Theses and Dissertations (Chemistry)

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Synthesis and applications of ruthenium(II) complexes featuring ONO ligands
Awe, Babatunde (University of Pretoria, 2025-10)
This study set out to design, synthesise, and evaluate ruthenium(II) complexes bearing ONO-type pincer ligands in combination with diverse donor systems which included N-donor, P-donor, N-heterocyclic carbene (NHC), and pincer frameworks with the dual aim of achieving high-performance catalytic activity under mild conditions and assessing their potential as anticancer agents. The research spanned the preparation of 29 Ru(II) complexes (26 of which are new) grouped into three major ligand classes, each characterised structurally and electronically, screened for transfer hydrogenation and/or alcohol oxidation catalysis, and, in selected cases, evaluated for biological activity. Electrochemical and computational studies were integrated throughout to offer mechanistic insight into the observed reactivities and behaviours.
Comparison of gaseous polycyclic aromatic hydrocarbon concentrations arising from the use of different indoor combustion devices
Joubert, Serena (University of Pretoria, 2025)
This study investigated household air pollution (HAP). The targeted domestic environments were houses that were part of an intervention initiative conducted by an external industry party, during which wood or coal (W/C) stoves were replaced with liquid petroleum gas (LPG) stoves. These houses were part of the Reconstruction and Development Program (RDP) and were located in eMbalenhle, Mpumalanga, South Africa (a settlement near Secunda). As part of the intervention initiative the interiors of the targeted houses were also retrofitted and this included improved insulation. The changes made in an intervention initiative is easy to document, however, showcasing the impact of the changes on air quality and human health requires data. This work aimed to document the impact of the intervention initiative on the air quality in the targeted environments and to facilitate an understanding of the related human health impacts. HAP has been strongly linked to numerous negative human health impacts, and domestic activities that emit toxic compounds warrant investigation. Research targeting HAP allows the development of strategies to mitigate the causes of the associated detrimental health effects. Domestic activities that entail solid fuel combustion such as cooking and heating with wood stoves have been strongly linked to exposure to harmful chemicals, such as polycyclic aromatic hydrocarbons (PAHs). As such, PAHs are widely studied when considering the relationship between domestic combustion and indoor air quality. However, in Africa, despite a widespread use of solid fuels for cooking and heating activities, there is a paucity of research that has quantified PAH emissions from indoor combustion and more such research is required to better understand the health and life quality impacts. This work addressed this research gap by quantifying gaseous PAH concentrations resulting from indoor combustion in domestic environments as well as in the related ambient environment. Multichannel polydimethylsiloxane traps were used to sample gaseous PAHs, and samples were analysed by thermal desorption-comprehensive gas chromatography-time-of-flight mass spectrometry. This investigation was focused on measuring and comparing the concentration of gaseous PAHs arising during the use of various fuels in different combustion devices. The sixteen US EPA priority PAHs with the addition of two naphthalene derivatives were targeted. Additionally, portable instruments were used to gather supplementary data to better understand the overall impact of the combustion devices on the indoor air quality. The particulate matter (PM) measurements from ultrasonic personal air samplers or UPAS instruments, specifically that of PM2.5 (PM diameter ≤ 2.5 µm), were of interest, as human exposure to PM is also associated with several adverse health impacts. Sampling was conducted to be representative of the standard practices within a targeted household; residents of each house started their combustion device in the usual manner and heated 1 L of water to a rolling boil, after which a 10 min trap sampling interval was initiated. After sample analysis and data collection, an artificial intelligence tool was used to develop algorithms which were used to consolidate and process the large data sets into sensible results. In addition to the indoor investigation, ambient samples and outdoor measurements in the residential area were taken to understand how the indoor results compared to the air that residents were generally exposed to. In the indoor investigation, two types of combustion devices were targeted for comparison purposes – specifically the use of W/C stoves and the replacement LPG stoves. The main focus of this work was to compare results relating to the air quality during the use of the two types of target stoves, however in a few instances non-target stoves were included. In total, 20 houses were sampled both before (pre) and after (post) the intervention initiative and measurements were taken at eight ambient sites in both sampling campaigns. In addition, five