Electronic Theses and Dissertations (Masters)

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A comprehensive analysis of urban river pollution – the case of the Hennops river in Gauteng Province, South Africa
(University of the Witwatersrand, Johannesburg, 2023) Letseka, Thabiso Esaiah; Chimuka, L.; Richards, L.H.
The water quality of rivers is declining at an alarming rate due to pollution from anthropogenic activities associated with urbanization. To ensure ecological restoration and management of rivers, engaging in pollutant source apportionment, evaluation, and monitoring of water quality is of great significance. The study delivers a comprehensive assessment of the state of pollution in the Hennops river catchment facing pollution threats from rapid urbanization. The water quality assessment of the Hennops river was performed through chemical, microbiological, microplastics analysis and ecotoxicological approaches, spanning from upstream region in Tembisa to the downstream Hartbeespoort Dam. Standard methods were employed to assess physiochemical properties of the river’s water. Electrical conductivity and pH fell within the accepted criteria based on the standard water quality guidelines. However dissolved oxygen (DO) levels were below acceptable limits, ranging from 1.53 mg L-1 to 6.47 mg L-1. This signifies a substantial demand for oxygen in the river, likely due to the discharge of sewage from leaking pipes and wastewater treatment plants. This sewage introduces a high volume of organic matter, leading to an increased oxygen demand in the water. Microbiological pollution indicators were employed to assess the microbial water quality of the river. The study's findings revealed elevated bacterial counts, with Escherichia Coli (E. coli) reaching up to 2 250 cfu mL-1 upstream and decreasing to 30 cfu mL-1 downstream. These high counts suggest faecal contamination in the river water. Similar trends were observed with total coliform counts, high coliform counts 170 000 cfu mL-1 in the upstream which remained detectable even downstream and beyond the Hartbeespoort Dam, despite the dilution effects within the dam. The dam was identified as the primary repository for pollution originating upstream. Grab sampling followed by solid phase extraction (SPE) and the passive sampling using a Polar Organic Integrative Sampler (POCIS), were employed as sample preparation methods for preconcentration of methocarbamol, etilefrine, nevirapine, carbamazepine and venlafaxine from river water with subsequent analysis on Liquid Chromatography coupled to quadrupole time of flight mass spectrometry. Both methods yielded good figures of merit with limits of quantification in the range of 0.57 to 2.12 ng mL-1 for POCIS and 0.19 to 1.82 ng mL-1 for SPE. The compounds were detected in the water but at low levels (µgL-1 ), with detected concentrations of carbamazepine in the range 0.62 ng mL-1 – 0.32 ng mL-1 , methocarbamol detected in the range 0.11 ng mL-1 - 0.14 ng mL-1 and venlafaxine 0.50 ng mL-1 – 0.44 ng mL-1 using POCIS. The detected concentrations using SPE were in the range 0.13 ng mL-1 – 0.19 ng mL-1 for carbamazepine, while nevirapine and venlafaxine were detected although below limit of quantification. This underscores the advantage of using passive samplers, which enable the detection of fluctuating contaminant concentrations over time, in contrast to the one-time measurements obtained through grab sampling. In the case of microplastics in the water and sediment samples, five polymer types were identified: polyethylene (PE), polypropylene (PP), high density polyethylene, (HDPE), polyester and polystyrene. The predominant polymer type in surface water was PE (48.6 %), and that in sediment was PP (52.7 %). PE and PP were the most abundant polymer types in both phases, and as these also the leading polymers in plastics production. 80% of the identified microplastics were found to be fibre with most dominant sizes of 1-2 mm for sediments and 0.5-1 mm in water samples. The conducted tests deemed the river water not suitable for irrigation, drinking or recreational purposes and not capable to support aquatic life.
Carbon nitride-based catalysts for thermal carbon monoxide oxidation: Does phase matter?
(University of the Witwatersrand, Johannesburg, 2023-06) Mohamed, Ahmed Gamal Abdelmoneim; Ozoemena, Kenneth Ikechukwu; Abdullah, Aboubakr M.; Eid, Kamel
Carbon monoxide (CO) has a poisonous effect on all living organisms as it binds to the hemoglobin of blood cells, preventing oxygen uptake. Thus, the conversion of CO to less dangerous gas such as CO2 is an essential process. This work presented the utilization of carbon nitrides (C3Nx) in different phases (βgC3N4, βC3N5, βC3N6) for thermal carbon monoxide (CO) oxidation. Herein, gC3N4, C3N5, and C3N6 were prepared by pyrolysis of their amine precursors, which were doped with Fe by two distinct methods; mechanical mixing (Fe/C3Nx-M) and polymerization (Fe/C3Nx-P). The controlled preparation of Fe/gC3N4-P allowed the formation of hierarchical porous structures with high surface area (219 m2/g) compared to the Fe/gC3N4-M (77 m2/g). This enabled the ease of reactants diffusion, enhanced the electron transfer, and maximized the atomic utilization. Accordingly, Fe/gC3N4-P (T100= 245 °C) presented higher catalytic activity than Fe/gC3N4-M (T100= 291 °C). In addition, bimetallic FeTi/gC3N4-P and trimetallic FeTiCu/gC3N4-P catalysts achieved the complete conversion of carbon monoxide (CO) at lower temperatures; 175 and 147 °C, respectively, which was attributed to the enhanced reducibility, and synergistic effect of Ti and Cu. Besides, FeTi/gC3N4-P and FeTiCu/gC3N4-P showed higher catalytic activity than Pd/C commercial catalyst (T100= 198 °C). In addition, the trimetallic FeTiCu/gC3N4-P showed a stable catalytic behavior without any deactivation for more than ten hours. This study showed that the C3Nx phases worked successfully in the thermal catalytic CO oxidation. However, the gC3N4 phase is the most active one when doped with metal(s), as it offered higher crystallinity, graphitization, and thermal stability than C3N5 and C3N6. This study also paves the way for the utilization of gC3N4 as a support for different metals to be used efficiently in various thermal catalytic applications, not only CO Oxidation.
