http://hdl.handle.net/10468/289 2017-08-31T14:46:01Z http://hdl.handle.net/10468/3955 Supercritical carbon dioxide versus toluene as reaction media in silica functionalisation: Synthesis and characterisation of bonded aminopropyl silica intermediate Ashu-Arrah, Benjamin A.; Glennon, Jeremy D. This research reports supercritical carbon dioxide versus toluene as reaction media in silica functionalisation for use in liquid chromatography. Bonded aminopropyl silica (APS) intermediates were prepared when porous silica particles (Exsil-pure, 3 μm) were reacted with 3-aminopropyltriethoxysilane (3-APTES) or N,N-dimethylaminopropyltrimethoxysilane (DMAPTMS) using supercritical carbon dioxide (sc-CO2) and toluene as reaction media. Covalent bonding to silica was confirmed using elemental microanalysis (CHN), thermogravimetric analysis (TGA), zeta potential (ξ), diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, scanning electron microscopy (SEM) and solid-state nuclear magnetic resonance (CP/MAS NMR) spectroscopy. The results demonstrate that under sc-CO2 conditions of 100 °C/414 bar in a substantial reduced time of 3 h, the surface coverage of APS (evaluated from%C obtained from elemental analysis) prepared with APTES (%C: 8.03, 5.26 μmol/m−2) or DMAPTES (%C: 5.12, 4.58 μmol/m2) is somewhat higher when compared to organic based reactions under reflux in toluene at a temperature of 110 °C in 24 h with APTES (%C: 7.33, 4.71 μmol/m2) and DMAPTMS (%C: 4.93, 4.38 μmol/m2). Zeta potential measurements revealed a change in electrostatic surface charge from negative values for bare Exsil-pure silica to positive for functionalised APS materials indicating successful immobilization of the aminosilane onto the surface of silica. 2017-04-14T00:00:00Z http://hdl.handle.net/10468/4063 Guanine a-carboxy nucleoside phosphonate (G-a-CNP) shows a different inhibitory kinetic profile against the DNA polymerases of human immunodeficiency virus (HIV) and herpes viruses Balzarini, Jan; Menni, Michael; Das, Kalyan; van Berckelaer, Lizette; Ford, Alan; Maguire, Nuala M.; Liekens, Sandra; Boehmer, Paul E.; Arnold, Eddy; Götte, Matthias; Maguire, Anita R. α-Carboxy nucleoside phosphonates (α-CNPs) are modified nucleotides that represent a novel class of nucleotide-competing reverse transcriptase (RT) inhibitors (NcRTIs). They were designed to act directly against HIV-1 RT without the need for prior activation (phosphorylation). In this respect, they differ from the nucleoside or nucleotide RTIs [N(t)RTIs] that require conversion to their triphosphate forms before being inhibitory to HIV-1 RT. The guanine derivative (G-α-CNP) has now been synthesized and investigated for the first time. The (L)-(+)-enantiomer of G-α-CNP directly and competitively inhibits HIV-1 RT by interacting with the substrate active site of the enzyme. The (D)-(−)-enantiomer proved inactive against HIV-1 RT. In contrast, the (+)- and (−)-enantiomers of G-α-CNP inhibited herpes (i.e. HSV-1, HCMV) DNA polymerases in a non- or uncompetitive manner, strongly indicating interaction of the (L)-(+)- and the (D)-(−)-G-α-CNPs at a location different from the polymerase substrate active site of the herpes enzymes. Such entirely different inhibition profile of viral polymerases is unprecedented for a single antiviral drug molecule. Moreover, within the class of α-CNPs, subtle differences in their sensitivity to mutant HIV-1 RT enzymes were observed depending on the nature of the nucleobase in the α-CNP molecules. The unique properties of the α-CNPs make this class of compounds, including G-α-CNP, direct acting inhibitors of multiple viral DNA polymerases. 2017-04-06T00:00:00Z http://hdl.handle.net/10468/3931 Advances in the synthesis of acyclic peroxides O'Sullivan, Timothy P.; Gandhi, Hirenkumar; O'Reilly, Kate; Gupta, Manoj K.; Horgan, Conor C.; O'Leary, Eileen M. Peroxide-containing compounds are an attractive synthetic target, given their widespread abundance in nature, with many displaying potent antimalarial and antimicrobial properties. This review summarises the many developments in the synthesis of acyclic peroxides, with a particular focus on the past 20 years, and seeks to update organic chemists about these new approaches. The synthetic methodologies have been subdivided into metal-catalysed reactions, organocatalytic reactions, direct oxidation reactions, miscellaneous reactions and enzymatic routes to acyclic peroxides. 2017-03-31T00:00:00Z http://hdl.handle.net/10468/3795 Synthesis of cyclic alpha-diazo-beta-keto sulfoxides in batch and continuous flow McCaw, Patrick G.; Buckley, Naomi M.; Eccles, Kevin S.; Lawrence, Simon E.; Maguire, Anita R.; Collins, Stuart G. Diazo transfer to beta–keto sulfoxides to form stable isolable alpha-diazo-beta-keto sulfoxides has been achieved for the first time. Both monocyclic and benzofused ketone derived beta-keto sulfoxides were successfully explored as substrates for diazo transfer. Use of continuous flow leads to isolation of the desired compounds in enhanced yields relative to standard batch conditions, with short reaction times, increased safety profile and potential to scale up. 2017-03-08T00:00:00Z