houses were only sampled during the pre intervention campaign. Overall, the pre intervention dataset yielded the highest total target gas phase PAH concentration for an individual house, of 201 902.97 ng.m−3 whilst the lowest individual house result was obtained from the post intervention dataset at 253.45 ng.m−3. The total gas phase PAHs concentration was higher in 13 of the pre intervention campaign houses compared to post, whilst the total PAH concentrations excluding naphthalene were higher in 15 of the 20 houses in pre compared to post. The mean ± standard deviation (SD) (percentage relative standard deviation (%RSD)) indoor total gas phase PAH concentration was 23 359.75 ± 49089.07 ng.m−3 (210.14%) for the pre intervention campaign, which was much higher than the 1701.32 ± 2192.40 ng.m−3 (128.86%) for post intervention. The mean ± SD (%RSD) total gas phase PAHs concentration only including target stoves was also much higher for pre intervention conditions at 26 642.44 ± 52 775.18 ng.m−3 (198.09%) compared to post intervention 1326.98 ± 416.21 ng.m−3 (31.37%). The mean ± SD (%RSD) of the overall ambient total target gas phase PAH concentration was 257.58 ± 236.03 ng.m−3 (91.63%) and this result emphasised the scale of the pre intervention campaign results. The PAH concentrations were used to calculate the toxic equivalence (TEQ) related to the various conditions, as Σ TEQ values offer insight into the toxicity associated with measured levels of PAHs mixtures and consequently indicate improvements or the deterioration of the human health impacts related to the environments. A decrease in Σ TEQ was observed from pre to post intervention results, as the pre intervention mean ± SD (%RSD) Σ TEQ was 150.90 ± 523.31 ng.m−3 (345.79%) as compared to 1.94 ± 2.11 ng.m−3 (108.81%) for the post intervention. The mean ± SD (%RSD) Σ TEQ of the combined ambient measurements was markedly lower at 0.29 ± 0.30 ng.m−3 (103.25%). The UPAS instruments were not available for sampling in all the targeted environments, however from the available paired pre and post intervention results, the indoor pre intervention [PM2.5] mean ± SD (%RSD) was 699.7 ± 1111.2 µg.m−3 (142.6%), which was much higher than that of the post intervention campaign 15.0 ± 8.7 µg.m−3 (58.0%). Ultimately, it was observed that the intervention initiative led to an improvement in air quality based on the parameters studied, when comparing pre and post intervention results. This would imply that replacing W/C stoves with LPG stoves would improve the air quality during the indoor combustion device use, in addition to potential improvements relating to reductions in other priority pollutants, such as sulfur dioxide. This study therefore showed that the intervention resulted in clear improvements in indoor air quality and consequently human health.
Facile synthesis of iron-based metal-organic frameworks and carbon derivatives via unconventional precursors for gas storage applications
Mosupi, Amos Ramatlhodi Keaoleboga (University of Pretoria, 2025)
This study focused on the synthesis of iron-based metal-organic frameworks (MOFs) employing unconventional feedstock and synthetic procedures. Iron metal extracted in a form of salt from acid mine drainage (AMD) and terephthalic acid (H2BDC) derived from waste polyethylene terephthalate (PET) are explored as potential precursors for MOF synthesis. To reduce long synthesis times associated with the traditional solvothermal process, unconventional approaches (microwave- and sonochemical-assisted) employing shorter synthesis times were explored. These approaches were also intended to reduce the cost of manufacturing and operation on the preparation for MOFs for gas storage applications. Iron was extracted from AMD via selective precipitation where pH was maintained at 3.5. PET was depolymerized under autogenous pressure and controlled temperature to yield H2BDC monomer. In first instance, three synthetic procedures (i.e., conventional solvothermal, unconventional microwave-assisted and unconventional sonochemical-assisted synthesis) were employed for the synthesis of Fe-MIL-101. The obtained MOFs exhibited similar structural and morphological properties which are comparable to those previously reported. The microwave-assisted synthesis sample exhibited superior textural properties thus exhibiting high hydrogen adsorption at 1 bar and 77 K. The feasibility of using unconventional feedstock and methods for the synthesis of high-quality iron-based MIL-101 has been proven with an added advantage of shorter reaction times. In the second instance, similar unconventional precursors and methods were employed for the synthesis of the flexible MIL-53 and MIL-88B. The obtained materials exhibited the trigonal bipyramidal morphology which is associated with these materials. The samples displayed high crystallinity. Due to the inherent ‘breathing effect’ of these material and guest molecules within the pores, these materials exhibited low surface areas and pore volumes. The highest recorded surface areas were for the sonochemically prepared MIL-53 and MIL-88B samples with surface areas of 20 and 34 m2 g-1, respectively. To circumvent these drawbacks, a direct carbonization strategy was employed to enhance porosity and surface area. Post