Theses and Dissertations (Chemistry)

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Investigation of rheological and particle characterisation techniques for the optimization of accelerated stability testing of sunscreen emulsion
(University of Pretoria, 2024-11-29) Forbes, Patricia B.C.; ari.makhari@gmail.com; Makhari, Aritondaho Harriet
Skin cancer has become an increasing health concern as a result of exposure to ultraviolet (UV) radiation. This has motivated the development of sunscreen emulsions which shield humans from potentially harmful radiation. Sunscreen emulsions are composed of active ingredients (UV filters), stabilizers (emulsifiers, thickening agents, solvents and preservatives) and sensory enhancers such as moisturizers, fragrances and emollients. They are available in different forms namely, emulsions (creams and lotions), gels, aerosols, solid sticks, oils, mousses and ointments. Sunscreens are categorized based on their appeal to customers, varying ingredients and how they are formulated. Sunscreen emulsions are thermodynamically unstable and tend to separate into oil and aqueous phases as a result of various mechanisms such as creaming, sedimentation, flocculation, coalescence and Ostwald ripening. Surfactants or emulsifiers, such as cetearyl alcohol, sodium dodecyl sulphate, and sorbitan oleate, play a crucial role in stabilizing emulsions to prevent them from separating. Before sunscreen emulsions are released to the market, they are subjected to a variety of tests to ensure their quality, safety and adequate shelf life. This study aimed to investigate whether alternative analytical techniques can predict the stability of sunscreen emulsions in a short period as opposed to the currently used accelerated tests that require about three to six months. The focus of this study was to test various analytical techniques to characterize sunscreen emulsions, as an important local example of cosmetic emulsions, and thereby predict their shelf lives. The analyses were performed in comparison to the accelerated stability tests that are frequently practiced in cosmetic industries. Accelerated stability tests were conducted by exposing the formulations to different temperature conditions (5, 25, 40 and 50 oC) and monitoring the physiochemical properties of sunscreen emulsions for a period of up to six months. The physiochemical properties included organoleptic properties (colour, odour and appearance), pH, viscosity and density. A freeze-thaw test was also performed to monitor the thermal stability of the formulation when exposed to various temperatures for five days. The selected analytical methods, namely, rheological tests (steady flow behaviour, amplitude sweeps, frequency sweep and freeze-thaw), particle size and zeta potential, were used to evaluate the flowability, structural strength, viscoelastic behaviour, the response of the emulsion to thermal stress and particle characteristics, such as particle size and surface charge, of the dispersed particles. In this case it is noted that the particles are droplets dispersed in the emulsion. A variety of samples ranging from physical and chemical sunscreens which included creams and lotions were tested. Samples containing different emulsifier concentrations were prepared to enable the preparation of emulsions of varying stability. Accelerated stability tests showed that formulations with higher emulsifier concentrations did not show any phase separation which indicated stability, while the opposite was true for samples with lower emulsifier concentrations. The pH variation of each sample throughout the entire study period was less than 1 unit. The viscosity change was wider, as some samples showed more than 50% change, but the sample did not show any visible alterations that consumers could perceive. The concentration of the emulsifier did not affect the specific gravity, as there was no significant change observed during storage. All samples were thermally stable over the temperature range studied, as there was no visual alteration observed after the freeze-thaw test. In terms of analytical techniques, the stability of one formulation was predicted within a week. All samples showed a shear thinning behaviour which is a typically expected behaviour for cosmetics. The concentration of the emulsifier was directly proportional to the zero-shear viscosity, with stable samples having a higher zero-shear viscosity which slows down the time required for phase separation to occur. Stable samples had a high consistency index compared to unstable samples that had lower values. The tested viscoelastic behaviour showed that all samples behaved as viscoelastic solids which were denoted by a storage modulus (G’) that was greater than the loss modulus (G”). Stable samples also showed a structural development (gel structure formation) which was characterized by a higher linear viscoelastic range, yield stress and flow point whereas the opposite was observed for the unstable emulsions. Frequency sweep results showed a crossover point for some of the unstable samples indicating the possibility of phase separation. However, some unstable samples did not show the crossover point within the tested frequency range. The formulations with the highest G’ at low frequency indicated stability. The particle sizes were inversely proportional to the emulsifier concentration resulting in stable samples showing smaller particle sizes and monodisperse distribution. There was no correlation between the zeta potential and the concentration of the emulsifier. All the samples were also thermally stable, characterized by a small structural change when exposed to varying temperatures. Most of the proposed analytical methods generated results that corresponded to the accelerated stability results. They also showed a potential to reduce the time and cost required for stability testing of sunscreens and will assist formulators to launch their sunscreens to the market in a shorter period. In order to make the proposed methods accessible to smaller cosmetic houses, which may have limited financial and scientific resources, it is suggested that they be implemented at central, commercial analytical facilities to which samples may be submitted for analysis. Additionally, these methods will assist manufacturers in choosing the adequate concentration of emulsifiers and to analyse the quality of the sunscreen emulsion when raw materials are substituted. The methods may also find application with respect to other emulsion-based products, aside from sunscreens. Further research needs to be done for the frequency sweep of physical sunscreen creams to enable the method to differentiate between stable and unstable sunscreen creams.
Advancing the analytical characterization of natural organic matter in water
(University of Pretoria, 2024-11) Forbes, Patricia B.C.; Marais, Savia S.; nokeriboitumelo@gmail.com; Nokeri, Boitumelo Koketso
The right to clean water is a fundamental human right, the responsibility for which rests upon water service institutions to ensure that the water supplied to consumers is free of and safe from any harmful substances, which is also important for sustainable livelihoods and a healthy economy. As such, when treating water for drinking purposes, it is crucial to consider the composition of natural organic matter (NOM) in the source water and during the treatment process. NOM is a complex mixture of organic compounds, such as humic and non-humic substances with a range of chemical properties, which are present in various environments of the ecosystem such as soils, natural surface waters, ground waters and sediments. NOM may contribute to the yellow-brown colour of water; it can incur an unpleasant taste or odour to water; and it contributes to the bacterial regrowth and corrosion in water distribution networks. Additionally, NOM in water may react with disinfectants to produce potentially carcinogenic disinfection by-products (DBPs). Therefore, there is a growing need for NOM research into combining conventional and advanced analytical techniques to provide a robust tool for its efficient characterization, thereby guiding drinking water treatment. A comparative study was undertaken to gain a better understanding of the composition of NOM in water across different seasons by characterizing NOM present in source water and after rapid gravity sand filtration at two drinking water treatment plants of Africa’s largest bulk water provider, situated in Gauteng. This was achieved by means of conventional techniques: dissolved organic carbon (DOC), ultraviolet absorbance at 254 nm (UV254) and specific ultraviolet absorbance (SUVA), as well as advanced techniques such as solid phase extraction (SPE) and fluorescence excitation-emission matrices (FEEM). Further, a novel approach using ultra-performance liquid chromatography - high resolution mass spectrometry (UPLC-HRMS) was developed to enhance the understanding of the composition and concentration of NOM in water. Before the characterization of the sampled water, aspects of sample storage and preparation were explored to ensure sample integrity was maintained during transportation and storage, thereby contributing to accurate reporting of results. As such, a range of storage conditions and durations were assessed and it was found that storing water samples for up to 34 days in the dark, at room temperature or at 5 oC gave more similar results to the initial sample measurements than storage under direct sunlight or UV radiation, as determined by DOC and UV254 measurements. As a result, it was recommended that samples are stored at 5 oC in amber storage containers for a maximum of 34 days to maintain sample integrity and minimise degradation. Additionally, syringe and membrane filters from different brands were pre-washed with ultrapure water to investigate the presence of possible residual contaminants from the filter material that may leach into the water samples during sample preparation and thereby impact on NOM analysis. The results indicated that there were indeed retained UV-active contaminants in the filter materials of which 81 to 91% were removed after washing with 25 mL of ultrapure water. Furthermore, there were no significant differences in the UV254 measurements of the 25 mL pre-wash eluate fraction across the different brands. For this reason, the deciding factors for the chosen filter employed in this study were the amount of UV-active contaminants present in each filter in the first wash, the cost of the filters, their ease of use and the amount of plastic/consumable waste generated. Following the seasonal collection of the water samples, characterization using the conventional techniques indicated changes in NOM character during the sampling period with season which were also due to the location of the point of water abstraction for each treatment plant with differences in discharges into the source water. The Upper Vaal catchment area source water NOM consisted mainly of hydrophobic organic material of high molecular mass and aromaticity. Moreover, the obtained results indicated that both treatment plants were consistent with removing NOM content across different seasons, regardless of the differing raw water quality. DOC and UV254 results obtained from the cost-effective, portable, battery operated UV254 Go! analyzer were compared to results obtained from conventional laboratory based instruments, to assess its use for field-based measurements. There was a strong correlation between the UV254 measurements obtained with these instruments, which showed the potential of the UV254 Go! as a convenient and cost-effective means to directly determine NOM aromaticity in the field. However, the UV254 Go! reported higher DOC measurements than the conventional total organic carbon (TOC) analyzer, as a result more experiments are needed to determine an empirical correction factor to correct for the difference. Fractionation using the established modified polarity rapid assessment method (mPRAM) sorbents (namely C18, CN and NH2) and alternative sorbents (hydrophilic-lipophilic-balanced (HLB) and Carbon S (CS)), which had not been previously investigated for this application, showed promising results. The obtained fractions were measured for DOC and UV254 which showed that the water samples from both treatment plants were mainly composed of non-polar hydrophobic (HPO) components across all seasons, with UV254 measurements decreasing after treatment. Regardless of its water-wettable properties, the alternative HLB sorbent fractions showed a stronger retention of the somewhat less polar NOM components. The results indicated a stronger elution solvent is required. The alternative CS sorbent showed stronger retention than the HLB sorbent and holds potential in the fractionation of non-humic acid and non-fulvic NOM components in water. The observed variability in the respective fractions highlighted the importance of detailed NOM monitoring and characterization. FEEM analysis of the unfractionated seasonal water samples indicated that NOM components varied per treatment plant, season and between the raw and treated water, and further indicated that the source water from the Upper Vaal catchment area is primarily composed of aromatic and marine humic acid-like components. UPLC-HRMS analysis for NOM characterization revealed that NOM components are better ionized in the negative electrospray ionization (ESI) mode and thus better represent the composition of NOM than ionization in the positive ESI mode. Due to the extensive number of peaks in the ESI mass spectra, chemometrics was employed to deconvolute the data, revealing similarities and differences between seasonal water samples and SPE polarity fractions. Principal component analysis (PCA) score plots showed a clear difference in NOM composition between the seasons with winter and autumn indicating chemical similarity. Additionally, PCA highlighted that the raw water and water after sand filtration (treated) were similar to each other but dissimilar to the mPRAM fractions. With regards to the HLB sorbent, PCA showed poor separation of the respective fractions, suggesting either lack of strong retention of NOM components or very strong retention of some components which were not eluted with the solvents used. Unlike the mPRAM sorbents, the HLB and CS sorbents could successfully differentiate between the winter and autumn water fractions, showing potential in the use of these sorbents for NOM fractionation. The CS sorbent fractions were dissimilar to each of the mPRAM sorbent fractions, proving that the sorbent may add a new dimension to the PRAM technique, as it provides a novel separation of NOM components. Overall, this study contributes to informing drinking water utilities about seasonal NOM variability and fluctuating source water quality, and supports the implementation of adaptive treatment processes to maintain safe drinking water. It provides novel approaches to more comprehensive NOM monitoring and characterization, providing valuable insight into the efficiency of the treatment processes employed at leading drinking water treatment plants, thereby confirming the quality of water supplied to South African consumers.
