Synthesis,Computational Studies and Assessment of in Vitro Activity of Squalene Derivatives as Carbonic Anhydrase Inhibitors

We report novel molecules incorporating the nontoxic squalene scaffold and different carbonic anhydrase inhibitors (CAIs). Potent inhibitory action, in the low-nanomolar range, was detected against isoforms hCA II for sulfonamide derivatives, which proved to be selective against this isoform over the tumor-associate hCA IX and XII isoforms. On the other hand, coumarin derivatives showed weak potency but high selectivity against the tumor-associated isoform CA IX. These compounds are interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. In addition, an in silico study of inhibitor-bound hCA II revealed extensive interactions with the hydrophobic pocket of the active site and provided molecular insights into the binding properties of these new inhibitors.     

Surface morphology evaluation of polymer beads based on divinylbenzene by atomic force microscopy

Macroporous poly(styrene‐co‐divinylbenzene) and poly(divinylbenzene) beads were synthesized by modified suspension polymerization in the presence of different mixtures of toluene and heptane as porogen agent. Through atomic force microscopy, it was possible to identify the microspheres and the channels between them that constitute the bead pores. It was also possible to make a comparison with the results obtained by nitrogen desorption, a traditional technique used to determine the porosity of macroporous copolymers in the dry state. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 541–551, 2002; DOI 10.1002/app.10290     

Study on emulsion copolymerization of styrene andn-butyl acrylate

Summary The emulsion copolymerization of styrene and n-butyl acrylate has been investigated. Copolymers were obtained at 70°C in the presence of sodium lauryl sulfate, an anionic micelle generator and ammonium persulfate as initiator. The ideal time of reaction, the effect of the amount of initiator, temperature and comonomer composition were also studied. The copolymers have been characterized through gel permeation chromatography (GPC) and Fourier transform infrared spectroscopy (FTIR).     

The influence of some synthesis parameters on Ziegler-Natta catalyst performance

The role of di-n-butyl ether (DBE) in the synthesis of highly active and stereospecific catalyst for propylene polymerization has been investigated. The ether was used as internal base (IB) or complexed with TiCl₄ and diethylaluminium chloride (DEAC) in iso-octane solution (System A) or complexed with triethylaluminium (TEA) in toluene solution (System B). Many differences were observed in the catalyst performance. The activity, the catalyst stereospecificity and the polymer bulk density were evaluated.     

Nutritional recovery of mild and moderately malnourished children under two different treatment approaches (ambulatory versus day-care)

This retrospective analysis was conducted between May 1997 and May 2000 at the Centro de Atención Nutricional Infantil de Antímano, CANIA, in Caracas, Venezuela to assess the efficacy of two treatments (ambulatory versus day-care) of mild and moderate malnourished children. Inclusion criteria were: children under 10 years old with mild and moderate malnourishment, who attended a minimum of 3 control visits during a period of 12 months. One hundred fourteen malnourished children were included: fifty seven in ambulatory treatment and fifty seven in day-care treatment paired per nutritional diagnosis, gender and age (thirty nine mild and eighteen moderate malnourished children). The nutritional recovery criterion was weight for height above tenth percentile. No relation was found between treatment approaches and nutritional recovery at 3 and 6 months of treatment. In the group of mild malnourished children, the percentage of recovered patients at 3 months of treatment, that kept their recovered condition at 6 months was 83% (15/18) in the ambulatory treatment and 82% (18/22) in the day-care treatment Age of children, associated disease, acute morbidity, dietetic risk and mother's education and age were not associated with nutritional recovery at 6 months of treatment (p > 0.05). The day-care approach resulted as effective as ambulatory in mild malnourished children. In moderate malnourished new studies will need to be conducted with greater number of patients.     

