Characteristics of lipid micro- and nanoparticles based on supercritical formation for potential pharmaceutical application

The interest of the pharmaceutical industry in lipid drug delivery systems due to their prolonged release profile, biocompatibility, reduction of side effects, and so on is already known. However, conventional methods of preparation of these structures for their use and production in the pharmaceutical industry are difficult since these methods are usually multi-step and involve high amount of organic solvent. Furthermore, some processes need extreme conditions, which can lead to an increase of heterogeneity of particle size and degradation of the drug. An alternative for drug delivery system production is the utilization of supercritical fluid technique. Lipid particles produced by supercritical fluid have shown different physicochemical properties in comparison to lipid particles produced by classical methods. Such particles have shown more physical stability and narrower size distribution. So, in this paper, a critical overview of supercritical fluid-based processes for the production of lipid micro- and nanoparticles is given and the most important characteristics of each process are highlighted.     

A nested online scheduling and nonlinear model predictive control framework for multi-product continuous systems

In the pursuit of integrated scheduling and control frameworks for chemical processes, it is important to develop accurate integrated models and computational strategies such that optimal decisions can be made in a dynamic environment. In this study, a recently developed switched system formulation that integrates scheduling and control decisions is extended to closed-loop operation embedded with nonlinear model predictive control (NMPC). The resulting framework is a nested online scheduling and control loop that allows to obtain fast and accurate solutions as no model reduction is needed and no integer variables are involved in the formulations. In the outer loop, the integrated model is solved to calculate an optimal product switching sequence such that the process economics is optimized, whereas in the inner loop, an NMPC implements the scheduling decisions. The proposed scheme was tested on two multi-product continuous systems. Unexpected large disturbances and rush orders were handled effectively.     

Optimal control and the Pontryagin's principle in chemical engineering: History,theory, and challenges

In the mid-1950s, Pontryagin et al. published a principle that became a fundamental concept in optimal control (OC) theory. The principle provides theoretical and practical methods to find the solution of OC problems, in particular, open-loop control problems. In chemical engineering, the principle has played an important role as a decision making framework for more than 60 years. This study gathers the main contributions on the application of the Pontryagin's principle to the dynamic optimization of chemical processes. A concise overview of the optimality conditions for a wide class of constrained OC problems is provided. Numerical methods to solve the necessary conditions and strategies to address inequality constraints are summarized. The information and illustrative case study presented in this work can be used as a guide to implement the principle in different settings. Opportunities for further application of the principle in relevant chemical engineering problems are also discussed.     

A new combined computational and NMR-spectroscopical strategy for the identification of additional conformational constraints of the bound ligand in an aprotic solvent

This study documents the feasibility of switching to an aprotic medium in sugar receptor research. The solvent change offers additional insights into mechanistic details of receptor--carbohydrate ligand interactions. If a receptor retained binding capacity in an aprotic medium, solvent-exchangeable protons of the ligand would not undergo transfer and could act as additional sensors, thus improving the level of reliability in conformational analysis. To probe this possibility, we first focused on hevein, the smallest lectin found in nature. The NMR-spectroscopic measurements verified complexation, albeit with progressively reduced affinity by more than 1.5 orders of magnitude, in mixtures of up to 50% dimethyl sulfoxide (DMSO). Since hevein lacks the compact beta-strand arrangement of other sugar receptors, such a structural motif may confer enhanced resistance to solvent exchange. Two settings of solid-phase activity assays proved this assumption for three types of alpha- and/or beta-galactoside-binding proteins, that is, a human immunoglobulin G (IgG) subfraction, the mistletoe lectin, and a member of the galectin family of animal lectins. Computer-assisted calculations and NMR experiments also revealed no conspicuous impact of the solvent on the conformational properties of the tested ligands. To define all possible nuclear Overhauser effect (NOE) contacts in a certain conformation and to predict involvement of exchangeable protons, we established a new screening protocol applicable during a given molecular dynamics (MD) trajectory and calculated population densities of distinct contacts. Experimentally, transferred NOE (tr-NOE) experiments with IgG molecules and the disaccharide Gal'alpha1-3Galbeta1-R in DMSO as solvent disclosed that such an additional crosspeak, that is, Gal'OH2--GalOH4, was even detectable for the bound ligand under conditions in which spin diffusion effects are suppressed. Further measurements with the plant lectin and galectins confirmed line broadening of ligand signals and gave access to characteristic crosspeaks in the aprotic solvent and its mixtures with water. Our combined biochemical, computational, and NMR-spectroscopical strategy is expected to contribute notably to the precise elucidation of the geometry of ligands bound to compactly folded sugar receptors and of the role of water molecules in protein--ligand (carbohydrate) recognition, with relevance to areas beyond the glycosciences.     

