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Palladium-Catalyzed Allylation/Benzylation of H-Phosphinate Esters with Alcohols

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2016-09
Abstract: 

The Pd-catalyzed direct alkylation of H-phosphinic acids and hypophosphorous acid with allylic/benzylic alcohols has been described previously. Here, the extension of this methodology to H-phosphinate esters is presented. The new reaction appears general, although its scope is narrower than with the acids, and its mechanism is likely different. Various alcohols are examined in their reaction with phosphinylidene compounds R1R 2P(O)H.

Document type: 
Article
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Synthesis and Electronic Structure Determination of Uranium(VI) Ligand Radical Complexes

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2016-07
Abstract: 

 

 Pentagonal bipyramidal uranyl complexes of salen ligands, N,N’-bis(3-tert-butyl-(5R)-salicylidene)-1,2-phenylenediamine, in which R = tBu (1a), OMe (1b), and NMe2 (1c), were prepared and the electronic structure of the one-electron oxidized species [1a-c]+ were investigated in solution. The solid-state structures of 1a and 1b were solved by X-ray crystallography, and in the case of 1b an asymmetric UO22+ unit was found due to an intermolecular hydrogen bonding interaction. Electrochemical investigation of 1a-c by cyclic voltammetry showed that each complex exhibited at least one quasi-reversible redox process assigned to the oxidation of the phenolate moieties to phenoxyl radicals. The trend in redox potentials matches the electron-donating ability of the para-phenolate substituents. The electron paramagnetic resonance spectra of cations [1a-c]+ exhibited gav values of 1.997, 1.999, and 1.995, respectively, reflecting the ligand radical character of the oxidized forms, and in addition, spin-orbit coupling to the uranium centre. Chemical oxidation as monitored by ultraviolet-visible-near-infrared (UV-vis-NIR) spectroscopy afforded the one-electron oxidized species. Weak low energy intra-ligand charge transfer (CT) transitions were observed for [1a-c]+ indicating localization of the ligand radical to form a phenolate / phenoxyl radical species. Further analysis using density functional theory (DFT) calculations predicted a localized phenoxyl radical for [1a-c]+ with a small but significant contribution of the phenylenediamine unit to the spin density. Time-dependent DFT (TD-DFT) calculations provided further insight into the nature of the low energy transitions, predicting both phenolate to phenoxyl intervalence charge transfer (IVCT) and phenylenediamine to phenoxyl CT character. Overall, [1a-c]+ are determined to be relatively localized ligand radical complexes, in which localization is enhanced as the electron donating ability of the para-phenolate substituents is increased (NMe2 > OMe > tBu).

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Article
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Characterization of free radicals in clathrate hydrates of pyrrole, thiophene and isoxazole by muon spin spectroscopy

Peer reviewed: 
No, item is not peer reviewed.
Date created: 
2017-05-25
Abstract: 

Gas hydrates have long been of interest to the petrochemical industry but there has been growing interest in potential applications for carbon dioxide sequestration and hydrogen storage. This has prompted many fundamental studies of structure and host-guest interactions, but there has been relatively little investigation of chemical reactions of the guest molecules. In previous work we have shown that it is possible to use muon spin spectroscopy to characterize H-atom-like muonium and muoniated free radicals formed in clathrate hydrates. Muonium forms in clathrate hydrates of cyclopentane and tetrahydrofuran, whereas furan and its dihydro- derivatives form radicals. The current work extends studies to clathrates hydrates of other 5-membered heterocycles: thiophene, pyrrole and isoxazole. All form structure II hydrates. In addition to the clathrates, pure liquid samples of the heterocycles were studied to aid in the assignment of radical signals and for comparison with the enclathrated radicals. Similar to furan, two distinct radicals are formed when muonium reacts with thiophene and pyrrole. However, only one muoniated radical was detected from isoxazole. Muon, proton and nitrogen hyperfine constants were determined and compared with values predicted by DFT calculations to aid the structure assignments. The results show that Mu adds preferentially to the carbon adjacent to the heteroatom in thiophene and pyrrole, and to the carbon adjacent to O in isoxazole. The same radicals are formed in clathrates, but the spectra have broader signals, suggesting slower tumbling. Furthermore, additional signals in the avoided level-crossing spectra indicate anisotropy consistent with restricted motion of the radicals in the clathrate cages.

Document type: 
Article

Method Comparison for Analyzing Wound Healing Rates

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2017-01
Abstract: 

Wound healing scratch assay is a frequently used method to characterize cell migration, which is an important biological process in the course of development, tissue repair, and immune response for example. The measurement of wound healing rate, however, varies among different studies. Here we summarized these measurements into three types: I) Direct Rate Average; II) Regression Rate Average; and III) Average Distance Regression Rate. Using Chinese Hamster Ovary (CHO) cells as a model, we compared the three types of analyses on quantifying the wound closing rate, and discovered that type I & III measurements are more resistant to outliers and type II analysis is more sensitive to outliers. We hope this study can help researchers to better use this simple yet effective assay.

