Synthesis of spongidines A and D: marine metabolites phospholipase A2 inhibitors

Two different strategies for the synthesis of spongidines A and D are presented. Herein we describe a route based in an amino acid insertion followed by aromatization. Another alternative is the construction of a pyridine derivative followed by N-alkylation. Both methodologies have intermediate 5 as a key compound, which is eventually accessible from methyl isoanticopalate.     

Protein delivery based on uncoated and chitosan-coated mesoporous silicon microparticles

Mesoporous silicon is a biocompatible, biodegradable material that is receiving increased attention for pharmaceutical applications due to its extensive specific surface. This feature enables to load a variety of drugs in mesoporous silicon devices by simple adsorption-based procedures. In this work, we have addressed the fabrication and characterization of two new mesoporous silicon devices prepared by electrochemistry and intended for protein delivery, namely: (i) mesoporous silicon microparticles and (ii) chitosan-coated mesoporous silicon microparticles. Both carriers were investigated for their capacity to load a therapeutic protein (insulin) and a model antigen (bovine serum albumin) by adsorption. Our results show that mesoporous silicon microparticles prepared by electrochemical methods present moderate affinity for insulin and high affinity for albumin. However, mesoporous silicon presents an extensive capacity to load both proteins, leading to systems were protein could represent the major mass fraction of the formulation. The possibility to form a chitosan coating on the microparticles surface was confirmed both qualitatively by atomic force microscopy and quantitatively by a colorimetric method. Mesoporous silicon microparticles with mean pore size of 35 nm released the loaded insulin quickly, but not instantaneously. This profile could be slowed to a certain extent by the chitosan coating modification. With their high protein loading, their capacity to provide a controlled release of insulin over a period of 60-90 min, and the potential mucoadhesive effect of the chitosan coating, these composite devices comprise several features that render them interesting candidates as transmucosal protein delivery systems.     

Structural characterization and Curie temperature determination of a sodium strontium niobate ferroelectric nanostructured powder

The Curie temperature and its correlation with the magnitude of the displacement of the niobium atom from the center of [NbO₆] octahedra in NaSr₂Nb₅O₁₅ nanostructured powder were investigated. A single powder was prepared by high-energy ball milling. A powder with an average crystallite size of 37 nm was prepared by calcining the precursor at 1423 K. The refinement of the structural parameters was carried out by the Rietveld method. NaSr₂Nb₅O₁₅ exhibits tetragonal symmetry with the tungsten bronze structure (a=b=12.3495 (6) Å, c=3.8911 (2) Å, V=593.432 (5) Å³, and Z=2). The site occupancy of the Na⁺ and Sr²⁺ cations and the interatomic distances between the niobium and oxygen atoms were derived. The [NbO₆] octahedron undergoes both rotation and tilting depending on the crystallographic site. The Curie temperature of the powder was derived using both the impedance and infrared spectroscopy methods.     

An efficient and regioselective synthesis of 1,1′-oxalylbis[3-(alkyl/aryl/heteroaryl)-5-(trihalomethyl)-1H-pyrazoles] from 4-alkoxy-1,1,1-trihaloalk-3-en-2-ones

Abstract  

This work describes the regioselective synthesis of two new series of 1,1′-oxalylbis[3-(alkyl/aryl/heteroaryl)-4,5-dihydro-5-hydroxy-5-(trihalomethyl)-1H-pyrazoles], where the 3-substituents are H, Me, C₆H₅, 4-FC₆H₄, 4-ClC₆H₄, 4-BrC₆H₄, 4-NO₂C₆H₄, 4,4′-BiPh, and 2-furyl, in a one-pot methodology with ethanol as solvent, from the reaction of 4-alkoxy-4-(alkyl/aryl/heteroaryl)-1,1,1-trihaloalk-3-en-2-ones with oxalyldihydrazide (51–89%). Complementarily, the dehydration reactions of five examples of the described oxalylbispyrazolines are also reported, which furnished the respective 1,1′-oxalylbis[3-(alkyl/aryl/heteroaryl)-5-(trihalomethyl)-1H-pyrazoles] in 53–78% yields without the two C(O)–N bond cleavages.     

Evaluation of grinding methods for pellets preparation aiming at the analysis of plant materials by laser induced breakdown spectrometry

It has been demonstrated that laser induced breakdown spectrometry (LIBS) can be used as an alternative method for the determination of macro (P, K, Ca, Mg) and micronutrients (B, Fe, Cu, Mn, Zn) in pellets of plant materials. However, information is required regarding the sample preparation for plant analysis by LIBS. In this work, methods involving cryogenic grinding and planetary ball milling were evaluated for leaves comminution before pellets preparation. The particle sizes were associated to chemical sample properties such as fiber and cellulose contents, as well as to pellets porosity and density. The pellets were ablated at 30 different sites by applying 25 laser pulses per site (Nd:YAG@1064 nm, 5 ns, 10 Hz, 25 J cm⁻²). The plasma emission collected by lenses was directed through an optical fiber towards a high resolution echelle spectrometer equipped with an ICCD. Delay time and integration time gate were fixed at 2.0 and 4.5 μs, respectively. Experiments carried out with pellets of sugarcane, orange tree and soy leaves showed a significant effect of the plant species for choosing the most appropriate grinding conditions. By using ball milling with agate materials, 20 min grinding for orange tree and soy, and 60 min for sugarcane leaves led to particle size distributions generally lower than 75 μm. Cryogenic grinding yielded similar particle size distributions after 10 min for orange tree, 20 min for soy and 30 min for sugarcane leaves. There was up to 50% emission signal enhancement on LIBS measurements for most elements by improving particle size distribution and consequently the pellet porosity.     