Synthesis and characterization of zeolitic imidazolate framework derived activated carbon materials for carbon dioxide adsorption
(University of Pretoria, 2024-11-29) Langmi, Henrietta Wakuna ; u21816493@tuks.co.za; Khethula, Nwabisa
The rising levels of CO2 emissions from industrial activities (especially combustion of fossil fuels in power plants) are spiralling out of control, resulting in devastating global warming effects. Carbon capture and storage is among the most efficient systems to curb CO2 levels in the atmosphere with post-combustion capture being a promising technology. In post-combustion capture, adsorption is attractive with research geared towards enhancing the efficacy of adsorbents by increasing their capacity and improving selectivity for CO2 while minimizing adsorption of impurities. The challenge is to find a stable and hydrophobic adsorbent without compromising the surface properties and structure. In this study, zeolitic imidazolate frameworks (ZIFs) (i.e. ZIF-8, ZIF-67, and their core-shells) were utilized together with cellulose acetate (CA) as an extra source of carbon for the synthesis of activated carbons (ACs). For determination of optimum conditions, variation of synthesis parameters including activation temperature, activation time and precursor ratio were conducted for the ZIF-8 derived ACs. All prepared samples were characterized and CO2 adsorption-desorption at 298 K and 1 bar were measured for selected ACs. The results showed the feasibility of producing highly porous AC adsorbents through the utilization of ZIFs with CA as an additional carbon source. It was found that even though ZIF-8 and ZIF-67 were synthesized utilizing the same organic ligand and solvent, they produced distinct levels of porosity in the derived ACs. The ZIF-8 demonstrated the capacity to generate increased microporosity (up to 1823 m2g-1; 0.80 cc/g) and specific surface area (up to 2190 m2g-1) for the ACs, while ZIF-67 yielded highly mesoporous and decreased surface area (601 m2g-1) ACs owing to their different metal ions. This was further reflected in the ACs derived from core-shell ZIFs, which had textural properties that were intermediate between those of the parent ACs. The variation in temperature from 550 up to 750 °C led to a reduction in surface area and microporosity compared to the initial findings at 850°C. This trend was similarly observed in the experiments involving precursor ratio and activation time variation. An increase in the ratio (from 1:10 up to 4:10) resulted in a higher presence of unreacted particles, and lower surface area and microporosity. Reducing the duration from 2 h to 1 h prevented the evaporation of metal ions, while prolonging the duration to 2.5 h led to the collapse of pores. Evaluation of CO2 adsorption capacity revealed a strong correlation with microporosity of the ACs. The highest adsorption capacity was 3.29 mmol g-1 obtained for ZIF-8 derived AC. All the ACs adsorbed CO2 and exhibited complete reversibility. Hence, the utilization of ZIF-derived ACs as adsorbents for CO2 capture in post-combustion processes is feasible.
Chemical safety and security : laboratory personnel views
(University of Pretoria, 2024-08) Tekane, Rethabile; Mathabathe, Kgadi Clarrie; francinah.futhane@up.ac.za; Futhane, Francinah Phuthi
Although chemical safety and security fall under chemical risk management, research has shown that knowledge about chemical safety is more prevalent at post-secondary institutions than chemical security knowledge. Knowledge about chemical safety and security is essential because chemical safety protects students and workers from chemical hazards, whereas chemical security prevents the misuse of chemicals. This qualitative study aimed to learn more about laboratory personnel's views regarding their laboratories' chemical safety and security practices. Face-to-face semi-structured interviews probing the ten laboratory personnel's beliefs, knowledge, and understanding of chemical safety and security practices employed in their laboratories were conducted. Narratology was used as a theoretical framework whereas thematic analysis was used for data analysis. The study's findings revealed that, although the laboratory personnel were familiar with the term chemical safety, most of them did not know about the term chemical security, emerging as a reason for concern. It was through the current study that personnel were for the first-time hearing about the term chemical security. Furthermore, regarding chemical safety and security practices, laboratory personnel prioritise limited access to laboratories and the proper handling of chemicals. Emerging from the findings was the personnel’s need for detailed training workshops concentrating on both chemical safety and security, emphasising the need for mandatory attendance of these workshops by laboratory demonstrators to improve chemical safety and security practices in these spaces. The findings revealed laboratory personnel’s knowledge gaps regarding chemical security. Providing training workshops concentrating on both chemical safety and security will aid in the awareness and literacy of chemical safety and security amongst laboratory personnel who are critical and yet a hidden profession in these spaces of learning and research.
Cellulose-metal organic framework nanocomposite adsorbent films for water remediation
(University of Pretoria, 2024-10) Nombona, Nolwazi; lebaugangmanamela@gmail.com; Manamela, Lebogang
This study evaluates the effectiveness of adsorbent films for the adsorptive removal of organic dyes, particularly methylene blue (MB) from aqueous solutions. The adsorbent films consist of solvothermally synthesized metal-organic framework (MOF)/crystalline nanocellulose (CNC) composites, supported on a cellulose acetate (CA) substrate. Three adsorbent films were fabricated, i.e. CA-supported MOF-5/CNC (1), CA-supported Cu-BDC/CNC (2), and CA-supported Ni-BDC/CNC (3). This composition results in water-stable adsorbent films, which are recyclable with minimized secondary contamination. The successful preparation of the adsorbent films was verified by several characterization techniques such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET) analysis and X-ray photoelectron spectroscopy (XPS). Batch adsorption experiments were carried out for the decontamination of MB from aqueous solutions under different conditions including varying pH, contact time, initial MB concentration, and temperature. The optimum adsorption conditions were at pH 11, at 360 minutes, at an initial MB concentration of 6 mg/L, and at 25 °C. Under these conditions, the adsorbent films achieved adsorption capacities between 2.79 - 4.29 mg/g, with corresponding maximum % removals between 77 - 85 %. The adsorption isotherms and kinetic models revealed multilayer chemical adsorption on the surface of film 1 as indicated by the experimental results which were best described by the Freundlich isotherm and pseudo-second-order kinetic models. On the surfaces of films 2 and 3, the isotherms and kinetic models revealed monolayer chemical adsorption according to the Langmuir isotherm and pseudo-second-order kinetic models. Thermodynamic parameters showed the adsorption processes were exothermic in nature and feasible. The films showed good recyclability, after five adsorption cycles, film 1 maintained 76% of its original adsorption capacity, film 2 maintained 73%, and film 3 67%. The films showed pH-dependent selectivity, demonstrating preferential affinity for anionic methyl orange (MO) at acidic pH and a preference for cationic MB at alkaline pH. The practical applicability of the adsorbent films was assessed in the treatment of real textile industry effluent where the films achieved between 20 - 45 % effluent removal. The economic assessment of the adsorption processes was conducted by considering the cost of chemicals and the energy cost of the adsorption process. The adsorption costs for films were calculated to be between USD 43.60 and 53.00. These findings suggest that cellulose derivatives and MOFs have the potential to perform synergistically to result in stable, recyclable, versatile, and cost-effective adsorbents for the removal of organic dyes from polluted water.
