Y(OTf)3 catalyzed substitution dependent oxidative C(sp)–C(sp) cleavage and regioselective dehydration of β-allyl-β-hydroxydithioesters: alternate route to α,β-unsaturated ketones and functionalized dienes

β-Allyl-β-hydroxydithioesters have been generated by the regioselective Grignard addition to the β-oxodithioesters. They have been successfully employed in selective C(sp³)–C(sp³) bond cleavage to construct α,β-unsaturated ketone residues by the treatment of an emerging catalyst yttrium(III)triflate for the first time. On the other hand, hetaryl substituted β-allyl-β-hydroxydithioesters led to the useful diene precursors through selective dehydration under the similar conditions.     

Structural evidence of differential forms of nanosponges of beta-cyclodextrin and its effect on solubilization of a model drug

Nanosponges (NS) are a recently developed class of hyper-branched polymers, nano-structured to form three dimensional meshwork; obtained by reacting cyclodextrins with a cross linker like diphenyl carbonate. Herein, we report an anomalous behavior of NS with regards to physical and morphological characteristics and drug encapsulation behavior by minor synthetic modification. Two distinct forms viz. crystalline and para-crystalline of NS were identified and extensively characterized by use of high resolution transmission electron microscopy (HR-TEM), X-ray powder diffraction (XRPD), scanning electron microscope, atomic force microscope, optical microscope and Fourier transform infra-red attenuated total reflectance spectroscopy (FTIR-ATR). Dimension of the crystal lattice was found to be equal to 0.61 nm. Higher magnifications clearly showed a zone axis with a hexagonal symmetry as that of beta-cyclodextrin. XRPD patterns were in concurrence with the HR-TEM results. Solubility studies with a model drug dexamethasone (DEX) showed more than three folds increase in the solubility of the drug in the crystalline NS as compared to the para-crystalline ones. Percent drug association and drug loading for DEX was found to be higher in the crystalline type of NS. An In vitro drug kinetic study evidenced a faster release of DEX from the crystalline type NS. The particle sizes of the formulations were as follows: crystalline NS: 688.6 ± 38.0 nm, para-crystalline NS: 702.2 ± 21.2 nm with polydispersity indices of 0.155 and 0.132; zeta-potential of ?26.55 ± 1.7 and ?23.42 ± 2.1 respectively. Differential scanning calorimetry and thermogravimetric analysis revealed that both forms encapsulated the drug satisfactorily. FTIR-ATR and Raman spectroscopy showed weak interactions. Crystallinity of NS was thus found to be an important factor in solubilization, in vitro kinetics and encapsulation behavior and can be tuned to give a tailored drug release profile or formulation characteristics.     

An efficient one-pot three-component synthesis of functionalized pyrimido[4,5-b]quinolines and indeno fused pyrido[2,3-d]pyrimidines in water

A simple, efficient, and high yielding one-pot protocol for the synthesis of pyrimido[4,5-b]quinolines and indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidines has been developed by three-component domino coupling of 6-amino-1,3-dimethyluracil, aldehydes, and cyclic 1,3-diketones in ecofriendly solvent water promoted by PTSA. The protocol avoids the use of expensive catalysts, toxic solvents, and chromatographic separation. The generality and functional tolerance of this convergent and environmentally benign method is demonstrated.     

Bent-core V-shaped mesogens consisting of salicylaldimine mesogenic segments: synthesis and characterization of mesomorphic behaviour

A series of bent-core V-shaped mesogens consisting of salicylaldimine mesogenic segments have been synthesized and their mesomorphic behaviour characterized. In an attempt to understand structure–property relationships, the lengths of the terminal alkoxy chains have been varied from C₂ to C₁₂, C₁₆ and C₁₈, resulting in 13 new bent-core V-shaped molecules. The thermal behaviour of these new compounds has been investigated by optical microscopy, calorimetry and X-ray diffraction studies. In general the compounds show conventional mesophases similar to those shown by calamitic LCs. The materials exhibit good thermal stability, even though their melting and clearing transition temperatures are high as a result of the presence of intramolecular hydrogen bonding between the H-atom of the hydroxyl group and the N-atom of the imine functionality. The phase appearing in the first member of the series with ethoxy chains is a nematic, while the C₃ to C₆ derivatives exhibit a smectic A phase as well as a nematic phase. The higher homologues, C₇ to C₁₂, C₁₆ and C₁₈, show only the smectic A phase. X-ray studies reveal that the SmA phase has a partially bilayer (interdigitated) structure. Remarkably, in some cases, the smectic A phase supercools well below room temperature. It is apparent from our studies that increasing the length of the alkoxy chains promotes smectic behaviour, in agreement with the general observation made for such bent-core molecules.     