Bile salt structural effect on the thermodynamic properties of a catanionic mixed adsorbed monolayer

The interfacial effects of two bile salts (sodium deoxycholate (NaDC) and sodium dehydrocholate (NaDHC)) in a catanionic mixed adsorbed monolayer have been investigated at 25 °C. The surfactant interfacial composition, the interfacial orientation of the molecules and the energy changes are analysed to show a thermodynamic evidence of the hydrophobic BSs effect during its intercalation into interfacial adsorbed didodecyldimethyl ammonium bromide (DDAB) molecules. Both mixed systems (NaDC–DDAB and NaDHC–DDAB) have analogous adsorption efficiencies, which are similar from a pure DDAB monolayer and superior to that obtained for both bile salts molecules. Nevertheless, their adsorption effectiveness is different: NaDC causes an increment of Γ while NaDHC produces the opposite effect. The adsorption efficiency in surface tension reduction is due to the existence of interfacial synergistic interactions (confirmed by the analysis of β ^γ and ΔG _ad ⁰ values). Maximum synergistic interaction is seen for α _BSs = 0.4. The hydrophobic steroid backbone of NaDHC molecule presents a deep interfacial penetration than NaDC. This fact causes a great disturbance of DDAB hydrocarbon tails and conduces to a large separation of molecules (high A _m values) which explains the reduction of adsorption effectiveness (low Γ _m values).     

Characterization of diazeniumdiolate nitric oxide donors (NONOates) by electrospray ionization mass spectrometry

Diazeniumdiolates (also called NONOates) have been analyzed by electrospray ionization mass spectrometry (ESI-MS). The samples used are commercially available and included Diethylamine NONOate, DETA NONOate, Spermine NONOate, MAHMA NONOate, PROLI NONOate, Dipropylenetriamine NONOate, PAPA NONOate, and Sulpho NONOate. These compounds have been found to ionize upon ESI by protonation, deprotonation and sodiation. The MS(n) experiments provided strong evidence that such ions release NO, HNO, N(2)O, NO(2), N(2)O(2), N(3)O(3), N(4)O(3) and N(4)O(4) when collisionally activated. Thus, the facile donation of NO units is a property of such compounds. Negative-mode mass spectrometry has been particularly useful for the analysis of most of the NONOates studied here. The experiments have demonstrated the capabilities of mass spectrometry, along with CAD (MS/MS), to detect and characterize such compounds.     

High-performance liquid chromatography-diode array detection-electrospray ionization multi-stage mass spectrometric screening of an insect/plant system: the case of Spodoptera littoralis/Lycopersicon esculentum phenolics and alkaloids

High-performance liquid chromatography-diode array detection-electrospray ionization multi-stage mass spectrometry (HPLC-DAD-ESI-MS(n)) is considered to be a very valuable tool for the characterization of compounds found in trace amounts in natural matrices, as their previous isolation and clean-up steps can be avoided. Micro-scale separation increases the potential of this analytical technique, allowing the determination of compounds in reduced samples. Spodoptera littoralis represents a major challenge to Solanaceae plants, as it is one of the most deleterious pests. The S. littoralis/Lycopersicon esculentum system was studied for the first time concerning glycoalkaloids and phenolics. Using HPLC-DAD-ESI-MS(n) we were able to characterize 15 phenolic compounds in L. esculentum leaves. Nine of them are reported for the first time. Some differences were found between leaves of cerasiforme and 'Bull's heart' varieties. However, in the materials of S. littoralis (larvae, adults, exuviae and excrements) reared in both L. esculentum leaves no phenolics were identified. α-Tomatine was the main glycoalkaloid in the host plant. The glycoalkaloid composition of the different S. littoralis materials was distinct, with α-tomatine and dehydrotomatine being the main detected compounds in larvae and excrements. These results add knowledge to the ecological interaction in this insect/plant duo, for which it is hard to obtain considerable sample amounts.     

Electrospray ionization mass spectrometric fragmentation of hydroquinone derivatives

The fragmentation patterns of nine di-, tri- and tetracyclic hydroquinones with potential antitumor activity were rationalized by invoking competing mechanisms that included sterically accelerated homolytic cleavage, Meerwein-type rearrangements and dehydrations through elimination or intramolecular nucleophilic substitution.