Separation of terbutaline enantiomers in capillary electrophoresis with neutral cyclodextrin-type chiral selectors and investigation of the structure of selector-selectand complexes using nuclear magnetic resonance spectroscopy

The major goal of this study was to determine the affinity pattern of the terbutaline (TB) enantiomers toward α-, β-, γ-, and heptakis(2,3-di-O-acetyl)-β-cyclodextrins and using NMR spectroscopy for the understanding of the fine mechanisms of interaction between the cyclodextrins (CD) and TB enantiomers. It was shown once again that CE in combination with NMR spectroscopy represents a sensitive tool to study the affinity patterns and structure of CD complexes with chiral guests. Opposite affinity patterns of TB enantiomers toward native α- and β-CDs were associated with significant differences between the structure of the related complexes in solution. In particular, the complex between TB enantiomers and α-CD was of the external type, whereas an inclusion complex was formed between TB enantiomers and β-CD. One of the possible structures of the complex between TB and heptakis(2,3-di-O-acetyl)-β-CD (HDA-β-CD) was quite similar to that of TB and β-CD, although the chiral recognition pattern and enantioselectivity of TB complexation with these two CDs were very different.     

Theoretical investigation of the molecular structure,vibrational spectra,and molecular docking of tramadol using density functional theory

The optimized molecular structures, harmonic vibrational wavenumbers, and the corresponding vibrational assignments of (1S,2S)-tramadol and (1R,2R)-tramadol are computationally examined using the B3LYP density functional theory method together with the standard 6–311++G(d,p) and def2-TVZP basis sets. The optimized structures show that phenolic rings of both 1R,2R and 1S,2S tramadol adopt planar geometry, which are slightly distorted due to the substitution at the meta-position; and the six-membered cyclohexane adopts a slightly distorted chair conformation. The 1S,2S enantiomer is energetically more favorable than 1R,2R with the energy differences of 1.32 and 1.03 kcal/mol obtained at B3LYP/6–311++G(d,p) and B3LYP/Def2-TVZP levels, respectively. The analysis of the binding pocket in the silico molecular docking with the m-opioid receptor shows that it originated two clusters with the 1S,2S enantiomer and one cluster with the 1R,2R enantiomer of tramadol. The results point to a more stable complex of the m-opioid receptor with the 1R,2R enantiomer of tramadol.     

Continental and Antarctic Lichens: isolation,identification and molecular modeling of the depside tenuiorin from the Antarctic lichen Umbilicaria antarctica as tau protein inhibitor

Abstract

Alzheimer´s disease (AD) is the most common form of dementia involving Aβ and tau protein. So far, AD cure remains elusive, but considering that AD progresses throughout tau pathology, which turns tau protein an appropriate target, besides tau is also included in other neurodegenerative disorders named as tauopathies. Here, we have isolated seventeen compounds belonging to six lichens species. Due to scarce of spectroscopic data of the compound 5,7-dihydroxy-6-methylphthalide, we explained their structural elucidation based on NMR data. In this study, we show that only tenuiorin from Umbilicaria antarctica inhibited 50% of tau 4R at 100?µM. Then, we shown that molecular interactions of tenuiorin with the steric zipper model of the hexapeptide ³⁰⁶VQIVYK³¹¹ were studied by docking calculations and the results suggested that tenuiorin forms both hydrogen bonds with lysine and glutamine side chains and forms several hydrophobic interactions with valine and lysine from ³⁰⁶VQIVYK³¹¹ motif.     

Stereoselective allylation of 4-oxoazetidine-2-carbaldehydes. Application To the stereocontrolled synthesis of fused tricyclic beta-lactams via intramolecular diels-alder reaction of 2-azetidinone-tethered trienes

Allylation reactions of racemic and optically pure 4-oxoazetidine-2-carbaldehydes were investigated both under anhydrous conditions and in aqueous media. Different Lewis acid or metal mediators showed varied diastereoselectivities on product formation during allylation reactions of the above aldehydes with allyltrimethylsilane, allyltributylstannane, or allyl bromide. Under standard reaction conditions, tin(IV) chloride-promoted addition of allyltrimethylsilane to 4-oxoazetidine-2-carbaldehydes provided the highest diastereoselectivity and the best yield. Boron trifluoride-diethyl ether-promoted reaction of allyltributylstannane provided slightly lower diastereoselectivity with the same facial preference. Indium-promoted allylation showed a reverse diastereofacial preference, although the observed selectivity is not synthetically useful. The mesylates of these homoallylic alcohols were used for the stereoselective preparation of cis-4-butadienyl-2-azetidinones. Interestingly, mesylates having an extra alkene or alkyne tether at position 1 or 3 of the beta-lactam ring, on heating in a sealed tube with equimolecular amounts of DBU in toluene, yielded fused tricyclic 2-azetidinones through a tandem one-pot elimination-intramolecular Diels-Alder reaction.     

