School of Chemistry - Research Publications

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    DFT Studies on the Stereoselectivity of α-Silyloxy Diazoalkane Cycloadditions.
    O'Connor, MJ ; Liu, H ; Lee, D ; Zhou, T ; Xia, Y (MDPI AG, 2015-12-02)
    The intramolecular [3+2] cycloaddition (32CA) of alkene-tethered α-silyloxydiazoalkanes provides variable stereoselectivity in generating bicyclic pyrazolines where the silyloxy group is either syn or anti to the newly formed pyrazoline ring. To elucidate the origin of the stereoselectivity, density functional theory (DFT) calculations were carried out for the energy of each transition state structure (TSs) and product. Steric effects were identified as the major determining factors in the diastereoselectivity of the 32CA reaction with regards to substrate structure (cyclic or acyclic α-silyloxydiazoalkanes).
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    Differential composition of DHA and very-long-chain PUFAs in rod and cone photoreceptors
    Agbaga, M-P ; Merriman, DK ; Brush, RS ; Lydic, TA ; Conley, SM ; Naash, MI ; Jackson, S ; Woods, AS ; Reid, GE ; Busik, JV ; Anderson, RE (ELSEVIER, 2018-09-01)
    Long-chain PUFAs (LC-PUFAs; C20-C22; e.g., DHA and arachidonic acid) are highly enriched in vertebrate retina, where they are elongated to very-long-chain PUFAs (VLC-PUFAs; C 28) by the elongation of very-long-chain fatty acids-4 (ELOVL4) enzyme. These fatty acids play essential roles in modulating neuronal function and health. The relevance of different lipid requirements in rods and cones to disease processes, such as age-related macular degeneration, however, remains unclear. To better understand the role of LC-PUFAs and VLC-PUFAs in the retina, we investigated the lipid compositions of whole retinas or photoreceptor outer segment (OS) membranes in rodents with rod- or cone-dominant retinas. We analyzed fatty acid methyl esters and the molecular species of glycerophospholipids (phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine) by GC-MS/GC-flame ionization detection and ESI-MS/MS, respectively. We found that whole retinas and OS membranes in rod-dominant animals compared with cone-dominant animals had higher amounts of LC-PUFAs and VLC-PUFAs. Compared with those of rod-dominant animals, retinas and OS membranes from cone-dominant animals also had about 2-fold lower levels of di-DHA (22:6/22:6) molecular species of glycerophospholipids. Because PUFAs are necessary for optimal G protein-coupled receptor signaling in rods, these findings suggest that cones may not have the same lipid requirements as rods.
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    A monophasic extraction strategy for the simultaneous lipidome analysis of polar and nonpolar retina lipids
    Lydic, TA ; Busik, JV ; Reid, GE (ELSEVIER, 2014-08-01)
    Lipid extraction using a monophasic chloroform/methanol/water mixture, coupled with functional group selective derivatization and direct infusion nano-ESI-high-resolution/accurate MS, is shown to facilitate the simultaneous analysis of both highly polar and nonpolar lipids from a single retina lipid extract, including low abundance highly polar ganglioside lipids, nonpolar sphingolipids, and abundant glycerophospholipids. Quantitative comparison showed that the monophasic lipid extraction method yielded similar lipid distributions to those obtained from established "gold standard" biphasic lipid extraction methods known to enrich for either highly polar gangliosides or nonpolar lipids, respectively, with only modest relative ion suppression effects. This improved lipid extraction and analysis strategy therefore enables detailed lipidome analyses of lipid species across a broad range of polarities and abundances, from minimal amounts of biological samples and without need for multiple lipid class-specific extractions or chromatographic separation prior to analysis.
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    n-3 PUFAs enhance the frequency of murine B-cell subsets and restore the impairment of antibody production to a T-independent antigen in obesity
    Teague, H ; Fhaner, CJ ; Harris, M ; Duriancik, DM ; Reid, GE ; Shaikh, SR (ELSEVIER, 2013-11-01)
    The role of n-3 polyunsaturated fatty acids (PUFA) on in vivo B-cell immunity is unknown. We first investigated how n-3 PUFAs impacted in vivo B-cell phenotypes and antibody production in the absence and presence of antigen compared with a control diet. Lean mice consuming n-3 PUFAs for 4 weeks displayed increased percentage and frequency of splenic transitional 1 B cells. Upon stimulation with trinitrophenylated-lipopolysaccharide, n-3 PUFAs increased the number of splenic transitional 1/2, follicular, premarginal, and marginal zone B cells. n-3 PUFAs also increased surface, but not circulating, IgM. We next tested the effects of n-3 PUFAs in a model of obesity that is associated with suppressed humoral immunity. An obesogenic diet after ten weeks of feeding, relative to a lean control, had no effect on the frequency of B cells but lowered circulating IgM upon antigen stimulation. Administration of n-3 PUFAs to lean and obese mice increased the percentage and/or frequency of transitional 1 and marginal zone B cells. Furthermore, n-3 PUFAs in lean and obese mice increased circulating IgM relative to controls. Altogether, the data show n-3 PUFAs enhance B cell-mediated immunity in vivo, which has implications for immunocompromised populations, such as the obese.