carbonization, the highest recorded surface area was 947 m2 g-1 for the carbonized sonochemical MIL-53. The prepared derived carbons displayed reasonable H2 uptakes at 1 bar and 77 K, and CO2 capacities at 1 bar and 298 K. The use of waste materials and industrial by-products (i.e., H2BDC and AMD-Fe) generated MOFs with exceptional properties, which then prompted further evaluation of AMD-Fe with additional metals present in AMD. The inductively coupled plasma mass spectroscopy showed that AMD is made up of primarily Fe and other metals (i.e., Al, Ca, Mg, Mn and Zn) at varying concentrations. The effect of the presence of these metals on morphological and textural properties of Fe-MIL-88B and Fe-MIL-101 was then investigated, employing the conventional solvothermal process. Bimetallic (FeM1) and trimetallic (FeM1M2) combinations were tested, where Fe is paired with each metal and further paired with two more metals. Some combinations resulted in octahedral morphology, while others resulted in mixed morphologies of octahedral and hexagonal bipyramidal shapes. Elemental analysis confirmed that the resulting MOF samples were mainly dominated by iron metal clusters and only trace amounts (< 1.25 ppm) of Mg, Mn and Zn were detected. Recorded surface area values were in the range 26 – 2117 m2 g-1 with the highest pore volume at 0.91 cm3 g-1. Only a limited number of samples displayed surface area high enough to be evaluated for H2 at 77 K and 1 bar as well as CO2 at 298 K and 20 bar. FeMn-MIL-101 exhibited a surface area of 2117 m2/g and H2 uptake of 1.44 wt% at 1 bar and 77 K as well as 6.17 mmol/g of CO2 uptake at 20 bar and 298 K. This study proved that the use of iron-rich AMD with moderate concentrations of other metals can result in MOFs with reasonable properties as it is with pristine precursors. This study has shown the potential of waste materials and unconventional procedures for cost-effective and sustainable preparation of MOFs, which could open doors for industrialization.
The interaction of cholesterol with mycolic acid and phosphatidylcholine liposomal membrane : application to electrochemical sensing of tuberculosis and cholesterol
Mathebula, Nsovo Samuel (University of Pretoria, 2025-12)
This thesis utilizes a combination of electrochemical experiments and Density Functional Theory (DFT) calculations to primarily investigate the interactions among cholesterol, mycolic acid, and phosphatidylcholine, with the goal of enhancing the electrochemical detection of tuberculosis (TB). The immunodetection of active TB, especially in HIV-positive patients, is crucial for effective treatment and disease eradication. Mycolic acid is recognized as one of the most important antigens for the immunodetection of TB antibodies. However, the interaction between anti-mycolic acid antibodies (AMAA) and mycolic acid antigens (MAA) for TB detection is significantly hindered by the cross-reactivity of cholesterol / anti-cholesterol antibodies (AChA) due to the cholesteroid nature of MAA. For the electrochemical experiments: A glassy carbon electrode modified with MAA-confined activated carbon (GCE-AC-MAA) was fabricated to serve as the electrochemical TB immunosensor. TB-positive serum used as control experiment showed nearly similar electrochemistry (CV and EIS) which confirms the cross- reactivity of AChA in the presence of PC/MAA. The best protocol for the detection of TB was found to be the pre-incubation of the TB serum in liposome alone (free AMAA available) and then detect with the electrochemical immunosensor. The cross-reactivity of AChA with the sensor platform, PC/MA, was also investigated using DFT calculations. The DFT results demonstrated that cholesterol interacts with MAA, with the interaction becoming stronger in the presence of liposomes. Noteworthy, cholesterol (Ch) also naturally interacts with PC liposomes in the human body. Thus, to determine the optimal platform for electrochemical cholesterol detection, this study examined the interactions between Ch-PC and Ch-MA. Key parameters from DFT calculations revealed that Ch-PC interactions are weaker than Ch-MA interactions. For Ch-PC, the adsorption energy (Ead ≈ -13.778 eV) was smaller than those for Ch-MA (Ead ≈ -7.506 eV). Additionally, the p-band center for Ch-PC (- 12.2874 eV) is farther from the Fermi level compared to Ch-MA (-11.3922 eV). The bond length between Ch and PC (3.745 Å) was also longer (and thus weaker) than that between Ch and MA (2.748 Å). The above findings were corroborated by results from an electrochemical capacitive biosensor for cholesterol detection. These findings confirm that cholesterol’s interaction with PC is relatively weak, making PC a promising electrode platform for cholesterol detection. The capacitive biosensor demonstrated excellent performance metrics, including a wide linear range (20–120 µM), high sensitivity (m = 19.39 Ω µM⁻¹), and low limits of detection (LoD ≈ 11.3 µM) and quantification (LoQ ≈ 37.7 µM). These values are comparable to, and in some cases better than, those reported in the literature. In conclusion, this thesis provides a foundation for optimizing PC-based electrochemical biosensing platforms for cholesterol detection and offers insights into mitigating cross-reactivity challenges in TB immunodetection.
