Synthetic, spectrometric and computer modelling studies of novel ATP analogues

This study has been concerned with the design and synthesis of A TP analogues with the potential to act as inhibitors of glutamine synthetase - a novel target for therapeutic intervention in the treatment of tuberculosis. Using a structural -analogy approach, various 3-indolylalkanoic acid, benzimidazole and pyrazolo[3,4-dJpyrimidine derivatives have been prepared and characterized. Alkylation of the heterocyclic bases using 4-(bromomethyl)-2,2-dimethyl-1 ,3-d ioxolane, 2-(bromomethoxy)ethyl acetate and 2-(chloroethoxy)ethanol in the presence of either NaH or BulOK afforded the corresponding N-alkylated derivatives of benzimidazole and 4-aminopyrazolo[3,4-dJpyrimidine (4-APP). Similar reactions with 3-indo lylalkanoic esters resulted in O-alkyl cleavage with the formation of new esters. Alkylation of benzimidazole with allyl bromide, 4-bromobutene and 2-methylbut-2-ene has also been shown to afford the corresponding l-alkenylbenzimidazoles in moderate to excellent yield (43-96%). Subsequent oxidation of these products using CTAP, gave the dihydroxy derivatives in poor to good yields (26-77%). Phosphorylation of various hydroxy derivatives of benzimidazole and 4-APP has been achieved using diethyl chlorophosphate to afford the corresponding monophosphate and 1,2-diphosphate esters. Glycosylation of each of the heterocyclic bases has been successfully achieved using 1,2,3,4,6-penta-O-acetyl-D-glucopyranose and SnCl4 in acetonitri le, while methanolysis of the resulting tetraacetates, using methanolic NaOMe, afforded the hydroxy derivatives in good yield (50-70%). Various 1- and 2-dimensional NMR spectroscopic methods (e.g., IH, 13C, lip, COSY, HSQC and HMBC) have been used to confirm the structures of the synthesized A IP analogues. The application of NMR prediction programmes has been explored, permitting assessment of their agreement with the experimental data and confirmation of assigned structures. High-resolution electron impact (EI) mass spectrometric data have been used to explore the mass fragmentation pathways exhibited by selected derivatives, and certain common fragmentations have been identified. Molecular modelling of selected products as potential glutamine synthetase ligands has been performed on the Accelrys Cerius2 platform, and interactive receptor-ligand docking studies have been conducted using the Ligand-Fit module. These studies have revealed possible hydrogen-boding interactions between the selected analogues and various amino acid residues in the glutamine synthetase active site

Synthesis and evaluation of PGM-selective ligands

A series of polydentate POM-selective, sulfur-containing amide ligands have been synthesized from ro-dibromoalkanes and mercaptoacetanilide, The resulting 3,6- dithiaoctanediamides and 3,7-dithianonanediamides, some of which contain a polymerisable group, were all characterized by high-resolution MS, IR, I Hand I3C NMR spectroscopic methods. Various approaches to the polymerisable ligands were explored, the most efficient proving to be the incorporation of an allyl ether moiety in the mercaptoacetanilide. The corresponding Pd(U) and Pt(II) complexes were also prepared from the metal chloride salts and characterized by elemental analysis and spectroscopic methods. The NMR data indicates that both the cis- and transcomplexes were formed, while the IR data indicates cis- coordination of the chlorine . ligands. Molecularly imprinted polymers (MIP's), prepared using platinum(II) mercaptoacetanilide and 3,6-dithiadiamide complexes, showed high selectivity for , , palladium(II) [in the presence of Pt(II), CoCII), Cu(II) and Ni(II)] as determined by . ICP-MS analysis. The more kinetically inert Pt(II) ions however, slowly displaced Pd(II), confirming the Pt(II) selectivity of the MIP's. Solvent extraction studies were conducted to explore the selectivity of the 3,6- dithiaoctanediamides and 3,7-dithianonanediamides for Pd(U) over CoCII), Cu(U) and Ni(II). The ICP-MS data indicate that, in general, equilibration was achieved within ten minutes and that the longer-chain amides were less selective than the shorter-chain analogues.KMBT_363Adobe Acrobat 9.54 Paper Capture Plug-i

The development of a stress management model for staff at the National Health Laboratory Services (NHLS)

The research problem addressed in this study, was to identify strategies that could be employed to reduce stress related problems in the workplace. As the business environment is increasingly subjected to fast changing forces which include increased competition, the pressure for quality and advanced technology, innovation, and an increase in the pace of doing business, the demands on employees have grown equally dramatically. It is therefore essential to develop strategies for managing stress to give employees the required additional energy to handle particularly difficult and stressful work situations. It is important that organisations provide the assistance and support on the issue of stress as part of their proactive approach to managing employee health and safety, by drawing up contingency plans, and to have the necessary infrastructure to deal with such problems. This study investigates the strategies that can be implemented in organisations to reduce stressful situations affecting employees. The information gleaned from the literature and empirical studies enabled the development of a model for stress management in the workplace

Modes of market entry and strategies for selected South African companies doing business in the Democratic Republic of the Congo

Thesis (MBA)--North-West University, Potchefstroom Campus, 2012.This research identifies modes of market entry as well as strategies embarked on by South African companies that are currently doing business in the DRC. Data collection was performed through one–on–one interviews with executives of the South African companies that are in the different sectors of business in the DRC. Research has found that the mode adopted for entry was related to the degree to which the company has committed its resources, across all sectors involved. The DRC is potentially one of the richest countries in Africa, with rich mineral resources, timber (75% of the country is forested) and extensive energy resources, however it is one of the poorest, with real GDP per capita falling from $380 in 1960 to$167 by 2010. The top–ranked countries in Africa are South Africa (29), Mauritius (32), and Namibia (42). Guinea–Bissau (173) and the Democratic Republic of Congo (175) rank lowest in the region. The Democratic Republic of Congo also ranks lowest in the world. Doing business in Africa became easier in 2005–2006 because reformers simplified business regulations, strengthened property rights, eased tax burdens, increased access to credit, and reduced the cost of exporting and importing. “Such progress is sorely needed. African countries would greatly benefit from new enterprises and jobs, which can come with more business–friendly regulations,” said Michael Klein, World Bank–IFC vice president for finance and private sector development and IFC chief economist. “Big improvements are possible. If an African country adopts the region’s best practices in the 10 areas covered by Doing Business, it would rank eleventh globally.” Operational challenges in the DRC were found to be the same as what all emerging countries are experiencing in the continent, such as: lack of skills, corruption and lack of law enforcement, poor infrastructure, exchange rate volatility, successful informal sector, and crime and anti–South Africa sentiments. These challenges lead to higher costs of doing business in the DRC for South African companies. This research further gives a proposal for a model that South African companies can Modes of market entry and strategies for selected South African Companies doing business in the DRC consider as part of their strategic planning process when internationalising their business into the DRC.Master

Molecular imprinting science and technology : A survey of the literature for the years 2004 - 2011

Herein, we present a survey of the literature covering the development of molecular imprinting science and technology over the years 2004-2011. In total, 3779 references to the original papers, reviews, edited volumes and monographs from this period are included, along with recently identified uncited materials from prior to 2004, which were omitted in the first instalment of this series covering the years 1930-2003. In the presentation of the assembled references, a section presenting reviews and monographs covering the area is followed by sections describing fundamental aspects of molecular imprinting including the development of novel polymer formats. Thereafter, literature describing efforts to apply these polymeric materials to a range of application areas is presented. Current trends and areas of rapid development are discussed. Copyright © 2014 John Wiley & Sons, Ltd