186 research outputs found
Student perceptions of chemistry experiments with different technological interfaces: a comparative study
No full textMicrocomputer based laboratory activities have been suggested to have a number of benefits in science education. However, their implementation produces mixed results, and student perception data have in the past yielded responses that are negative regarding the technology. This work presents a case study of three first year undergraduate chemistry experiments in which negative views of hand-held graphic data logger devices were significantly alleviated by replacing them with notebook computers equipped with equivalent software. Widespread improvements in student perceptions of their laboratory experience were observed, prominently including reduced negativity concerning the equipment, an increased perception of understanding, an increased perception of simplicity, and more positive perceptions of overall laboratory experience. These improvements, which were not limited to perceptions directly concerning the technology specifically, suggest a broad range of substantial advantages is present in providing a suitable user interface.Samuel J. Priest, Simon M. Pyke, and Natalie M. Williamso
N-(4,4-Dimethoxy-1-oxo-1lambda(6)-thianylidene)-4-methyl-1-benzenesulfonamide
No full textThe definitive version is available at www.blackwell-synergy.comIn the title compound, C14H21NO5S2, the imine group belonging to the tosylamide substituent occupies an axial position at the S atom of the thiane ring; the latter adopts a chair conformation. The torsion angle C(Ph)-S(O2)-N=S in the bridge between the two rings is -93.6 (2)° and the S-N=S bond angle is 122.15 (14)°.Steffen P. Creaser, Simon M. Pyke and Edward R. T. Tiekin
Michael addition of acrolein to lysinyl and N-terminal residues of a model peptide: targets for cytoprotective hydrazino drugs
No full textThe definitive version may be found at www.wiley.comThe antihypertensive drug hydralazine blocks acrolein-mediated toxicity by trapping both free aldehyde- and acrolein-adducted proteins, with the latter property more closely related to cytoprotection in cellular models. Here we report the identification of products from 'protein adduct-trapping' reactions using electrospray ionisation mass spectrometry (ESI-MS). Reaction of a 13-residue peptide containing a single lysine with acrolein for 30 min generated ions corresponding to mono- and bis-Michael-adducted peptides. An ion corresponding to a cyclic species formed from bis-adducted lysine was conspicuous at later times (60, 180 min). Tandem mass spectrometric (MS/MS) analysis revealed Michael adduction also occurred on the N-terminus, with a novel N-terminal (3-formyl-3,4-dehydropiperidino) species formed on this residue. Addition of hydralazine to acrolein-adducted peptides generated a diverse range of hydrazones that were also characterised by MS/MS analysis. The results confirm that mass spectrometry is a powerful tool for characterising the reactions of noxious electrophiles with biological macromolecules.Lisa M. Kaminskas, Simon M. Pyke, Philip C. Burcha
Dinuclear organoplatinum (II)-methyldiphenylphosphine complexes of nicotinic acid
No full textThe preparation and characterisation of a series of novel, dinuclear organoplatinum(II) complexes of methyldiphenylphosphine, trans-[Pt(PMePh2)2(C5H4N(CO 2H))-μ-aryl-Pt(PMePh2)2(C5H 4N(CO2H))](OTf)2 (aryl = phenyl, 4,4′-biphenyl, 4,4″-p-terphenyl, or 4,4′-benzophenone; OTf = triflate), in which nicotinic acid acts a nitrogen-donor ligand are described. The key structural feature of each complex is the presence of a carboxylic acid group at each end of the molecule. This allows for their association via intermolecular hydrogen-bonds in low polarity solvents. The complexes are potentially useful tectons (building blocks) for the construction of metal-containing supramolecular assemblies. © 2000 Published by Elsevier Science S.A. All rights reserved.Michael G. Crisp, Simon M. Pyke, Louis M. Rendinahttp://www.elsevier.com/wps/find/journaldescription.cws_home/504090/description#descriptio