CpMetal N-heterocyclic carbene complexes : synthesis and applications
(University of Pretoria, 2017) Landman, Marile; frikkie.malan@up.ac.za; Malan, Frederick Pieter
The synthesis and catalytic application of new half-sandwich Ni(II), Cr(III), and Ru(II) complexes, all stabilised by either symmetric or asymmetric N-heterocyclic carbene (NHC) ligands, were investigated. The study entailed the synthesis of novel imidazolium halide salts as ligand precursors to the metal-NHC complexes. A range of nine (three symmetric, six asymmetric) imidazolium bromide salts were synthesised and characterized, with N-substituents including either electron-donating or electron-withdrawing groups. The ligands were reacted with nickelocene under inert conditions to form nine [CpNiBr(NHC)] complexes. These complexes were evaluated as catalysts in the Suzuki-Miyaura cross-coupling reaction for which moderate to good activity (53-79% conversion, maximum TOF = 320 h-1) was observed. The catalytic activity of these complexes in the anaerobic oxidation of secondary alcohols was also assessed. Moderate activity (52-84% conversion, TOF = 14-86 h-1) was observed using conventional heating, and excellent activity (90-98% conversion) using microwave heating. DFT studies provided insight into the better performance of the complexes featuring electron-donating NHCs as opposed to those with electron-withdrawing NHC ligands. In addition, DFT-supported energy profile studies explained the lack of formation of α-arylation byproducts, found for similar studies in the literature. By-product formation of the type [NiBr2(NHC)2] during synthesis of the above mentioned nickel NHC complexes led to the subsequent investigation of the reactivity and properties of the biscarbene complexes. Reaction of thiophenol with [CpNiBr(NHC)] or the biscarbene complexes, yielded complexes of the type [CpNi(SPh)(NHC)] and [Ni(SPh)2(NHC)2]. A detailed DFT study revealed structural preferences that were correlated with the experimentally observed structures. The electronic differences among the [CpNiBr(NHC)] complexes were further evaluated through a DFT-supported electrochemistry study, which showed some electrochemical variances due to the different N-alkyl substituents present in the nickel complexes. Reaction of chromocene with the novel non-NO2-containing imidazolium bromide salts, followed by chromium oxidation using CCl4, allowed for the formation, purification and characterisation of five [CpCrBrCl(NHC)] complexes. Exposure of these heterohalo complexes to excess CHCl3 or CCl4 leads to the formation of complexes [CpCrCl2(NHC)]. Upon reaction of chromocene with the novel NO2-containing imidazolium salts, a ligand decomposition reaction occurs. C-N bond cleavage and imidazole protonation result in the formation of [C4H7N2][CpCrBrCl2]. The catalytic activity of the six Cr(III)-NHC complexes was evaluated in the base-free glucose dehydration reaction for which moderate activity (52-81% conversion) was observed. Supplementary DFT studies added insight into the electrochemical properties of the Cr(III) complexes. A range of six new bidentate (benz)imidazolium chloride salts (one symmetric, five asymmetric), each bearing an N-2-methylallyl substituent were synthesised and complexed to ruthenium(II) (three different Ru(II) precursors) via silver transmetallation. Eight new cationic complexes [(C5H4R)Ru(EPh3)(NHC)]PF6 (R = H, Me; E = P, As; NHC = Im(R')(2-methylallyl), BIm(Bn)(2-methylallyl); R' = alkyl) were isolated, purified and characterised. DFT studies illustrated the electronic properties of the complexes, while a catalytic study (tandem transfer hydrogenation-epoxidation of ketone substrates) showed moderate activity (39-62% conversion, TOF = 4-12 h-1) for all of the complexes. Finally, a range of four new C(2)-protected bidentate imidazolium chloride salts (one symmetric, three asymmetric), each containing either an N-2-methylallyl or N-picolyl substituent, were synthesised and characterised. These ligands were found suitable as ligand precursors to abnormal NHCs, and hence were reacted with [(p-cym)RuCl2]2 or [CpRuCl(PPh3)2] to form ten new Ru(II)-NHC complexes (eight Ru-aNHC and two Ru-NHC complexes). The Ru-NHC complexes formed as by-products due to Ag-mediated C(2)-dealkylation in selected cases. The strength of the Ru-aNHC bond was probed in an 1H-NMR titration study with DCl, which showed its superior bond strength when compared to analogous normally bound Ru-NHC complexes. The catalytic activity of the latter ten complexes was screened in both the transfer hydrogenation and alcohol oxidation reactions. The complexes are therefore more suitable as transfer hydrogenation catalysts (50-93% conversion, TOF = 22-60 h-1) than for application in alcohol oxidation catalysis (56-77% conversion, TOF = 2-11 h-1).
Chemical reactivity of Bushveld Igneous Complex mine residues for mineral beneficiation
(University of Pretoria, 2024-12-02) Van der Merwe, E.M. (Elizabet Margaretha); Doucet, Frédéric J.; sameeramohamed007@gmail.com; Mohamed, Sameera
Background The mining sector in South Africa plays a crucial role in the country's economy, contributing approximately R 202.05 billion South African rand (around 11.18 billion U.S. dollars) to the country's Gross Domestic Product (GDP) in 2023. This sector is a significant contributor to economic activity, job creation and foreign investment. The Bushveld Igneous Complex (BIC), a large geological formation, hosts the world's largest known reserves of Platinum group metals (PGM), the country’s largest produced commodity. Mining in the BIC generated ca. 57% of the accumulated revenue from South African mining activities. Although mining contributes significantly to the economy, it also contributes significantly to the generation of toxic waste streams, including acid mine drainage (AMD) and large volumes of solid mine residues, such as mine rocks, tailings, and slimes. Managing these mine residues has become a major environmental concern for mining operations worldwide and has resulted in the implementation of stricter regulations to address the environmental and social risks associated with the disposal and management of these waste materials. Consequently, there is a constant demand for innovative and sustainable solutions, including developing valorisation technologies for recovering metals and minerals, which will assist in minimising their disposal and make the treatment processes more economically viable. Mine residues from the BIC have been previously assessed as a secondary resource of major elements (e.g., Fe, Al) via a thermochemical solid-solid treatment using ammonium-based extracting agents followed by aqueous dissolution. This process has been considered for the extraction of elements and conversion into products for various applications such as mineral carbonation technologies and wastewater remediation. However, the valorisation of the residues into value-added products was not investigated. This study demonstrated that strategic elements such as Al, Ca, Cr, Fe and Si can be extracted from different BIC mine residues via extractive acid leaching, and via thermochemical treatment using ammonium sulphate (NH4)2SO4 as an extracting agent followed by acid leaching and converted into value added products such as calcium aluminate (CaAl2O4) and silica (SiO2) nanoparticles for various industrial applications. This study also examined the reactivity of specific mineral phases contained in BIC mine residues, such as Platinum Group Metal (PGM) tailings and mineral-rich concentrates and slimes, during thermochemical treatment and acid leaching processes to better understand their contributions to elemental extraction efficiency. PGM tailings PGM tailings obtained from the Two Rivers mine were used to improve the previously conceptualised thermochemical and leaching process using ((NH4)2SO4) as an extracting agent. The effect of thermochemical treatment and duration was investigated, as well as the effectiveness of HNO3 vs H2SO4 as leaching agents. Lowering the thermochemical treatment temperature and increasing the duration from 550 ⁰C for 45 mins to 420 ⁰C for 6 h achieved a comparable extent of mineralogical transformation and could favour the possible scaling-up of the process and improve the overall extent of reagent recovery for potential reuse during the thermochemical treatment step. H2SO4 was found to be as suitable as HNO3 as a leachant, with no negative effect on elemental extraction efficiency. The use of commercial reagents for the synthesis of Fe nanoparticles was initially investigated and successfully yielded Fe nanoparticles with properties consistent with those reported in the literature. This method was then applied to the filtrates, obtained after thermochemical treatment using (NH4)2SO4 and acid leaching of the tailings, but proved unsuccessful due to the presence of Al, Cr, Mg and Si contaminants, which were co-extracted during the leaching step. This result led to the development of a selective separation scheme aimed at recovering Fe from the filtrates. Precipitation experiments indicated that co precipitation of Al, Cr, and Fe impeded the formation of magnetic Fe-based nanoparticles. These results identified the complexities involved in nanoparticle synthesis from mine tailings containing diverse mineral phases. Further investigation was conducted into the reactivity of major individual mineral phases, such as plagioclase, enstatite and hematite, during direct acid leaching compared to thermochemical treatment. Mineral-rich concentrates and slimes The reactivity of plagioclase-rich concentrates and slime, enstatite and hematite were assessed during thermochemical treatment using (NH4)2SO4 and a direct acid leaching processes. Plagioclase was found to have limited reactivity with (NH4)2SO4 when subjected to thermochemical treatment under the experimental conditions tested. Thermochemical treatment at 550 ⁰C for 45 mins improved the extraction of Al, Fe, Na and, to a lesser extent, Ca from the other mineral phases present in the plagioclase-rich concentrates. In comparison, direct acid leaching achieved high extraction efficiencies, particularly for Al, Ca and Na, which were derived from the plagioclase phase. Direct acid leaching in HNO3 at 95⁰C allowed for the complete leaching of the plagioclase concentrate. However, longer durations of up to 24 h were required to achieve stoichiometric leaching of elements into solution. The enstatite concentrates showed limited reactivity during thermochemical treatment with (NH4)2SO4, as indicated by similar extraction efficiencies obtained for Mg and Fe, which are the main elements present in enstatite. Direct acid leaching achieved minimal extraction of Fe and Ti from the hematite concentrate; however, the extent of reactivity of the hematite mineral during thermochemical treatment could not be ascertained due to the amorphosity of the concentrate. Based on these results, the focus shifted towards the use of the plagioclase-rich slime, which had increased reactivity, for conversion into value-added products. Plagioclase-rich slime The Ca and Al-rich filtrates obtained after direct acid leaching of the plagioclase-rich slime were used to investigate for the initial synthesis of CaAl2O4 nanoparticles. The synthesis was conducted using the solution combustion synthesis method with urea and glycine as fuels. Characterisation of the resulting products indicated a product mixture comprising Ca, Al, Mg, Fe, and Si-rich oxides, spinel, and silicate phases. The presence of these multiple mineral phases confirmed the challenge related to the heterogeneity of the precursor solution, which contained Mg, Fe and Si, which were co-extracted from the plagioclase slime. This highlighted the need to further purify the filtrate to enhance homogeneity, particularly for the synthesis of CaAl2O4 products from a plagioclase-rich mine slime. To address this challenge, purification of the plagioclase slime filtrate was successfully achieved via a multistage process. This process entailed a calcination pre-treatment followed by direct acid leaching for elemental extraction. Subsequent precipitation and separation processes were used to produce SiO2 nanoparticles with high levels of purity. The remaining solutions were then used to synthesise Ca and Al rich products. Through these improvements, Ca and Al-based products were successfully synthesised. The most promising products contained only three calcium aluminate phases, which were much less compared to the number of phases identified in the other synthesised products. Results from this study have demonstrated the potential of elemental extraction and the sustainable synthesis of nanoparticles from a BIC mine residue. Future work will be required to improve the physical properties of the products. The economics of the process will also need to be considered to ensure its feasibility and long term sustainability. Implications of this study The exploratory lab-scale study presented in this thesis demonstrates the potential utilisation of mine residues, particularly those from the BIC. The extraction of valuable elements and the synthesis of nanomaterials from these residues, could potentially offer a sustainable approach to mineral processing and waste management and could reduce environmental damage associated with traditional mining and tailings disposal, while also creating new value-added products. If these lab-scale processes can be scaled up to industrial level, the results could contribute to South Africa’s economic output. Secondary mineral extraction techniques could enhance the recovery of metals from tailings, increasing the overall yield of valuable resources from existing mining operations. Second, the synthesis of nanomaterials from mine residues could create new industries and products.