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Article
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Electronic Structure Description of a Doubly Oxidized Bimetallic Cobalt Complex with Pro-Radical Ligands

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2016
Abstract: 

The geometric and electronic structure of a doubly oxidized bimetallic Co complex containing two redox-active salen moieties connected via a 1,2-phenylene linker has been investigated and compared to an oxidized monomeric analogue. Both complexes, CoL1 and Co2L2 are oxidized to the mono- and di-cations respectively with AgSbF6 and characterized by X-ray crystallography for the monomer, and Vis-NIR spectroscopy, electron paramagnetic (EPR) spectroscopy, SQUID magnetometry and density functional theory (DFT) calculations for both the monomer and dimer. Both complexes exhibit a water molecule coordinated in the apical position upon oxidation. [CoL1-H2O]+ displays a broad NIR band at 8500 cm-1 (8400 M-1cm-1) which is consistent with recent reports on oxidized Co salen complexes (Kochem, A. et. al., Inorg Chem., 2012, 51, 10557-10571, Kurahashi, T. et. al., Inorg. Chem., 2013, 52, 3908-3919). DFT calculations predict a triplet ground state with significant ligand and metal contributions to the singularly occupied molecular orbital (SOMO). The majority (~75%) of the total spin density is localized on the metal, highlighting both high spin Co(III) and Co(II)L• character in the electronic ground state. Further oxidation of CoL1 to the dication affords a low spin Co(III) phenoxyl radical species. The NIR features for [Co2L2-2H2O]2+ at 8600 cm-1 (17800 M-1cm-1) are doubly intense in comparison to [CoL1-H2O]+ owing to the description of [Co2L2-2H2O]2+ as two non-interacting oxidized Co salen complexes bound via the central phenylene linker. Interestingly, TD-DFT calculations predict two electronic transitions that are 353 cm-1 apart. The NIR spectrum of the analogous Ni complex, [Ni2L2]2+, exhibits two intense transitions (4890 cm-1/26500 M-1cm-1 and 4200 cm-1/21200 M-1cm-1) due to exciton coupling in the excited state. Only one broad band is observed in the NIR spectrum for [Co2L2-2H2O]2+ as a result of the contracted donor and acceptor orbitals and overall CT character.

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Article
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8-Hydroxyquinoline Schiff-base Compounds as Antioxidants and Modulators of Copper-Mediated Aβ Peptide Aggregation

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2104-10
Abstract: 

One of the hallmarks of Alzheimer's disease (AD) in the brain are amyloid-β (Aβ) plaques, and metal ions such as copper(II) and zinc(II) have been shown to play a role in the aggregation and toxicity of the Aβ peptide, the major constituent of these extracellular aggregates. Metal binding agents can promote the disaggregation of Aβ plaques, and have shown promise as AD therapeutics. Herein, we describe the syntheses and characterization of an acetohydrazone (8-H2QH), a thiosemicarbazone (8-H2QT), and a semicarbazone (8-H2QS) derived from 8-hydroxyquinoline. The three compounds are shown to be neutral at pH 7.4, and are potent antioxidants as measured by a Trolox Equivalent Antioxidant Capacity (TEAC) assay. The ligands form complexes with CuII, 8-H2QT in a 1:1 metal:ligand ratio, and 8-H2QH and 8-H2QS in a 1:2 metal:ligand ratio. A preliminary aggregation inhibition assay using the Aβ1–40 peptide showed that 8-H2QS and 8-H2QH inhibit peptide aggregation in the presence of CuII. Native gel electrophoresis/Western blot and TEM images were obtained to give a more detailed picture of the extent and pathways of Aβ aggregation using the more neurotoxic Aβ1 −42 in the presence and absence of CuII, 8-H2QH, 8-H2QS and the drug candidate PBT2. An increase in the formation of oligomeric species is evident in the presence of CuII. However, in the presence of ligands and CuII, the results match those for the peptide alone, suggesting that the ligands function by sequestering CuII and limiting oligomer formation in this assay.

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Article
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Characterization of Free Radicals in Clathrate Hydrates of Furan, 2,3-Dihydrofuran and 2,5-Dihydrofuran by Muon Spin Spectroscopy

Peer reviewed: 
Yes, item is peer reviewed.
Abstract: 

In addition to their importance as abundant hydrocarbon deposits in nature, clathrate hydrates are being studied as potential media for hydrogen and carbon dioxide storage, and as “nano-reactors” for small molecules. However, little is known about the behaviour of reactive species in such materials. We have employed muon spin spectroscopy to characterize various organic free radicals which reside as isolated guests in structure II clathrates. The radicals are formed by reaction of atomic muonium (Mu) with the guest molecules: furan and two isomeric dihydrofurans. Muonium is essentially a light isotope of hydrogen, and adds to unsaturated molecules in the same manner as H. We have determined muon and proton hyperfine coupling constants for the muoniated radicals formed in the clathrates and also in neat liquids at the same temperature. DFT calculations were used to guide the spectral assignments and distinguish between competing radical products for Mu addition to furan and 2,3-dihydrofuran. Relative signal amplitudes provide yields and thus the relative reactivities of the C4 and C5 addition sites in these molecules. Spectral features, hyperfine constants and reactivities all indicate that the radicals do not tumble freely in the clathrate cages in the same way that they do in liquids.