Volatile organic compound monitoring at industrial water treatment facilities utilising passive air samplers
Leakwe, Ntoko Moses (University of Pretoria, 2025-12-17)
Sasol is a petrochemical company which produces petroleum products and other chemical feedstocks from low grade coal through the Fischer Tropsch process. This process also produces reaction water as byproduct which is a complex mixture containing various organic and inorganic compounds that result from both the syngas conversion and secondary reactions. Given the complex composition of the reaction water, Sasol has developed a comprehensive water treatment strategy, through its Water Recovery Facility, with the main objective of removing contaminants, such as volatile organic compounds, phenols, and other hydrocarbons, through biological treatment (aerobic digestion) and storing the treated water in artificial lagoons (holding dams) before recycling the water back into the factory for use as utility water. As effective as this process of organic contaminants removal is, small amounts of organic contaminants can still remain and thereby result in the emission of volatile organic compounds (VOCs), specifically benzene, toluene ethylbenzene and xylenes (BTEXs), into the atmosphere. The extended storage times in the holding dams, further increases the risk of VOC emissions, and large surface areas can lead to water evaporation also exacerbating emissions, necessitating air quality monitoring around the treatment facility. Effective monitoring and control of these VOC/BTEX emissions is critical for ensuring compliance with environmental regulations and safeguarding both environmental and public health. However, the concentration of airborne VOCs around Sasol’s water treatment facilities is likely to be very low, presenting a unique challenge for traditional air sampling methods. Techniques such as sampling into Tedlar® bags or stainless-steel canisters are not suitable in these settings due to their limited pre-concentration capabilities and physical impracticality for detecting trace amounts of VOCs in outdoor environments. Given the low expected concentrations of VOCs in and around Sasol’s water treatment facilities, there was a pressing need to develop and implement more sensitive and practical methods for air monitoring. This study sought to address this gap by evaluating the efficacy of passive air sampling techniques, specifically Radiello® diffusive samplers, which offer pre-concentration capabilities necessary for detecting low concentrations of VOCs in outdoor environments. Passive sampling, combined with initial active sampling experiments, was therefore conducted to allow for the development of more precise and reliable quantification methods for VOCs around the water treatment unit. Selecting the most suitable locations to conduct sampling was of paramount importance for this study, and after careful examination of the water recovery facility (WRF) at Sasol Secunda, seven sampling sites, across three locations, were identified based on the effluent stages during the treatment process. The first location was the actual treatment facility where the aerobic digestion takes place; this location was expected to have the highest levels of VOCs among all three locations. The second location identified was the primary dams where the secondary aeration and settling of microorganisms takes place. The third location which was identified was the secondary dams (holding dams) where the water is stored before being recycled back to the factory for reuse. This location was expected to have the lowest concentration of VOCs. By virtue of the first location being in an area where the raw reaction water is received, the water is agitated due to the factory discharge and the water has not been treated yet, the highest level of VOCs was expected at this site. Active sampling was conducted at this location as a screening test to determine the composition and approximate concentrations of the target VOCs that would thus be expected to be found in and around the WRF. The screening sampling campaign was conducted following NIOSH method 1501 using a Gilian® GilAir™ Plus personal air sampling pump, and adsorbing VOCs onto Anasorb® coconut shell charcoal due to its sorbent strength and high surface area. Passive or diffusive sampling was conducted at two locations at Sasol’s water recovery holding dams, the primary holding dams, with two sampling sites and the secondary holding dams also with two sampling sites. Based on literature, Radiello® passive samplers were found to be the most suitable for testing in this study and were therefore chosen for use. This is primarily based on design, as the