Development and characterization of flow systems for voltammetric analysis
(University of Pretoria, 1998) Van Staden, J.F.; Matoetoe, 'M'angaka C.
Flow-through systems are progressively becoming more important in all branches of analytical chemistry. The increased demand for analysis of more complex environmental samples has resulted in development of reliable, versatile and sensitive techniques. A combination of voltammetric analysis such as differential pulse anodic stripping voltammetry (DP ASV) with flow systems satisfy all the above requirements. Although this combination has great potential, practically it has not been realised yet. This may be partly due to the use of traditional mercury electrodes which has many complications. In order to improve the use of this technique, a glassy carbon electrode (GC) which is more suitable to flow systems compared to mercury-based electrodes was studied. This study describes the electrochemical behaviour of chemicals on the GC electrode in flow systems. The use of a GC with flow systems as a means of detection proved to be very effective and can make electrochemistry more accessible to unskilled scientists. Having characterised and optimised all instrumental parameters of the system, practical evaluation of the technique as a trace metal analyser was explored. Future improvements necessary for optimum development of the technique are also mentioned.
Electrochemical reduction of Formic acid using an earth abundant catalyst
(University of Pretoria, 2019-11) Radhakrishnan, Shankara Gayathri; u13181867@tuks.co.za; Ndlangamandla, Simphiwe
Copper is one of the most useful electrocatalysts for electrochemically converting CO2 to hydrocarbons and alcohols. Unfortunately, copper suffers from a lack of selectivity and efficiency. Earth-abundant electrocatalysts such as metal porphyrins have been shown to be highly stable and highly selective for products such as carbon monoxide and formic acid. Formic acid is formed with high efficiency on a wide range of materials and can be further reduced to other useful products such as hydrocarbons and alcohols. The aim of this project is to conduct electrochemical formic acid reduction to hydrocarbons or alcohols using copper (II) tetraphenyl porphyrin. Electrochemical Formic acid reduction was conducted using a Proton Exchange Membrane (PEM) cell electrolyser. Water electrolysis was conducted at the anode using a 70:30 IrO2: TaC electrocatalyst. A control experiment was first conducted with a freebase tetraphenyl porphyrin cathode. Thereafter all experiments were repeated with Cu (II) tetraphenyl porphyrin. Products were characterized using liquid injection gas chromatography. Formic acid reduction with freebase tetraphenyl porphyrin did not yield any products at both -1.8 V and -2.1 V. Copper (II) tetraphenyl porphyrin yielded isopropanol and the most conductive copper (II) tetraphenyl porphyrin electrode produced isopropanol with a faradic efficiency of 4.5 % at -2.1 V with current density of -1.71 mA/cm2. The least conductive Cu (II) tetraphenyl porphyrin electrode exhibited a current density of -0.055 mA/cm2 at -2.1 V but produced isopropanol with a faradaic efficiency of 30.4 %. This shows that a high current density does not necessarily equate to an enhanced faradaic efficiency of formic acid reduction to isopropanol. No isopropanol was detected from formic acid reduction using freebase tetraphenyl porphyrin. This indicates that the mechanism of formic acid reduction to isopropanol requires the presence of the copper central metal as the active site.
The design, synthesis and biological evaluation of novel compounds against biomarkers of Alzheimer’s disease
(University of Pretoria, 2019-06) Riley, Darren L.; Panayides, Jenny-Lee; Steenkamp, Vanessa; divanggreunen@gmail.com; Van Greunen, Divan Gerald
Alzheimer’s disease (AD) is the most common neurodegenerative disease accounting for an estimated 60 – 80 % of dementia cases. The disease affected 5.5 million Americans older than 65 years in 2018 alone, and this number is projected to increase to 13.8 million by 2050. The total cost of care in the United States for people with AD was $277 billion in 2018, making it one of the costliest diseases to treat. Statistics on the prevalence of dementia in South Africa are very limited and according to a study performed in the rural areas of the Eastern Cape in 2017, it was estimated that 352 000 individuals older than 60 are living with dementia. Unfortunately, there are currently no approved therapies which target AD pathology directly and therefore current treatments focus on relieving symptomatic and behavioral aspects of AD. Thus, a lot of focus has been placed on the development of new drugs for different biomarkers as potential treatment of AD. This study consists of the design, synthesis and biological evaluation of novel compounds against biomarkers of AD. In this study, four different series of compounds, consisting of ninety-one analogues, were synthesized as novel compounds against biomarkers of AD. These included; (i) series 1: N-benzylpiperidine carboxamide derivatives; (ii) series 2: 1-(5,6-dimethoxy-8H-indeno[1,2-d]thiazole-2-yl)urea derivatives; (iii) series 3: 1-amino-3-(indeno[1,2-b]indol-5(10H)-yl)propan-2-ol derivatives; and (iv) series 4: 6,7-dimethoxy-1-phenyl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide derivatives. All compounds were evaluated for activity against acetylcholinesterase (AChE), the major biomarker of AD. Derivatized compounds of series 1 were assessed for activity against butyrylcholinesterase (BuChE). Derivatized compounds of series 3 were assessed for activity against the amyloid precursor protein cleaving enzyme 1 (BACE1). The first series of fifteen compounds based upon the skeleton of 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate, a compound previously synthesized, were synthesized and evaluated for activity against acetylcholinesterase. A second series of thirty-five compounds designed to have dual acetylcholinesterase and glycogen synthase kinase 3 inhibitory activity, were synthesized based upon the skeleton of 1-benzyl-N-(5,6-dimethoxy-8H-indeno[1,2-d]thiazol-2-yl)piperidine-4-carboxamide. A third series of seventeen compounds with potential β-secretase 1 inhibitors were designed and synthesized based upon the skeleton of 1-(3,6-dichloro-9H-carbazol-9-yl)-3-(naphthalen-1-ylamino)propan-2-ol, a compound previously reported in literature by Macchia and co-workers. A fourth series consisting of twenty-four potential N-methyl-D-aspartate (NMDA) receptor antagonists were designed and synthesized based upon scaffolds previously reported in the literature by the Liotta and Kawai research groups. In order to prepare large quantities of donepezil for use as a stock reagent for the development of libraries of potential BACE1 inhibitors, the preparation of donepezil using continuous flow conditions was attempted. The highest yield obtained for the benzylation of ethyl isonipecotate was 83% at 90 °C with a residence time of 45 minutes as compared to the batch process which took 3 hours to complete with a yield of 79%. Reduction of the (E)-2-[(1-benzylpiperidin-4-yl)methylene]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one to afford the final product donepezil was obtained with a yield of 80% after 4.5 hours, with no observable de-benzylation in flow as compared to the batch process which was completed after 6 hours with a yield of 78%. Due to time constraints, Stage 2 of the flow synthesis of donepezil could not be completed. However, with only two of the three steps completed for the flow process, the yield of the individual steps was already improved, and there was a reduction in the reaction time.
Analytical approaches for haloacetic acid disinfection byproducts in treated water
(University of Pretoria, 2024-05) Forbes, Patricia B.C.; petravdermerwe@gmail.com; Van der Merwe, Petra
Water quality is vitally important for basic human health and key in growing economies and in overcoming poverty. Disinfection of source water is therefore indispensable, however, it may introduce new adverse health risks to consumers due to the formation of disinfection byproducts (DBPs). Many of the over 700 DBPs discovered to date are cytotoxic, genotoxic, potentially carcinogenic, or pose other health risks. Minimizing exposure of the public to these compounds is therefore crucial. The focus of this study was the investigation and development of analytical approaches for haloacetic acid (HAA) DBPs, which over the past two decades have been increasingly included in drinking water guidelines globally. The United States Environmental Protection Agency (US EPA) and the European Union (EU), for example, limit the maximum concentration to 60 μg/L in drinking water for a combination of five HAAs (HAA5: monochloroacetic acid (MCAA), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), monobromoacetic acid (MBAA), and dibromoacetic acid (DBAA)), whilst the World Health Organization (WHO) stipulates maximum concentrations of 20, 50, and 200 μg/L for MCAA, DCAA and TCAA, respectively. Although the current South African National Standard for drinking water quality (SANS 241), does not include HAAs, a draft which proposes their inclusion was released in 2022 for public comment. Implementation of these regulations calls for accurate and especially sensitive methods for HAAs, as they are expected to be present at trace (low μg/L) levels in water. Despite two standard methods for HAAs published by the US EPA, extensive research is being done to develop improved methods, specifically addressing the issues of time and labour costs, whilst considering the environmental impact which has grown in importance since these methods emerged. However, much of this research disregards the needs of laboratories in developing countries. This study thus focused on improving HAA analysis methods in a developing country context, with consideration of the environmental footprint thereof. Since gas chromatography (GC)-based analysis, and therefore the appropriate instruments, are more commonly available than high resolution and comprehensive chromatography-based methods, the US EPA Method 552.3 (from hereon called EPA Method), which utilizes GC-electron capture detection (ECD) analysis, was considered as a basis for this research. Due to the acidic nature of the analytes and the water matrix, an extraction and derivatization step are required prior to analysis, making the method time and labour intensive. Each of these steps was considered and alternative approaches to simplify them were explored, starting with the analysis, followed by the derivatization, and finally the extraction. In terms of analysis, GC-mass spectrometry (MS) was contrasted with GC-ECD, and the feasibility of liquid chromatography (LC)-MS analysis was investigated, as this would eliminate the need for extraction and derivatization. Although both GC-based instruments had their respective advantages, the sensitivity achieved with the GC-ECD remained superior (limit of detection: 0.34 – 5.45 μg/L for GC-ECD versus 5.00 – 30.0 μg/L for GC-MS). Analyte concentrations in Pretoria tap water samples were below these detection limits using the EPA Method with GC-ECD analysis. Sensitivities achieved with LC-MS analysis (Waters® Synapt ultra performance LC – high definition MS (UPLC-HDMS) quadrupole/time