Strong antiferromagnetic coupling in doubly N,O oximato-bridged dinuclear copper(II) complexes

The use of di-2-pyridyl ketone oxime, (py)pkoH, and phenyl 2-pyridyl ketone oxime, ppkoH, in copper(II) hexafluoroacetylacetonate chemistry is reported. The reaction of CuCl₂·2H₂O with one and two equivalents of ppkoH and Na(hfac), respectively, in CH₂Cl₂ affords the dinuclear complex [Cu₂(hfac)₂(ppko)₂] (1) in excellent yield. The replacement of ppkoH by (py)pkoH gives the isostructural compound [Cu₂(hfac)₂{(py)pko}₂] (2) in good yield. The Cu^II atoms in both 1 and 2 are doubly bridged by the oximate groups of two η¹:η¹:η¹:μ₂ ppko⁻ and (py)pko⁻ ligands, respectively. The bridging Cu–(R–NO)–Cu′ units are not planar, with the torsion angles being 23.2° (1) and 20.3° (2). A bidentate chelating hfac⁻ ligand completes five-coordination at each square pyramidal metal ion. The hfac⁻-free reaction system CuCl₂·2H₂O/(py)pkoH/NEt₃ (1:2:1) gives instead the mononuclear complex [CuCl{(py)pko}{(py)pkoH}] (3) in very good yield. The Cu^II atom is coordinated by two N,N′-bidentate (py)pko⁻/(py)pkoH chelates and a monodentate chloride anion resulting in a distorted square pyramidal geometry around the metal center. Variable-temperature, solid-state dc magnetic studies were carried out on the representative dinuclear complex 1 in the 2.0–300 K range. The data indicate a very strong antiferromagnetic exchange interaction and a resulting S = 0 ground state, which is well isolated from the S = 1 excited state. The J value of −720 cm⁻¹ was derived from the fitting of the experimental data using the Hamiltonian H = −J(S₁ · S₂).     

Vacuum-assisted headspace solid phase microextraction: Improved extraction of semivolatiles by non-equilibrium headspace sampling under reduced pressure conditions

A new headspace solid-phase microextraction (HSSPME) procedure carried out under vacuum conditions is proposed here where sample volumes commonly used in HSSPME (9 mL) were introduced into pre-evacuated commercially available large sampling chambers (1000 mL) prior to HSSPME sampling. The proposed procedure ensured reproducible conditions for HSSPME and excluded the possibility of analyte losses. A theoretical model was formulated demonstrating for the first time the pressure dependence of HSSPME sampling procedure under non equilibrium conditions. Although reduced pressure conditions during HSSPME sampling are not expected to increase the amount of analytes extracted at equilibrium, they greatly increase extraction rates compared to HSSPME under atmospheric pressure due to the enhancement of evaporation rates in the presence of an air-evacuated headspace. The effect is larger for semivolatiles whose evaporation rates are controlled by mass transfer resistance in the thin gas film adjacent to the sample/headspace interface. Parameters that affect HSSPME extraction were investigated under both vacuum and atmospheric conditions and the experimental data obtained were used to discuss and verify the theory. The use of an excessively large headspace volume was also considered. The applicability of Vac-HSSPME was assessed using chlorophenols as model compounds yielding linearities better than 0.9915 and detection limits in the low-ppt level. The repeatability was found to vary from 3.1 to 8.6%.     

Solid-Phase Synthesis of a Biotin Derivative and its Application to the Development of Anti-Biotin Antibodies

A biotin derivative, namely biotin–aminocaproic acid–lysine (BAL), was synthesized with solid-phase chemistry, conjugated to a carrier-protein, and used for rabbit immunization. The aminocaproic acid–lysine “long-arm” was used in order to project the biotin-hapten above the carrier-protein surface. Lysine was selected due to its N^ε-amino group, through which BAL was conjugated to the carrier-protein. BAL was synthesized on a commercially available resin with the Fmoc-solid-phase strategy; this has simplified the experimental procedure, overcome the need for intermediate purification steps, and led to a final product of high purity, with high yield. The anti-BAL antibodies recognized free biotin, as shown with an in-house-developed ELISA, in which biotin conjugated to a synthetic “lysine–dendrimer” was used to coat the ELISA microwells. In immunocytology and Western-blot experiments, the anti-BAL antibodies led to similar results with those obtained with streptavidin. Synthetic derivatives of hapten molecules that can be easily prepared with solid-phase chemistry, such as BAL, may be used for the development of specific antibodies for the corresponding hapten.     