Radiello® passive samplers are radial rather than axial, giving them a much larger surface area. The Radiello® passive sampling device for VOCs and BTEXs contains a Carbograph 4 (graphitized carbon) adsorbent cartridge onto which VOCs are trapped by adsorption and are recovered by thermal desorption with analysis by gas chromatography - mass spectrometry (GC-MS). The cartridge is housed in a diffusive body, either white or yellow. The yellow diffusive bodies are used whenever the sampling rate must be reduced due to higher ambient concentrations of the target analytes, whilst the white diffusive body is used whenever the sampling rate does not pose a risk of saturation and back diffusion. Passive sampling devices must be deployed under chemically non-emitting weatherproof hoods to moderate the effect of local weather conditions such as solar heating, rain and strong winds, therefore passive sampling hoods were constructed in-house. The passive samplers were deployed by attaching the cartridge housing diffusive body onto the passive sample device hood and tying the hood onto a structure at approximately 1.5 m above the water surface. The first passive sampling campaign was conducted in July 2023 (winter), using the white diffusive bodies with 24-hour deployment. The second passive sampling campaign was also daily sampling, i.e. 24-hour deployment, however both diffusive body types were used, in February 2024 (summer). A final sampling campaign involved longer term sampling carried out for 96 and 196 hours, respectively, with the yellow diffusive body. The second and third campaigns were conducted simultaneously. For analyses, the Radiello® cartridges were inserted inside an empty thermal desorption tube, and they were thermally desorbed into the GC-MS. Gas phase VOC/BTEX standards are required for the effective evaluation of sorbents and for the generation of truly matrix matched calibration standards, in which the analytes of interest have been introduced onto the sorbents in the gas phase in the same manner as the samples. The LiqMix Cascade Gasmix system provides for this, as it is a dilution, calibration injection system designed for automatic generation of customized calibration gas mixtures by controlled evaporation of liquid standards and dynamic dilution/mixing thereof with one or several inert gases. The Cascade is a feature of the LiqMix that enables a second stage dilution of the gas generated by the LiqMix instrument reducing the analyte concentration down to the parts per billion level. It offers an effective way for on-site generation of gas standards for analytes that are not commercially available in cylinders, like unstable, reactive compounds or complex multicomponent gas mixtures. A BTEX standard stock solution in methanol was transferred with a gas tight syringe into a 75 mL stainless steel cylinder (an accessory of the LiqMIx) connected to the LiqMix Cascade instrument for gas phase BTEX standard preparation. Repeatability and reproducibility of the LiqMix Cascade instrument was tested by directly connecting the transfer line of LiqMix into a GC-MS. Ten repeat analyses were conducted with the LiqMix set to produce 500 ppbv and 1000 ppbv BTEX streams, followed by five repeats at 1500, 2000 and 2500 ppbv, respectively. The average %RSD for these tests was 1.60% for benzene, toluene for 3.66%, ethylbenzene for 5.58% and 4.58% for o-xylene. During analysis it was observed that, because of differences in the volatility of the BTEX components, calibration standards needed to be prepared in two batches. The first batch contained benzene and toluene where the LiqMix was set volatise at 35 OC and the second batch contained ethylbenzene and o-xylene which were volatilised at 60 OC. The LiqMix was further used to prepare gas phase BTEX standards adsorbed onto the carbon tubes, both the SKC glass tube (from active sampling) and the Radiello® cartridge. A series of standards in the 4 – 100 μg range on the SKC carbon tubes and 10 – 100 ng on the Radiello® cartridges were prepared, producing R2 values of 0.9998 for benzene, 0.9989 for toluene, 0.9994 for ethylbenzene and 0.9998 for o-xylene on the SKC carbon tubes. Linearity produced on the Radiello® cartridges was also very good with R2 values of 0.9941 for benzene, 0.9899 for toluene, 0.9917 for ethylbenzene and 0.9955 for o-xylene. A trueness test was done by adsorbing 4000 μg of BTEX gas phase standard produced by the LiqMix onto the SKC carbon tube and desorbing it into 2 mL methanol to make a 2000 mg/L BTEX standard solution. The LiqMix standard was tested against a certified 2000 mg/L standard and the mean difference between the two was 1.21 mg/L with a %RSD of 1.27% (n=5). The LiqMix