Doctoral Degrees (Chemistry)
Permanent URI for this collection
Browse
Browsing Doctoral Degrees (Chemistry) by SDG "SDG4"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Assessment of antiretroviral drugs uptake by vegetables from contaminated soil and their adsorption by exfoliated graphite in river and wastewater.(2022) Kunene, Philisiwe Nganaki.; Mahlambi, Precious Nokwethemba.This study was directed toward vegetable uptake of the commonly used antiretroviral drugs (ARVDs), abacavir, nevirapine, and efavirenz. Antiretroviral drugs are used to treat the human immune-deficiency virus (HIV). South Africa (SA) is one of the countries with a high number of infected people on ARV therapy, therefore, the ARVDs are anticipated to be existing at high concentrations in the South African environment than in other countries worldwide. In recent years, the presence of ARVDs in the environment has drawn attention; hence studies have reported their presence in aquatic environments while very few studies have been conducted on their uptake using vegetables. This work was therefore based on the optimization and application of sensitive, simple, cost-effective, and robust techniques for quantifying ARVDs in vegetables. Based on this information, ultrasonic extraction (UE) and microwave-assisted extraction (MAE) were used to isolate target compounds from vegetable samples to the aqueous phase. Dispersive liquid-liquid microextraction (DLLME) and solid-phase extraction (SPE) were utilized to preconcentration and clean up the extracts from UE and MAE, respectively. A liquid chromatography photodiode array detector (LC-PDA) was utilized to detect and quantify the extracted compounds. The UE with and without DLLME cleanup were compared with each other, also, MAE with and without SPE cleanup were compared with each other. The methods comparison was done in terms of their detection (LOD) and quantification limits (LOQ), extraction efficiencies (%Recovery), relative standard deviations (%RSD), and concentrations of ARVDs found in vegetable samples. In comparison of UE and ultrasonic-assisted dispersive liquid-liquid microextraction (UADLLME), the LOD and LOQ obtained ranged between 0.0081 - 0.015 μg/kg and 0.027 - 0.049 μg/kg for UE and 0.0028 -0.0051 μg/kg and 0.0094 - 0.017 μg/kg for UADLLME respectively. High recoveries ranging from 93 to 113% in UE and 85 to 103% in UADLLME with less than 10% RSD in both procedures were obtained. These results indicated that UADLLME is more sensitive than the UE method, although they are both accurate and precise. The UE can be recommended for routine analysis as UADLLME showed the inability to extract analytes from root vegetables. The optimized UE and UADLLME methods were applied to extract ARVDs from vegetables bought from local fruit and veggie supermarket. Vegetables were categorized as root (carrot, potato, and sweet potatoes), leaf (cabbage and lettuce), and fruit (green paper, butternut, and tomato). The target ARVDs were quantified in most samples with concentrations up to 8.18 μg/kg. The concentrations obtained were slightly high in UADLLME than in UE as a result of its high sensitivity. Efavirenz was the most dominant drug, while the potato was the most contaminated vegetable. In the comparison of MAE and MAESPE, the obtained LOD and LOQ ranged from 0.020 to 0.032 μg/kg and 0.068 to 0.109 μg/kg for MAE and 0.019 to 0.066 μg/L and 0.065 to 0.22 μg/L for MAE-SPE. The obtained recoveries ranged from 85 to 103% for MAE and from 82 to 98 % for MAE-SPE, respectively, and the RSDs were all less than 6%. These results showed that both methods have comparable sensitivity; however, the recoveries values for MAE were slightly higher than those obtained in MAE-SPE, which signals MAE’s high accuracy. The optimized MAE and MAE-SPE methods were applied to remove ARVDs in the root (potatoes, onions, and beetroot), leaf (lettuce, and spinach), and fruit (green paper, cucumber, and eggplant) vegetables bought from local fruit and veggie supermarket. The obtained ARVDs concentration range was 1.48 ± 0.5 - 27.9 ± 1.2 μg/kg. The MAE-SPE