School of Chemistry (ETDs)

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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.
Trimetallic nanoparticles immobilised on polymeric membranes for the degradation of organic pollutants in water
(University of the Witwatersrand, Johannesburg, 2021) Kgatle, Masaku; Moloto, Nosipho; Sikhwivhilu, Keneiloe; Ndlovu, Gebhu
Water is one of the most essential resources in the world, but its scarcity has become an issue of global concern. The scarcity of water is largely the result of climate change, water pollution and increasing population growth which limits the availability of water resources. Moreover, South Africa has been making headlines since 2010 due to water shortages experienced. It is, therefore crucial to find cost-effective ways to expand the water supply and address the issue of water pollution. This study seeks to tackle the problem of water pollution emanating from textile industries. Over the last few years, nanotechnology and membrane technology have appeared as some of the most widely used methods for the mitigation of water pollution problems. Particularly, nanoscale zerovalent iron (nZVI) has emerged as one of the most broadly used nanoparticles in wastewater treatment and remediation owing to its low-cost and high effectiveness. However, because of its ease of aggregation and consequent loss of reactivity, nZVI is coupled with one or more transition metals to produce multimetallic systems. Nanoparticles alone quickly agglomerate and form large micro-scale particles owing to the magnetic forces thus losing their mobility and chemical reactivity. To avoid these issues, the nanoparticles are stabilized on polymeric membranes. In this study, two trimetallic nanoparticle systems were synthesized, characterized and tested for catalytic activity. The polyvinylpyrrolidone (PVP)-stabilized Fe/Cu/Ag nanoparticles were synthesized by the sodium borohydride chemical reduction method. These nanoparticles were characterized using XRD, XPS, EDX and TEM. The XRD, EDX and XPS techniques showed the presence of all three metals, including iron oxides due to the oxidation of iron in air. The obtained TEM images showed the characteristic core-shell morphology of the nZVI-based nanoparticles. The evaluation of the catalytic activity of the nanoparticles was conducted using methyl orange (MO) dye as the model pollutant and this showed a remarkable degradation efficiency within few minutes. The effect of parameters such as MO solution pH, initial MO dye concentration and nanoparticle dosage in MO degradation was investigated. The nanoparticles were found to have performed better at lower pH, lower initial MO dye concentration and higher nanoparticle dosage. The degradation of MO dye was monitored using UV-Vis analysis and occurred within 1 min. The degradation was found to follow a pseudo first-order kinetic model and was vastly influenced by the studied parameters. The analysis of by-products and reaction pathway were done using LC-MS and this further confirmed that the degradation of MO was indeed rapid. The Fe/Cu/Ag trimetallic nanoparticles were demonstrated as suitable and effectual alternative for the remediation of textile dye wastewater. For the second trimetallic system, three different trimetallic nanoparticles (Fe/(Zn/Ag), Fe/Zn/Ag and Fe/ Ag/Zn) with different metal addition sequences were synthesized. The prepared nanoparticles were characterized using XRD, EDX and TEM analyses. The techniques proved successful synthesis of the nanoparticles and XRD and EDX showed the presence of the three metals together with the oxides. The evaluation of the catalytic reactivity of the nanoparticles was conducted in a series of batch experiments using MO dye as the model pollutant. About 100% of the MO dye was degraded by Fe/ Ag/Zn trimetallic nanoparticles within 1 min and the second-order rate constant obtained was 0.0744 ppm- 1min-\ the rate of reaction was higher than that of the other trimetallic systems. Using Fe/ Ag/Zn trimetallic nanoparticles, parametric tests were conducted at different MO solution pH, initial MO concentration and nanoparticle dosage. The results showed that the reactivity of the Fe/Ag/Zn trimetallic nanoparticles was highly dependent on the aforementioned parameters. Like the Fe/Cu/Ag system, the Fe/Ag/Zn performed better at lower pH, lower initial MO dye concentration and higher nanoparticle dosage. The overall kinetic study showed the removal of MO using Fe/Ag/Zn system to follow a second-order kinetic model. The elucidation of the degradation pathway and MO by-products identification were done using LC-MS and the mechanism of degradation displayed the degradation of methyl orange to proceed via azo-bond cleavage. Moreover, the Fe/ Ag/Zn nanoparticles proved to be effective at degrading methyl orange dye and can be used to treat azo-dye wastewater from textile industries. The Fe/Cu/ Ag trimetallic nanoparticle system was immobilized on a polymethacrylic acid grafted polyethersulfone (PMAA-g-PES) membrane to minimize the issue of recoverability and nanoparticle agglomeration. The nanocomposite membranes were prepared by loading different quantities of Fe/Cu/Ag trimetallic nanoparticles onto the PMAA-g-PES membrane for optimization purposes. Characterization was performed using FTIR, NMR, XPS, SEM/EDS and AFM analyses. The PMAA g-PES and nanocomposite membranes were found to have a porous top layer and a rough surface. Moreover, the addition of nanoparticles did not cause any significant changes in the membrane structure, however, further addition of nano particles led to the blockage of pores. The performance of the synthesized membranes was tested using pure water flux and MO (anionic dye) and methylene blue (MB) (cationic dye) dye removal capacity. The negatively charged membranes were found to have more affinity for MB dye than the MO dye and this was ascribed to the charge interaction between the membrane surface and the dyes. The nanocomposite with 5% Fe/Cu/Ag trimetallic nanoparticle loading on PMAA-g-PES membrane (M4-5% membrane) was found to have the best adsorption capacity with about 60% MB dye removal efficiency. Furthermore, the effect of process parameters such as pH, temperature and H2O2 concentration on the removal of MB was studied. The removal efficiency was found to be higher at higher pH and lower temperature. About 100% removal efficiency was obtained when the process was performed at pH 9 in the presence of H2O2 via adsorption and Fenton degradation. This showed that a hybrid of processes was convenient for the removal of MB dye by adsorption (primarily) and degradation using the nanocomposite membrane. Adsorption equilibrium data were assessed using the Langmuir, Freundlich and Temkin models; the Temkin model was the most convenient to explain the adsorption of MB onto M4-5% membrane. Moreover, lcinetic studies were performed on four kinetic models: pseudo first-order, pseudo second order, intraparticle diffusion and elovich models. The pseudo second-order was found to be the best suitable to explain the adsorption of MB onto M4-5% membrane. Thus, the adsorption of MB onto the nanocomposite membrane is an exothermic chemical process that occurs on a heterogeneous surface. Therefore, the nanocomposite membrane has the prospective to be applied in the removal of cationic textile dyes in the presence of an oxidiser.