of flight (QToF) mass analyser and Waters® Xevo-G2 LC-QToF mass analyser), were even poorer than with the GC-based instruments. Nonetheless, seven analytes could be tentatively identified based on mass spectra in spiked real water samples. Furthermore, experiments revealed that filtration of real water samples did not negatively influence analyte peak areas, whilst addition of formic acid (FA) had no benefit. Furthermore, two analytes (DCAA and TCAA) could be detected with the Waters® Xevo-G2 LC-QToFMS in swimming pool water obtained from LC de Villiers sports campus. Although two different solvent elution methods were explored, further method development could potentially improve sensitivity. The Fischer esterification of HAAs to the methyl esters required by the EPA Method is the most time-consuming step, thus an alternative derivatization to the octyl esters was explored and optimized. Reaction time and temperature could be drastically reduced from 2 hours to 30 min, and 50 °C to 30 °C, which consequently saved energy, making the octyl derivatization a greener option than the Fischer esterification. However, application of this derivatization in an adaptation of the EPA Method with GC-ECD analysis, demonstrated that the liquid-liquid extraction (LLE) into the hexane solvent of the octyl derivatives was unsatisfactory. Therefore, despite successful improvement of the derivatization step, integration thereof with the other steps in the complete HAA analysis protocol and application thereof to spiked deionized water and treated swimming pool water proved difficult. Further exploration utilising other solvents which are appropriate for the octyl derivatization, and which may improve the extraction efficiency of HAAs from water is necessary. As an alternative to the labour- and time-intensive LLE, thin film extraction was considered. This extraction is fast, simple, and environmentally conscious as sample handling is reduced and solvent volumes minimized. Polydimethylsiloxane (PDMS) thin films were prepared in-house with a novel spin-coating technique which allowed for effortless addition of sorbents to the PDMS in different variations, as well as geometric alterations. Two sorbents, hydrophilic-lipophilic balance (HLB) and Carboxen® particles, were either added to the PDMS prior to film synthesis or during the curing process, followed by characterization using microscopy. PDMS, HLB and Carboxen® were thus sorbents of interest, however, due to the proprietary nature of Carboxen® only HLB and PDMS could be interfaced with different analyte variations in a computational model. This model was verified by comparing the binding energies to experimentally obtained extraction efficiencies of the various film types. These were determined by quantifying the residual analyte concentrations in water after extraction with the films by immersion in HAA spiked deionized water for 24 hours. Further information on the interactions occurring at a molecular level could be obtained from the model, as well as insights into which ester derivatives of the analytes would be best extracted by each respective sorbent. Both, the experimental and computational data predicted good extraction potentials with HLB particles. From the experimental data it was determined that Carboxen® showed great extraction efficiencies for the analytes of a lower molecular mass (95 – 218 g/mol), whereas HLB extracted those of a larger molecular mass (163 – 297 g/mol) better. Moreover, films with the sorbents added to the surface during the curing process achieved the highest extraction efficiencies, with HLB reaching efficiencies up to 93% and Carboxen® up to 58%. The application of thin film extractions in HAA methods needs to be explored further but could be beneficial in a variety of applications: firstly, in a pre-concentration step for LC-based analysis to increase the sensitivity, secondly, in a GC-based method with thermal desorption and in-line gaseous derivatization, or thirdly, simply as the analyte extraction step, followed by solvent back-extraction, derivatization and analysis. The research presented in this dissertation thus critically evaluates existing methods for the analysis of HAAs in treated waters and explores a number of alternatives to make these methods faster, more environmentally friendly, and cost effective, whilst not compromising on sensitivity and accuracy. In this manner, this research contributes to the evolution of new analytical approaches for HAA water disinfection byproducts which are of global importance.
Synthesis, characterization and applications of polymer based conjugate materials for infectious diseases of poverty
(University of Pretoria, 2018-12) Pilcher, Lynne A.; Balogun, Mohammed; tshweull@gmail.com; Tshweu, Lesego Lovius
The major disease burden for the majority of the world’s population is due to infectious diseases. The most prevalent are HIV/AIDS, tuberculosis, lower respiratory tract infections, diarrhoeal diseases and malaria. In particular, malaria and tuberculosis have not benefited much from new technological developments in disease management. Most of the drugs used are several decades old and have significant toxicity profiles which impact patient compliance. New potential drugs being discovered stumble on the road to the clinic because of solubility issues. Many just end up being shelved. It is estimated that over 70% of new chemical entities have poor solubility issues. On the other hand, HIV/AIDS remains a major health problem worldwide, as currently there is no cure available. Chronic intake of highly active antiretroviral treatment (HAART) is compulsory to control HIV infection and any non-adherence leads to a quick increase in the viral load. Poor targeting ability of antiretrovirals (ARVs) to latent sites of infection is the main reason for the relapse. Nanomedicines have significantly improved the clinical management of deadly diseases like cancer. Conventional drugs show improved pharmacological indices when designed as nanomedicines. It improves solubility, absorption, clinical performance, and reduces the amount of drug needed to achieve the desired therapeutic effect. The resultant effect is improved solubility and reduced toxicity. The most common method to design nanomedicines is through physical entrapment or encapsulation in polymeric carriers. Today, however, modern delivery systems are being designed by chemical synthesis. Either the drugs are chemically linked to the polymeric carriers or the polymers are chemically derivatized to be more efficient at encapsulating the active agents. In this project, we report on our attempts to chemically modify polymers with active drugs to synthesize smart macromolecular pro-drugs or produce more efficient drug encapsulation systems. The work presented in this project is outlined in the following six chapters. Chapter 1 contains the literature review of the major infectious diseases; namely HIV/AIDS, tuberculosis and malaria; what has been done to increase patient compliance or success of available drugs i.e (to reduce the viral load or attempted to cure the virus with the ARVs in the field of HIV/AIDS, or administration of combination therapy in anti-tuberculosis/malarial field to minimize drug resistance and increase therapeutic success). The use of nanomedicine to ameliorate problems associated with treatment regime for infectious diseases is discussed. Methods for nanoencapsulation or inclusion of the existing drugs within the approved materials is described in detail. A concise general introduction to polymer therapeutics is discussed, followed by a review of polymers that are normally used in polymer-drug conjugation; highlighting advantages and disadvantages of each. Finally a clinical perspective on the use of polymer-drug conjugation for infectious diseases is outlined. Chapter 2 introduces the problems associated with the current ARVs used in the treatment of HIV/AIDS and emphasizes the need to target latent sites of infection using aptamer technology. Aptamers were subsequently conjugated to polyethylene glycol (PEG) using carbodiimide chemistry. The TZM-bl neutralization assay and in vitro stability in human breast milk studies showed that aptamers maintained their binding integrity after pegylation and were more stable than the parent aptamers. Finally the conjugated aptamers were nanoencapsulated into poly(epsilon-caprolactone) [PCL] nanoparticles using a double emulsion method. Nanoparticles of less than 150 nm were produced with a higher surface charge, showing that the nanoparticles were stable. The in vitro binding assay using electrochemical methods showed that the nanoparticles coated with PEGylated RNA aptamers had higher affinity and specifity to HIV-1 gp 120. The overall results demonstrated that these nanoparticles could be used in HIV drug delivery applications to help minimize changes associated with ARVs. Chapter 3 describes nanomedicinal formulations of the anti-TB drug moxifloxacin (Mox). Mox is a relatively hydrophilic drug. The target pathological site where the Mycobacterium tuberculosis resides is a lipid dense granuloma in the lungs. Hence, a large dose will have to be administered to deliver an adequate therapeutic dose i.e. 400 mg is required for Mox. Mox was covalently conjugated into PEG via a releasable amide bond. Similarly a hybrid system was formed by nanoencapsulating the PEG-Mox conjugate into PCL nanoparticles using double emulsion method. The system constitutes the PCL, which is envisaged to increase the hydrophobicity of the PEG-Mox conjugate. PEG-Mox conjugates and PCL-Mox nanoparticles were found to be hemocompatible, inducing only minimal hemolysis. Mox was more toxic than the PEG-Mox conjugate and PCL-Mox nanoparticles. In vitro stability in human plasma showed that PCL-Mox nanoparticles were stable for over 72 hrs. Data obtained emphasizes that PCL nanoparticles could be used as a drug delivery system to minimize the high toxicity of TB drugs Chapter 4 establishes the conjugation of the hydrophobic drug, lumefantrine [Lumf] to water soluble polymers. Lumf is insoluble in water with an octanol-water partition coefficient (logp) of 8.34. As a result a series of Lumf prodrug conjugates were synthesized using two different polymers (polyethylene glycol and p-NAM-stat-p-AA). Average particle size below 200 nm was achieved and PDI values were always below 0.2, which is an indication of the relatively homogeneous size distribution achieved with carbodiimide chemistry. We have for the first time, by applying the polymer therapeutics techniques, synthesized a polymer-drug conjugate of Lumf which has increased the solubility of the drug more than 103 times. Chapter 5 gives the conclusions of the experimental chapters. Through the three different experimental chapters, we have demonstrated that polymer based drug conjugates can be used to address different issues: (1) drug delivery through coating nanoparticles with appropriate aptamers, (2) drug toxicity through encapsulation of a toxic drug in a heamocompatible nanoparticle and (3) greatly improved aqueous solubility of a hydrophobic drug. Furthermore, while there has been much excellent work using polymer based drug conjugates in cancer, we have explored the approach to tackle different problems related to three different infectious diseases of poverty, namely HIV, TB and malaria.