resulted in low concentration compared to MAE without cleanup. Beetroot exhibited high concentrations of the target ARVDs, while nevirapine was found to have high concentration and as a dominant compound. The results obtained revealed that the vegetables from the studied area are contaminted with ARVDs, which could indicate their possible irrigation with wastewater effluent or the use of sludge as biosolids in the agricultural areas. This is a concern as it leads to unintentional consumption by consumers which could lead to drug resistance by the human body or have human health effects. The study was then expanded by conducting the phytoremediation approach to investigate the uptake of abacavir, nevirapine, and efavirenz by beetroot, spinach, and tomato from the contaminated soil. The three selected vegetable plants were planted and irrigated with ARVDs spiked (at 2000 and 5000 μg/L) water over a period of three months. The optimized UE and LC-PDA methods were used to extract and quantify the selected ARVDs from the target vegetables and soil. The obtained results showed that the studied vegetables have the potential to take up abacavir, nevirapine, and efavirenz from contaminated soil, be absorbed by the root, and translocate to the aerial part of the plants. Abacavir was found at high concentrations to a maximum of 40.21 μg/kg in the root, 18.43 μg/kg in the stem, and 6.77 μg/kg in the soil, while efavirenz was the highest concentrations, up to 35.44 μg/kg in leaves and 8.86 μg/kg in fruits. Spinach root accumulated more ARVDs than beetroot and tomato. The bio-accumulation factor ranged from 2.0-14 μg/kg in beetroot, 3.6 - 15 μg/kg in spinach, and 6 – 10 μg/kg in tomato. The root concentration factor range was 0.047 – 17.6 μg/kg; 0.34-5.9 μg/kg, and 0.14-2.82 μg/kg in beetroot, spinach, and tomato, respectively. The translocation factor range obtained was 0.40 – 38 μg/kg, 0.08 – 19 μg/kg, and 0.14 – 49 μg/kg in beetroot, spinach, and tomato, respectively. However, the accumulation of ARVDs in all studied plants showed that they could be used in phytoremediation. The results obtained in the phytoremediation approach revealed that the utilization of the contaminated water has an influence on the presence ARVDs in vegetables; hence this work also focused on evaluating the exfoliated graphite adsorption of ARVDs in water. Natural graphite was intercalated with acids and exfoliated with thermal shock to obtain the exfoliated graphite. The scanning electron microscopy images showed that the exfoliated graphite had increased c-axis distance between the layers with accordion-like structure which were confirmed by the lower density of exfoliated graphite material (0.0068 gmL-1) compared to the natural graphite (0.54 g mL-1). Fourier Transformed Infrared Spectroscopy results showed the C=C in natural and exfoliated graphite at 1635 cm-1 stretching. The phenolic, alcoholic, and carboxylic groups were observed from 1000 to 1700 cm-1 for the intercalated and exfoliated graphite. The Energy-dispersive X-ray results further confirmed these results, which showed carbon and oxygen peaks in the intercalated and exfoliated graphite spectrum, whereas natural graphite showed only a carbon peak. Raman spectroscopy results showed that the material’s crystallinity was not affected by the intercalation and exfoliation processes as observed from the ratios of the G and D peaks and the G' and D'. Natural, intercalated and exfoliated graphite contained the D, G, D', and G' peaks at about 1350 cm-1, 1570 cm-1, 2440 cm-1, and 2720 cm-1, respectively. The exfoliated graphite material showed the characteristic of a hexagonal phase graphitic structure by (002) and (110) reflections in the X-ray diffraction results. The exfoliated graphite adsorption method was optimized based on the pH of a solution, adsorbent dosage, and adsorption time prior to application to water samples. The optimum pH solution, adsorbent dosage, and adsorption time were 7, 30 mg, 0.01 μg/L, and 30 minutes respectively. The kinetics and isotherm studies were conducted to assess the model that best fit and explain