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    1,2-Addition versus homoconjugate addition reactions of indoles and electron-rich arenes to alpha-cyclopropyl N-acyliminium ions: synthetic and computational studies
    Ryder, GM ; Wille, U ; Willis, AC ; Pyne, SG (ROYAL SOC CHEMISTRY, 2019-08-07)
    An investigation of the reactivity of α-cyclopropyl N-acyliminium ions towards indoles has resulted in the unprecedented synthesis of 5-cyclopropyl-5-(3-indoyl)pyrrolidin-2-ones via 1,2-addition reactions and, in the case of highly electron deficient indoles and electron rich arenes, spiroheterocycles via sequential homoconjugate and 1,2-addition reactions with often high diastereoselective control at the C-5 quaternary stereocentres. Computational studies provided support for the proposed mechanisms and stereochemical outcome of these reactions, clearly showing that the 1,2-addition pathway is kinetically controlled. In reactions where the 1,2-adduct is destabilised, for example when the arene ring is less nucleophilic, the 1,2-addition is reversible and the thermodynamically preferred homoconjugate addition and subsequent rearrangement and cyclisation reactions become the major pathway.
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    Direct Assembly of Large Area Nanoparticle Arrays
    Zhang, H ; Cadusch, J ; Kinnear, C ; James, T ; Roberts, A ; Mulvaney, P (AMER CHEMICAL SOC, 2018-08-01)
    A major goal of nanotechnology is the assembly of nanoscale building blocks into functional optical, electrical, or chemical devices. Many of these applications depend on an ability to optically or electrically address single nanoparticles. However, positioning large numbers of single nanocrystals with nanometer precision on a substrate for integration into solid-state devices remains a fundamental roadblock. Here, we report fast, scalable assembly of thousands of single nanoparticles using electrophoretic deposition. We demonstrate that gold nanospheres down to 30 nm in size and gold nanorods <100 nm in length can be assembled into predefined patterns on transparent conductive substrates within a few seconds. We find that rod orientation can be preserved during deposition. As proof of high fidelity scale-up, we have created centimeter scale patterns comprising more than 1 million gold nanorods.
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    Tuning the properties of pH responsive nanoparticles to control cellular interactions in vitro and ex vivo
    Mann, SK ; Dufour, A ; Glass, JJ ; De Rose, R ; Kent, SJ ; Such, GK ; Johnston, APR (ROYAL SOC CHEMISTRY, 2016-01-01)
    Engineering the properties of nanoparticles to limit non-specific cellular interactions is critical for developing effective drug delivery systems. Differences between interactions with cultured cells and human blood highlights the need for appropriate assays
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    Automated preparation of 2-[F-18]fluoropropionate labeled peptides using a flexible, multi-stage synthesis platform (iPHASE Flexlab)
    Haskali, MB ; Roselt, PD ; Hicks, RJ ; Hutton, CA (WILEY, 2018-02-01)
    Radiolabelled peptides are vital tools used in positron emission tomography imaging for the diagnosis of disease, drug discovery, and biomedical research. Peptides are typically labeled through conjugation to a radiolabelled prosthetic group, which usually necessitates complex, multi-step procedures, especially for fluorine-18 labeled peptides. Herein, we describe the automated synthesis and formulation of 2-[18 F]fluoropropionate labeled RGD-peptides through use of the iPHASE Flexlab as an effective dual-stage radiochemical synthesis module. The fully automated preparation of the monomeric RGD-peptides, [18 F]FP-GalactoRGD and [18 F]FP-c(RGDy(SO3 )K), was accomplished in under 90 minutes with n.d.c. radiochemical yields ca. 7% from fluoride. Similarly, the automated preparation of the dimeric RGD-peptides, [18 F]F-PRGD2 and [18 F]FP-E(RGDy(SO3 )K)2 , was accomplished in under 105 minutes with n.d.c. yields ca. 4% from fluoride.
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    Additive-Morphology Interplay and Loss Channels in "All-Small-Molecule" Bulk-heterojunction (BHJ) Solar Cells with the Nonfullerene Acceptor IDTTBM
    Liang, R-Z ; Babics, M ; Seitkhan, A ; Wang, K ; Geraghty, PB ; Lopatin, S ; Cruciani, F ; Firdaus, Y ; Caporuscio, M ; Jones, DJ ; Beaujuge, PM (WILEY-V C H VERLAG GMBH, 2018-02-14)
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    Antimicrobial Peptide Structures: From Model Membranes to Live Cells
    Sani, M-A ; Separovic, F (WILEY-V C H VERLAG GMBH, 2018-01-09)
    The rise in antibiotic resistance has led to a renewed interest in antimicrobial peptides (AMPs) that target membranes. The mode of action of AMPs involves the disruption of the lipid bilayer and leads to growth inhibition and death of the bacteria. However, details at the molecular level of how these peptides kill bacteria and the reasons for the observed differences in selectivity remain unclear. Structural information is crucial for defining the molecular mechanism by which these peptides recognize, self-assemble and interact with a particular lipid membrane. Solid-state NMR is a non-invasive technique that allows the study of the structural details of lipid-peptide and peptide-peptide interactions. Following on from studies of antibiotic and lytic peptides, gramicidin A and melittin, respectively, we investigated maculatin 1.1, an AMP from the skin of Australian tree frogs that acts against Gram-positive bacteria. By using perdeuterated phospholipids and specifically labelled peptides, 2 H, 31 P and {31 P}15 N REDOR solid-state NMR experiments have been used to localize, maculatin 1.1 in neutral and anionic model membranes. However, the structure, location and activity depend on the composition of the model membrane and current advances in solid-state NMR spectroscopy now allow structure determination of AMPs in live bacteria.