Characterization, quantification, and recovery of rare earth elements(rees) in South African coal fly ash samples
(University of the Witwatersrand, Johannesburg, 2024) Michael Rampfumedzi, Tshilidzi; Chimuka, Luke
Rare earth elements (REEs) are naturally distributed throughout the Earth's crust, typically in low concentrations. They are not typically found in isolation but are rather present in various minerals, often in amounts too minute for cost-effective extraction. Fly ash is among the sources that are deemed economically viable for extracting REEs. The objective of this study was to create environmentally sustainable approaches for measuring and reclaiming rare earth elements (REEs) in coal fly ash (CAF) samples. The study involved analyzing fly ash samples collected from various coal power stations using a range of standard and advanced techniques, including X-ray fluorescence (XRF), X-ray diffraction(XRD), scanning electron microscopy (SEM), and inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES). The XRF only shows the presence of REEs from all three fly ash samples with a range of 40 to 100 ppm and mineral oxide ranging from 0.1 to 50 %. The XRD results show that fly ash sample is a siliceous-rich sample with abundant minerals such as quartz (SiO2), magnetite (Fe3O4), and mullite (Al4.52Si1.48O9.74). The SEM analysis of the sample confirmed the presence of rare earth minerals, including monazite which is a light atomic mass (LREE), xenotime, a heavy atomic mass (HREE), and perrierite-bearing minerals. The results obtained from the instrumental analysis show that the ICP-MS instrument is the more effective analytical technique for REE analysis in this context as compared to ICP-OES. Using certified reference materials, the results obtained by two acids digestion technique, acids digestion and sodium peroxide fusion in, CGL 111, CGL 124, and AMISO276, were compared to validate whether the methods are reliable. The acid digestion approach demonstrated greater effectiveness in comparison to the sodium peroxide fusion method. The recovery percentage (%) from ICP‒MS showed an excellent percentage yield (80 – 120%) compared to the ICP‒OES instrument (50 –120%). The ICP‒MS data indicate that all fly ash samples have a high concentration of LREEs and a lower concentration of HREEs. Excellent recovery was obtained by ICP‒MS in a developed microwave acid digestion method. The concentration of REEs obtained from ICP - MS and OES in fly ash samples ranged from 50 ppm to 200 ppm for light rare earth elements and 0.5 ppm to 20 ppm for heavy rare earth elements. The total REE ( TREE) concentrations in all fly ash samples range from 400 ppm to 600 ppm
Defect–engineered lithium titanate anode materials for lithium–ion batteries
(University of the Witwatersrand, Johannesburg, 2023-10) Podile, Seromo; Haruna, Aderemi Bashiru; Ozoemena, Kenneth Ikechukwu
Energy is one of the aspects that plays a central role in moving society forward since it is one of the most important agenda of global economic and energy forums. There is an urgent need to move to clean energy given the environmental and the health benefits resulting from implementing energy systems that utilize green energy. The proposed energy sources in these systems are primarily natural (e.g. wind and solar), which means they are beyond human control and would work better if coupled with energy storage devices (ESDs). From this emerge the importance of energy storage systems (ESSs) which mostly perform based on the materials utilized to assemble the devices. In this study, we seek to enhance the power and energy densities of two of the prominent energy storage systems, namely lithium-ion batteries (LIBs) and lithium-ion capacitors (LICs), using modified commercial lithium titanate (LTO) materials as anodes. The materials consist of the pristine LTO (LTO-p), LTO coated with cerium fluoride (LTO-CeF3) and dry and wet irradiated pristine LTO (LTO-p-md and LTO-p-mw) and LTO coated with cerium fluoride (LTO-CeF3-md and LTO-CeF3-mw). Microwave irradiation was used to study the possible defect that the radiation can bring to the materials and possibly use the microwave effect to improve their electrochemistry. The effects of the coated layer of CeF3 and microwave irradiation on the structure of the commercial LTO were extensively studied using powder X-ray diffractometer (XRD), Raman spectroscopy, transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), Energy-dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA) and Brunauer-Emmett-Teller (BET) theory. Structural investigations of TEM micrographs revealed CeF3 was present on the surface of the coated LTO materials. Further analysis did show that some portion of the CeF3 coating layer was co-doped into the LTO nanostructures. The findings from XRD and XPS analyses showed that co doping promoted a mixed state of Ti3+ and Ti4+ resulting from charge compensation when Ce3+ and F possibly substituted Ti4+ and O2-. This mixed state of titanium ions allowed the materials to have high electric conductivity than the pristine LTO (LTO-p). The spectrographs obtained from XPS analysis also showed that LTO microwave irradiated materials without coating experienced the same mixed states, which may have originated from oxygen vacancies that allowed for charge compensation when some of the LTO-p Ti4+ had to turn to Ti3+. The HRTEM analysis demonstrated changes to the lattice planes spacing of the modified LTO materials and these changes supported the (111) lattice plane shifts observed in the XRD analysis. The electrochemistry of the lithium-ion battery was studied on all the materials using cycling voltammetry (CV), galvanostatic charge-discharge (GCD) and electrochemical impedance spectroscopy (EIS) techniques. From GCD technique, the results indicated that the modified materials had higher specific capacities than LTO-p at all rates under rate capability studies. All as prepared materials were stable with coulombic efficiency of almost 100% for 100 cycles using 1 C, with modified materials surpassing LTO-p specific capacity. Cycling at a high rate (5 C) for 1000 cycles, saw LTO-md, LTO-mw, LTO-CeF3 and LTO-CeF3-md having high-capacity degradation after 500 cycles. It was also observed that initial capacities were retained up to the 1000th cycle for LTO-CeF3-mw and LTO-p. With an aim of comparing LTO-p and LTO-CeF3 half cells, these two materials were further studied for lithium-ion capacitors (LICs). This choice was based on LTO-CeF3 having a better charge-discharge profile, high specific capacity and coulombic efficiency than LTO-p. The improvements resulted from the coating layer (leveraging the high ionic conductivity and chemically inert properties of CeF3) and the observed defects seen on the XPS studies created by the coating synthesis process. The LTO-CeF3 anode was paired with a carbon black cathode to construct a full LIC cell. The assembled cell produced a maximal energy density of 107.4 Wh kg 1 with an accompanying power density of 2000 W kg-1, and it yielded a power density of 10 000 W kg -1 with an energy density of 61.8 Wh kg -1.