Selective biocatalytic hydroxylation of unactivated methylene C-H bonds in cyclic alkyl substrates
No full textThe cytochrome P450 monooxygenase CYP101B1 from Novosphingobium aromaticivorans selectively hydroxylated methylene C-H bonds in cycloalkyl rings. Cycloketones and cycloalkyl esters containing C6, C8, C10 and C12 rings were oxidised with high selectively on the opposite side of the ring to the carbonyl substituent. Cyclodecanone was oxidised to oxabicycloundecanol derivatives in equilibrium with the hydroxycyclodecanones.Md Raihan Sarkar, Samrat Dasgupta, Simon M. Pyke and Stephen G. Bel
Complexation of zinc(II) and cadmium(II) by hydroxyethyl- and bis(hydroxyethyl)-1,4,7-triazacyclononane in water
No full textCopyright © CSIRO 2003The complexation of Zn2+ by hydroxyethyl- and bis(hydroxyethyl)-1,4,7-triazacyclononane ((2) and (3)) in aqueous solution at 298.2 K and I = 0.10 mol dm−3 (NaNO3) is characterized by log(K/dm3 mol−1) = 10.45 ± 0.05 and 11.32 ± 0.02 and a deprotonation assigned to coordinated water is characterized by pKa = 8.87 ± 0.11 and 8.50 ± 0.03, respectively. For the analogous Cd2+ complexes log(K/dm3 mol−1) = 8.74 ± 0.02 and 9.79 ± 0.02, respectively, and no deprotonation of coordinated water is detected. The synthesis of (2) is described.Steffen P. Creaser, Simon M. Pyke and Stephen F. Lincol
Strong protein adduct trapping accompanies abolition of acrolein-mediated hepatotoxicity by hydralazine in mice
No full textAcrolein is a highly reactive ,-unsaturated aldehyde that readily alkylates nucleophilic centers in cell macromolecules. Typically, such reactions proceed via Michael addition chemistry, forming adducts that retain an electrophilic carbonyl group. Since these species participate in secondary deleterious reactions, we hypothesize that inactivation of carbonyl adducts may attenuate acrolein toxicity. Indeed, we recently established that the nucleophilic antihypertensive drug hydralazine readily "traps" acrolein adducts in cell proteins and strongly suppresses acrolein-mediated toxicity in isolated hepatocytes. This work sought to determine whether hydralazine prevents the in vivo hepatotoxicity of the acrolein precursor allyl alcohol in whole mice and whether adduct trapping accompanies any such hepatoprotection. Mice received allyl alcohol alone or in conjunction with several doses of hydralazine. Four hours later, mice were sacrificed to allow for the determination of liver enzymes in plasma as markers of hepatic injury, whereas livers were assessed for glutathione and hydralazine-stabilized protein adducts. Hydralazine afforded strong, dose-dependent protection against the increases in plasma marker enzymes but not the hepatic glutathione depletion produced by allyl alcohol. Western blotting revealed intense, dose-dependent adduct trapping by hydralazine in numerous liver proteins over a broad 26- to 200-kDA mass range. In keeping with these findings, immunohistochemical analysis of liver slices indicated diffuse, extranuclear adduct trapping by hydralazine that was uniformly distributed across the liver lobule, with partial localization in parenchymal cell membranes. These findings concur with our hypothesis that hydralazine readily inactivates reactive carbonyl-retaining protein adducts formed by acrolein, thereby preventing secondary reactions that trigger cellular death.Lisa M. Kaminskas, Simon M. Pyke, and Philip C. Burcha
Differences in lysine adduction by acrolein and methyl vinyl ketone: Implications for cytotoxicity in cultured hepatocytes