Cascade instrument can thus reduce the cost of analysing ambient air for VOCs by providing on-demand gas phase standard mixtures, eliminating the high cost of buying gas standard mixtures in cylinders. This in turn will reduce the risks associated with these high-pressure gas cylinders and provide a safer alternative method for preparation of hazardous gas mixtures. The on-demand gas standard preparation offered by the LiqMix also reduces the need for storage and disposal of unused gas mixtures thereby contributing positively to safety and environmental aspects. The accurate quantification of BTEXs adsorbed during the passive sampling campaigns could be achieved by employing this matrix matched approach. Total BTEX concentrations of 0.71 – 2.37 μg/m3 across the different sampling sites were observed during the winter sampling, dominated by xylenes and ethylbenzene which made up 62 and 25% of the total BTEXs, respectively, whilst benzene and toluene contributed 8 and 5% to the total BTEX. The summer sampling campaign showed a significant reduction in the BTEX emitted, ranging between 0.31 – 0.32 μg/m3 over the two week-long sampling periods. These concentrations were again dominated by xylenes making up 75% of the total BTEXs, followed by toluene at 17%, whilst ethylbenzene and benzene both contributed 4% to the total. These concentrations were well within the Occupational Safety and Health Act limits. During the study the impact of repeated thermal desorption on the physicochemical properties of the Carbograph 4 sorbent material used in Radiello® cartridges was evaluated, focusing on surface area and pore size distribution. Nitrogen physisorption analysis showed that while the average pore diameter remained unchanged, regenerated cartridges exhibited a ±20% increase in surface area and ±15% increase in pore volume, suggesting some particle fragmentation. Despite these changes, the sorbent maintained a surface area of 157 m²/g, within the medium-strength category, indicating that mechanical integrity was preserved throughout the study. Further research is needed to determine the maximum number of regeneration cycles that can be performed without compromising VOC sampling performance. While Radiello® recommends different applications for its white and yellow diffusive bodies, this study demonstrates that white diffusive bodies can be effectively used with RAD130 cartridges for thermal desorption, provided that the sampling duration is short, ideally <24 hours. This enables rapid passive sampling in response to sporadic fugitive emissions, which may be missed by longer-term sampling with yellow bodies. The approach allows for quick detection and intervention, enhancing responsiveness in dynamic emission environments. In conclusion, this study was successful in demonstrating the efficacy of passive sampling techniques, in particular the Radiello® diffusive samplers, using either the white or the yellow diffusive bodies, in monitoring VOC/BTEX emissions at Sasol’s water treatment facility, taking cognizance of the expected concentrations during the sampling period. If the expected levels of VOCs are below 0.1 μg/m3, a longer sampling period of up to a week is required and for this the yellow diffusive bodies are ideal. On the other hand, if the expected levels of VOCs are greater than 0.1 μg/m3, samplers can be deployed for 24-hours, and the use of the white diffusive bodies can be sufficient. The LiqMix Cascade system proved to be a cost effective and reliable method for generating on-demand gas phase standards, significantly improving the accuracy and reproducibility of BTEX quantification. It is recommended that full method validation and uncertainty estimations be conducted prior to routine implementation of the developed methods. The observed seasonal variations in BTEX concentrations highlight the impact of environmental factors on VOC emissions, with winter showing higher levels compared to summer. However, all measured concentrations remained within regulatory limits, confirming the effectiveness of Sasol’s water treatment and emission control strategies. The study also showed the effectiveness of Sasol’s Water Recovery Treatment Facility in VOC abatement, where significant reduction in VOCs from the ppm levels when the reaction water is introduced to the treatment plant down to low ppb levels downstream at the holding dams. This study provides a valuable framework for future air quality monitoring initiatives, emphasizing the importance of cost-effective, sensitive, and reliable sampling techniques in industrial environments to ensure compliance with environmental regulations and protection of the health of the public as well as employees.