Colloidal synthesis and characterization of molybdenum and tungsten-based phosphide electrocatalysts for hydrogen evolution reaction
(2022) Nkabinde, Siyabonga Sipho; Moloto , Nosipho
The production of hydrogen gas via hydrogen evolution reaction (HER) in acidic media has become an important area of research in light of the increasing demand for sustainable and environmentally friendly sources of energy. However, its large-scale production is currently being hindered by the lack of inexpensive and highly efficient non-noble electrocatalysts. Transition metal phosphides (TMPs) have transpired as favourable catalysts that can be prepared from cheap and readily available sources. Up to now, TMPs have been commonly prepared using solid-state and solid-gas reactions, which rely on the use of high temperatures and hence generate inhomogeneity in the prepared materials. Inhomogeneous materials are unattractive as catalysts because the correlation between a catalyst and its structural features cannot be systematically studied. For this reason, colloidal synthesis has emerged as a powerful method in the synthesis of TMPs as it allows for control over the resulting physical features (i.e. size, morphology, crystal phase, crystallinity etc.). The ability to tailor these physical properties provides room for improving the catalytic activity. By using the colloidal synthesis method, we have successfully prepared molybdenum and tungsten-based phosphide nanoparticles and studied the effect of their physical features on HER activity. In chapter 3, we report a facile colloidal synthesis method to produce an amorphous phase of molybdenum phosphide (MoP) by using trioctylphosphine (TOP) as a phosphorus source, molybdenum pentachloride (MoCl5) as a metal source and 1-octadecene (1-ODE) as a solvent/reducing agent. The use of the forementioned precursors promoted the formation of very small, shape controlled and well dispersed amorphous molybdenum phosphide (MoP) nanoparticles. Annealing (800 °C) of the amorphous MoP nanoparticles resulted in the formation of a crystalline MoP phase with a slightly bigger size but retained its dispersity and morphology upon exposure to high temperature. The amorphous and crystalline MoP phases were compared as HER electrocatalysts. HER results indicated that the amorphous MoP phase exhibited enhanced catalytic activity in hydrogen evolution reaction compared to the crystalline MoP phase. The high activity displayed by the amorphous MoP was attributed to the small sizes and the high density of unsaturated active sites characteristic of nanoparticles lacking long range crystalline order.
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.
A study of the support effect of carbon dots-derived graphene-like sheets on the autoreduction of cobalt nanoparticles for Fischer–Tropsch synthesis
(2022) Mokoloko, Lerato Lydia
The aim of this study was to synthesize and characterize carbon dots (CDs) and to use them as a support material for cobalt (Co) based Fischer-Tropsch synthesis (FTS) reactions. The CDs were chosen for this study due to their small size (< 10 nm), easy surface functionalization and synthesis. The small size of the CDs was required for the study of inverse catalyst support effects. An inverse supported catalyst (in this case, the Co/CDs catalyst) refers to the dispersion of a support material that has a small size (d < 5 nm) onto the surface of a metal catalyst with a similar small size (d > 8 nm). The synthesis of this proposed catalyst was successful. FTS studies on the Co ‘supported’ CDs were attempted. Extremely poor FT activity was observed. Post analysis of the catalyst revealed that the CDs did not retain their quasi-spherical and small particle size morphology under the FTS reaction conditions (temperature 220 °C, 10 bar P; H2:CO ratio = 2:1). Instead, upon exposure to a heat treatment, the CDs were transformed into layered structures with a unique resemblance to graphene-based nanosheets (GNSs). This transformation impacted on the use of these catalysts in the FTS reaction. However, this result indicated an unusual transformation of the CDs into another carbon shape. In light of the fascinating transformation phenomenon, annealing studies were then conducted to investigate the effect of annealing temperatures on the CDs structural changes. The CDs (average d= ~ 2.5 nm) used in this study were obtained from the microwave-assisted carbonization of L-ascorbic acid and subjected to a heat treatment (i.e. annealing) at temperatures between 200 and 700 ℃ in a horizontal CVD apparatus under an inert nitrogen gas. It was observed that annealing transformed the CDs from 0-D qausi-spherical nanoparticles to 3- D multi-layered carbons (at 300-600 ℃) and finally 2-D layered materials (at 700 ℃). Furthermore, annealing at 700 ℃ yielded a 2-D single-layered material with comparable properties to traditionally reduced graphene oxide (rGO). A wide range of characterization techniques were used to gain an insight into the physicochemical properties of these novel CDs-derived allotropes as well as to rationalize their mechanism of formation. After evaluating the properties of these materials, it was clear that the surface oxygen functional groups, observed from XPS, 13C NMR and other studies, were responsible for the CDs to rGO transformation. It was proposed that the CDs are assembled to form rGO (and other CDs-rGO derivatives) by either the Ostwald ripening (in which the carbons agglomerated via a gas phase) or a solid phase reaction (involving reaction of CD edges). To further investigate the effect of annealing on the evolution of CDs to layered carbon structures, N-doped CDs (or NCDs) were also studied. The method used to make the pristine CDs was modified by incorporating urea as a nitrogen source to make the NCDs. Annealing the NCDs at temperatures between 200 and 700 ℃ also transformed the quasi-spherical NCDs (average d = ~ 4.1 nm) to multi-layered carbon sheets at temperature as low as 200 ℃. The CD transformation was