Improved synthesis of tocopherol fatty alcohols and analogs: microglial activation modulators

The synthesis of tocopherol fatty alcohols (TFAs), potent microglial activation modulators, was achieved via C-alkylation of trimethylhydroquinone. Several analogs, in particular water-soluble prodrugs, have been synthesized using a Wittig reaction and their antioxidant activities have been evaluated.     

Characterization of internal structure of hydrated agar and gelatin matrices by cryo‐SEM

There has been a considerable interest in recent years in developing polymer gel matrices for many important applications such as 2DE for quantization and separation of a variety of proteins and drug delivery system to control the release of active agents. However, a well‐defined knowledge of the ultrastructures of the gels has been elusive. In this study, we report the characterization of two different polymers used in 2DE: Gelatin, a naturally occurring polymer derived from collagen (protein) and agar, a polymer of polysaccharide (sugar) origin. Low‐temperature SEM is used to examine the internal structure of these gels in their frozen natural hydrated states. Results of this study show that both polymers have an array of hollow cells that resembles honeycomb structures. While agar pores are almost circular, the corresponding Gaussian curve is very broad exhibiting a range of radii from nearly 370 to 700 nm. Gelatin pores are smaller and more homogeneous reflecting a narrower distribution from nearly 320 to 650 nm. Overall, these ultrastructural findings could be used to correlate with functions of the polymers.     

Densitometric high-performance thin-layer chromatography methods for the quantification of oleuropein in Olea europaea leaves and pharmaceutical preparation utilizing normal- and reversed-phase silica gel plates

Two validated, simple and precise densitometric high-performance thin-layer chromatography (HPTLC) quantification methods were proposed for both qualitative and quantitative estimation of oleuropein in Olea europaea leaves and a pharmaceutical product utilizing normal-phase and reversed-phase silica gel TLC plates. In method I, 10 × 20 cm glass plates coated with 0.2 mm thin layers of normal-phase silica gel 60 containing F₂₅₄ (E-Merck, Germany) and a mixture of ethyl acetate‒methanol‒water (8:1:0.5, V/V) were used as the stationary and the mobile phase, respectively. Method II utilized 10 × 20 cm glass-backed plates supporting 0.2 mm layers of RP-18 silica gel 60 containing F₂₅₄ (E-Merck, Germany) as the stationary phase and green solvents mixture composed of ethanol‒water (5.5:4.5, V/V) as the mobile phase. The two methods resulted in sharp, symmetrical, well-resolved peaks at R_F values of 0.47 ± 0.02 and 0.78 ± 0.03 with linearity ranges 200‒1400 ng/spot (r² = 0.9994) and 200‒1400 ng/spot (r² = 0.9996) for method I and method II, respectively. Spots corresponding to oleuropein were scanned at 200 nm. The two methods complied with the ICH guidelines for validation. Due to simplicity, low cost and short analysis time, the methods can be good alternatives for the quality control of different products containing olive leaves extract or pure oleuropein.

     

Solid supported fluoronitroaryl triazenes as immobilized and convertible Sanger reagents--synthesis and SNAr reactions towards a novel preparation of 1-alkyl-5-nitro-1H-benzotriazoles

Synthesis of novel fluoronitroaryl triazenes in liquid phase and on solid support have been described; mild displacement of the fluoride ion with various nucleophiles provides access to substituted arenes which in turn can be cleaved to provide a unique access to 1-alkyl-5-nitro-1H-benzotriazole.     

An exact root-free method for the expected queue length for a class of discrete-time queueing systems

Queueing Systems - For a class of discrete-time queueing systems, we present a new exact method of computing both the expectation and the distribution of the queue length. This class of systems...     

A new mixed integer program and extended look-ahead heuristic algorithm for the block relocation problem

This paper considers the block relocation problem (BRP), in which a set of identically-sized items is to be retrieved from a set of last-in-first-out (LIFO) stacks in a specific order using the fewest number of moves. The problem is encountered in the maritime container shipping industry and other industries where inventory is stored in stacks. After surveying the work done on the BRP, we introduce “BRP-III”—a new mathematical formulation for the BRP—and show that it has considerably fewer decision variables and better runtime performance than the other formulation in the literature. We then introduce a new look-ahead algorithm (LA-N) that is an extension of the algorithms from the literature and show that the new algorithm generally obtains better solutions than the other algorithms and has minimal CPU runtime.     