Design and synthesis of triazine derivatives as non-nucleoside reverse transcriptase inhibitors
(University of the Witwatersrand, Johannesburg, 2024) Munetsi, Wendy; Bode, Moira; Ngwira, Kennedy
This research work was carried out to investigate the properties of different groups that can be used to modify the triazine core with the aim of designing a new library of possible HIV non- nucleoside reverse transcriptase inhibitors (NNRTIs). Triazine derivatives have been used extensively in the synthesis of numerous classes of drugs due to their significant biological activity. In this project, the specific focus was to synthesize 1,3,5-triazine derivatives by successive nucleophilic substitution reactions of the Cl atoms from cyanuric chloride. In the first step of the substitution reactions, 2,4,6-trichloro-1,3,5-triazine was reacted with various anilines, phenols and thiophenols which acted as nucleophiles to displace one of the Cl atoms upon reaction completion. The yields varied from 28% -90% with the best yields being observed when the anilines were used as a nucleophile and most of the substituents in this first step were anilines. The substituents used at each step of the substitution were vital in terms of determining the order of the reaction to enable a successful reaction. The introduction of different linkers to the triazine core such as -NH, -S, -O yielded compounds with different properties expected to provide significant interactions in the NNRTI binding pocket. We expected better binding properties from the -NH bearing compounds due to hydrogen bond formations with amino acid residues inside the allosteric binding pocket of the HIV-1 RT. The success of the second step of the substitution reactions was identified to be dependent on the substituent attached to the triazine ring from the first step. Some reactions were not successful when a stronger nucleophile was used in the first step and a weaker nucleophile was being used as the incoming nucleophile substituting the second Cl atom. Therefore, these reactions were repeated and the order of the reaction rearranged. Temperatures were increased and reaction times were increased at this stage as the reactivity of the triazine ring was reduced and therefore higher kinetic energy was required for successful reactions. In general, the synthesized triazine derivatives bearing two aromatic substituents exhibited the most significant presence of tautomers. The final stage in the synthesis of the trisubstituted triazine derivatives was relatively complex and required much higher temperatures and longer reaction times. The reactions were also performed at smaller scales and difficulties with the purification processes also contributed to the loss of product thereby resulting in lower yields, with one of the compounds giving a yield of 11%. The results obtained from the anti-HIV assay studies from the selected compounds tested, showed that antiviral activity was observed in triazine derivatives with electron withdrawing groups attached to the aromatic substituent as well as -NH and -O linkers at the right and left wing of the triazine core, respectively.
Determination of U and Th Radioisotopes in environmental samples by ICP-QMS
(University of the Witwatersrand, Johannesburg, 2023-07) Rikhotso, Xikhongelo Valentia; Sehata, James; Chimuka, Luke
Not Available
Development of a Commercial Manufacturing Process of 9-[(R)-2- (phosphonomethoxy)propyl] adenine (PMPA): A Key Intermediate for the Production of Tenofovir-based HIV Medicines
(University of the Witwatersrand, Johannesburg, 2023) Mbutho, Banele; Gohain, Mukut; De Koning, Charles
South Africa runs the largest antiretroviral (ARV) program in the world and yet 99% of the active pharmaceutical ingredients (APIs) used to make ARVs are imported from China. Dependence on imported APIs has major cost implications and influences the medication’s security of supply. This project was concerned with making it possible to produce the APIs tenofovir, a precursor for tenofovir disoproxil fumarate and tenofovir alafenamide locally and at a lower cost. A new synthetic route recently introduced by Medicines 4 All (M4ALL) was studied and used in this dissertation. The four-step process that produces an adenine derivative was optimized and scaled into a commercial industrial process producing tenofovir intermediates in repeatable yield and purity. This route was determined to be the most cost-effective since it utilized low cost and commercially available diaminomaleonitrile and triethyl orthoformate as starting materials—contrary to the synthetic routes currently used by the 17 largest tenofovir manufacturers. Key process improvements included a decrease in the number of solvents used and the minimization of by-product formation. Results showed that high yields of tenofovir intermediates were successfully synthesized using this new route. As such, the chemical company we conducted this research in, Chemical Process Technology Pharma will be able to employ this synthetic methodology to affordably produce the APIs used in the manufacturing of ARVs locally improving access to affordable medication.
Diastereoselective conjugate addition reactions using diverse nucleophiles on a variety of Morita-Baylis-Hillman (MBH) adducts
(University of the Witwatersrand, Johannesburg, 2023-09) Bhom, Nafisa; Bode, Moira L.
The Morita-Baylis-Hillman (MBH) reaction involves the formation of a new carbon-carbon bond, generating an MBH adduct. These MBH adducts are multi-functional molecules, which can be used as synthons for the generation of complex and diverse compounds. The first part of the work described here involved the synthesis of a series of diverse ester and nitrile MBH adducts obtained as racemic mixtures. The MBH adducts were protected using different protecting groups, which could potentially control the diastereoselectivity and the formation of alternative products in the subsequent conjugate addition reaction. Conjugate addition reactions were performed on the protected MBH adducts using different nucleophiles to obtain the product as diastereomers. These reactions were monitored to detect whether diastereomers were obtained or not. The diastereomeric ratios obtained using different substrates, protecting groups and nucleophiles were determined. The best diastereomeric ratio was 3:1, obtained for the piperidine and benzylamine addition on the TBDMS protected nitrile adducts 192a/b and 196a/b. The addition of sulfur nucleophiles gave the conjugate addition product only and the addition of nitrogen nucleophiles gave both conjugate addition and allylic substitution products. It was found that the protecting groups did not have an effect on the diastereomeric ratio obtained, nor on the formation of alternative products. The last step performed in the sequence was the deprotection of the conjugate addition products. The configuration of the major and the minor diastereomers were determined, the major product was assigned as the syn diastereomer. The major:minor diastereomeric ratio for compound 208a/b was 3:1 and for compound 209a/b, a ratio of 2:1 was obtained. The next part of the work involved the synthesis of MBH adducts with amide as the electron withdrawing group. The originally proposed route involved the synthesis of MBH esters and their conversion into amides. The conjugate addition reactions were attempted on these amide adducts, but were unsuccessful. A number of alternative routes were attempted for the synthesis of amide adducts and conjugate addition products resulting from these adducts. From all the alternative routes, the best route was the originally proposed route.