also associated with the loss of surface functional groups, with % O and N contents of ca. 17 and 16 % (pristine NCDs) being reduced to ca. 8 and 7 % for NCDs annealed at 700 ℃. A similar mechanism for the formation of these N-doped layered carbon structures by annealing was also proposed here. For these samples, it was also observed that the N-bonds, especially the sp3 type nitrogen bonds found on the edges of the NCDs, also took part in the coalescence of the NCDs to give the layered materials. XPS data suggested that in the process, these sp3 type nitrogen bonds were transformed into sp2 pyrrolic-N, pyridinic-N and GraphiticN groups. The annealed CDs products were used to support Co (called Co3O4/T250, Co3O4/T400 and Co3O4/T700 where T is the temperature at which the CDs were annealed) for use in FT studies. Studies were conducted to evaluate the effect Co hydrogen reduction temperatures verses autoreduction temperature, catalyst thermal stability and performance in the FTS reaction at 220 °C (10 bar P; H2:CO ratio = 2:1). Upon investigation of the reduction behaviour of the Co/CDs derivative catalysts using in situ PXRD, it was found that these materials can successfully facilitate autoreduction of Co3O4 to Co face-centered-cubic (fcc) at temperatures > 400 ℃ by a reduction pathway similar to that observed using conventional H2 reduction conditions. As expected, the reduction under H2 took place at a lower activation temperature (> 250 ℃) than the autoreduction process. It was also noted that these novel carbon support derived from CDs gave reduced FTS performance compared to the unsupported Co, especially towards C5+ yields (< 30 % for all Co supported catalysts). These novel CDs-derived allotropes were found to have limited use as supports in Co-based FTS, due to Co agglomeration. These NCDs-derived allotropes (annealed at 200 ℃, 400 ℃ and 700 ℃) were incorporated as active layers in the fabrication of chemoresistive sensing device detection of volatile organic compounds (VOCs). These layered showed enhanced chemical vapour sensing properties, especially for methanol and ethanol detection at room temperature. Therefore, although there are great limitations for applications of these CDs-derived layered allotropes in FTS reaction, these materials show a much better potential for applications in facile and cost effective VOC sensors. Further studies on this will be conducted.
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.
The Design, Synthesis and Structure-Activity Relationship of Antitubercular Lassomycin Derivatives
(University of the Witwatersrand, Johannesburg, 2023) Ngqinayo, Ntombizanele; Makatini, Maya
Tuberculosis (TB) is a potentially fatal infectious disease caused by Mycobacterium tuberculosis (Mtb) and is a global health risk responsible for over 1.5 million deaths worldwide annually. Tuberculosis is treated with a combinatory regimen of approved first- line drugs such as rifampicin and isoniazid as well as second-line anti-TB drugs such as fluoroquinolones, most of which use similar mechanisms to cause cell death. The formation of multidrug resistance (MDR) TB strains, biofilms, and dormant persister cells (non- replicating cells) are some factors that prolong TB treatment and hence the need for developing novel antitubercular agents with a different mode of action. Furthermore, the emergence of multidrug resistance TB poses a challenge in controlling and eradicating tuberculosis. Lassomycin is a novel antimicrobial peptide (AMP) that has garnered much interest across various research groups due to its ability to effectively target and kill Mtb, including MDR strains and latent TB, with a potency that is similar to that of rifampicin. Lassomycin is highly basic and targets the highly acidic N-terminal domain (NTD) of the caseinolytic enzyme that forms part of the caseinolytic protease crucial for Mtb cell survival. Lassomycin has an unusual mode of action that causes Mtb cell death by disrupting the highly controlled and tightly regulated proteolysis by inhibiting proteolytic activities as well as increasing unfoldase activities. Thus, lassomycin shows great potential as a candidate for drug development. This study aimed to design lassomycin derivatives with improved stability and potency; and synthesize them using shorter and cost-effective synthetic routes. Peptide modifications includes (i) replacing the macrolactam ring in the peptide sequence with a disulfide bridge via a simpler ring-formation method resulting in an enlarged cyclic ring; (ii) replacing ‘difficult’ arginine residues with less basic lysine residues; (iii) forming cationic derivatives by increasing the number of basic lysine residues to enhance selectivity for the bacterial membrane; (iv) conjugating peptide derivatives to lipophilic molecules including palmitic acid and 1-adamantane carboxylic acid to improve bacterial cell penetration and binding; (v) conjugating the peptides to silver nanoparticles for improved drug delivery and antimicrobial effect; (vi) incorporating N-methylated residues to improve peptide stability; (vii) making non-polar peptide derivatives by replacing all basic amino acids with alanine to investigate the importance of the basic residues and study structure activity relationship (SAR) (viii) synthesizing linear derivatives in order to investigate the effect of the ring and (ix) shortening the peptide sequences to include only the cyclic ring or the tail sequence portions in order to shorten the synthetic route. Peptides were synthesized via the Fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis strategy (SPPS) and purified using a semi-preparative High-Performance Liquid Chromatogram (prep-HPLC). They were then analysed using High-Performance Liquid Chromatography Mass Spectrometry (HPLC-MS), Circular Dichroism (CD), and nuclear magnetic resonance (NMR) spectroscopy. Silver nanoparticles and the peptide conjugates were characterized using ultraviolet-visible (UV-Vis) spectrophotometry and transmission electron microscopy (TEM) imaging. Two-dimensional (2D) Nuclear magnetic resonance (NMR) spectroscopy, including [1H, 1H] COSY, [1H, 1H] TOCSY, [1H, 13C] HSQC, [1H, 1H] HMBC and [1H, 1H] ROESY were used to determine the structural conformation of Pep-2- NN, a lassomycin derivative that has activity against tuberculosis. Furthermore, the secondary structure of selected derivatives was examined using circular dichroism (CD) spectroscopy. Computational studies were utilized to determine the structure of the active lassomycin derivatives, Pep-2-NN and Pep-2-NNA. All the peptide derivatives were successfully synthesized, including non-polar, short-chained, and those conjugated to silver nanoparticles and lipophilic molecules. The disulfide bridge was successfully added to replace the lactam bridge of the parent lassomycin peptide by oxidising sidechain thiol groups of two cysteine residues inserted at appropriate positions in the sequences. All the peptides were purified to varying degrees of success, and their behaviour was analysed to investigate structure-activity relationships. The silver nanoparticles were successfully synthesized in-house and conjugated to Pep-2-NN. Transmission Electron Microscopy (TEM) imaging revealed that the silver nanoparticles have a spherical morphology at sizes that ranged between 7 nm and 9 nm whilst peptide conjugated nanoparticles were between 9 – 12 nm. Caseinolytic protease (ClpP1P2 or ClpP) assay studies revealed that the peptides display inhibiting and activating properties when screened against the protease, including lassomycin derivatives with shortened chains such as Ring-2-NNA-Ada, Ring-2-NN, and Tail-2-NN. The secondary structure of selected lassomycin derivatives was studied using circular dichroism (CD), revealing that the structures are comprised of anti-parallel beta- (β) sheets at slightly higher proportions followed by alpha- (α) helix and, to some extent, β-turn motif. Computational studies were conducted on selected derivatives to predict their secondary structure and revealed that the peptides form stable α-helical conformations. NMR revealed that Pep-2-NN formed a ‘knotted’ structure, where the tail sequence was threaded inside the cyclic ring with a curved loop, and certain residues in the ring acted as ‘steric plugs’ to prevent unthreading. In conclusion, the insertion of the disulfide bridge remains an effective alternative to the lactam bond found originally on lassomycin and can result in the formation of biologically active derivatives with the desired stable ‘lasso’ conformation.
Biophysical studies of metal chelate binding by HSA: Towards an understanding of metallodrug transport
(University of the Witwatersrand, Johannesburg, 2023) Sookai, Sheldon; Munro, Orde
Human serum albumin (HSA) is the most abundant blood protein, transporting many exogenous compounds including clinically deployed and investigational drugs that are generally organic in nature. HSA may largely influence the pharmacokinetics and pharmacodynamics of these drugs. Therefore, studying their interactions with HSA is vital in progressing drug development. In this thesis we present work on the synthesis and characterisation of five Schiff base bis(pyrrolide-imine) ligands that were metalated with either Au(III) (Chapters 2 and 3) or Pt(II) (Chapters 4 and 5). One of the ligands H2L1 was further metalated with Ni(II) and Pd(II) (Chapter 6). In Chapters 2 and 3 focus on a patented class of anti-cancer bis(pyrrolide-imine) Au(III) Schiff base chelates. Three Au(III) chelates were synthesized in Chapter 2 and underwent National Cancer Institute (NCI)-60 cytotoxic screening. Among them, AuL1 and AuL3 underwent full-five dose testing and recorded GI50 values of 7.3 µM and 11.5 µM, and IC50 values of 15.7 µM and 30.9 µM, respectively. AuL1 was tested further and found to be an interfacial poison of topoisomerase II at 0.5–5 µM and a catalytic inhibitor at 50 µM. In Chapter 3, two chiral tetradentate cyclohexane-1,2-diamine-bridged bis(pyrrole-imine) Au(III) complexes were reported, both of which were found to be cytotoxic in the NCI-60 screen. The chiral Au(III) chelates had a different mode of action compared to AuL1. Hierarchical cluster analysis suggest that their mode of action is similar to that of taxol. All five Au(III) chelates bound to HSA with moderate affinity (104–105 M–1) and minimally perturbed the structure of the protein. This highlights the potential for the Au(III) complexes to be transported by the HSA-mediated pathway. Chapters 4 and 5 focused on the synthesis of novel and previously reported Pt(II) Schiff base chelates to spectroscopically and computationally study their interaction with HSA and elucidate if the chelates could act as theranostic agents. It was found that switching the linking bis(imine) carbon linkage altered the binding affinity of the complex. However, the Pt(II) ion ensured that all three Pt(II) chelates preferred binding to Sudlow’s site II of HSA. The data was corroborated by molecular docking simulations and ONIOM calculations. Only 2 was found to be cytotoxic when irradiated with UV light but was found to act as a photosensitizer rather than a theranostic agent. Chapter 6 investigated the influence of d8 metal ions (Ni(II), Pd(II) and Pt(II) within the same ligand scaffold (H2PrPyrr) binding to HAS, which was investigated by steady state fluorescence quenching. The affinity constants, Ka, ranged from -3.5 -103 M−1 to-1- 106 M–1 at 37 C, following the order Pd(PrPyrr) > Pt(PrPyrr) > Ni(PrPyrr) >H2PrPyrr. The Pd(II) chelate was prone to hydrolysis and had a unique binding mode which we attribute to the unusually high binding affinity. The complexes uptake is enthalpically driven, hinging mainly on London dispersion forces. In summation, twelve metal complexes were successfully synthesized, of which 11 bound to HSA with a moderate binding affinity. The Au(III) chelates preferred Sudlow’s site I, while the Pt(II) chelates preferred Sudlow’s site II. Overall, the metal complexes bound fully intact to HSA.
