Vinylogous Organocatalytic Triple Cascade Reaction: Forging Six Stereocenters in Complex Spiro‐Oxindolic Cyclohexanes

We report a triple vinylogous cascade reaction, yielding valuable spiro‐oxindolic cyclohexane derivatives. The three‐component domino process proceeds by way of a catalyzed Michael/1,6‐addition/vinylogous aldol sequence affording the products with six stereogenic centers and very high control over the stereochemistry. The chemistry is based on a rare example of asymmetric 1,6‐addition to linear 2,4‐dienals proceeding with complete δ‐site selectivity. Key to the reaction development was a directing group positioned at the β‐dienal position, which was essential for achieving highly predictable reaction outcomes.

     

Dynamic mechanical properties and hysteresis loss of epoxidized natural rubber chemically bonded to the silica surface

High‐temperature (180°C) molding of epoxidized natural rubber (ENR) filled with precipitated silica leads to chemical bond formation between epoxy groups of ENR and silanol groups of silica. The extent of chemical bond formation is further enhanced in the presence of the silane coupling agent N‐3‐N‐(vinyl benzyl amino)ethyl‐γ‐amino‐propyl trimethoxy silane mono hydrogen chloride (trade name Z‐6032). The results of hysteresis loss measurements show that hysteresis loss increases with increase in coupling agent loading as a result of the higher modulus of the compounds compared to that of the ENR–silica mix. The dynamic mechanical property measurements show that the addition of coupling agent increases the glass‐transition temperature. Whereas strain‐dependent dynamic mechanical properties show that filler structure breakdown increases with increasing loading of coupling agent. Sulfur‐cured systems show higher filler structure breakdown compared to that of nonsulfur systems. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 2171–2177, 2002     

Process optimisation in sunflower oil extraction by supercritical CO2

A continuous process for the extraction of sunflower oil using supercritical CO₂, featuring multiple extractors, one oil separator and three cascaded CO₂ recovery vessels operating at different pressures, was devised and studied. For every single equipment of the plant making up the process a mathematical model was built. Experimental tests—consisting in measurements of oil solubility in supercritical CO₂—were carried out in a laboratory-scale apparatus to characterise the behaviour of sunflower oil in the separation from the supercritical fluid. The mathematical model of the whole process was coded in the commercial gPROMS process modelling environment where both its simulation and optimisation—this latter assuming the overall oil production cost as the objective function—were carried out. The process- and economics-related results are discussed and compared with those obtained with traditional and cold-pressing extraction.     

Rare‐earth‐doped SiO2‐CaF2 glass ceramic nano‐particle with upconversion properties

Rare‐earth‐doped upconversion nano‐phosphor shows new possibilities in the field of bioimaging because of its unique properties like higher penetration depth, low signal to noise ratio (SNR), good photo stability, and zero auto fluorescence. The oxyfluoride glass system is the combination of both fluoride and oxide where fluoride host offers high optical transparency due to low phonon energy and oxide network offers high physical stability. Thus, in the present work, an attempt has been made to synthesize 1 mol% Er³⁺ doped SiO₂‐CaF₂ glass ceramic nano‐particles through sol‐gel route. The synthesized glass ceramic particles were heat treated at 4 different temperatures starting from 600°C to 900°C.The X‐ray diffraction (XRD) analysis and Transmission electron microscopy (TEM) analysis confirmed the formation of CaF₂ nano‐crystals in the matrix which is 20‐30 nm in size. The vibrational spectroscopic analysis of the glass ceramics sample has been investigated by Fourier transform infrared (FTIR) spectroscopy. The UV‐Visible‐NIR spectroscopy analysis was carried out to analyze the absorption intensity in the near infrared region. Upon 980 nm excitation, the sample shows red emission corresponds to ⁴F_9/2→⁴I_15/2 energy level transition. The prepared nano‐particles showed excellent biocompatibility when tasted on MG‐63 osteoblast cells.     

Thermal regimes of Li‐ion conductivity in β‐eucryptite

While it is well‐established that ionic conduction in lithium aluminosilicates proceeds via hopping of Li ions, the nature of the various hoping‐based mechanisms in different temperature regimes has not been fully elucidated. The difficulties associated with investigating the conduction have to do with the presence of grains and grain boundaries of different orientations in these usually polycrystalline materials. Herein, we use electrochemical impedance spectroscopy (EIS) to investigate the ion conduction mechanisms in β‐eucryptite, which is a prototypical lithium aluminosilicate. In the absence of significant structural transitions in grain boundaries, we find that there are three conduction regimes for the one‐dimensional ionic motion along the c axis channels in the grains, and determine the activation energies for each of these temperature regimes. Activation energies computed from molecular statics calculations of the potential energy landscape encountered by Li ions suggest that at temperatures below 440°C conduction proceeds via cooperative or correlated motion, in agreement with established literature. Between 440°C and 500°C, the activation barriers extracted from EIS measurements are large and consistent with those from atomistic calculations for uncorrelated Li ion hopping. Above 500°C the activation barriers decrease significantly, which indicates that after the transition to the Li‐disordered phase of β‐eucryptite, the Li ion motion largely regains the correlated character.     