Using the perceptions of lecturers and students to design a spiral curriculum for a chemistry module in the academic development programme
Mosala, Tisetso Innocent (University of Pretoria, 2025)
This emergent phenomenographic study examined the additional chemistry course offered to first-year students at a research-intensive university in South Africa. The study aimed to achieve four goals: 1) to explore students' perceptions of the course, 2) to investigate lecturers' views of the course, 3) to identify how organic chemistry concepts should be structured into introductory and advanced phases within a spiral curriculum, and 4) to design a model that can guide the development of a spiral curriculum in any educational context. To address goal 1, open-ended questionnaires and semi-structured interviews were used to gather students' views on the additional chemistry course. The students’ data revealed that they valued the support provided in the course, such as tutorial sessions and collaborative learning opportunities. Moreover, students expressed that they appreciated tools like the Chirality-2 app for reinforcing concepts; however, some students reported that the organic chemistry section was taught in a fragmented way that felt rushed. Furthermore, students expressed that they were taught many organic chemistry reactions within a short period of time. As a result, many students resorted to rote memorization rather than conceptual understanding. To achieve goal 2, open-ended questionnaires and semi-structured interviews were used to collect lecturers' views of the course. The lecturers shared sentiments similar to those of the students, noting that the course attempted to cover both introductory and advanced concepts within a limited teaching period. The lecturers also pointed out that they made incorrect assumptions regarding what students had been taught in their previous first-year chemistry course. These assumptions resulted in them not including fundamental concepts such as hybridization in the additional chemistry curriculum. To achieve goal 3, the Delphi method was employed to collect the views of organic chemistry experts. The experts were asked to classify a total of 77 organic chemistry concepts from the additional chemistry course. Through the Delphi consensus-driven process, 36 concepts were identified as suitable for the introductory phase, including structure and bonding, functional groups, periodic trends, and basic isomerism. The remaining 41 concepts, such as organic reactions and mechanisms, were classified as more appropriate for teaching in the advanced phase of the spiral curriculum. This classification by organic chemistry experts provided an evidence-based categorization of concepts in the course content that supports progressive learning and enhances students' cognitive development. For goal 4, the modeling framework developed by Justi and Gilbert (2002) was adapted to design a model that could be followed in designing a spiral curriculum fit for use in any educational context. The original seven stages of Justi and Gilbert's framework were tailored to four, namely, 1) defining the purpose of the model, 2) producing and designing the model, 3) validating the model, and 4) modifying the model. The developed model was then used to design a sample spiral curriculum for an organic chemistry course, allowing for the sequential progression of concepts from foundational to advanced concepts. The study makes several contributions to teaching practice and curriculum reform. From the teaching perspective, it highlights the importance of aligning students' prior knowledge from previous courses to their current course to avoid teaching based on assumptions about knowledge that is in place. A curriculum that is responsive to student prior knowledge is necessary particularly in organic chemistry courses where most students begin without sufficient prior knowledge. The findings of the current study point to the need for horizontal curriculum alignment (Martone & Sireci, 2009), ensuring coherence between courses taught in the same academic level so that each course builds logically on the previous one. Moreover, the study highlights the value of using the student voice to evaluate and improve the curriculum. Furthermore, the study presents a transferable model for designing a spiral curriculum. This model integrates disciplinary expert views alongside the lived experiences of students and lecturers.
Flow chemistry investigations into the synthesis of donepezil, sevoflurane and Suzuki-Miyaura cross couplings
Dibokwane, Lerato Shirley (University of Pretoria, 2025-01-24)
This dissertation investigates the implementation of flow chemistry in the synthesis of active pharmaceutical ingredients (API) and translation of organic transformations, aiming to address challenges such as low process efficiency and scalability that are associated with batch manufacturing. In this research, we developed a three-step flow-based synthetic pathway for the anti-Alzheimer’s disease agent donepezil. The first step involved a selective reduction of ethyl-1-benzylpiperidine-4-carboxylate to 1-benzylpiperidine-4-carboxylate. The reduction was optimized using design of experiments (DoE) to afford full conversion of the carboxylate to form 95% of 1-benzylpiperidine-4-carbaldehyde in the product mixture with minimal over-reduction to the unwanted (1-benzylpiperidine-4-yl)methanol (5%) at -60 °C in just 2 min, a huge improvement from the batch counterpart which required 150 min at -78 °C for the same outcome. Thereafter, an aldol condensation to afford (E)-2-[(1-benzylpiperidine-4-yl)methylene]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one was optimized systematically using DoE to afford the corresponding alkene with a quantified yield of 95%. A final hydrogenation step was optimized by carefully controlling the residence time over a Pd/C packed catalyst, ensuring 90% quantified yield of donepezil after only 13.4 min while the batch hydrogenation required the use of a poisoning catalyst and a long reaction time of 240 min to achieve close to quantitative yield of the donepezil. The sequential integration of the three steps enabled the staggered continuous production of donepezil with a throughput of approximately 2.50 g h-1 and an overall isolated yield of 50%. Our research group has also been involved in the fabrication of reactors to mitigate flow chemistry challenges such as handling solids. As such, we demonstrated the application of a bespoke screw reactor for handling different complexities of solids formed during in-line HCl salt formations of amines and the recrystallizations of several α,β-unsaturated carbonyl compounds. Overall, twenty-one salt formations and nine recrystallizations were effectively conducted and of all the reactions conducted, less than 3% resulted in blockages. We also demonstrated the use of diazonium salts as coupling partners in the Suzuki-Miyaura cross coupling reaction via a heterogeneous flow set-up using 10% Pd/C as the catalyst. The 4-methylbenzenediazonium tetrafluoroborate salt and the catalyst were effectively introduced into the system as a slurry hence avoiding the dissolution of the diazonium salt in the inhibiting acetonitrile solvent. The yield of the reaction was promoted by higher equivalences of the diazonium salt (4.00 eq.), higher temperatures (80 °C) and residence times closer to 9.5 min to quantify a maximum yield of 4-methyl-1,1’-biphenyl at 76%. Lastly, we demonstrated initial proof of concept for the continuous photochemical chlorination of 1,1,1,3,3,3-hexafluoro-2-methoxypropane, an intermediate of sevoflurane, an anaesthetic. The chlorine gas used in the reaction was generated in situ from the reaction of aqueous NaOCl and HCl with yields ranging between 71 - 79%. The photochemical reaction was promoted by increasing the amount of chlorine gas at 80 °C but this was also accompanied by an increase in unidentified by-products.