Fast oxide ion conductors for solid oxide fuel cells: average and local structure – property correlations in solid solutions of bi2o3
(University of the Witwatersrand, Johannesburg, 2023) Masina,Sikhumbuzo Mfanawemphi; Billing, David Gordon
In this thesis, substituted Bi2O3 systems were fabricated and characterized. W, Dy, Erand Nb were used as substituents in a goal to stabilise the highly conductive δ-Bi2O3like phases (hence forth referred to as the δ-phases) to ambient temperatures. Changes in both the average and local structures of the substituted Bi2O3 systems were correlated with the physical property conductivity. In the first part of the thesis, powder X-ray diffraction and Raman spectroscopy were used to show that WO3 on its own did not stabilise the δ-phase at ambient temperatures. The true equilibrium phase in the Bi2O3- WO3 system was a mixture of two tetragonal phases 7Bi2O3·2WO3 and 7Bi2O3·WO3. The co-doping strategy was used to fabricate the Bi2O3-Dy2O3-WO3 system (DWSB, where D =Dy, SB = stabilised Bi2O3). The δ-phase was stabilised with a minimum of 15 mol% total substituent concentration. Powder X-ray diffraction indicated that the δ- phases obtained in this system were metastable and degraded after isothermal annealing at ~ 500 °C for 100 hours. Addition of Er to the DWSB system to create the novel system Bi2O3-Dy2O3-Er2O3-WO3 (DEWSB, where E=Er) was found to significantly improve the stability of the δ-phase when annealed at virtually identical conditions as DWSB. The rest of the thesis is focused on the effect of each substituent cation on phase stability, local structure and the ageing phenomenon–the decrease in ionic conductivity upon isothermal annealing without any observable changes in average structure under powder X-ray diffraction. X-ray pair distribution function, X-ray absorption spectroscopy and photoluminescence were used to probe the local structure around the host Bi cations and some of the substituent cations (Dy, Er, W). The results indicated that some of the Bi cations are displaced away from the 4a site of the defect fluorite structure (Fm-3m) and that at the local level, the Bi cations assume an arrangement similar to that found in the monoclinic α-Bi2O3 phase. Dy and Er were also found to prefer local environments similar to those in their parent oxides. The resemblance increased as the material aged and might explain why the conductivity decreases upon ageing
The microwave assisted synthesis of doped carbon dot/carbon nano-onion composites: A novel all-carbon counter electrode for dye-sensitized solar cell
(University of the Witwatersrand, Johannesburg, 2023) Masemola, Khanyisile; Moloto, Nosipho; Maubane-Nkadimeng, Manoko S.; Coville, Neil J.
Human society's development is heavily reliant on stable energy supply, and fossil energy sources have long been a very reliable energy source for this objective. However, being a non-renewable energy source, fossil fuel depletion is unavoidable and impending in this or future generations. To solve this issue, renewable energy, particularly solar energy, has received a lot of attention since it directly turns solar energy into electrical power with no environmental consequences. Various photovoltaic technologies based on organic, inorganic, and hybrid solar cells have been successfully manufactured to date. However, much study has been concentrated on organic solar cells for household and other commercial uses due to its inherent cheap module cost and ease of production. But dye-sensitized solar cells (DSSCs) have been reported to be the most efficient and simplest applied organic solar cell technology. In this study, carbon dot: onion-like carbon nanomaterial composites (Cdots: OLCNs) were synthesized for possible future application in electronic devices with particular attention to dye-sensitized solar cells. The nitrogen-doped carbon dots (NCdots) and functionalized onion-like carbon nanomaterials (OLCNs) were synthesized using a one-step hydrothermal microwave assisted irradiation method and flame pyrolysis method using liquid fuels, respectively. The as-synthesized OLCNs where purified and washed using an organic solvent n-pentane to obtain pristine OLCNs (p-OLCNs) which were further functionalized with N2 gas to obtained nitrogen-doped CNOs (N- OLCNs) and H2O2 to give oxygenated OLCNs (ox-OLCNs). For the synthesis of NCdots, various precursors (ethylenediamine, urea and fumaronitrile) were used to evaluate the effect of different nitrogen sources on the properties of these materials. Photoluminescence spectroscopy showed that the resulting NCdots exhibited the conventional excitation-dependency behavior. The NCdots which presented with the highest fluorescence quantum yield (made from ethylenediamine) were used to make the subsequent NCdot: OLCNs composites. The as-prepared p-/ox-/N-OLCNs all showed similar morphologies typical of chain-like carbon nanostructures, according to transmission and scanning electron microscopy studies, but with varying particle sizes of 42 nm, 125nm and 85 nm, respectively. The corresponding nanocomposites were used as counter electrode materials in DSSCs. The application of all the nanocomposites in the DSSCs resulted in cell efficiencies, current densities, open circuit voltages and fill factors that were lower than that of a conventional platinum (Pt) electrode. All nanocomposites tested presented with cell efficiencies <1%. Furthermore, the cells displayed some photovoltaic effect of minimal activity in the absence of light, under dark field conditions implying it is still a photovoltaic material. This photocurrent generated by the cell in the dark is suggested to be a dominant contributor to the low performance of the cells. However, what was remarkable was that this photovoltaic effect, primarily due to the thermal activity from the long lasting glow of the NCdots specifically, was found to be stable and efficient in response as infrared radiation even without being illuminated with light for 5 minutes. This suggests that the NCdots: OLCNs composites have potential application, possibly as efficient diodes rather than for use in DSSCs.