Fabrication of polyaniline/indium oxide /onion-like carbon ternary nanocomposite for room tempera ture gas sensing applications
(University of the Witwatersrand, Johannesburg, 2022-08) Mathe, Boipelo Nicholette; Linganiso, E.C; Tetana, Z; Moma, J
Monitoring and documenting chemical stimuli or environmental fluctuations is vital to daily health care and environmental monitoring. This objective can be accomplished through the development of high-performance sensors able to detect toxic gases such as ammonia, volatile organic compounds (VOCs) and many more. The modification of carbon nano-onions with metal oxides/conducting polymer could enhance sensing performances at room temperature. This research focuses on the development of a flexible room temperature gas sensor for ammonia sensing with a sensing layer composed of indium oxide (In2O3)/onion-like carbons (OLCs)/ polyaniline (PANI). The current sensors were tested at a 40-45 percentage humidity. Polyaniline was produced utilizing the rapid polymerization technique with aniline and ammonium persulfate as precursors. Carbon nano-onions were obtained by the flame pyrolysis process with candle wax as the carbon source. The present study compared two microwave-assisted solution-phase methods for the synthesis of indium oxides. The first methods produced indium hydroxide (In(OH)3) followed by its conversion to In2O3 through annealing at 400 oC, and the second used a one-step method where ethanol was used as a solvent instead of water. Different reaction times were used to determine the effect of microwave power on the indium oxide formed through a solution-phase method, and several characterizations techniques were performed to characterize the products, including transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscopy, Brunauer-Emmett-Teller, X-ray photoelectron spectroscopy and Ultraviolet-visible spectroscopy. The ternary In2O3/PANI/OLCs nanocomposite was fabricated using physical mixing by adding varying amounts of In2O3 to fixed quantities of PANI and OLCs. Using gold-plated interdigitated electrodes (IDEs) embedded on a printed circuit board (PCB) substrate, inexpensive and room temperature functional sensors based on plain PANI, OLCs, OLCs/PANI, and OLCs/PANI/In2O3 were developed. The sensors based on ternary composites outperformed of sensors based on pure PANI, OLCs, and PANI/OLCs, due synergic effect of PANI, OLCs and In2O3 when combined. The sensor with the highest response among the sensors with the ternary nanocomposite as the sensing layer, was chosen for further evaluations of recovery time, reaction time, repeatability, and selectivity. The sensor containing (4.6 mg) B-In2O3/PANI/OLCs was particularly responsive to ammonia in comparison to other analytes (hexane, isopropanol, acetone), with the response and recovery durations of 2.2 minutes and 4.3 minutes, respectively, spanning a concentration range of 25 ppm to 125 ppm. Current results showed that In2O3 materials can be successfully applied in room temperature gas sensing application and further enhance the sensing response to levels that cannot be obtained when using PANI or OLC individually.
Geochemical Investigation Into Holocene Palaeoenvironmental Change Along The Southern Cape Coast, South Africa
(University of the Witwatersrand, Johannesburg, 2023-06) Dyubele, Viwe; Quick, Lynne; Humphries, Marc
Climatic conditions across southern Africa are affected by the complex interaction of different atmospheric and oceanic circulation systems, the understanding of which is important to predicting future climate change. Palaeoenvironmental reconstruction is an essential tool to understand long-term environmental change and the response of ecosystems to such changes. This study examines the geochemical composition of a sediment core (WR1-1) extracted from a freshwater wetland located near Plettenberg Bay on the southern Cape coast. The wetland is located ~4 m above present sea level and positioned ~500 m from the modern coast. Situated within the year-round rainfall zone, the site is influenced by tropical easterly flow and the southern westerlies. Elemental and stable isotope geochemistry are used to reconstruct the palaeoenvironmental change at the site over the last ~8000 cal yr BP. Variations in CaO/Al2O3, Sr/Al2O3 and δ13C indicate that marine conditions dominated from 7300 to 6400 cal yr BP. Marine influence at the site decreased dramatically from ~6300 cal yr BP, as the system transitioned to a freshwater back-barrier wetland. Enrichments in SiO2/Al2O3 and Zr/Al2O3 track changes in depositional energy and suggest that the period 3800 – 3200 cal yr BP was associated with increased aeolian activity. This is interpreted to reflect increased aridity and is consistent with geochemical and pollen records from nearby sites at Eilandvlei and Voëlvlei. This suggests that a shift to more arid conditions during this time was a broad feature of the climate in the year-round rainfall zone of South Africa. The timing of this event corresponds with a marked decrease in Antarctic sea ice and pronounced aridity along the east coast of South Africa, suggesting that mid to late Holocene aridity in the YRZ was likely driven by declines in moisture from both westerly and easterly wind systems.
Imputation of missing values and the application of transfer machine learning to predict water quality in acid mine drainage treatment plants
(University of the Witwatersrand, Johannesburg, 2024) Hasrod, Taskeen
Access to clean water is one of the most difficult challenges of the 21st century. Natural unpolluted water bodies are becoming one of the most dramatically declining resources due to environmental pollution. In countries like South Africa which has a mining-centred economy, toxic pollution from mine tailing dumps and unused mines leach into the underground water table and contaminate it. This is known as Acid Mine Drainage (AMD) and poses a grave threat to humans, animals and the environment due to its toxic element and acidic content. It is, therefore, imperative that sustainable wastewater treatment procedures be put in place in order to decrease the toxicity of the AMD such that clean water may be recovered. An efficient circular economy is created in the process since original wastewater can be recycled to not only provide clean water, but also valuable byproducts such as sulphur (from the elevate sulphate content) and other important minerals. Traditional analytical chemistry methods used to measure sulphate are usually time-consuming, expensive and inefficient, thereby, leading to incomplete analytical results being reported. To address this, this study aimed at imputing missing values for sulphate concentrations in one AMD treatment plant dataset and then using that to conduct transfer learning to predict concentrations in two other AMD treatment plants datasets. The approach involved using historical water data and applying geochemical modelling as a thermodynamical tool to assess the water chemistry and conduct preliminary data cleaning. Based on this, Machine Learning (ML) was then used to predict the sulphate concentrations, thus, addressing limited data on this parameter in the datasets. With complete and accurate sulphate concentrations, it is possible to conduct further modelling and experimental work aimed at recovering important minerals such as octathiocane, S8 (a commercial form of sulphur), gypsum and metals. Historical data obtained from the three AMD treatment plants in Johannesburg, South Africa (viz., Central Rand, East Rand and West Rand) were obtained and the larger Central Rand dataset was split into smaller untreated AMD (Pump A and Pump B) subsets. Thermodynamic and solution equilibria aspects of the water were assessed using the PHREEQC geochemical modelling code. This served as a preliminary data cleanup step. Eight baseline as well as three ensemble machine learning regression models were trained on the Central Rand subsets and compared to each other to find the best performing model that was then used to conduct Transfer Learning (TL) onto the East Rand and West Rand datasets to predict their sulphate levels. The findings pointed to