Preparation and characterization of blends of high density polyethylene and poly(ethylene‐co‐1‐octene) elastomer

Mechanical, thermal, and morphological properties of blends of high density polyethylene and poly(ethylene‐co‐1‐octene) (PEO) were evaluated. The blends were prepared in a single screw extruder at 230°C and 50 rpm with volume fraction of elastomer varying in the range from 0.05 to 0.8. Factors such as chemical similarity and melt viscosity favor the interdiffusion process of phases, resulting in better interfacial adhesion. A synergistic effect on the strength at break and elongation at break for a particular range of blend composition was observed. Blends with a volume fraction of PEO higher than 5% presented a super tough behavior at room temperature. Thermal analysis showed that there is a certain degree of interaction between high density polyethylene and PEO. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 1991–1995, 2001     

Ethylene-propylene copolymers by a supported Ziegler-Natta catalyst based on TiCl4/MgCl2

Ethylene-propylene copolymers have been prepared by using Ziegler-Natta catalysts based on TiCl₄, MgCl₂, PCl₃ and (n-Bu)₃PO₄. The catalysts TiCl₄/MgCl₂/PCl₃ and TiCl₄/MgCl₂/(n-Bu)₃PO₄ were prepared by reacting TiCl₄ with pretreated MgCl₂. The support was prepared by ball milling of MgCl₂ with varied amounts of PCl₃ or (n-Bu)₃PO₄. The addition of PCl₃ has remarkably increased the MgCl₂ surface area in comparison with (n-Bu)₃PO₄. The effects of PCl₃ and (n-Bu)₃PO₄ on ethylene homopolymerization, ethylene-propylene copolymerization and on copolymer properties were evaluated. The catalyst system containing PCl₃ permitted to synthesize propylene-ethylene copolymers with up to 75% (w/w) of propylene and provided control of copolymer crystallinity. The reduction of the copolymer molecular weight distribution suggested that PCl₃ acted as an internal donor, poisoning some active catalytic sites. Received: 2 April 1997/Revised: 6 June 1997/Accepted: 18 June 1997     

Ligand Binding Promiscuity of Human Liver Fatty Acid Binding Protein: Structural and Dynamic Insights from an Interaction Study with Glycocholate and Oleate

Human liver fatty acid binding protein (hL‐FABP) has been reported to act as an intracellular shuttle of lipid molecules, thus playing a central role in systemic metabolic homeostasis. The involvement of hL‐FABP in the transport of bile salts has been postulated but scarcely investigated. Here we describe a thorough NMR investigation of glycocholate (GCA) binding to hL‐FABP. The protein molecule bound a single molecule of GCA, in contrast to the 1:2 stoichiometry observed with fatty acids. GCA was found to occupy the large internal cavity of hL‐FABP, without requiring major conformational rearrangement of the protein backbone; rather, this led to increased stability, similar to that estimated for the hL‐FABP:oleate complex. Fast‐timescale dynamics appeared not to be significantly perturbed in the presence of ligands. Slow motions (unlike for other proteins of the family) were retained or enhanced upon binding, consistent with a requirement for structural plasticity for promiscuous recognition.     

On the Determination of the Concentration of Crystal Nuclei in Glasses by DSC

An interesting technique was proposed by Ray et al. over a decade ago to determine the number density of nucleation sites, N_q, or the nucleation rate, I(T), in glasses that exhibit internal nucleation. Their approach is based on the measurement of the areas under the differential scanning calorimetry (DSC) crystallization peaks of partially crystallized glass samples. In this study, we review their method and test a modified equation recently proposed by some of us, which also takes into account the crystal morphology and impingement. We compare N_q obtained with both methods for a Li₂O·2SiO₂ glass. Small glass monoliths were treated at 620°C for different time periods for crystal growth, without any nucleation treatment, and subsequently analyzed by DSC up to 800°C. We thus estimated N_q from the area under the DSC crystallization peaks. The corrected approach resulted in N_q values which were not affected by the pair of growth times chosen, as expected, but the obtained values were two‐ to fivefold lower than those calculated with the Ray model. Taking into account previously reported nucleation rates and the corresponding induction periods as a function of temperature (for specimens of the same glass batch), we estimated the number of nuclei formed during the DSC heating/cooling steps, and also measured them by optical microscopy (OM). Finally, we compared the obtained values from OM with the N_q values determined by the DSC method. The N_q resulting from the original and new equations were approximately two orders of magnitude larger than those experimentally determined for the same glass using optical microscopy. This difference is attributed to the formation of new nuclei during the heating and cooling paths of the DSC runs and to surface crystallization, which are not taken into account in the DSC expressions.