Use of transaminases for the biosynthesis of enantiopure building blocks of two essential medicines: Ethambutol and Dolutegravir
(University of the Witwatersrand, Johannesburg, 2023) Maboya, Josephine; Pienaar, Daniel
(S)-2-Amino butan-1-ol and (R)-3–amino butan-1-ol play an important role as intermediates in the synthesis of the anti-tuberculosis drug ethambutol and HIV integrase inhibitor drug dolutegravir respectively. The current industrial preparation of these enantioenriched amino alcohols is quite a challenging process; it typically involves the use of harsh chemicals, results in low yields, and generates hazardous waste materials. Consequently, these methods tend to be expensive, and it has been demonstrated that the cost of these intermediates has a significant impact on the overall costs of the synthesis of the entire drug. Therefore, it is not surprising that the convenient, cost–effective, and environmentally benign production of these optically pure amino alcohols is still the subject of ongoing investigations. The chemo-enzymatic approach holds great potential to replace the conventional routes for the synthesis of enantiopure amines. Transaminase enzymes (ATAs), in particular, have gained much attention over time due to their remarkable capability to transform inexpensive ketone starting materials into valuable enantiopure amino alcohols. Through the utilization of the isopropyl amine donor system, pro-chiral ketone starting materials were effectively transformed into the desired (S)-isopropyl 2-aminobutanoate and (R)-isopropyl 3-aminobutanoate using transaminase biocatalysis. These reactions proceeded well under milder conditions such as ambient temperature and pressure conditions, and impressively under an aqueous environment. Three (S)-enantiomer selective “hit “enzymes were discovered (ATA-189, ATA-194, and ATA-254) for the biotransformation of alpha-keto ester substrate into an enantio-enriched amino ester product, with enantiomeric excess ranging between 95-99% and the yield was 15-73% depending on the enzyme and reaction conditions. However, when it came to dolutegravir intermediate, a different scenario unfolded. In this case, the majority of the ATA enzymes in our enzyme library fortuitously exhibited selectivity for the (R)-enantiomer. In particular, four highly enantioselective enzymes (ATA-254, ATA-261, ATA-262, and ATA-234) were discovered, demonstrating % e.e ranging from 93% to 99.99%, with corresponding yields from 38% to 45%. The successful biotransformation of an inexpensive pro-chiral starting material into highly valuable enantioenriched amino ester intermediates represents a significant achievement. Coupled with an effective reduction method to convert these intermediates into the corresponding amino alcohols, this biotransformation process holds immense potential for enabling the sustainable and cost- effective production of both of the valuable ethambutol and dolutegravir amine intermediates
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.
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.
Quantitative analysis of gold in low-grade tailings from different matrices, coupled with a study into the associated uncertainties
(University of the Witwatersrand, Johannesburg, 2023) Mashale, Kedibone Nicholine; Tshilongo, James; Chimuka, Luke
Gold is one of the precious group elements that is used for various purposes, such as jewellery, auto catalysts and as a form of investment. Various countries have gold reserves, with South Africa being the leading gold producer between 1980 and 2007. However, as of 2022, it is ranked as the eighth largest producer of gold, contributing 3% to the global contribution. The majority of gold is mainly mined from the Witwatersrand Basin in Johannesburg. It is well known that mining has been ongoing for decades, which means that a significant amount of land has been mined across the country. During gold mining, a large proportion of the ore material from which the gold is extracted is waste, together with the chemicals that were used, and this waste is termed mine tailings. This implies that based on the years that gold mining has occurred for and the depth of mining, a significant amount of the tailings have been deposited into free land around the mines, some of which are close to communities. The tailings consist of traces of gold that were left due to inefficient extraction processes and other components, such as base metals. The disadvantage of this is that due to the other chemical composition of these tailings, they have the potential to be dangerous to the environment. Some tailings contain minerals such as jarosite (KFe2(SO4)2(OH)6) that cause acid mine drainage, while heavy metals such as lead, mercury, arsenic and chromium can leach into surface and ground waters, causing pollution. Furthermore, they pose a danger if the dams that they are stored in collapse, which was recently witnessed in South Africa. Because of these factors, there have been various advances made towards the beneficiation of tailings, such as utilizing them to make glass or bricks for construction. A major advancement was the reprocessing of these mine tailings to recover or extract the remaining gold, which benefits both the environment and the mining houses. Therefore, in a move to support this initiative, scientists have taken to the laboratory to develop new or optimize existing methods for the extraction and quantification of gold, which is expected to be of a low grade over time. Various methods can be used for the quantification of gold, including the conventional fire assay, wet and dry chlorination and acid digestion. Most of these are suitable for medium- to high-grade gold ores but are known to experience challenges in regard to low-grade ores. The aim of this research was therefore to find the optimum method for the quantification of gold from mine tailings emanating from the Ventersdorp Contact Reef (VCR) and Barberton Greenstone Belt (GBS). Subsequent to chemical analysis, the samples were characterized for mineralogy using X-ray diffraction (XRD) and Brunauer‒Emmett‒Teller (BET) surface area
The Synthesis of Pyrido-fused 8-Methoxy Carbazoles by Using a Light-Assisted, Base Mediated Cyclization Reaction
(University of the Witwatersrand, Johannesburg, 2023) Magagula, Bongi Florence; Ntsimango, Songeziwe; De Koning, Charles B.
Nitrogen-containing compounds such as indoles and carbazoles are significant classes of the N-heterocycles that show great promise as anti-cancer compounds. Indoles such as 2,3-diarylindole, 3-pyranyl indole and carbazoles such as 9-methoxyellipticine are compounds which possess anticancer or antitumor properties. Due to the favourable biological activities of N-heterocyclic compounds, medicinal and synthetic chemists have developed numerous methodologies for their synthesis. In this research project, the broad aim was to synthesize pyrido-fused carbazoles from 5-methoxyindole using methodologies that have been previously used in our laboratories and by other chemists while changing the position of the nitrogen atom on the pyrido-fused carbazoles. The first step in the synthesis of these carbazoles was the treatment of 5-methoxyindole with di-tert-butyl dicarbonate in the presence of 4-dimethylaminopyridine (DMAP) which gave the desired protected indole, tert-butyl 5-methoxy-1H-indole-1-carboxylate in excellent yields (90-99%). Exposure of the tert-butyl 5-methoxy-1H-indole-1-carboxylate to lithium 2,2,6,6-tetramethypiperidide followed by quenching with triisopropyl borate and hydrochloric acid gave (1-(tert-butoxycarbonyl)-5-ethoxy-1H-indol-2-yl)boronic acid. Using this and various halogen substituted pyridines, for example 3-bromo-4-methylpyridine in the Suzuki-Miyaura coupling reaction gave tert-butyl 5-ethoxy-2-(4methylpyridin-3-yl)-1H-indole-1-carboxylate (83% yield). This was further reacted with paraformaldehyde and iron (III) chloride or phosphorus oxychloride and DMF. After the removal of tert-butoxycarbonyl protecting group utilizing various methods this produced 5-methoxy-2-(4-methylpyridin-3-yl)-1H-indole-3-carbaldehyde (48% yield). 5-Methoxy-2-(4-methylpyridin-3-yl)-1H-indole-3-carbaldehyde possesses all the carbons of the final compounds and is suitably functionalized to partake in the key photo-induced and ase-mediated cyclization reaction. Previous studies pointed to the necessity of an alkyl protecting group on the indole-N atom. As a result, the indole nitrogen atom was then protected again with a methyl or a benzyl group; where the N-benzyl could be removed at a later stage. For example, reaction of 5-methoxy-2-(4-methylpyridin-3-yl)-1H-indole-3-carbaldehyde dissolved in THF, potassium hexamethyldisilazide and benzyl bromide furnished 1-benzyl-5-methoxy-2-(4-methylpyridin-3-yl)-1H-indole-3-carbaldehyde (83% yield). The key step in this synthesis was the light-assisted, base-mediated cyclization reaction which has been reported by de Koning and co-workers, where a solution of 1-benzyl-5-methoxy-2-(4-methylpyridin-3-yl)-1H-indole-3-carbaldehyde dissolved in dry DMF and potassium tert-butoxide was heated and irradiated with medium mercury lamp yielding the desired pyrido fused carbazole, 11-benzyl-8-methoxy-11H-pyrido[3,4-a]carbazole in a good yield of 70%. Following the outlined synthetic procedure depicted above, we were able to synthesize 5 analogues of 11-benzyl-8-methoxy-1H-pyrido[3,4-a]carbazole.