Systems thinking for sustainability in chemistry education using life cycle inventories of aspirin synthesis
(University of Pretoria, 2024) Pilcher, Lynne A.; Dikobe, Dorine; cathrinechimude@gmail.com; Chimude, Cathrine
As part of a chemistry education research project, this study was designed to assess the effectiveness of an intervention using Life Cycle Inventories (LCI) of pharmaceutical production in introducing systems thinking for sustainability in chemistry education to first year engineering students. Aspirin synthesis was used as an exemplar drug and system. To accomplish the research objective, the research followed a case study design and collected qualitative data. All first-year engineering students taking the 2022 CHM 171 module participated in the one-time intervention. The CHM 171 module is offered by chemistry department on behalf of the Faculty of Engineering, Built Environment and Information Technology (EBIT) of the University of Pretoria. The research participants were drawn from a population of students who had given consent to their data being analysed. This gave rise to 130 individual pre-practical exercises, 85 pre- and post-practical quizzes, and 20 group worksheets being analysed for research purposes. The intervention was centred around a single 3-hour practical session. The data were collected at three points in time: pre-, during, and post-practical. At the beginning of the intervention, the participants were assigned a pre-practical exercise and a pre-practical quiz to collect data on their prior systems thinking skills. The participants then worked in groups during the practical session, where they were introduced to the concepts of life cycle inventories followed by systems thinking. They answered various questions in their groups, covering different dimensions of systems thinking for sustainability. After the practical session, the participants then worked individually on a post-practical quiz, similar in nature to the pre-practical quiz. The post-practical quiz was used to gather their systems thinking for sustainability skills post-intervention. Rubrics, designed through inductive thematic analysis, were used to score participants’ responses for the pre-and post-practical quizzes. The Systems Thinking Hierarchical (STH) model was used for the deductive thematic analysis on the pre- and post-practical quizzes, and the group worksheets, to determine the systems thinking skills shown in the participants’ responses. Quantitative analysis was performed on the pre- and post-practical quizzes to determine if there were any changes between the scores of the two quizzes. A paired T-test revealed that the participants’ systems thinking skills had improved moving from the pre- to post-practical quizzes. The deductive analysis using the STH model showed that the quality of answers had also improved in the post-practical quizzes, and the group worksheets, revealing a move from simplistic reasoning to holistic thinking. The results reveal that the LCIs of aspirin synthesis can be used to introduce systems thinking in chemistry education. Implementation into the curriculum is important as it aids understanding of systems thinking and sustainability.
Molecular modelling and crystallographic investigation of novel synthetic cathinone 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MMMP)
(University of Pretoria, 2024-03-28) Slabbert, Cara; Govender, Krishna; u16152582@tuks.co.za; Van Heerden, Lanzo Jacques
2-Methyl-4'-(methylthio)-2-morpholinopropiophenone (MMMP) is a highly modified synthetic cathinone derived from natural occurring cathinone, the main psychoactive alkaloid present in Catha edulis Forsk. or khat. Synthetic cathinones (SCs) belong to the drug class of new psychoactive substances (NPS) which consists of analogues of commonly known abused drugs designed to mimic the psychoactive properties of illicit drugs to circumvent current drug legislations. From a structural perspective, cathinone is a β-keto analogue of amphetamine and SCs are often referred to as “bk-amphetamines”. SCs are capable of evoking psychoactive effects similar to that of amphetamines and cocaine increasing their popularity amongst users as “legal highs”. MMMP itself is commercially available and readily used in the polymer and printing industry in the fixing of thin films, plastics and inks as a Type 1 fragmenting photoinitiator. It was hypothesised that MMMP might have psychoactive properties due to its cathinone origin and isolation in confiscated drug samples. This hypothesis was investigated through molecular modelling techniques to determine if MMMP was capable of interacting with 25 protein targets consisting of 24 monoamine receptors and a transporter which act as common targets for psychoactive substances. From the initial molecular docking results two protein targets, serotonin-1A (SER1A) and serotonin transporter (SERT), were identified as the most likely to form a complex with MMMP. Further analysis through Molecular Dynamics (MD) simulations to evaluate the stability and movement of these complexes revealed that MMMP has a higher probability of interacting and forming a strong complex with the SERT binding pocket, but a weaker complex is formed with SER1A. The crystal structure of MMMP was successfully elucidated through single crystal X-ray diffraction (SCXRD). Analysis of the crystal structure revealed that MMMP crystallises in the non-centrosymmetric space group, Pca21. The unit cell consist of four crystallographically independent conformers with each conformer interacting with itself, with conformers within the same unit cell as well as with conformers in adjacent unit cells through a series of intra- and intermolecular interactions. Three symmetry elements, two glide planes and a screw axis, were also identified.
Development of a novel passive sampler for gaseous mercury monitoring
(University of Pretoria, 2024-06-04) Forbes, Patricia B.C.; Martin, Lynwill; u16341334@tuks.co.za; Kempkes, Geyan
Mercury as a pollutant has a longstanding history of environmental and health impacts. The ubiquitous global presence of mercury in the environment in combination with its toxicity has given rise to global efforts to control releases and limit exposure and risks associated with the use of mercury. Despite the global transport and deposition of mercury in the environment, there are some areas which lack monitoring data, mainly the southern hemisphere. South Africa, specifically, requires more robust and consistent monitoring, however, implementation of commercially available methods is costly and alternative means of Hg quantitation are needed. Consequently, passive air sampling provides a promising approach to obtain additional data regarding the spatial distribution of Hg across South Africa. Herein a set of novel sulfur-doped 3-D graphene foams were synthesized, characterized, and then employed in a radial passive sampling setup to capture total gaseous mercury (TGM). A chemical vapour deposition (CVD) method was optimized to generate a pristine graphene foam as a cylindrical cartridge. The pristine material was subsequently doped by means of various methods and sulfur sources, namely dimethyl sulfoxide (DMSO), sodium sulfide (Na2S.9H2O), thiourea (SC(NH2)2) and elemental sulfur (S8). Prior to their use in real-world sampling of atmospheric Hg, these derivatized foams were chemically and physically characterized alongside the pristine precursor (where possible) to provide insights into doping efficiencies, surface area differences between foam variants, mass losses upon analysis, surface functionality introduced during doping, and the influence of the polymethyl methacrylate (PMMA) support layer. These characterizations included scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), Raman spectroscopy, thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). It was found that the multiple-layered nature of the material, as well as the inherent thinness of the graphene, contributed significantly to the variance seen in the characterization data sets. In addition to this, the influence of the PMMA support layer was identified and the efficient removal thereof was also catered for as it was found to impact characterization and doping efficiencies. Following characterization, selected sorbents, which included the pristine precursor as a candidate foam and point of comparison, were utilized in passive air samplers (PASs) that were deployed in a total of four different deployments, encompassing two at a chosen impacted site (Witbank) and a two at a less impacted site (University of Pretoria). Despite inherently low atmospheric Hg concentrations (ng/m3), the radial passive sampler employed in this study was expected to facilitate high uptake rates of Hg and be viable for ambient atmospheric Hg capture, especially at the impacted site where there are surrounding coal-fired power station point sources. The PASs were also further evaluated by comparison to a globally calibrated commercial passive sampler, the MerPAS®, which was deployed concurrently in the final deployment set at each site. iii Studies were done to determine the linear uptake of Hg by the DMSO-doped graphene foam sorbent specifically, but although linear Hg uptake was not observed, successive deployments offered better Hg capture from the pool of other derivatized foams, including the pristine graphene foam precursor. For all sorbents there was a difference in the mean Hg concentration between the two chosen sites, confirming Witbank as an impacted site. The two best performing foams were the thiourea-doped variant, followed by the sodium sulfide variant. Direct comparison to the Hg captured by the PASs deployed to the responses for the MerPAS® showed a promising similarity in effective Hg capture when the mass differences between the MerPAS® activated carbon sorbent and the graphene foams were considered. The methods which offered the highest doping efficiencies were the thiourea and sodium sulfide-based methods, respectively, which were expected to directly improve Hg captured on the surface of the resulting foams. The results of the deployment, however, inferred that a direct increase in sulfur content alone did not lead to a corresponding increase in captured Hg. Instead, an interplay between the surface area, sulfur content and Hg sorbed was identified which requires further investigation. Quantification of Hg on the deployed samplers was achieved by thermal desorption from the sorbent, amalgamation with gold and then atomic absorption spectroscopy (AAS) by means of a direct mercury analyser. The method was validated by successful participation in a global interlaboratory proficiency testing scheme, for which a Z score of -1.042 was obtained. The calibration procedure for analysis of deployed foams was also optimized as a final matrix-matched calibration, for which the influence of the graphene foam matrix on calibration accuracy and precision was also assessed. The use of intermittent cleaning steps and their effect on the accuracy of the calibration was found to contribute to achieving better fits and more reproducible responses. With respect to a NIST 2962c bituminous coal reference material (0.5% sulfur mass fraction), a reproducibility of 7 % RSD (N=11) and error of 1 % (N=11) were achieved for the final deployments and a limit of detection (LoD) of 0.083 ng Hg was achieved for the final optimized calibration. Quality control limits were also established with respect to the calibration, wherein threshold limits of ±20% around the expected value for the NIST standard reference material (SRM) and a 30 μg/kg aqueous quality control standard were maintained for up to ~six months. Overall, the sorbents utilized in this study require more extensive characterization to offer further insight into the observed trends in their variable Hg capture, surface areas and sulfur contents. The PAS also requires further optimization prior to widespread applications and use in areas of low ambient airborne concentrations. The PASs based on thiourea and sodium sulfide-doped graphene foams that were developed for the first time in this study offered the best Hg capture and should be further optimized. The novel S doped graphene foam PAS shows good potential to bridge the monitoring gaps prevalent in atmospheric Hg monitoring data in South Africa.