Aggregation of Alcohols Ethoxylates in n-Heptane

The solubility and aggregation process of polyethoxylated non-ionic surfactants, of general formula C _i H_2i+1–(O–CH₂–CH₂) _j –OH with i = 6, 8, 10 and j = 3–6 (C _i EO _j ), in heptane were studied. The aggregation of C _i EO _j surfactants in heptane was investigated by using methylene blue (MB) as an absorption probe. In solutions of MB in the presence of these surfactants in heptane, at concentrations larger than the re-dissolution concentration, the UV bands associated to free MB (A ₁) and MB–EO complex (A ₂) were detected. The ratio of these intensities A ₂/A ₁, was used to study the kinetics of the complex formation in pure surfactant. The value of A ₂/A ₁ depends on the surfactant structure and the media wherein MB is dissolved, being larger in the pure surfactant than in heptane solutions. These results are explained in terms of solvent effect and aggregate structures on the complex formation.

Sex Pheromone of the Bud Borer <Emphasis Type="Italic">Epinotia aporema</Emphasis>: Chemical Identification and Male Behavioral Response

Epinotia aporema (Walsingham) is a Neotropical pest of legumes in southern South America. Its importance has increased during the last decade owing to the significant growth of soybean production in the region. Monitoring of E. aporema is difficult due to the cryptic behavior of the larvae, and hence, chemical control is carried out preventively. We analyzed the female-produced sex pheromone so as to develop monitoring traps and explore pheromone-based control methods. We analyzed pheromone gland extracts by combined chromatographic, spectrometric, and electrophysiological methods. Based on the comparison of retention indices, mass spectra, and electroantennogram (EAD) activity of the insect-produced compounds with those of synthetic standards, we identified two EAD-active compounds, (Z,Z)-7,9-dodecadienol and (Z,Z)-7,9-dodecadienyl acetate (15:1 ratio), as sex pheromone components of E. aporema. We also studied the behavior of males in wind tunnel tests using virgin females and different combinations of synthetic standards (15:1, 1:1, and 1:0 alcohol/acetate) as stimuli. A significantly greater percentage of males reached the chemical source with the 15:1 synthetic mixture than with any of the other treatments, indicating that these two compounds are pheromone components. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The ring transformations of 1,2,3,4-diepoxybutane (2,2′-bioxirane) catalysed by various aluminosilicates

The transformations of a molecule containing two adjacent epoxide rings, 2,2-bioxirane that is, were studied over various acidic aluminosilicates (HZSM-5, HY-FAU, AlMCM-41), for the first time, In the 373–473 K temperature range, in a pulse reactor, a ring-opening–ring-enlargment reaction producing furan only occured over the zeolites and it was the predominant reaction on AlMCM-41 as well. The driving force of this transformation route is water formation via elimination from 2,2-bioxirane. Suprising is the lack of the mono- or dialdehyde, the would-be products of the cleavage of the sterically more hindered C–O bonds – an acid-catalysed reaction typical for alkyl-substituted oxiranes.     

Catalytic Epoxidation and Sulfoxidation Activity of a Dioxomolybdenum(VI) Complex Bearing a Chiral Tetradentate Oxazoline Ligand

A dioxomolybdenum(vi) complex bearing a tetradentate anionic N,O oxazoline ligand with four stereocenters has been studied as a catalyst in the liquid-phase epoxidation of 17 different aliphatic and aromatic olefins (including prochiral, racemate or pure enantiomers) using tert-butyl hydroperoxide as the oxidant. Epoxide selectivities of up to 100% and variable epoxide yields (3–100% within 24 h) were obtained. Although the complex generally exhibited low or no chiral induction ability, diastereoselectivity was significant in some cases (in the reaction of limonene, for example). Kinetic studies and recycling tests with the substrates cis-cyclooctene and trans-β-methylstyrene showed that the catalyst is stable and reusable, and recycling is facilitated by immobilization of the complex in a room temperature ionic liquid. Preliminary results show that the complex may have a broad substrate scope, not only for olefin epoxidation, but also for the dehydrogenation of alcohols to carbonyl compounds and the sulfoxidation of sulfides to sulfoxides.     

Characterization of grape seed oil from different grape varieties (Vitis vinifera)

In this work, oil obtained from seeds of different red grape varieties, grown in the Autonomous Regions of Castilla‐La Mancha and Murcia (Spain), was characterized by determining physicochemical and sensory quality parameters, stability, and the composition in fatty acids and sterols. The physicochemical quality parameters (free acidity, peroxide index, K₂₇₀ and wax) scored high (meaning low quality) compared with virgin olive oils, while the negative sensory attributes stood out over the positive ones. Therefore, the oil was not considered suitable for table use without undergoing a refining process. The samples showed high linoleic and low linolenic acid contents, while β‐sitosterol was the main sterol found. Drying grape seeds with hot air before extraction gave higher physicochemical quality, total phenolic content and stability, and lower wax content in comparison to air‐drying of seeds. The drying process affected the sterol composition but not the fatty acid composition.