Investigation of rheological and particle characterisation techniques for the optimization of accelerated stability testing of sunscreen emulsion
Makhari, Aritondaho Harriet (University of Pretoria, 2024-11-29)
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
Nokeri, Boitumelo Koketso (University of Pretoria, 2024-11)
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
Khethula, Nwabisa (University of Pretoria, 2024-11-29)
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
Futhane, Francinah Phuthi (University of Pretoria, 2024-08)
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
Manamela, Lebogang (University of Pretoria, 2024-10)
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
Malan, F.P. (Frederick) (University of Pretoria, 2017)
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).
Metal organic frameworks as electrocatalysts for CO2 reduction
Sharma, Saraswati (University of Pretoria, 2024-11)
Metal-Organic Frameworks (MOFs) have received significant attention as porous and crystalline materials with potential in gas storage, catalysis, and separation due to their high surface area, tuneable porosity, and various structural characteristics. MOFs have recently emerged as potential candidates for the electrochemical reduction of CO2, an essential process in mitigating the negative consequences of increasing atmospheric CO2 levels, which contribute to global warming, desertification, and ocean acidification. Electrochemical CO2 reduction offers an environmentally friendly approach to converting CO2 into valuable compounds such as methanol, hydrocarbons, and formic acid. In this study three MOF electrocatalysts were synthesised using a solvothermal method, these were MOF-5, Cu-BTC MOF, and Ir(III)CpCl@COMOC-4 MOF. The synthesized MOFs were characterized using various techniques; including Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and Brunauer-Emmett-Teller (BET) analysis. The XRD results revealed diffractogram patterns consistent with previously reported results for the MOFs. SEM analysis showed distinct morphologies for the MOFs. MOF-5 had a cubic morphology, Cu-BTC MOF had an octahedral morphology and Ir(III)CpCl@COMOC-4 MOF displayed irregular structure characterized by visible pores on the surface. The Cu-BTC MOF had the highest specific surface area of 634 m2/g followed by MOF-5 at 630 m2/g and lastly Ir(III)CpCl@COMOC-4 MOF at 273 m2/g. Electrochemical catalysis using cyclic voltammetry, revealed CO2 reduction capabilities across all three MOFs. The CO2 reduction process was indicated by a shift in the MOF redox peaks in the presence of CO2 with increase currents. Differential electrochemical mass spectrometry (DEMS) is required to validate the product(s) formed. The findings indicate that the MOFs show promise as electrocatalysts for CO2 reduction underscoring their potential as candidates for environmentally friendly CO2 conversion technology.
Chemical reactivity of Bushveld Igneous Complex mine residues for mineral beneficiation
Mohamed, Sameera (University of Pretoria, 2024-12-02)
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
Matoetoe, 'M'angaka C. (University of Pretoria, 1998)
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
Ndlangamandla, Simphiwe (University of Pretoria, 2019-11)
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
Van Greunen, Divan Gerald (University of Pretoria, 2019-06)
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
Van der Merwe, Petra (University of Pretoria, 2024-05)
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
Tshweu, Lesego Lovius (University of Pretoria, 2018-12)
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.

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