Serial identification and structural analysis of synthetic cannabinoids found in herbal mixtures in South Africa
(University of Pretoria, 2024-04-12) Slabbert, Cara; Wooding, Madelien; Malan, F.P. (Frederick); u21758868@tuks.co.za; Mudau, Mbavhalelo Wendy
The primary objective of this study was to identify and characterise SCBs in herbal mixtures from South Africa using a serial identification approach. The analysis of seised herbal mixtures was carried out using ultra-performance liquid chromatography coupled with a high-resolution mass spectrometer (UPLC-HRMS) and gas chromatography coupled with amass selective detector (GCMSD). The study identified three SCBs associated with fatalities: N-[[1-[(4-fluorophenyl)methyl]-1Hindazol- 3-yl]carbonyl]-L-valine, methyl ester (AMB-FUBINACA), N-[[1-(5-fluoropentyl)-1H-indazol-3- yl]carbonyl]-3-methyl-D/L-valine, methyl ester (5F-ADB), N-[[1-(5-fluoropentyl)-1H-indazol-3- yl]carbonyl]-3-methyl-L-valine, ethyl ester (5F-EDMB-PINACA) and fifteen other non-SCBs compounds. The study of MS fragment ions predicted possible fragmentation pathways and found that the identified SCBs and analysed reference standards are susceptible to the amide linker group cleavage, followed by cleavage of the fluorinated side chain. These findings suggest that abundant iv fragment ions can be used to screen uncharacterised SCBs belonging to the same family or sharing similar pharmacores. Additionally, we validated isolated SCBs from herbal mixtures using NMR spectroscopy where a reference standard was not available and obtained crystal data using SC-XRD. 1H-NMR and 13C-NMR spectral fingerprinting allowed for cross-validation of the isolated 5F-ADB. 1H-NMR spectroscopy was also successfully used to cross-validate the reference standard (S)-5F-EMBICA, supplied as (S)-5FABICA. SC-XRD crystal data results of (S)-5F-EMBICA were obtained with low quality and hence crossvalidated by NMR spectroscopy. This research, for the first time, to our knowledge reports the 1HNMR spectroscopy data of (S)-5F-EMBICA and its crystal structure and crystallography data. Finally, we conducted in silico analysis to estimate the pharmacokinetics and physicochemical properties of the SCB compounds. We utilised the SwissADME web tool for this purpose, which revealed several key findings, including the lipophilicity enantiomeric discrimination, side chain fluorogroup type effects, hydrophobic nature, TPSA analysis, GI absorption levels and BBB permeation, P-gp binding, and probability for CYP3A4 inhibition. These findings suggest that the SwissADME web tool can be used as a first line of pharmacokinetic properties prediction for SCBs in the absence of bioassays and expertise in advanced computer modelling. In silico analysis was also carried out to characterise selected SCBs further through docking pose predictions on the CB1 receptor using the Maestro molecular modelling software by Schrödinger. The results showed that the indazole ring of the SCB interacts via π-π stacking with phenylalanine residues, particularly Phe 268, Phe 170, Phe 174, and His 178. The study concludes that the (S)-enantiomer has a higher CB1 affinity and more π-π stacking interactions with phenylalanine residues which are important for CB1 agonism. These results can be used to predict the properties of uncharacterised SCBs before their spread in the illicit drug market.
Structures and magnetic properties of ionic hybrids of metal halides and carboxyalkylamines.
(University of Pretoria, 2024-05-17) Rademeyer, Melanie; Sheppard, Charles; shalenebothma@gmail.com; Bothma, Shalene Natalia
Organic-inorganic hybrid materials combine an organic- and inorganic component at the molecular scale. The resulting hybrid material retains the properties of each component, allowing for the design of a material with specific properties through the selection of the components. This study investigated the structural characteristics and magnetic properties of ionic hybrid compounds prepared from metal halides and n-aminoalkanoic acids, HOOC(CH2)nNH2. In the presence of an acid, the organic component is protonated to form an n-carboxyalkylammonium cation, HOOC(CH2)nNH3+, while the inorganic component forms a perhalidometallate anion, [MaXb]z-, where M is a metal ion and X a halido ligand. Three families of compounds were investigated, namely compounds obtained through the combination of n-aminoalkanoic acids with CuCl2, CuBr2, or MnCl2, in an acidic medium. The metal ions Cu2+ and Mn2+ were chosen to impart magnetic properties to the materials. n-Aminoalkanoic acids of different chain lengths were selected to investigate the effect cation chain length on the structures and magnetic properties. The cations (HOOC(CH2)nNH3+), with n = 2, 3, 4, 5 and 10, were selected. A family of bis(n-carboxyalkylammonium) tetrachloridocuprates, (HOOC(CH2)nNH3)2[CuCl4], was obtained through the combination of the n-aminoalkanoic acids with CuCl2. These compounds exhibit two-dimensional hybrid halide perovskite structures in which bilayers of organic cations alternate with inorganic layers consisting of corner-sharing [CuCl6]4-¬ polyhedra. The compounds with n = 3 and 5 undergo phase transitions to incommensurate phases. Ferromagnetic intralayer interactions, occurring at temperature TC, are observed in these compounds. The ferromagnetic intralayer exchange interactions, JK¬, fall in the range of 13.3(1) K to 15.1(8) K, while TC ranged from 7.9 K to 13.4 K. Weak, interlayer antiferromagnetic interactions were observed for some of the compounds. The combination of the n-aminoalkanoic acids with CuBr2 gave bis(n-carboxyalkylammonium) tetrabromidocuprates, (HOOC(CH2)nNH3)2[CuBr4], and the compounds exhibit two-dimensional hybrid halide perovskite structures. Ferromagnetic intralayer interactions are present, with JK observed between 20.4(1) K to 23.7(3) K, while TC ranged between 10.5 K to 13.4 K. Weak, interlayer antiferromagnetic interactions were identified in all the members of this family. An interesting odd-even effect is observed for the compounds obtained from the combination of the n-aminoalkanoic acids with MnCl2. When the number of carbon atoms in the cation is even, bis(n-carboxyalkylammonium) tetrachloridomanganates, (HOOC(CH2)nNH3)2[MnCl4], are formed, which display two-dimensional hybrid halide perovskite structures. Antiferromagnetic intralayer interactions are present, occurring at temperature TN, with 2JK¬ ranging from -7.72(4) K to -8.28(5) K, and TN¬ ranging from 43 K to 45 K. When the number of carbon atoms in the cation is odd, bis(n-carboxyalkylammonium) diaquatetrachloridomanganates, (HOOC(CH2)nNH3)2[MnCl4(H2O)2], are formed. These compounds have layered structures containing [MnCl4(H2O)2]2- anions. Weak antiferromagnetic intralayer interactions are present, with 2JK = -0.14(2) K when n = 2 and 4. The study showed that the compounds' magnetic properties can be tailored by selecting different components. Magneto-structural correlations were identified in these families of compounds and in related compounds reported in the literature. Identifying these relationships contributes to the fundamental understanding of the magnetic behaviour of these materials.
Synthesis of an 8-membered oxygen-containing benzo-fused heterocycle using flow technologies
(University of Pretoria, 2024-03) Riley, Darren L.; Panayides, Jenny-Lee; bernicecurrie@gmail.com; Currie, Bernice Mercia
Flow chemistry has become an appealing alternative synthetic technology globally over the last few decades finding application in both academic and industrial laboratories driven largely by the fact that it commonly provides higher selectivity, yield and purity compared to batch chemistry that has become time-consuming, ineffective, and challenging to scale up. This dissertation describes the application and development of a flow process towards the synthesis of an 8-membered oxygen-containing benzo-fused heterocycle. The synthesis consisted of six stages that included two allylation steps, a Claisen rearrangement, an alcohol protection, an aldehyde reduction and a ring-closing metathesis step. The target molecule, (Z)-7-isopropoxy-8-methoxy-3,6-dihydro-1H-benzo[c]oxocine 25, was selected with an interest in developing an improved approach to accessing the scaffold for future structure-activity relationship screening and demonstrating that modern process technologies like flow can also be used routinely to perform fundamental research in a more sustainable and responsible manner. In summary, all six steps were successfully translated into flow and improved yields were shown with the use of greener solvents and operating at unconventionally high temperature and pressures especially when considering the Claisen rearrangement step. Design of experiment was also used in the last two stages which included i) the second allylation which required a strong base such as sodium hydride and was used as a slurry pumping through peristaltic pumps, and ii) the final ring closing metathesis stage in which two ruthenium-based catalysts were investigated with the use of a greener solvent. It was found that the flow approach yielded an overall percentage yield of 37.7 % in 105 minutes, compared to the batch approach that yielded an overall percentage yield of 0.77 % in 154 hours.