the experimental data obtained. The kinetic model and adsorption isotherm studies showed that the experimental data fit well pseudo-second-order kinetics and is well explained by Freundlich’s adsorption isotherm. The maximum adsorption capacity of the exfoliated graphite (EG) for ARVDs ranges between 1.660-197.0, 1.660-232.5, and 1.650-237.7 mg/g for abacavir, nevirapine, and efavirenz, respectively. These results showed that under proper operating conditions, the EG adsorbent could potentially be applied as a water purifying tool for the removal of ARVDs pollutants.Item Comparison of extraction methods efficiency for the extraction of polycyclic aromatic hydrocarbons and phenolics in water matrices, sludge and sediment: sources of origin and ecological risk assessment.(2023) Ndwabu, Sinayo.; Mahlambi, Precious Nokwethemba.; Malungana, Mncedisi.Polycyclic aromatic hydrocarbons (PAHs) and phenolic compounds (PCs) are persistent and environmentally toxic compounds. This study therefore aimed to determine the levels of both PAHs and PCs in river water, wastewater, sludge and sediment samples. The evaluation of their origin source and ecological risk was also determined. The status of both these contaminants in South African environment is still not fully investigated, which is a gap this study intended to fill together with previous studies that have been carried-out. The PAHs and PCs were extracted using different extraction methods which include a solid phase extraction (SPE) and dispersive liquid-liquid micro-extraction (DLLME) in water matrices. The microwave assisted extraction (MAE) and Ultrasonication (UE) coupled with either filtering (F) or F + SPE as a clean-up technique was used for extraction of solid samples. The analytes extracted form water or sediment were determined using GC-MS. The PAH %recoveries obtained under optimum conditions in liquid samples were determined to be 72.1 - 118% for SPE and 70.7 – 88.4% for DLLME while the LOD and LOQ were 5.00 – 18.0 ng/L and 10.0 – 44.0 ng/L for SPE while they were 6.00 – 20.0 ng/L and 11.0 – 63.0 ng/L for DLLME. The recovery test for PAHs in solid samples gave a range of 93.7% - 121% for UE and 79.6% - 122% for MAE while the LOD and LOQ ranged from 0.0250 μg/kg to 1.21 μg/kg & 0.0800 μg/kg to 3.54 μg/kg for MAE and from 0.0840 μg/kg to 0.215 μg/kg & 0.0190 μg/kg to 0.642 μg/kg for UE respectively. The LOD and LOQs for PCs in both water and solid matrices were 0.01 – 2.00 μg/L and 0.02 – 6.07 μg/L for SPE, 0.05 – 1.20 μg/kg and 0.17 – 3.17 μg/kg for MAE and 0.09 – 1.33 μg/kg and 0.26 - 3.54 μg/kg for UE correspondingly, their %recovery test gave ranges of 75.2 – 112% (SPE), 80.9 – 110% (MAE) and 79.3 – 119% (UE).The optimization and validation of these methods indicated that they can be used for the extraction of PAHs or PCs in liquid samples, however, SPE when compared to DLLME showed to be more accurate and sensitive. Moreover, in solid samples the clean-up method was a deciding factor, with F + SPE cleaned samples giving higher concentrations of both PCs and PAHs than the filtered ones in both MAE and UE. The concentrations of PAHs ranged from nd (not detected) to 1046 ng/L in river water and nd to 778 ng/L in wastewater samples with naphthalene showing dominance over all other PAHs in both water matrices. The PC concentrations at 4.12 to 1134 μg/L for wastewater and nd to 98.0 μg/L for river water were high but still within the maximum allowable limit except for 2.4-DCP (2.4 dichlorophenol) at Wdv4. The concentrations obtained from F + SPE cleaned samples were higher for both PAHs and PCs with a range from 95.96 to 926.0 μg/kg and 1.30 to 310 μg/kg compared to concentrations from filtered only samples at 21.61 to 380.6 μg/kg and 0.90 to 266 μg/kg respectively. Pyrene showed dominance over all other PAHs in both sludge and sediments while 2.4-DCP and PCP dominated the sludge and sediment samples respectively. PAHs were determined to be of petrogenic (water matrices) and pyrolytic (solid samples) origin and on average posed low (water matrices) and a medium to high (solid matrices) ecological