 is a potent immunostimulatory saponin that is currently under clinical investigation as an adjuvant in various vaccines to treat infectious diseases, cancers, and cognitive disorders. Herein, we report the design, synthesis, and preclinical evaluation of simplified QS-21 congeners to define key structural features that are critical for adjuvant activity. Truncation of the linear tetrasaccharide domain revealed that a trisaccharide variant is equipotent to QS-21, while the corresponding disaccharide and monosaccharide congeners are more toxic and less potent, respectively. Modification of the acyl chain domain in the trisaccharide series revealed that a terminal carboxylic acid is well-tolerated while a terminal amine results in reduced adjuvant activity. Acylation of the terminal amine can, in some cases, restore adjuvant activity and enables the synthesis of fluorescently labeled QS-21 variants. Cellular studies with these probes revealed that, contrary to conventional wisdom, the most highly adjuvant active of these fluorescently labeled saponins does not simply associate with the plasma membrane, but rather is internalized by dendritic cells.     

Role of oxidant scavengers in the prevention of Ca²+ homeostasis disorders

A number of disorders, such as Alzheimer disease and diabetes mellitus, have in common the alteration of the redox balance, resulting in an increase in reactive oxygen species (ROS) generation that might lead to the development of apoptosis and cell death. It has long been known that ROS can significantly alter Ca2+ mobilization, an intracellular signal that is involved in the regulation of a wide variety of cellular functions. Cells have a limited capability to counteract the effects of oxidative stress, but evidence has been provided supporting the beneficial effects of exogenous ROS scavengers. Here, we review the effects of oxidative stress on intracellular Ca2+ homeostasis and the role of antioxidants in the prevention and treatment of disorders associated to abnormal Ca2+ mobilization induced by ROS.     

Reduction of integrable planar polynomial differential systems

The integrability problem consists in finding the class of functions, a first integral of a given planar polynomial differential system must belong to. We recall the characterization of systems which admit a Darboux, elementary, Liouvillian or Weierstrass first integral. The reduction problem of an integrable planar system consists in finding the class of functions, a map that reduces the original system (transforms into a simple system or equation) must belong to. We identify the class of functions of this map for polynomial, rational, Darboux, elementary, Liouvillian and Weierstrass integrable systems.     

Rapid phosphorus triester hydrolysis catalyzed by bimetallic tetrabenzimidazole complexes

Bimetallic complexes based on the binucleating ligand N,N,N',N'-tetrakis[(2-benzimidazolyl)methyl]-2-hydroxy-1,3-diaminopropane (1L) and its new toluoyl ester derivative (2L) catalyze the hydrolysis of phosphorus triesters at ambient temperature with activities rivalling the fastest known systems.     

Efficient synthetic access to the hetisine C20-diterpenoid alkaloids. A concise synthesis of nominine via oxidoisoquinolinium-1,3-dipolar and dienamine-Diels-Alder cycloadditions

A concise synthetic approach to the hetisine C20-diterpenoid alkaloids is reported. The total synthesis of (+/-)-nominine was accomplished in a 15-step sequence employing a dual cycloaddition strategy. Key features of the synthesis include a reversible intramolecular 4-oxidoisoquinolinium betaine dipolar cycloaddition in conjunction with a pyrrolidine-induced dienamine isomerization/Diels-Alder cascade.     

Strain-release rearrangement of N-vinyl-2-arylaziridines. Total synthesis of the anti-leukemia alkaloid (-)-deoxyharringtonine

Deoxyharringtonine (1) is among the most potent of the anti-leukemia alkaloids isolated from the Cephalotaxus genus. A convergent total synthesis of (-)-1 is reported, involving novel synthetic methods and strategies that include (1) the strain-release rearrangement of N-aryl-2-vinylaziridines for [3]benzazepine synthesis, (2) a vinylogous amide acylation-cycloaddition cascade for spiro-pyrrolidine construction, and (3) efficient acylation of the cephalotaxine core by alpha-(beta-lactone)carboxylic acid derivatives to access the biologically active cephalotaxus esters. These innovations should allow rapid access not only to other Cephalotaxus alkaloids but also to non-natural analogues of potential therapeutic utility.     

Polymerizable hexacatenar liquid crystals containing a luminescent oligo(p-phenylenevinylene) core

Polymerizable hexacatenar mesogens containing a photo-active oligo(p-phenylenevinylene) core were successfully synthesized by replacing the traditional n-alkoxy tails on the molecules with polymerizable hydrocarbon tails containing terminal isoprenyl or 1,3-dienyl units. It was found that for this particular liquid crystal (LC) platform, the incorporation of conventional radical polymerizable groups such as acrylates in the tails was not conducive to the formation of thermotropic LC phases, presumably due to their polar nature. The resulting photoluminescent isoprenyl and 1,3-dienyl hexacatenar monomers were found to form columnar hexagonal phases at elevated temperatures (c. 45-75°C), as determined by powder X-ray diffraction. Unfortunately, photoinitiated radical polymerization studies revealed that the mesogens are susceptible to photodegradation in the LC state at elevated temperatures, resulting in the loss of both LC order and emission properties during photopolymerization. Thermally initiated radical polymerization in the absence of light, however, afforded effective crosslinking with retention of both LC order and the desired emission properties. The resulting crosslinked columnar hexagonal phases were found to exhibit emission maxima at nearly identical wavelengths, with comparable intensities relative to the unpolymerized starting materials. The effect of the different polymerizable groups on the mesogenic behaviour, polymerization characteristics, and emission properties of the hexacatenar compounds is presented.     

Feasibility of using vanadium to form damascene structures with an air gap

We have studied the feasibility of fabricating multi-level interconnects using air as an interlayer dielectric material. In particular, we fabricated dual damascene structures using the via-first approach without etch stop layers required for trench formation, which opens up the possibility of further lowering the effective dielectric constant. Dual damascene structures were formed by sequential deposition of vanadium and vanadium pentoxide layers, which was followed by etching with hydrogen peroxide and water, respectively. Use of vanadium, vanadium pentoxide, and hydrogen peroxide was found suitable for the conventional silicon technology. Based on the findings in this study a novel process for the air gap formation was proposed, which may be applied even to the substrate level.