a high correlation of sulphate to temperature (°C), Total Dissolved Solids (mg/L) and most importantly, iron (mg/L). The linear correlation between iron and sulphate substantiated pyrite (FeS2) as their source following weathering. Water quality parameters were found to be dependent on factors such as weather and geography this was evident in the treated water that had quite different chemistry to that of the untreated AMD. Neutralisation agents used were based on those parameters, thus, further delineating the chemistry of the treated and untreated water. The best performing ML model was the Stacking Ensemble (SE) regressor trained on Pump B’s data and combined the best performing models namely, Linear Regressor (LR), Ridge Regressor (RD), K-Nearest Neighbours Regressor (KNNR), Decision Tree Regressor (DT), Extreme Gradient Boosting Regressor (XG), Random Forest Regressor (RF) and Multi-Layer Perceptron Artificial Neural Network Regressor (MLP) as the level 0 models and LR as the level 1 model. Level 0 consisted of training heterogenous base models to obtain the crucial features from the dataset. These individual predictions and features were then fed to a single meta-learner model in in the next layer (level 1) to generate a final prediction. The stacking ensemble model performed well and achieved Mean Squared Error (MSE) of 0.000011, Mean Absolute Error (MAE) of 0.002617 and R2 of 0.999737 in under 2 minutes. This model was selected to be used for TL to the East Rand and West Rand datasets. Ensemble methods (bagging, boosting and stacking) outperformed individual baseline models. However, when comparing stacking ensemble ML that combined all the baseline models with stacking ensemble ML that only combined the best performing models, it was found that there was no significant improvement in excluding bad models from the stack as long as the good models were included. In one case, it was actually beneficial to include the bad performing models. All models were trained in under 2 minutes which proved the benefit of using ML approaches compared to traditional approaches. The treated water data was highly uncorrelated such that model training was unsuccessful with the highest achievable R2 value being 0.14, thus, no treated water model was available for TL. TL was successfully conducted on the cleaned and modelled East Rand AMD dataset using the Central Rand (Pump B) stacking regressor and a high level of accuracy with respect to Mean Square Error (MSE), Mean Absolute Error (MAE) and R2 (MSE:0.00124, MAE:0.0290 and R2:0.963) between the predicted and true sulphate values was achieved. This was achieved despite a marked difference in the distributions between the Central Rand and East Rand datasets which further proved the power of utilizing ML for water data. TL was successful in imputing missing values in the West Rand dataset following prediction of sulphate levels in the cleaned and modelled West Rand AMD and treated water datasets. No true values for sulphate levels in the West Rand dataset were given, as such, accuracy comparisons could not be made. However, a general baseline idea of the amount of sulphate present in the West Rand treatment plant could now be understood. The sulphate levels in all three treatment plants (Central Rand, East Rand and West Rand) were found to greatly differ from each other with the Central Rand having the most normal distribution, the East Rand having the most precise distribution and the West Rand having the most variable distribution. Whilst the sulphate levels in the treated effluent waters could not be reliably predicted due to inherent issues (e.g., analytical inaccuracies and inconsistences) and poor correlations within the treated water datasets, sulphate levels in all three of the untreated AMD datasets were successfully predicted with a high degree of accuracy. This underpinned the observation made previously about the discrepancies between treated and untreated water. The study has shown that it is possible to impute missing values in one water dataset and use transfer learning to complete and consolidate another similar, but scarce, dataset(s). This approach has been lacking in the water industry, resulting in the reliance and use of traditional methods that are expensive and inadequate. This has caused water practitioners to abandon scarce datasets, thus, losing potentially valuable information that could be useful for water remediation and recovery of valuable resources from the water. As a spin off from the study, it has been indicated that automation of such data analysis is possible. This was achieved by developing a Graphical User Interface (GUI) for ease of use of the SE-ML model by those with little to no programming background nor ML knowledge e.g., the laboratory staff at the AMD treatment plants. This can also be used for teaching purposesin academia.
Investigation of rhombohedral 𝑩𝒊𝟐𝑶𝟑 as an oxide conducting electrolyte for solid oxide fuel cell applications
(University of the Witwatersrand, Johannesburg, 2023-09) Kerspuy, Tanner Royele Rowan; Billing, Caren; Erasmus, Rudolph M.; Billing, Dave Gordon
The synthesis of a bismuth system co-doped with neodymium (Nd3+) and yttrium (Y3+) was at the core of this project. The focus was placed on the synthesis of the rhombohedral phase of bismuth oxide, which has not been observed in pure bismuth oxide. Neodymium was selected as the main dopant (the one used in highest dopant concentration), due to its Shannon ionic radii. Upon doping with Nd3+ as a single dopant, it is observed that a mixture of the rhombohedral and monoclinic phases is obtained, thus noting that the single dopant system using Nd3+ does not stabilise the rhombohedral phase. When using a co-doped system of 15 mol % Nd3+ and 5 mol % Y3+ (15Nd5YSB), it is observed that we are able to obtain a stable phase pure rhombohedral phase, with a total dopant concentration of 20 mol%. The total dopant concentration % ranges selected ranged between 8.5-10 mol %, 20 mol % and 22.5 mol %. The Rietveld refinement of the X-ray diffraction data obtained for both the laboratory and synchrotron-based techniques indicate sample phase purity and phase stability for the samples under investigation. The refinements obtained for the samples indicated that not only one structure model was used to fit the experimental data. The structural models which fit the Rietveld refinements of the experimental data resulted in the observation of pure phase and mixed phase rhombohedral samples being observed. The Nd0.15Y0.05-Bi2O3 (15Nd5YSB)sample resulted in a phase pure rhombohedral structural model. Hereafter all samples will be referred to with the shorthand notation. The thermal analysis techniques are used to indicate the thermal dependence of the samples, this analysis also indicated phase stability across the temperature range of investigation as no phase transitions occurred throughout the heating and cooling cycles, and minimal weight loss is observed. The samples of importance in this study were the 12.5Nd10YSB sample which obtained a conductivity of 2.4511×10-5 S.cm-1 at 500 ℃, and the 15Nd5Y2.5TbSB sample which obtained a conductivity of 2.1725×10-5 S.cm-1 at 500 ℃. The Arrhenius plots obtained indicated stability 3 of these samples across the 200-500 ℃ temperature range with no discontinuities, which suggests no phase transitions, or order-to-disorder transitions. Variable temperature Raman spectroscopy indicated that the behaviour for all the samples analysed using Raman spectroscopy is consistent, however, a deviation was observed for the 15Nd5Y2.5ScSB sample which has a distinctive spot which exhibits different Raman shift behaviour as compared to all other samples. The VT-Raman spectroscopy spectra indicate a distinctive signature Raman peak at ~250 cm-1, which can be concluded to be the Raman peak which is indicative of the rhombohedral 𝐵𝑖2𝑂3, this peak also appears in the low cubic phase % sample after cooling back to room temperature. This assignment of the Raman spectral peak is confirmed through this peak being evident throughout all the spectra obtained and it being consistent throughout all the spectra observed.