 

Document type: 
Article

Do Housekeeping Genes Exist?

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2015
Abstract: 

The searching of human housekeeping (HK) genes has been a long quest since the emergence of transcriptomics, and is instrumental for us to understand the structure of genome and the fundamentals of biological processes. The resolved genes are frequently used in evolution studies and as normalization standards in quantitative gene-expression analysis. Within the past 20 years, more than a dozen HK-gene studies have been conducted, yet none of them sampled human tissues completely. We believe an integration of these results will help remove false positive genes owing to the inadequate sampling. Surprisingly, we only find one common gene across 15 examined HK-gene datasets comprising 187 different tissue and cell types. Our subsequent analyses suggest that it might not be appropriate to rigidly define HK genes as expressed in all tissue types that have diverse developmental, physiological, and pathological states. It might be beneficial to use more robustly identified HK functions for filtering criteria, in which the representing genes can be a subset of genome. These genes are not necessarily the same, and perhaps need not to be the same, everywhere in our body.

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Article
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Can We Disrupt the Sensing of Honey Bees by the Bee Parasite Varroa destructor?

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014-09-16
Abstract: 

Background

The ectoparasitic mite, Varroa destructor, is considered to be one of the most significant threats to apiculture around the world. Chemical cues are known to play a significant role in the host-finding behavior of Varroa. The mites distinguish between bees from different task groups, and prefer nurses over foragers. We examined the possibility of disrupting the Varroa – honey bee interaction by targeting the mite's olfactory system. In particular, we examined the effect of volatile compounds, ethers of cis 5-(2′-hydroxyethyl) cyclopent-2-en-1-ol or of dihydroquinone, resorcinol or catechol. We tested the effect of these compounds on the Varroa chemosensory organ by electrophysiology and on behavior in a choice bioassay. The electrophysiological studies were conducted on the isolated foreleg. In the behavioral bioassay, the mite's preference between a nurse and a forager bee was evaluated.

Principal findings

We found that in the presence of some compounds, the response of the Varroa chemosensory organ to honey bee headspace volatiles significantly decreased. This effect was dose dependent and, for some of the compounds, long lasting (>1 min). Furthermore, disruption of the Varroa volatile detection was accompanied by a reversal of the mite's preference from a nurse to a forager bee. Long-term inhibition of the electrophysiological responses of mites to the tested compounds was a good predictor for an alteration in the mite's host preference.

Conclusions

These data indicate the potential of the selected compounds to disrupt the Varroa - honey bee associations, thus opening new avenues for Varroa control.

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G-Quadruplex Structures Formed by Expanded Hexanucleotide Repeat RNA and DNA from the Neurodegenerative Disease-Linked C9orf72 Gene Efficiently Sequester and Activate Heme

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014-09-10
Abstract: 

The expansion of a (G4C2)n repeat within the human C9orf72 gene has been causally linked to a number of neurodegenerative diseases, most notably familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent studies have shown that the repeat expansion alters gene function in four ways, disrupting the gene's normal cellular roles and introducing toxic gain of function at the level of both DNA and RNA. (G4C2)n DNA, as well as the RNA transcribed from it, are found to fold into four-stranded G-quadruplex structures. It has been shown that the toxicity of the RNA G-quadruplexes, often localized in intracellular RNA foci, lies in their ability to sequester many important RNA binding proteins. Herein we propose that a distinct toxic property of such RNA and DNA G-quadruplexes from the C9orf72 gene may arise from their ability to bind and oxidatively activate cellular heme. We show that G-quadruplexes formed by both (G4C2)4 RNA and DNA not only complex tightly with heme but also enhance its intrinsic peroxidase and oxidase propensities. By contrast, the antisense (C4G2)4 RNA and DNA neither bind heme nor influence its oxidative activity. Curiously, the ability of C9orf72 DNA and transcripts to bind and activate heme mirror similar properties that have been reported for the Aβ peptide and its oligomers in Alzheimer's disease neurons. It is therefore conceivable that C9orf72 RNA G-quadruplex tangles play roles in sequestering intracellular heme and promoting oxidative damage in ALS and FTD analogous to those proposed for Aβ peptide and its tangles in Alzheimer's Disease. Given that neurodegenerative diseases in general are characterized by mitochondrial and respiratory malfunctions, the role of C9orf72 DNA and RNA in heme sequestration as well as its inappropriate activation in ALS and FTD neurons may warrant examination.

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Article
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