Cytotoxic salan-titanium(IV) complexes: high activity toward a range of sensitive and drug-resistant cell lines, and mechanistic insights

The cytotoxicities of highly efficient salan-Ti(IV) complexes toward a range of cell lines, including drug-resistant cells, are reported along with preliminary mechanistic insights. Five salan-Ti(IV) complexes were investigated toward eight different human and murine cancer-derived cell lines, including colon, ovarian, lung, cervical, pancreatic, leukemic, skin, and breast. The salan complexes are more active toward the cells analyzed than cisplatin and the known titanium compound (bzac)(2) Ti(OiPr)(2) , and no cell line resistant to the salan complexes was identified. Moreover, the salan-Ti(IV) complexes are highly active toward both cisplatin-sensitive (A2780) and cisplatin-resistant (A2780CisR) human ovarian cancer cell lines. Similarly, the salan complexes are cytotoxic toward multi-drug-resistant (ABCB1-expressing) mouse lymphoma cell lines HU-1 and HU-2. Importantly, minimal or no activity was observed toward primary murine cells (bone marrow, heart, liver, kidney, spleen, and lung), supporting selectivity for cancer cells. Additionally, the salan complexes maintain high cytotoxicity for up to 24 h following exposure to cell culture medium, whereas reference complexes (bzac)(2) Ti(OiPr)(2) and Cp(2) TiCl(2) rapidly lose much of their activity upon exposure to medium, within ~1 h. The upregulation of p53 followed by cell-cycle arrest in G(1) phase is likely one mechanism of action of the salan complexes. Taken together, the results indicate that these compounds are selectively toxic to cancer cells and are able to circumvent two independent mechanisms of drug resistance, thus expanding the scope of their potential medicinal utility.     

Probing Human Telomeric DNA and RNA Topology and Ligand Binding in a Cellular Model by Using Responsive Fluorescent Nucleoside Probes

The development of biophysical systems that enable an understanding of the structure and ligand‐binding properties of G‐quadruplex (GQ)‐forming nucleic acid sequences in cells or models that mimic the cellular environment would be highly beneficial in advancing GQ‐directed therapeutic strategies. Herein, the establishment of a biophysical platform to investigate the structure and recognition properties of human telomeric (H‐Telo) DNA and RNA repeats in a cell‐like confined environment by using conformation‐sensitive fluorescent nucleoside probes and a widely used cellular model, bis(2‐ethylhexyl) sodium sulfosuccinate reverse micelles (RMs), is described. The 2′‐deoxy and ribonucleoside probes, composed of a 5‐benzofuran uracil base analogue, faithfully report the aqueous micellar core through changes in their fluorescence properties. The nucleoside probes incorporated into different loops of H‐Telo DNA and RNA oligonucleotide repeats are minimally perturbing and photophysically signal the formation of respective GQ structures in both aqueous buffer and RMs. Furthermore, these sensors enable a direct comparison of the binding affinity of a ligand to H‐Telo DNA and RNA GQ structures in the bulk and confined environment of RMs. These results demonstrate that this combination of a GQ nucleoside probe and easy‐to‐handle RMs could provide new opportunities to study and devise screening‐compatible assays in a cell‐like environment to discover GQ binders of clinical potential.     

Fe-Zn Alloy Coating on Galvannealed (GA) Steel Sheet to Improve Product Qualities

Galvannealed steel sheets (GA) have become the mainstream steel sheet for automobile applications because of their superior corrosion resistance, paintability, and weldability. To impart specific properties, different coatings on GA steel sheet were reported to improve properties further. In this context, we have developed an electroplating process (flash coating) for bright and adherent Fe-Zn alloy coating on GA steel sheet to enhance performances such as weldability, frictional behavior, phosphatability, and defect coverage. A comparative study with bare GA steel sheet was carried out for better elastration. The electroplating time was reduced below 10 s for practical applicability in an industrial coating line by modulating the bath composition. Electroplating was performed at current density of 200-500 A/m² which yielded with higher cathode current efficiency of 85-95%. The performance results show that Fe-10 wt.% Zn-coated GA steel sheet (coating time 7 s) has better spot weldability, lower dynamic coefficient of friction (0.06-0.07 in lubrication), and better corrosion resistance compared to bare GA steel sheet. Uniform phosphate coating with globular crystal size of 2-5 µm was obtained on Fe-Zn flash-coated GA steel sheet. Hopeite was the main phosphate compound (77.9 wt.%) identified along with spencerite (13.6 wt.%) and phosphophyllite (8.5 wt.%).     

Effect of N-Vinyl-2-Pyrrolidone (NVP), a Bromodomain-Binding Small Chemical,on Osteoblast and Osteoclast Differentiation and Its Potential Application for Bone Regeneration

The human skeleton is a dynamic and remarkably organized organ system that provides mechanical support and performs a variety of additional functions. Bone tissue undergoes constant remodeling; an essential process to adapt architecture/resistance to growth and mechanical needs, but also to repair fractures and micro-damages. Despite bone’s ability to heal spontaneously, certain situations require an additional stimulation of bone regeneration, such as non-union fractures or after tumor resection. Among the growth factors used to increase bone regeneration, bone morphogenetic protein-2 (BMP2) is certainly the best described and studied. If clinically used in high quantities, BMP2 is associated with various adverse events, including fibrosis, overshooting bone formation, induction of inflammation and swelling. In previous studies, we have shown that it was possible to reduce BMP2 doses significantly, by increasing the response and sensitivity to it with small molecules called “BMP2 enhancers”. In the present study, we investigated the effect of N-Vinyl-2-pyrrolidone (NVP) on osteoblast and osteoclast differentiation in vitro and guided bone regeneration in vivo. We showed that NVP increases BMP2-induced osteoblast differentiation and decreases RANKL-induced osteoclast differentiation in a dose-dependent manner. Moreover, in a rabbit calvarial defect model, the histomorphometric analysis revealed that bony bridging and bony regenerated area achieved with NVP-loaded poly (lactic-co-glycolic acid (PLGA) membranes were significantly higher compared to unloaded membranes. Taken together, our results suggest that NVP sensitizes BMP2-dependent pathways, enhances BMP2 effect, and inhibits osteoclast differentiation. Thus, NVP could prove useful as “osteopromotive substance” in situations where a high rate of bone regeneration is required, and in the management of bone diseases associated with excessive bone resorption, like osteoporosis.