Magnetic enhancement of a high entropy spinel oxide electrocatalyst for rechargeable zinc-air batteries
(University of the Witwatersrand, Johannesburg, 2024) Hechter, Ernst Heznz; Ozoemena, Kenneth
The exploration of high entropy materials (HEMs) as electrocatalyst materials has only recently begun to accelerate. Similarly, the effect of magnetic fields on the oxygen evolution and reduction reactions has recently begun to attract great interest. In this work nanoparticles of the high entropy oxide (CuCoFeMnNi)3O4 were synthesized and supported on Vulcan carbon for use as a bifunctional OER/ORR catalyst in a rechargeable zinc-air battery (RZAB). The products were characterized to confirm and investigate the solid solution high entropy phase, and the electrochemistry was investigated with and without an external magnetic field. The HEMs demonstrated moderate intrinsic electrochemical properties, with overpotentials and current densities comparable to commercial platinum on carbon catalysts even at low loadings. Here is reported the most significant magnetic enhancement in RZAB power profile in literature at the time of writing, as well as improved RZAB stability and areal energy. This work offers insight into the mechanism of magnetic enhancement in the case of high entropy materials, and pioneers the use of combined strategies to achieve stable, cost-efficient and effective bifunctional OER/ORR electrocatalysis.
Manganese-Rich Nickel-Manganese-Cobalt Oxides as Hybrid Supercapacitor Electrode Materials
(University of the Witwatersrand, Johannesburg, 2023-09) Tshivhase, Funanani; Ozoemena, Kenneth Ikechukwu
Fossil fuels used as the conventional energy source play a substantial negative role in climatic changes and global warming. Their reservoirs on earth keep getting constrained, thus limiting their reliability. These issues make renewable energy sources an excellent alternative due to their abundance, environmental safety, affordability, and renewability. However, renewable energy is subjected to geographic limitations, and some sources are intermittent, which can be solved by applying energy storage devices. Asymmetric hybrid supercapacitors are an excellent choice due to the safety of aqueous electrolytes, exploitation of abundant metals in the metal oxides used, improvement of power and energy density and simple assembly and application. In this work, manganese-rich nickel-manganese-cobalt (MR-NMC) was studied and applied in asymmetric hybrid supercapacitors as a cathode material, and reduced graphene oxide (rGO) was used as an anode. Synthesis was done using co-precipitation-(Conv), laminar Taylor vortex flow reactor-(Lam), and microwave irradiation-(MW) approaches. Physical characterization was performed using XRD and TEM. Electrochemical studies were done using CV, GCD and EIS. Three full cells/two electrode systems were assembled and studied. Those cells were rGO//Conv MR-NMC, rGO//Lam MR-NMC and rGO//MW MR-NMC. The data obtained from electrochemistry tests was used for the calculations of specific capacitance, energy and power densities. rGO//MW MR-NMC cell had the highest specific capacitance response compared to rGO//Conv MR-NMC and rGO//Lam MR-NMC over the entire current density range used, where at the current density of 0.2 A g-1, rGO//MW MR-NMC had 44.77 F g-1, followed by rGO//Lam MR-NMC with 15,89 F g-1, then rGO//Conv MR-NMC with 13.68 F g-1. There was no significant difference in the specific capacitance responses of rGO//Conv MR-NMC and rGO//Lam MR-NMC. rGO//MW MR-NMC also exhibited higher energy density for the entire range of power density over rGO//Conv MR-NMC and rGO//Lam MR NMC. At the power density of 678,08 W kg-1, rGO//MW MR NMC had a specific energy density of 65 Wh kg-1, followed by rGO//Lam MR NMC with 23.45 Wh kg-1, then rGO//Conv MR-NMC with 19.82 Wh kg-1. Overall, the electrochemistry and the calculated perimeters thereafter showed that microwave irradiation is a reliable approach that can be used in the preparation of metal oxides used in energy storage devices for the improvement of electrochemical performance, which potentially enables the commercialization of these systems and management of energy crisis in South Africa, Africa and the world as a whole, hence the rGO//MW MR-NMC material performed better than the other two.
Metal Pincers as Antiviral Agents Targeting SARS-CoV-2 Spike Protein
(University of the Witwatersrand, Johannesburg, 2023-08) Bracken, Matthew Lee; Munro, Orde Q.
The purpose of this work was to prove the concept that complexes of bioavailable metal ions may be designed to target specific solvent-exposed amino acid residues on therapeutic protein targets. The complexes synthesized and studied were novel Zn(II) and Cu(II) NNN amide pincers. The chelates were designed by in silico methods to target solvent-exposed tyrosine residues on the receptor binding domain of SARS-CoV-2. These tyrosine residues are crucial for binding host cell receptors and by targeting these groups, the metal pincers may potentially act as antiviral fusion inhibitors for the treatment of COVID-19. Biophysical studies were carried out to determine the binding affinity between the chelate and phenolic residues. These studies identified the most likely binding site for the metal complex on the SARS-CoV-2 spike protein epitope. The novel chelates were crystalized and found to adopt hexameric metallocycle architecture.
Reconstructing Late Quaternary environmental change on the southern Cape coast of South Africa: A 30,000-year geochemical record from Pearly Beach
(University of the Witwatersrand, Johannesburg, 2023-11) Mey, Rachel Tess; Humphries, Marc; Quick, Lynne
The southern Cape coast of South Africa has undergone complex and dynamic climate changes due to its position at the boundary of major atmospheric and oceanic systems. However, climate changes that occurred in the region during the Last Glacial Maximum (30,000 – 18,000 cal yr BP) and the deglaciation period that followed (18,000 – 11,000) are still not fully understood. Climatic change along the southern Cape coast is of archaeological, cultural and environmental significance given the ecological diversity and hominin fossil, richness of the region. Moreover, predictions of future climate change and water scarcity management issues in the southern Cape make it vital to understand and response to future climate scenarios. To address this gap, this study investigated the geochemical composition of a 5.42 m sediment record (KSV 1) extracted from a freshwater coastal wetland near Pearly Beach on the southern Cape coast. The wetland, situated in the winter rainfall zone, is influenced by the southern westerly storm track, the South Atlantic anticyclone, and Agulhas-Benguela interactions, making it an ideal location to investigate changes to large-scale atmospheric and oceanic circulation systems. Using a combination of inorganic elemental (X-ray fluorescence, XRF) and stable carbon isotope (δ13C) analysis, this study presents a 30,000 year record of palaeoenvironemental change from Pearly Beach and considers these in relation to broad-scale climatic perturbations that occurred in southern Africa over this period. A chronology for the core was derived from radiocarbon dating of 8 bulk sediment samples. Sedimentation rates over the record averaged 0.02 cm/yr, giving the XRF analyses which were conducted at 2 cm intervals, an average temporal resolution of ~ 110 years. Sediments deposited 30,000 – 15,000 cal yr BP consist primarily of quartz-rich (60 – 90% SiO2) silt and fine sand with relatively low quantities of clay material. An increase in the relative proportion of Al2O3 from ~15,000 cal yr BP, coupled with a rise in sedimentation rate, marks an increase in the accumulation of fine-grained material within the wetland that is associated with a rise in global sea levels following deglaciation. A distinct shift to higher δ13C values around this time points to a change in vegetation community, with an increase in contribution from C4 drought-tolerant plants. The presence of calcium carbonate in sediments provides a strong indicator for marine intrusions at site and a pronounced increase in marine influence is inferred from ~8,500 cal yr BP, corresponding with the stabilisation of sea levels near to present-day levels. Variations in elements typically associated with heavyminerals (titanium and zirconium) are used to infer changes in depositional energy at the site. Enrichments in Ti and Zr suggest a period of enhanced transport energy between 18,800 and 14,500 cal yr BP. This is coupled with an increase in the Si/Al ratio and linked to enhanced aeolian activity. An increase in wind intensity during this period is attributed to the intensification in the Southern Hemisphere westerly winds at this time. This corresponds with available fossil pollen records, which suggest an increase in moisture at Pearly Beach 18,500 to 15,000 cal yr BP that was possibly linked to a slowdown in the Atlantic Meridional Overturning Circulation (AMOC) and build-up of heat in the southeast Atlantic. It is possible that a build-up of heat in the southeast Atlantic brought on by a slowdown in the AMOC increased moisture uptake in the frontal storms, resulting in stronger low-pressure systems and intensified storms, as reflected in the KSV-1 record. Comparisons with other records from South Africa, including Mfabeni, Cold Air Cave and Cango Caves, indicate that the central and eastern parts of the country experienced a cooling event ~18,500 and 14,500 cal yr BP. New geochemical data from Pearly Beach suggests that this cooling may have been linked to intensification of westerly winds at this time. An apparent lag effect in the warming of South Africa after deglaciation may be attributed to the enhanced influence of westerly winds during the glacial-interglacial period, which pushed cold air masses across the interior of the country. The complex interplay between local sea level changes, westerly wind dynamics, and regional climatic conditions underscores the significance of the geochemical record from Pearly Beach in understanding past environmental changes and their broader implications for southern Africa.