Dissolution of non-functionalized and functionalized nanomaterials in simulated biological and environmental fluids
(University of the Witwatersrand, Johannesburg, 2023-06) Mbanga, Odwa; Gulumian, Mary; Cukrowska, Ewa
The incorporation of nanoparticles in consumer products is exponentially high, however, research into their behaviour in biological and environmental surroundings is still very limited. In the present study, the static system and the continuous flow-through dissolution protocols were utilized to evaluate and elucidate the dissolution behaviour of gold, silver, and titanium dioxide nanoparticles. The behaviour of these particles was studied in a range of artificial physiological fluids and environmental media, to obtain a more precise comprehension of how they would react in the human body and the environment. The biodurability and persistence were estimated by calculating the dissolution kinetics of the nanoparticles in artificial physiological fluids and environmental media. The details of the current research are described as follows: An investigation into the dissolution of non-functionalized and functionalized gold nanoparticles was conducted as the first component of the research, examining the effect of surface functionalization on dissolution. The study determined the dissolution rates of functionalized and non-functionalized gold nanoparticles. Dissolution was observed to be significantly higher in acidic media than in alkaline media. The nanoparticle surface modification, particle aggregation, and chemical composition of the simulated fluid significantly affected the dissolution rate. It was concluded that gold nanoparticles are biodurable and have the potential to cause long-term health effect as well as high environmental persistency. This work has been published in the Journal of Nanoparticle Research and is presented in this thesis as Paper 1. Silver nanoparticles were also included in this study because they have many applications and industrial purposes. Therefore, their risk assessment was also of utmost importance. The results indicated that silver nanoparticle solubility was influenced by the alkalinity and acidity of artificial media. Low pH values and high ionic strength encouraged silver nanoparticle dissolution and accelerated the dissolution rate. The agglomeration state and reactivity of the particles changed upon exposure to simulated fluids, though their shape remained the same. The fast dissolution rates in most fluids indicated that the release of silver ions would cause short-term effects. This work has been published in Toxicology Reports and has been presented in this thesis as Paper 2. Although titanium dioxide nanoparticles are insoluble and undergo negligible dissolution, it was of utmost importance to investigate their behaviour in biological and environmental surroundings. This is as a result of the incorporation of these particles in everyday consumer products, in the nanosized range which raises concerns about their safety. Therefore, in Paper 3 presented in this thesis the dissolution kinetics of titanium dioxide nanoparticles in simulated body fluids representative of the lungs, stomach, blood plasma and media representing the aquatic ecosystem were investigated to anticipate how they behave in vivo. This work has been published in Toxicology In Vitro and presented in this thesis as Paper 3. The results indicated that titanium dioxide nanoparticles were very insoluble, and their dissolution was limited in all simulated fluids. Acidic media such as the synthetic stomach fluids were most successful in dissolving the particles, while alkaline media had lower dissolution. High ionic strength seawater also had a higher dissolution rate than freshwater. The dissolution rates of the particles were low, and their half-times were long. The results indicated that these particles could potentially cause health issues in the long term, as well as remain unchanged in the environment. This work has been published in Toxicology In Vitro and presented in this thesis as Paper 3. The last component of the research compared the dissolution kinetics of gold, silver and titanium dioxide nanoparticles through the use of the continuous flow-through system. The findings indicated that titanium dioxide nanoparticles were the most biodurable and persistent, followed by gold and silver nanoparticles. Therefore, it was suggested that product developers should use the OECD's guidelines for testing before releasing their product to the market to ensure its safety. This work has been published in Nanomaterials MDPI and presented in this thesis as Paper 4.