risk. The ILCRderm values at 4.98 x 10-1 and 2.62 x 10-1 (DahA) and 5.92 x 10-2 and 5.34 x 10-2 (PCP) were highfor adults compared to that of children at 1.92 x 10-1 and 1.01 x 10-1 (DahA) and 1.39 x 10-2 and 1.26 x 10-2 (PCP) for both sediment and sludge samples respectively. The low values of ILCRderm for children indicates that the have a high risk exposure even at low concentrations of the contaminants. The findings of this study showed that both areas (uMsunduzi river and Darvill wastewater works (WWW) of interest are polluted with PAHs and PCs therefore, more regulations such as the National Environmental Management: Waste Act (NEMWA) are needed to ensure environmental, human and animal safety.Item Targeting the tumour extracellular environment through rational modification of the SNX class of HSP90 inhibitors.(2023) Mathenjwa, Gciniwe Sindiswa.; Akerman, Matthew Piers.; Veale, Clinton Garenth Lancaster.; Bode, Moira Leanne.HSP90 remains a valuable target for cancer therapy. Unfortunately, targeting intracellular HSP90 has proven not to be a viable chemotherapeutic approach. Compensatory HSR induction and HSP70 overexpression are the main limitations of this approach. A growing body of evidence suggests that targeting the extracellular environment would be of advantage and devoid of the drawbacks observed with intracellular HSP90 inhibition. As a result, the development of extracellular HSP90 inhibitors represents a novel opportunity for cancer therapeutics. In view of this hypothesis, we aimed to design and synthesise extracellular inhibitors and to assay these compounds against HSP90. To develop extracellular HSP90 inhibitors, cell-impermeable analogues of the well-developed benzamide HSP90 inhibitor (SNX 2112) were designed, synthesised and biologically evaluated. The desired target compounds were synthesized using developed methodology, as well as modified methodology. In Chapter 3 we compared and evaluated a variety of reported synthetic methods to deliver the analogues of SNX 2112. Interested in a general procedure for the synthesis of our analogues, we initially attempted to afford both the methyl and the trifluoromethyl containing analogues via a β- triketone mediated procedure. Despite the success observed with the methyl analogues, the instability of a trifluoromethyl containing β-triketone, deemed this procedure not feasible for this class of compounds. Our continued effort towards a general procedure led to the investigation of a tosylhydrazone mediated tetrahydroindazolone condensation; unexpectedly attempts to synthesise the methyl containing analogues via this procedure led to a 1—5 nitrogen to carbon tosyl migration, which was further investigated for varying substrates, and these results are explained in detail in this thesis. It then became apparent that each of the reported methods had its merits and shortcomings, there was no one best method, rather the synthetic approach was mainly determined by the C-3 substituent. The key intermediates were then converted into the desired targeted compounds by tethering the HSP90 pharmacophore to flexible alkyl groups, attached to polar sulfonate and phosphonate functionalities. Hypothetically, introduction of polar alkyl groups, would inhibit cell penetration thus limiting them to the extracellular environment. Based on the goals of our study we were interested in three biological evaluations; to confirm that our modified compounds were still capable of inhibiting HSP90s ATPase activity, to evaluate if our modifications reduced intracellular HSP90 activity, whether they stimulated the pro-oncogenic HSR, and to evaluate their cytotoxicity. Preliminary biological assessment of our compounds was consistent with our hypothesis. Here we showed that our compounds did not inhibit intracellular HSP90, and did not stimulate HSP70 expression, a marker of induction of the compensatory HSR. Furthermore, our analogues displayed cytotoxicity in the nanomolar range against the HeLa cell line. These preliminary data support the feasibility of targeting extracellular HSP90 as a novel anticancer strategy.