Synthesis and characterization of nitrogen-doped hollow carbon spheres/ Cu2S composites for potential application as counter electrodes in dye sensitized solar cells
(2022) Majola, Thelma
Current solar cells have disadvantages that include weather dependency and high manufacturing costs. Dye-sensitized solar cells (DSSCs) have emerged as possible solutions for these drawbacks. Since it is predicted that the global warming effect will result in the sun emitting less energy. DSSCs have the added advantage of working in low-light conditions, and the ability to harness light energy from other devices. Although DSSCs have low production costs, their low efficiency due to the platinum (Pt) electrocatalyst limits their commercial implementation. DSSCs are made up of many components including dye, and counter electrode (CE). Modifications can be made on these components to improve efficiency and make the DSSC more eco-friendly. For instance, CE research has focused on finding substitute electrocatalysts. In this study copper sulfide (Cu2S) and hollow carbon spheres (HCSs) have been considered as viable substitutes for Pt since they exhibit good electrocatalytic properties. Carbon materials have corrosion resistance towards iodine, and Cu2S has superior oxidation resistance. Therefore, they can be used for electrolyte redox reactions at the CE in a DSSC. The properties of HCSs can be enhanced by making the carbon shell porous, increasing the number of carbon shells, or by doping the carbon shell with heteroatoms such as nitrogen (N). These modifications can improve the conductivity, surface area, adsorption, and electronic properties. For this research porous nitrogen doped single-shelled and double-shelled HCSs were synthesized. To prepare the HCSs, a carbon shell was coated on the surface of the mesoporous silica spheres using the chemical vapour deposition method (CVD) with acetylene or toluene as carbon precursors at 900 °C for 1 h. Thereafter, the silica template was etched using 10 % HF at room temperature for 24 h. It was found that toluene produced HCSs with a higher surface area. Unexpectedly, the double-shelled HCSs were found to exhibit low surface areas than the single-shelled HCSs. Nitrogen doping improved the properties of both the single and double-shelled HCSs. The nitrogen-doped, single-shelled mesoporous hollow carbon spheres (N-HCS) showed better properties for electrocatalysis than the double-shelled HCSs. The Cu2S nanoparticles were prepared using colloidal synthesis at 230 °C for 1 h with oleylamine (OLA) as the surfactant and 1-dodecanethiol (1-DDT) as the sulfur source. Different copper precursors were used which gave Cu2S with varying compositions. Both precursors produced particles with a hexagonal morphology, however, copper (II) acetylacetonate (Cu(acac)2) produced smaller particles (30 nm) compared to large particles (479 nm) from copper chloride (CuCl). A time study on the different copper sources showed a variance in nucleation and particle growth. The Cu2S-HCS composites were prepared using OLA as the surfactant, with different percentages of Cu2S and HCSs. The different composition mixtures were heated to 100 °C and then washed to remove the unreacted elements. The synthesized materials were analyzed using various techniques. TEM showed the spherical morphology of HCSs, the hexagonal morphology of Cu2S, and the successful formation of the composites. The surface area and porosity of the materials were measured using the BET technique. Graphitization of carbon and the phase composition of Cu2S was analyzed using PXRD. The successful incorporation of N within the structure of the N-HCSs was confirmed using XPS. The electrocatalytic activities of the composites were investigated using CV,EIS, Tafel polarization, I-V and compared to Pt under similar conditions. The 75 wt% N-HCS: 25 wt% Cu2S composite had higher current density, lower peak-to-peak separation, and high electrochemical double layer capacitive current, good adhesion to the FTO glass and great photovoltaic performance compared to Pt. This suggests that it was the better performing composite and has the potential to substitute Pt- CE in DSSCs.