Automated derivatization and analysis of malondialdehyde using column switching sample preparation HPLC with fluorescence detection

Analyte derivatization is advantageous for the analysis of malondialdehyde (MDA) as a biomarker of oxidative stress in biological samples. Conventionally, however, derivatization is time consuming, error-prone and has limited options for automation. We have addressed these challenges for the solid phase analytical derivatization of MDA from small volume tissue homogenate samples. A manual derivatization method was first developed using Amberlite XAD-2 (12 mg) as the solid phase. Subsequently an automated column switching process was developed that provided simultaneous derivatization and extraction of the MDA-DH hydrazone product on a cartridge packed with XAD-2, followed by quantitative elution of the product to an analytical LC column (Waters NovoPak C18, 3.9 x 150 mm). The LOD was 0.02 microg/mL and recovery was quantitative. The method was linear (r(2) >0.999) with precision < 5% from the LOQ (0.06 microg/mL) to at least 35 microg/mL. The method was successfully applied to the analysis of small volume (30 microL) mouse tissue homogenate samples. Endogenous levels of MDA in the tissues ranged from 20 to 40 nmol/g tissue (ca. 0.1-0.2 microg/mL homogenate). Compared to conventional MDA analyses, the current method has advantages in automation, selectivity, precision and sensitivity for analysis from very small sample volumes.     

Experimental study of the dynamics of front propagation in the Co(OH)2/NH4OH Liesegang system using spectrophotometry

In this paper we study the temporal dynamics of the Co(OH) 2/NH 4OH Liesegang system with redissolution by complex formation with ammonia using UV-vis spectrophotometry with a special setup. The formation of precipitate bands is accompanied with band redissolution at the top, and because of such precipitation-redissoultion dynamics, the bands appear as a propagating wave. The spectrophotometric technique developed in this study allows us to study at the kinetics of formation of the bands and their redissolution in great details. The formation, growth, and dissolution of multiple bands are monitored by the time evolution of the absorbance. It was found that the individual band formation is sudden and takes between 15 min to half an hour to form before the next band appears. The speed of formation of bands was different for different bands and the maxima of these speeds fit a Gaussian curve. The content of cobalt hydroxide in these bands was calculated and is shown to increase to a maximum away from the interface and then decreases. The bands later grow by further precipitation. This growth was demonstrated to be nonlinear in time. On the other hand, the dissolution of bands was shown to take place simultaneously and collectively among the multiple bands under study. The effect of the concentration of Co (+2) ions on the dynamics of band formation and dissolution was studied. A time law for this Liesegang system was also determined. The system was also found to be very sensitive to temperature fluctuations.     

Binding of the Zn2+ ion to ferric uptake regulation protein from E. coli and the competition with Fe2+ binding: a molecular modeling study of the effect on DNA binding and conformational changes of Fur

The three dimensional structure of Ferric uptake regulation protein dimer from E. coli, determined by molecular modeling, was docked on a DNA fragment (iron box) and Zn²⁺ ions were added in two steps. The first step involved the binding of one Zn²⁺ ion to what is known as the zinc site which consists of the residues Cys 92, Cys 95, Asp 137, Asp141, Arg139, Glu 140, His 145 and His 143 with an average metal-Nitrogen distance of 2.5 Å and metal-oxygen distance of 3.1–3.2 Å. The second Zn²⁺ ion is bound to the iron activating site formed from the residues Ile 50, His 71, Asn 72, Gly 97, Asp 105 and Ala 109. The binding of the second Zn²⁺ ion strengthened the binding of the first ion as indicated by the shortening of the zinc-residue distances. Fe²⁺, when added to the complex consisting of 2Zn²⁺/Fur dimer/DNA, replaced the Zn²⁺ ion in the zinc site and when a second Fe²⁺ was added, it replaced the second zinc ion in the iron activating site. The binding of both zinc and iron ions induced a similar change in Fur conformations, but shifted residues closer to DNA in a different manner. This is discussed along with a possible role for the Zn²⁺ ion in the Fur dimer binding of DNA in its repressor activity. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Naupliolide, a sesquiterpene lactone with a novel tetracyclic skeleton from Nauplius graveolens subsp. odorus

The aerial parts of Nauplius graveolens subsp. odorus (Schousb) Wikl. afforded a novel sesquiterpene lactone (1) named naupliolide together with the known 6,7,9,10-tetradehydroasteriscanolide 2 and asteriscunolides A-D 3a-d. The structure of compound 1 corresponds to a novel skeleton of 14,15-dimethyl-7,13-dioxotricyclic[6.4.0.0^9,11]dodeca-12,13-olide, and was established on the basis of spectroscopic methods including 2D-NMR. The coexistence of naupliolide 1 together with the structurally related sesquiterpene lactones asterisculolides A-D (3a-d) and 6,7,9,10-tetradehydroasteriscanolide 2, seems to indicate their biosynthetic relationship.