No full textCopyright © 2005 American Chemical SocietyAcrolein is a highly toxic environmental pollutant that readily alkylates the -amino group of lysine residues in proteins. In model systems, such chemistry involves sequential addition of two acrolein molecules to a given nitrogen, forming bis-Michael-adducted species that undergo aldol condensation and dehydration to form N-(3-formyl-3,4-dehydropiperidino)lysine. Whether this ability to form cyclic adducts participates in the toxicity of acrolein is unknown. To address this issue, we compared the chemistry of protein adduction by acrolein to that of its close structural analogue methyl vinyl ketone, expecting that the -methyl group would hinder the intramolecular cyclization of any bis-adducted species formed by methyl vinyl ketone. Both acrolein and methyl vinyl ketone displayed comparable protein carbonylating activity during in vitro studies with the model protein bovine serum albumin, confirming the ,,-unsaturated bond of both compounds is an efficient Michael acceptor for protein nucleophiles. However, differences in adduction chemistry became apparent during the use of electrospray ionization-MS to monitor reaction products in a lysine-containing peptide after modification by each compound. For example, although a Schiff base adduct was detected following reaction of the peptide with acrolein, an analogous species was not formed by methyl vinyl ketone. Furthermore, while ions corresponding to mono- and bis-Michael adducts were detected at the N-terminus and lysine residues following peptide modification by both carbonyls, only acrolein modification generated ions attributable to cyclic adducts. Despite these differences in adduction chemistry, in mouse hepatocytes, the two compounds exhibited very comparable abilities to induce rapid, concentration-dependent cell death as well as protein carbonylation. These findings suggest that the acute toxicity of short-chain ,-unsaturated carbonyl compounds involves their ability to form acyclic Michael addition adducts rather than Schiff conjugates or heterocyclic adducts.Lisa M. Kaminskas, Simon M. Pyke and Philip C. Burcha
Reactivity of hydrazinophthalazine drugs with the lipid peroxidation products acrolein and crotonaldehyde
No full text© Royal Society of Chemistry 2004The nucleophilic drug hydralazine strongly inhibits cell toxicity mediated by acrolein, a short chain 2-alkenal formed during lipid peroxidation. We here report the chemistry of acrolein-trapping by hydralazine, and show that together with its structural analogue dihydralazine, it also readily traps crotonaldehyde. Isolable reaction products included (1E)-acrylaldehyde phthalazin-1-ylhydrazone (E-APH), (1Z)-acrylaldehyde phthalazin-1-ylhydrazone (Z-APH), (1E,2E)-but-2-enal phthalazin-1-ylhydrazone (E-BPH) and (1Z,2E)-but-2-enal phthalazin-1-ylhydrazone (Z-BPH). Concentration-dependent formation of (1E)-acrylaldehyde phthalazin-1-ylhydrazone was observed in the culture media of cells co-exposed to hydralazine and the acrolein precursor allyl alcohol. These aldehyde-sequestering properties of hydrazinophthalazine drugs may contribute to the protection they provide against 2-alkenal-mediated toxicity.Lisa M. Kaminskas, Simon M. Pyke and Philip C. Burcha
Synthesis and cyclization to aurones and flavones of alkoxy-substituted aryl arylalkynyl ketones
No full text© CSIRO 2008Acylation of 1,3,5-tribenzyloxybenzene with alkoxy-substituted phenylpropioloyl chlorides provides the corresponding aryl alkoxylarylalkynyl ketones in which one of the benzyl groups has been removed. Cyclization of these phenolic ketones using basic reagents (potassium carbonate in acetone is best) provides the corresponding aurone system. When the phenolic group of the alkynyl ketones is protected as the t-butyldimethylsilyl ether followed by cyclization, using 18-crown-6 and potassium fluoride, mixtures of the corresponding aurones and flavones are produced. A by-product from the formation of the ketones is the corresponding β-chlorochalcone, which can also be cyclized to an aurone product using basic conditions. Similarly, the t-butyldimethylsilyl ethers of the HCl adducts can also be cyclized to a mixture of the corresponding aurones and flavones.Penelope J. Kerr, Simon M. Pyke and A. David War
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