Synthesis and characterization of novel short antimicrobial peptides with wound healing properties
(University of the Witwatersrand, Johannesburg, 2019) Machumele, Khanani Peggy; Makatini, Maya Mellisa
In recent years, there has been an increasing health crisis due to multidrug-resistant microbes. These pathogens are strains of bacteria that have become resistant to antibiotic drugs. In the year 2016, the World Health Organisation (WHO) had appealed to the members of states in the USA to create a priority list of other bacteria that are resistant to antibiotics in order to support research and development of effective drugs. According to literature, antimicrobial peptides have the potential to be potent agents against pathogens that have multidrug-resistant properties. Despite these studies, there are still substantial limitations (toxicity and susceptibility to proteases) that have affected their clinical and commercial development. In this study, the focus was on bacteria that infect wounds. The lack of potent chronic wound treatment has resulted in an enormous financial and physical burden on patients and the health care system. The stress of multi-resistant microbes heighten the challenges plagued on a patient due to untreatable infected wounds. Peptides which are able to kill bacteria and promote the wound healing process would greatly benefit patients. For example, patients with diabetic foot ulcers are prone to chronic wounds because of their condition, which may lead to amputation. Wound healing antimicrobial peptides are able to kill bacteria in the wound and induce the formation of collagen which will result in fewer amputations. The aim of this proposed research is to develop novel wound healing and antimicrobial compounds by derivatizing bioactive peptides into selective and protease-stable peptidomimetics. Tigerinin RC1 is an antimicrobial peptide with wound healing properties. It was chosen as a starting point for the design of analogues with drug-like properties and it was also conjugated to silver nanoparticle (AgNPs) to improve its bactericidal activity. In this study, 16 Tigerinin RC1 peptide analogues were successfully synthesized using the solid phase peptide synthesis strategy. Peptides were purified using the semi prep-HPLC however, the desired purity of > 90% was only achieved after two or more purification runs. Thus only 4 of the peptide analogues had a purity great than 90% which were KM-PEP-carb, KM-PEP-cyc-amide, KM-PEP-ada and KM-PEP-CT. These peptides were tested for antimicrobial activity and KM-PEP-cyc-amide peptide showed promising results with the minimum inhibitory concentration of 128 μg/ml against P. aeruginosa. Cytotoxicity studies also revealed that conjugation of KM-PEP-carb to AgNPs improved cytotoxicity because when 25 μg/ml of KM-PEP-carb was tested against human T cells the cell viability was -1.48% and when conjugated to AgNPs the cell viability increased to 35.17.
Tailored Fabrication of MXene/Chitosan Nanocomposites as Efficient Adsorbents for Heavy Metals Removal from Wastewater
(University of the Witwatersrand, Johannesburg, 2023-08) Ibrahim, Yassmin Ahmed Ismail; Eid, Kamel; Ozoemena, Kenneth Ikechukwu
MXene (Ti3C2Tx) has been extensively utilized in water purification systems, including toxic metal ions removal, owing to the unique layered structure and abundant oxygen surface groups. However, challenges such as aggregation and solubility of Ti3C2Tx nanosheets in water have prompted the need for innovative strategies. In this study, we introduce a i3C2Tx-incorporated chitosan matrix (MX/CS) adsorbent designed to address solubility concerns during water treatment. MX/CS adsorbents are tested towards the capture of “cadmium” (Cd 2+) and “Zinc” (Zn2+) ions in aqueous solutions at varied pH values (i.e., acid, neutral and alkaline), initial ions concentrations (25, 50 and 100 ppm), and varied Ti3C2Tx loading (i.e., 1, 5 and 10), to study the optimization adsorption parameters. In addition, the Ti3C2Tx nanosheets were activated/alkalinized at ratio (2:1, i.e., 2MX:OH/CS), where more negative-ions sites are provided, thus, enhancing the preferential sorption for heavy metal ions in terms of high adsorption capacities, and kinetics than the non-activated samples (MX-10/CS). Freundlich isotherms are predominated for the Cd2+ and Zn2+ ions adsorption on both adsorbents. A selectivity study reveals that Zn2+ ions got adsorbed faster on the adsorbents than Cd2+ ions because of its low atomic radii and electronegativity. Finally, the adsorbents will be generated and prepared for additional adsorption cycles to test their stability. The second part of this work is to present the novel fabrication of multifunctional hydrophobic polymeric foam MX nanocomposites for large-scale ultrafast wastewater treatment. Likewise, the foam nanocomposite will be tested for the adoption of multi-ions solution over wide pH rage to demonstrate the applicability of the novel adsorbent for large-scale applications. Overall, this research contributes to the advancement of water treatment technologies by enhancing the stability of MXene-based adsorbents and introducing an innovative fabrication method for hydrophobic polymeric foam MX nanocomposites. The outcomes demonstrate the applicability of these novel adsorbents for efficient and scalable water purification solutions.
The Design and Synthesis of Anti-Tubercular Lariatin a Peptidomimetics
(University of the Witwatersrand, Johannesburg, 2023-07) Nyembe, Priscilla Lebohang; Makatini, Maya Mellisa
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the major causes of death and morbidity worldwide. Approximately 10 million people worldwide are infected with Mtb annually, with an estimated 1.5 million deaths. However, potent anti-TB drugs with a new mechanism of action have not been developed in the last thirty years, and only 5 anti-TB drugs are still clinically used. Currently, available drugs and vaccines have failed to control its spread. Furthermore, the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb is a significant public health concern because most of the anti-TB drugs that have been in use for over 40 years are no longer effective for the treatment of these infections. Thus, there is an increased demand for novel anti-tubercular drugs with a different mode of action directed at new Mtb targets. Lariatin A, an anti-mycobacterial peptide, has received interest in the synthesis field due to its distinctive threaded structure which consist of a linear and cyclic portions and its unique bactericidal mechanism toward Mtb. This research focuses on designing and synthesizing derivatives of Lariatin A and investigating their binding properties to the mycobacterium caseinolytic protease (ClpP), a protein essential for the growth of Mtb. A simpler synthetic route for derivatizing Lariatin A peptides was achieved by incorporating two cysteine amino acid residues onto the sequence for cyclization of the peptide via the formation of a disulfide bond instead of a lactam bond. To further simplify the synthetic procedure, derivatives with shorter sequences as well as peptide-peptoids hybrids were also designed. Eight mimetics of Lariatin A were synthesized [Pep_PNL1 (1), Pep_PNL2 (2), Pep_HA (3), Pep_TA (4), Pep_TAA (5), Pep_HAP (6), Pep_PTA (7), Pep_PHA (8)]. The proposed derivatives were synthesized using the solid phase peptide synthesis technique and a sub-monomeric approach was followed to synthesize the peptide-peptoid hybrids. Purification of the peptides was achieved by utilizing semi-preparative High-Pressure Liquid Chromatography and they were characterized by Liquid Chromatography-Mass Spectrometry. The peptides were obtained in low to moderate yields, and the linear tail portion derivative (4) showed 70% ClpP inhibition, while the linear tail derivative coupled to the adamantane moiety (5) showed a 49% inhibition factor. NMR (nuclear magnetic resonance spectroscopy) and CD (circular dichroism) were utilized to determine the secondary structural features. The CD experiments indicated that peptide 1 adopts stable conformations while its separate tail (4) and cyclic (3) regions loss conformity. Pep_PTA (7) displayed the characteristics of both peptide and peptoid as seen from its formation of beta sheets. NMR and CD experiments confirmed that 4 exist in a helical conformation. Hence helical Lariatin A derivatives targeting the Mycobacterium tuberculosis caseinolytic protease can be synthesized using the solid phase peptide synthesis strategy.

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