Silver nanoparticle-modified cellulose nanocrystals for fouling control in membrane distillation
(University of the Witwatersrand, Johannesburg, 2023-06) Mpala, Josephine Tshepiso; Nthunya, Lebea; Richards, Heidi; Etale, Anita
A global reduction in water resources and the growing demand for fresh water has motivated the quest for the development of sustainable water-augmenting technologies. Membrane distillation (MD) is envisaged as an attractive desalination technology, surpassing cost challenges faced by conventional desalination technologies. Yet, its industrial commercialization faces multiple limitations, including the production of low water fluxes, membrane wetting and membrane fouling. This study sought to investigate the performance of silver nanoparticles (AgNPs) embedded on cellulose nanocrystals (CNCs) (CNC-capped AgNPs) to lessen the impact of biofouling in MD. This was conducted through coating the polyvinylidene fluoride (PVDF) membrane with CNCcapped AgNPs. Prior to coating with CNC-capped AgNPs, PVDF membrane properties were improved (for MD suitability) through blending with polyvinylpyrrolidone (PVP) and functionalized carbon nanotubes (f-CNTs). The resulting membrane had an improved overall porosity, and a respective increase in surface roughness (75%) and mechanical strength (45%). Pristine CNC-capped AgNPs’ characterization presented stable AgNPs with minimal leaching. Transmission electron microscopy (TEM) micrographs revealed a uniform dispersion of spherically shaped AgNPs exhibiting 13.3 ± 3.4 nm average diameter. The presence of AgNPs on the surface of CNCs afforded excellent thermal stability and good anti-microbial activity, mainly against E. coli, P. aeruginosa, S. aureus, S. epidermis, and S. saprophyticus. Following membrane modification, preliminary anti-bacterial tests conducted on the CNC/AgNP-modified PVDF membrane revealed a 98.7%, 52.3%, 78.0%, 53.9% and 93.3% reduction of E. coli, P. aeruginosa, S. aureus, S. epidermis, and S. saprophyticus cells, respectively, demonstrating its ability to control biofouling. Although the CNC/AgNP-modified PVDF membrane exhibited improved membrane properties, such as high surface roughness, high liquid entry pressure (LEP), and good hydrophobicity, its performance in MD (with artificial seawater as the feed stream) was poor, producing the lowest average water flux (0.179 ± 0.0303 kg/m2 /hr) compared to the unmodified PVDF membrane (0.528 ± 0.0838kg/m2 /hr), mainly due to pore blockage. However, upon spiking the artificial seawater with a monoculture of G. Stearothermophilus, the CNC/AgNP-modified PVDF membrane displayed the most stable water flux while the unmodified PVDF membrane’s water flux decreased by 79.3% over the 24-hour (h) period. This was attributed to the formation of a biofouling layer on the PVDF membrane which was absent on the CNC/AgNP-modified PVDF membrane. The AgNPs on the surface of the membrane afforded minimal bacterial deposition during operation. These results ascertain the possibility of biofouling minimization in MD using CNC-capped AgNPs, contributing to MD’s body of work for its ultimate realization for up-scaling.
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.
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.
Interfacial engineering of NbSe2 and TaSe2 to enhance their electrocatalytic activity for hydrogen production
(University of the Witwatersrand, Johannesburg, 2023-07) Kolokoto, Tshwarela; Moloto, Nosipho
There has been a need to replace fossil fuels, develop sustainable energy systems, and alleviate the negative environmental effects. These effects can be alleviated by developing efficient processes such as water-splitting, which can produce hydrogen gas in an environmentally friendly manner and, in turn, use it as a clean fuel. However, this process requires an effective electrocatalyst comparable to Pt and cost-effective. Herein, we demonstrate that the electrocatalytic activity of NbSe2 and TaSe2 can be improved by metal inclusion using interfacial engineering for the hydrogen evolution reaction (HER). The readily synthesised NbSe2 was decorated with 20% wt. Ni, 20% wt. Pt, 10% wt. Pt / 10% wt. Ni using two synthetic methods, namely the ex-situ and in-situ methods. The ex-situ samples had higher HER activities than the in-situ samples. Pt/PtO2-NbSe2 (derived from Pt decorated NbSe2 using the ex-situ method) showed a significantly enhanced HER activity compared to bare NbSe2. The Pt/PtO2-NbSe2 nanomaterial had the lowest overpotential, favourable kinetics and durability in an alkaline solution of 0.1 M KOH. The trend was as follows: Pt/PtO2-NbSe2 (Pt-decorated ex situ) > PtO-NbSe2 (Pt-decorated in-situ) > PtO/NiO-NbSe2 (Pt/Ni-decorated) > Ni/NiO-NbSe2 (Ni-decorated ex-situ) > Ni0.5Se/Ni(OH)2-NbSe2 (Ni-decorated in-situ) > NbSe2. In addition, NbSe2 was further decorated with 20% wt. Co using both the ex-situ and in-situ synthetic methods, and 10% wt. Pt / 10% wt. Co using the in-situ method. The ex-situ sample resulted in a higher HER activity compared to the in-situ samples. In particular, Co/Co3O4-NbSe2 nanomaterial (Co-decorated ex-situ) had the lowest overpotential, favourable kinetics and durability in an alkaline solution of 0.1 M KOH. The resultant trend was as follows: Co/Co3O4-NbSe2 (Co-decorated ex-situ) < Co3O4/CoSe2/PtO/PtO2-NbSe2 (Pt/Co-decorated in-situ) < Co3O4/CoSe2-NbSe2 (Co-decorated in-situ) < NbSe2. Consequently, the ex-situ method was the optimum synthetic method for forming NbSe2-based nanomaterials. TaSe2-based nanomaterials were formed similarly. TaSe2-based hybrids were formed by decorating TaSe2 with 20% wt. Ni, Co and Pt using the ex-situ method. The hybrid nanomaterials resulted in higher HER activities compared to pristine TaSe2 (i.e. Pt/PtO/PtO2-TaSe2 (Pt-decorated) > Ni/Ni(OH)2-TaSe2 (Ni-decorated) > Co/Co3O4-TaSe2 (Co-decorated) > TaSe2). Pt/PtO/PtO2-TaSe2 hybrid, in particular, resulted in the lowest overpotential under alkaline solutions (0.1 M KOH). Generally observed, was NbSe2-based electrocatalysts were better than TaSe2-based catalysts. In addition, the Pt-decorated ex-situ NbSe2 and Pt-decorated TaSe2 electrocatalysts were better than the model Pt/C catalyst, with the prior being the best overall. This is attributed to the basal sites of the NbSe2 and TaSe2. The ex-situ method was better than the in-situ method and this was due to the presence of metallic particles and the minimization of oxidation compared to the latter.