Anti-inflammatory and anti-diabetic properties of plant extracts and compounds from Scabiosa columbaria and Sclerocarya birrea
(University of Pretoria, 2023) Maharaj, Dashnie Naidoo; Maharaj, Vinesh J.; chidinma.ezeofor@unn.edu.ng; Ezeofor, Chidinma Christiana
Given that South Africa is home to around 10% of all flowering plant species known to humans, the country is blessed with an abundance of natural resources. About 24,000 plant species have yet to be fully uncovered for the benefit of humanity, making this a significant resource. The use of traditional medicine to cure illnesses is still widespread in South Africa despite the country's rapid urban and infrastructure development, more westernization, and accessibility to typical western medical institutions. Intricately woven within South African culture, the use of medicinal plants to heal illnesses is still prevalent. Additionally, due to Africa's failing healthcare system, using medicinal plants for health reasons is a well-accepted alternative that is practiced by all races, classes, and socio-economic classes. Bio-active extracts, fractions, and compounds have been identified as effective treatments for inflammatory and diabetic disorders based mostly on ethnomedicinal and empirical knowledge on traditional applications of plants. South Africa is a country with a high plant diversity of over 30,000 species of higher plants and 3,000 of these plant species have been found to be used in the traditional medicine for anti-inflammatory purposes. Inspired by the traditional uses of plant species, various scientists have studied the anti-inflammatory activities of South African plant species. Current cosmeceutical and drug discoveries rely on the massive screening of natural product libraries against various extracellular and intracellular molecular targets to find novel chemotypes with the desired mode of action. In the pharmaceutical and cosmeceutical industries, there is an increasing interest in the demand for natural ingredients with potential health benefits, such as anti-inflammatory, anti-diabetic, and anti-cancer properties, in an effort to replace or lessen the usage of synthetic products. With 60% of marketed pharmaceuticals and cosmeceuticals, natural ingredients have long been a key source of medicinal and cosmeceutical scaffolds. Nature continues to prove to be a source of new bioactive molecules with high safety profiles, despite the fact that many synthetic chemists are focused on synthesizing potent compounds with high toxicity profiles for pharmaceutical and cosmeceutical goals. Therefore, natural product chemists keep looking for novel leads. As a continuation of these efforts, this study aimed to identify and develop new natural anti-inflammatory ingredients from selected South African plant species for commercial application in different market sectors based on their traditional uses and literature data and to isolate and characterize biologically active compounds using modern hyphenated analytical techniques from biologically active plant species. A literature survey was carried out to identify South African plants based on their traditional uses to include in this study. A scoring system was applied to rank them and 3 plant species (Scabiosa columbaria, Commiphora pyracanthoides and Pelargonium capitatum) belonging to three families were selected. The 3 plant species were collected from the University of Pretoria Experimental farm, KwaZulu Natal and Limpopo and extracted singly using cosmetic acceptable solvents (acetone, ethanol water/ethanol (1:1) and water). The extracts were tested in different assays (anti-inflammatory and skin even tone). After testing different extracts of the plant species, the ethanol extract of S. columbaria roots was selected for further evaluation to identify the compound/s responsible for the anti-inflammatory activity and development as a potential active herbal ingredient based on good anti-inflammatory efficacy data and no anti-inflammatory reports in the literature. UPLC-QTOF-MS analysis of the ethanol extract of S. columbaria roots led to the tentative identification of fifteen compounds which are loganic acid (53) scrophuloside A1 (peak 2), 3,4-dicaffeoylquinic acid (peak 3), cantleyoside (peak 4), sylvestroside III (peak 5), triplostoside A (54), hederagenin (55), maslinic acid (peak 8), 2-isoursolic acid (56), glycyrrhetaldehyde (peak 10), pomaceic acid (57), euscaphic acid (58) and 3-oxoglycyrrhetinic acid (61). The presence of loganic acid (62), cantleyoside -dimethyl-acetal (63), ursolic acid (64), 2-isoursolic acid (65), 24-nor-2α,3β-dihydroxyolean-4(23),12-ene (66) and hederagenin (67) in the ethanol extract of S. columbaria roots was confirmed by isolation and structure elucidation of the compounds using MS and NMR data. Significant reduction of nitric oxide levels in RAW 264.7 macrophages was observed for ursolic acid (64) (12.5, 25 and 50 µg mL-1; 0.0702, 0.0558 and 0.0357 µg/mLrespectively), 24-nor-2α,3β-dihydroxyolean-4(23),12-ene (66) (12.5, 25 and 50 µg mL-1; 0.0543, 0.0327 and 0.0231 µg/mLrespectively) and hederagenin (67) (12.5 and 25 µg mL-1; 0.0735 and 0.0513 µg/mLrespectively) compared to the positive control aminoguanidine (12.5 µg mL-1; 0.0336 µg mL-1). At a concentration of 25 and 50 µg mL-1, 24-nor-2α,3β-dihydroxyolean-4(23),12-ene (66) demonstrated a potent reduction in nitric oxide level in RAW 264.7 macrophages. The compounds identified in the ethanol extract of S. columbaria roots will be used as chemical markers for quality control purposes, for batch-to-batch reproducibility that is required for commercializing the herbal ingredient. The anti-inflammatory activity of 24-nor-2α,3β-dihydroxyolean-4(23),12-ene (66) has been reported for the first time in this work. The active compounds (ursolic acid (64), 24-nor-2α,3β-dihydroxyolean-4(23),12-ene (66) and hederagenin (67)) were structurally similar and contained a β-hydroxy group at C-3. The compound 2- isoursolic acid (65) was inactive and had a hydroxy group at C-2 instead of C-3, which suggests that the position of the β-hydroxy group may play a role in the nitric oxide inhibition activity. A concentrated form of the ethanol extract of S. columbaria roots can be developed to have a higher concentration of the active compounds for commercial application as an anti-inflammatory ingredient. Diabetes is a global health problem and a national economic burden. Although there are many anti-diabetic medications on the market, there is still a need for innovative treatment agents with increased efficacy and less side effects. Because they are more diverse and have minimal side effects than synthetic medications, pharmaceuticals made from natural products are more appealing. In line with this quest, the Department of Science and Innovation (DSI) established the African Traditional Medicines collaboration, where research was carried out to find and create a new natural anti-diabetic ingredient. S. birrea was chosen because its leaves and stem bark have historically been used to treat conditions including diabetic mellitus. Although type-2 diabetes mellitus was reportedly inhibited by S. birrea leaf extract, the compounds responsible for the anti-diabetic activity have not yet been identified, and their discovery will be helpful for commercial use. In order to discover the chemical compounds in S. birrea that are responsible for the anti-diabetic activity and to employ them as chemical markers for quality control purposes, this Ph.D. research was carried out. Of all the extracts of S. birrea leaves tested, aqueous extract 4 showed statistically significant activity including at the lowest test concentration (0.01 µg mL-1) and was selected to isolate and identify the compounds responsible for the anti-diabetic activity (glucose uptake activity). UPLC-QTOF-MS analysis of the spray-dried aqueous leaf extracts of S. birrea (aqueous extracts 1 and 4) led to the tentative identification of sixteen compounds which are quinic acid (peak 1), gallic acid (peak 2), procyanidin B2 (peak 3), gallocatechin (peak 4), Pistafolin A (peak 5), epicatechin (peak 6), myricetin-3-O-β-D-glucuronide (88), gossypin (peak 8), quercetin-3-O-(6''-galloyl)-β-D-glucopyranoside (peak 9), myricetin-3-O-α-L-rhamnopyranoside (peak 10), quercetin-3-O-β-D-glucuronide (89), quercetin-3-O-arabinoside (peak 12), quercetin-3-O-α-L-rhamnopyranoside (peak 13), kaempferol-3-O-α-L-rhamnopyranoside (peak 14), myricetin (90) and quercetin (peak 16). The presence of myricetin (91), myricetin-3-O-β-D-glucuronide (92) and quercetin-3-O-β-D-glucuronide (93) in the aqueous leaf extract of S. birrea was confirmed by isolation and structure elucidation of the compounds using MS and NMR data. Myricetin-3-O-α-L-rhamnopyranoside (peak 10), gallic acid (peak 2), quercetin-3-O-arabinoside (peak 12) and quercetin-3-O-α-L-rhamnopyranoside (peak 13) were previously reported to occur in S. birrea. Quinic acid (peak 1), myricetin (90) and quercetin (peak 16) were previously reported to have anti-diabetic activity. Myricetin-3-O-β-D-glucuronide (92) and quercetin-3-O-β-D-glucuronide (93) have not been previously reported to occur in S. birrea. Myricetin (91), myricetin-3-O-β-D-glucuronide (92) and quercetin-3-O-β-D-glucuronide (93) signiﬁcantly increased the glucose uptake in differentiated C2C12 myocyte cells at different test concentrations; myricetin (91) (0.1 and 10 µg mL-1; 85.7 and 109.1%, respectively), myricetin-3-O-β-D-glucuronide (92) (0.1 and 10 µg mL-1; 61.6 and 88.8%, respectively) and quercetin-3-O-β-D-glucuronide (93) (0.1 and 10 µg mL-1; 40.9 and 43.9%, respectively) compared to the treatment of insulin (0.1 µM; 100%). At a concentration of 10 µg mL-1, myricetin (91) demonstrated both a potent and concentration-dependent stimulatory action on glucose uptake in the C2C12 myocytes, matching that of insulin, the positive control. Myricetin-3-O-β-D-glucuronide (92) has not been previously reported to have anti-diabetic activity, and the combination of this compound with other known anti-diabetic compounds in S. birrea contributes to the plant’s anti-diabetic efficacy. These anti-diabetic compounds will be used as chemical markers for quality control purposes required for commercializing the herbal ingredient. This study provides scientiﬁc data to support the commercial application of the aqueous extract of S. birrea leaves as an anti-diabetic ingredient. By finding novel active components and molecules responsible for the biological efficacy to be exploited as chemical markers for commercial application, the project's ultimate purpose was accomplished. The indigenous knowledge on the use of medicinal plants proves to be useful for identifying ingredients and developing products for the various market sectors, and this research provides scientific evidence on the value of South Africa's plant biodiversity as a continuing source of biologically active ingredients. Secondly the bioassay guided isolation method used in the isolation of active compounds proved to be a useful technique with the bioassay acting as a specific detector at every purification step. Though it can be criticized for being time consuming and resource intensive compared to the conventional method of isolation, the approach compensates for these shortcomings by its effectiveness.
The electrochemical reduction of CO2 to value-added products
(University of Pretoria, 2024-02-23) Radhakrishnan, Shankara Gayathri; u17023000@tuks.co.za; Klopper, Reinard
Carbon dioxide is the fourth most abundant gas in the atmosphere making up 0.035 %. Carbon dioxide prevents heat from escaping into the outer space and is used by plants to make oxygen. The levels of carbon dioxide have significantly increased since the start of the industrialisation era and the effects thereof is felt on a global scale. The aim of this project is to electrochemically transform the inert CO2 molecule into value added products such as formic acid, carbon monoxide, methanol, methane etc., as an energy storage media and reduce its global footprint. Use of water electrolysis as a medium for production of hydrogen ion (green hydrogen route) has been employed. IrO2:TaC 70:30 wt. % was selected as a suitable anode electrocatalyst and In2O3 enriched with 0.15 wt. % PTFE as the cathode electrocatalyst under investigation. The electrocatalysts synthesized were characterised using scanning electron microscopy and powder X-ray diffraction techniques. The IrO2:TaC 70:30 wt. % proved to be a good system for the water electrolysis in accordance to our previous studies and with literature1,2 Catalyst inks were prepared to deposit the electrocatalysts via spray coating methods thereby making 5 sets of catalyst coated membranes. The anode electrocatalyst IrO2:TaC 70:30 wt % was deposited directly onto the Nafion® membrane while the cathode electrocatalyst PTFE infused In2O3 onto the carbon paper gas diffusion layer. Humidified gaseous CO2 as well as studies were also performed along with the usual aqueous CO2 which eliminates solubility issues and the need of electrolytes. Linear sweep voltammetry for ECR revealed onset potentials ranging from -1.10 V to -1.49 V which corroborated with literature while showing some changes with each membrane, accompanied with high current densities and low ohmic resistance. Tafel slopes revealed mechanistic changes over potentials applied indicating a possible change in product formation with increasing potentials. Chronoamperometry experiments were conducted using applied potentials of -1.6 V, and, -1.8 V, with average current densities reaching up to -99 mA/cm2 in bubbled CO2 and -223.32 mA/cm2 in CO2 humidified in H2SO4. Gas injected gas chromatography was used to analyse gaseous products. Products obtained were carbon monoxide, methane, ethane, and ethylene with the best results yielding a Faradaic efficiency of 4.36 % for ethane formation.

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