Collective motion artifacts arising in long‐duration molecular dynamics simulations

We tested a variety of molecular dynamics simulation strategies in long‐duration (up to several nanoseconds) constant‐temperature simulations of liquid water under periodic boundary conditions. Such long durations are necessary to achieve adequate conformational sampling in simulations of membrane assemblies and other large biomolecular systems. Under a variety of circumstances, serious artifacts arise in the form of spurious collective behavior that becomes obvious only after the simulation has gone at least several hundred picoseconds. The potential energy of the system drops and the system changes from a liquid to an icy or glassy state. The underlying cause is accumulated center‐of‐mass motion of the system, coupled with velocity rescaling associated with constant‐temperature control. The velocity rescaling in the constant‐temperature algorithm reduces the thermal velocity as the net center‐of‐mass velocity grows, effectively causing the kinetic energy of the system to drain from thermal motions into coordinated motions. We found that the incidence and magnitude of the underlying artifactual motion leading to the spurious transition is mediated by: choice of method for computing electrostatic interactions; choice of ensemble; size of the simulation cell; SHAKE tolerance; frequency of nonbonded pairlist updating; and closeness of coupling to the temperature bath. The appearance of the spurious transition can be avoided by periodically subtracting net center‐of‐mass motion during the dynamics, or by improving the accuracy of the simulation by means of tightening SHAKE tolerance and updating nonbonded pairlists every timestep. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 121–131, 2000     

Asymptotic analysis of wall modes in a flexible tube revisited

The stability of wall modes in fluid flow through a flexible tube of radius R surrounded by a viscoelastic material in the region R < r < HR is analysed using a combination of asymptotic and numerical methods. The fluid is Newtonian, while the flexible wall is modelled as an incompressible viscoelastic solid. In the limit of high Reynolds number (Re), the vorticity of the wall modes is confined to a region of thickness O(Re ^-1/3) in the fluid near the wall of the tube. Previous numerical studies on the stability of Hagen-Poiseuille flow in a flexible tube to axisymmetric disturbances have shown that the flow could be unstable in the limit of high Re, while previous high Reynolds number asymptotic analyses have revealed only stable modes. To resolve this discrepancy, the present work re-examines the asymptotic analysis of wall modes in a flexible tube using a new set of scaling assumptions. It is shown that wall modes in Hagen-Poiseuille flow in a flexible tube are indeed unstable in the limit of high Re in the scaling regime Re∼Σ^3/4. Here Σ is a nondimensional parameter characterising the elasticity of the wall, and Σ≡ρGR ²/η², where ρ and η are the density and viscosity of the fluid, and G is the shear modulus of the wall medium. The results from the present asymptotic analysis are in excellent agreement with the previous numerical results. Importantly, the present work shows that the different types of unstable modes at high Reynolds number reported in previous numerical studies are qualitatively the same: they all belong to the class of unstable wall modes predicted in this paper. Received 12 June 2000 and Received in final form 8 November 2000     

Efficient Plastic Waste Recycling Using Polymer

This study explores the possible uses of polymers to facilitate the more efficient recycling of plastic waste. Recycling plastics has been singled out as one way to mitigate the damaging effects of plastic trash on the environment. However, traditional recycling methods can only go so far, therefore innovative approaches are needed. This research investigates how a variety of polymers may be able to improve recycling operations. The study simulates the recycling procedure and employs experimental analysis to compare the performance of various polymers. Results show that by selecting the right polymers, recycling plastic trash can be made much more efficient, cutting down on both waste and energy consumption. The results have important ramifications for the plastic waste recycling sector and point the way towards fruitful future study in this area.     

Cathepsin K Inhibitors for Treatment of Osteoporosis

Cysteine Proteases have been implicated in a broad spectrum of disease processes including cancer, arthritis, and viral and parasitie diseases^[1]. Cathepsin K, a cysteine protease of the papain superfamily, is selectively expressed in osteoclasts and has been implicated in the process of bone resouption^[2]. It is therefore considered a promising therapeutic target for treating diseases charccterized by excessive bone loss, such as osteoporosis^[3]. Several chemotypes of cathepsin K inhibitors will be reviewed. The design and synthesis of potent inhibitors will also be discussed.     

An approximate analysis of thickness-stretch waves in an elastic plate

Two-dimensional equations for coupled extensional and thickness-stretch waves in an elastic plate are simplified by eliminating the extensional displacements in a systematic manner; the result is a single equation governing thickness-stretch motions. A similar reduction is also performed for coupled extensional, thickness-stretch, and symmetric thickness-shear waves. The procedure is similar to that used in the thickness-shear approximation, wherein the flexural displacement is eliminated from the equations for coupled flexural and thickness-shear motions. The resulting equations are used to discuss the energy-trapped vibration of plates in thickness-stretch modes.