Parameterization of Org27569: An allosteric modulator of the cannabinoid CB1 G protein‐coupled receptor

The cannabinoid CB₁ receptor is a class A G protein‐coupled receptor (GPCR) that is the most widely expressed GPCR in the brain. Many GPCRs contain allosteric binding sites for endogenous and/or synthetic ligands, which are topographically distinct from the agonist‐binding site that is known as the orthosteric site. While both endogenous and synthetic ligands that act at the CB₁ orthosteric site have been known for some time, compounds that act at a CB₁ allosteric site have only recently been discovered. The most studied of these is 5‐chloro‐3‐ethyl‐1H‐indole‐2‐carboxylic acid [2‐(4‐piperidin‐1‐ylphenyl)ethyl]amide (Org27569). Because allosteric ligands are thought to act through conformational changes in the receptor that are transmitted from the allosteric to the orthosteric site, computational studies of the structural and dynamic interactions of Org27569 with the CB₁ receptor are crucial to achieve a molecular level understanding of the basis of action of this important new class of compounds. To date, such computational studies have not been possible due to the lack of a complete set of molecular mechanics force field parameters for Org27569. Here, we present the development of missing CHARMM force field parameters for Org27569 using previously published methods and the validation and application of these new parameters using normal mode analysis and molecular dynamics simulations combined with experimental infrared measurements. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011     

Design and testing of a new sampler for simplified vacuum-assisted headspace solid-phase microextraction

The design and testing of a new and low-cost experimental setup used for vacuum-assisted headspace solid-phase microextraction (Vac-HSSPME) is reported here. The device consists of a specially designed O-ring seal screw cap offering gas-tight seal to commercially available headspace vials. The new polytetrafluoroethylene (PTFE) cap was molded by a local manufacturer and had a hole that could tightly accommodate a septum. All operations were performed through the septum: air evacuation of the sampler, sample introduction and HSSPME sampling. The analytical performance of the new sampler was evaluated using 22 mL headspace vials with 9 mL water samples spiked with polychlorinated biphenyls (PCBs). Several experimental parameters were controlled and the optimized conditions were: 1000 rpm agitation speed; 30 min extraction time; 40 °C sampling temperature; polydimethylsiloxane-divinylbenzene (PDMS-DVB) fiber. The lack of accurate Henry's law constant (K_H) values and information regarding how they change with temperature was a major limitation in predicting the phase location of evaporation resistance during Vac-HSSPME. Nevertheless, the combined effects of system conditions indicated the increasing importance of gas phase resistance with increasing degree of PCBs chlorination. Stirring enhancements were not recorded for the higher chlorinated PCBs suggesting that the hyperhydrophobic gas/water interface was the preferred location for these compounds. Analytically, the developed method was found to yield linear calibration curves with limits of detection in the sub ng L⁻¹ level and relative standard deviations ranging between 5.8 and 14%. To compensate for the low recoveries of the higher chlorinated PCB congeners in spiked river water the standard addition methodology was applied. Overall, the compact design of the new and reusable sample container allows efficient HSSPME sampling of organic analytes in water within short extraction times and at low sampling temperatures compared to other published HSSPME methods.     

Synthesis of (R)-dihydropyridones as key intermediates for an efficient access to piperidine alkaloids

The efficient transformation of D-glucal to (2R)-hydroxymethyldihydropyridinone 5 in seven steps and 35 % overall yield is reported. Dihydropyridone 5 constitutes a versatile chiral building block for the synthesis of various piperidine alkaloids. In this regard, 5 was converted to piperidinol 13 and piperidinone 15, that may be further elaborated for the syntheses of (+)-desoxoprosophylline (1) and deoxymannojirimycin (3) or D-mannolactam (4), respectively.     

Evidence of the Beneficial Effects of Ursolic Acid against Lung Cancer

Lung cancer is the leading cause of cancer-related deaths globally. Despite current treatment approaches that include surgery, chemotherapy, radiation and immunotherapies, lung cancer accounted for 1.79 million deaths worldwide in 2020, emphasizing the urgent need to find novel agents and approaches for more effective treatment. Traditionally, chemicals derived from plants, such as paclitaxel and docetaxel, have been used in cancer treatment, and in recent years, research has focused on finding other plant-derived chemicals that can be used in the fight against lung cancer. Ursolic acid is a polyphenol found in high concentrations in cranberries and other fruits and has been demonstrated to have anti-inflammatory, antioxidant and anticancer properties. In this review, we summarize recent research examining the effects of ursolic acid and its derivatives on lung cancer. Data from in vitro cell culture and in vivo animal studies show potent anticancer effects of ursolic acid and indicate the need for clinical studies.     

Clustering and colocalization in transmission immunoelectron microscopy: a brief review

This mini-review tries to summarize the state of the art of stereological and statistical approaches used in clustering (in single immunogold labelling) and colocalization (in double immunogold labelling) studies of gold particles in transmission immunoelectron microscopy. The point pattern analysis may be useful to compare experimental pattern data to the null hypothesis of complete spatial randomness (CSR), and, furthermore to quantify the amount of clustering and/or colocalization. In particular, this paper gives an overview about the most recent literature on the subject and different approaches will be only briefly summarized.