Heritability of Stroop and flanker performance in 12-year old children

Background  

There is great interest in appropriate phenotypes that serve as indicator of genetically transmitted frontal (dys)function, such as ADHD. Here we investigate the ability to deal with response conflict, and we ask to what extent performance variation on response interference tasks is caused by genetic variation. We tested a large sample of 12-year old monozygotic and dizygotic twins on two well-known and closely related response interference tasks; the color Stroop task and the Eriksen flanker task. Using structural equation modelling we assessed the heritability of several performance indices derived from those tasks.     

Atomic transport and chemical stability during annealing of ultrathin Al2O3 films on Si

Ultrathin films of Al2O3 deposited on Si were submitted to rapid thermal annealing in vacuum or in oxygen atmosphere, in the temperature range from 600 to 800 degrees C. Nuclear reaction profiling with subnanometric depth resolution evidenced mobility of O, Al, and Si species, and angle-resolved x-ray photoelectron spectroscopy revealed the formation of Si-Al-O compounds in near-surface regions, under oxidizing atmosphere at and above 700 degrees C. Under vacuum annealing all species remained essentially immobile. A model is presented based on diffusion-reaction equations capable of explaining the mobilities and reproducing the obtained profiles.     

The contribution of high frequencies to human brain activity underlying horizontal localization of natural spatial sounds

Background  

In the field of auditory neuroscience, much research has focused on the neural processes underlying human sound localization. A recent magnetoencephalography (MEG) study investigated localization-related brain activity by measuring the N1m event-related response originating in the auditory cortex. It was found that the dynamic range of the right-hemispheric N1m response, defined as the mean difference in response magnitude between contralateral and ipsilateral stimulation, reflects cortical activity related to the discrimination of horizontal sound direction. Interestingly, the results also suggested that the presence of realistic spectral information within horizontally located spatial sounds resulted in a larger right-hemispheric N1m dynamic range. Spectral cues being predominant at high frequencies, the present study further investigated the issue by removing frequencies from the spatial stimuli with low-pass filtering. This resulted in a stepwise elimination of direction-specific spectral information. Interaural time and level differences were kept constant. The original, unfiltered stimuli were broadband noise signals presented from five frontal horizontal directions and binaurally recorded for eight human subjects with miniature microphones placed in each subject's ear canals. Stimuli were presented to the subjects during MEG registration and in a behavioral listening experiment.     

Eleven-dimensional CJS supergravity and the D'Auria–Fré group

An action for eleven-dimensional standard supergravity genuinely invariant under the D'Auria–Fré group is proposed. The construction of the action is carried out through a generalization of the Stelle–West–Grignani–Nardelli formalism. The action is genuinely invariant under this group without the need to impose auxiliary conditions such as a torsion-free condition.     

Application of thiophilic chromatography to deplete serum immunoglobulins in sample preparation for bidimensional electrophoresis

Serum is a typical sample for non-invasive studies in clinical research. Its proteome characterization is challenging, since requires extensive protein depletion. Methods used nowadays for removal of high-abundance proteins are expensive or show quite often a low loading capacity, which has strong repercussions on the number of samples and replicates per analysis.In order to deplete immunoglobulins (Igs) and albumin (HSA) from 1 mL serum samples, we have developed a protocol based on a combination of thiophilic chromatography, not previously used in clinical proteomics, and a HSA-specific resin. Ig/HSA-depleted samples, immunoglobulinome and albuminone were analyzed by 2-DE. Thiophilic chromatography, coupled with HSA-depletion, allows a good 2-DE resolution as well as the visualization of new spots. Moreover, it yields enough protein to evaluate technical variability and facilitate subsequent protein identification. To validate the protocol, we carried out a preliminary comparative study between triplicate Igs/HSA-depleted serum samples from healthy control individuals and recently diagnosed/untreated rheumatoid arthritis (RA) patients. RA patients showed several acute phase proteins, as well as additional serum proteins, differentially and significantly regulated.Therefore, thiophilic chromatography can be used as an efficient and economical method in 2-DE to deplete immunoglobulins from large human serum samples before a more extensive fractioning.