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Item Embargo Stereo-directing effect of molecularly imprinted polymers on cinnamic acids(2025-09-05) Maseko, Nontlantla Regina; Mniyakeni-Moleele, S. S,.; Tavengwa, N. T.The pursuit of enantiomerically and diastereomerically pure compounds is a paramount concern in pharmaceutical synthesis and various other industries, as different isomers often exhibit drastically different even opposite and toxic biological activities. Traditional separation methods are often inefficient, costly, and environmentally unsustainable, necessitating an exploration of good separation and purification techniques. The study addresses this challenge by exploring, for the first time, the stereo-directing potential of molecularly imprinted polymers (MIPs) in reactions involving cinnamic acid derivatives, specifically focusing on (2E)-3-(4-methoxyphenyl) prop-2-enoic acid (trans-4-methoxy cinnamic acid (t-4MCA)). To the best of our knowledge, no prior studies have reported the synthesis of MIPs using t-4MCA as a template, nor the application of MIPs as catalysts in the Wittig reaction or for the selective separation of cis and trans isomers resulting from photoisomerization. The work represents a novel approach to stereoselective synthesis and purification. MIPs were synthesized via precipitation polymerization using t-4MCA as the template, methacrylic acid (MAA) as the functional monomer, and ethylene glycol dimethacrylate (EEDGMA) as the cross-linker in a 1:4:20 molar ratio. A “dummy” template paracetamol (PCM) was also used to create a comparative MIP. Non-imprinted polymers (NIPs) were synthesized as controls. Complete template removal was verified after 8 washing cycles using UV-VIS spectroscopy. Brunauer-Emmert-Teller (BET), Fourier transform Infra-red (FTIR), thermogravimetric analysis (TGA), and ultraviolet (UV) spectroscopy were employed to characterize the unwashed MIPs, washed MIPS and NIPs. The characterization confirmed the formation of amorphous, mesoporous material with high surface areas, particularly after template removal. The disappearance of the vinyl C=C stretch (1635 cm-1) in the FTIR spectra confirmed complete polymerization while the peaks for the polymer backbone were confirmed by C-H vibrations at ⁓2980 cm-1 and ⁓1451 cm-1. The t-4MCA MIP exhibited a BET surface area of 175.2 m2 g-1 and a pore volumeof 0.190 cm3 g-1, markedly higher than the NIP (7.9 m2 g-1 and 0.009 cm3 g-1). TGA showed maximumdecomposition temperatures of 375oC, 379oC and 389oC for the washed t-4MCA MIP, unwashed t-4MCAMIP, and NIP, respectively, highlighting the good thermal stability of the polymer network. Swellingstudies showed differential swelling behavior dependent on solvent, with acetonitrile showing a highdegree of swelling for MIPs and ethanol for the NIPs. Adsorption studies, optimized using a 5:5 v/v methanol/water washing solution 10 mg of polymer mass, pH 7, and a 60-min contact time, revealed a maximum adsorption capacity (qm) of 3.00 mg g-1, for t-4MCA on the MIP, significantly exceeding that of the NIP (2.60 mg g-1) and PCM MIPs (2.4 mg g-1), with an imprinting factor of 1.14. Selectivity studies using structurally analogues ferulic acid, (E)-3-(4-hydroxyphenyl)prop-2-enoic acid (trans-4-hydroxy cinnamic acid (t-4HCA)), and ethyl (E)-3-(4-methoxyphenyl) acrylate (Et-MOPA) demonstrated a significant cross-reactivity with ferulic acid (k` = 0.356), moderate cross-reactivity with t-4HCA (k` = 2.340) and minimal cross-reactivity with Et-MOPA (k` = 1.635). Optimum photoisomerization of t-4MCA at 3 h resulted in the MIP increasing the reaction rate by a 21.63% increase in the cis isomer proportion. At 12 h, after total equilibration, there was evidence of an increased yield of the cis isomer of almost 10%. The Wittig reaction of 4-methoxybenzaldehyde yielded a percentage cis/trans ratio of 3/97. Crucially, conducting the reaction in the presence of the t-4MCA MIP improved the ratio to 6/94, an increase in the cis isomer ratio. This research demonstrated, for the first time, an attempt at the application of t-4MCA-imprinted MIPs as both selective adsorbents and stereo-directing agents. The MIPs significantly enhanced the proportion of the cis isomer in the photoisomerization reaction and, uniquely, in the Wittig reaction, highlighting their potential for efficient and sustainable production of diastereomerically pure pharmaceuticals and fine chemicals.Item Embargo Synthesis and Characterization of Pillared Graphene and Holey Graphene(2025-09-05) Makhado, Rinae; van Ree, T.; Legodi, M. A.Pillared graphene (pG) and holey graphene (hG) are derivatives of graphene designed to overcome issues with agglomeration and restacking between graphene sheets, which limit surface area and ion diffusion. These two types of graphenes have enhanced catalytic properties due to holes and pillars between the sheets. Graphene oxide (GO) is synthesized from graphite using Tour’s method and then reduced to reduced graphene oxide (rGO) with ascorbic acid as a reducing agent. Pillaring agents (maleoyl chloride, fumaryl chloride, oxalyl chloride) are inserted using Friedel–Crafts acylation, and holes are created using gradual thermal annealing. The infrared spectroscopic data confirmed the presence of polar groups such as hydroxyl and carboxyl groups on GO and rGO indicating that both GO and rGO were synthesized successfully. On IR analysis of the pillared graphenes synthesized using the three pillaring agents (maleoyl chloride, fumaryl chloride, oxalyl chloride) and the holey graphenes, it reveals the various vibrational stretches such as C-H, C=O, C=C, and C-O stretches at specific wavenumbers. The functionalized holey graphenes also showed similar vibrational bands. Overall, the results indicate successful synthesis of both pillared and holey graphenes using three different pillaring agents. XRD confirms the reduction of GO to rGO, this is evidenced by a decrease in interlayer spacing and the absence of an OH functional group in the IR spectra. It also reveals that the pillared graphene and holey graphene materials are fairly crystalline and also shows that the materials are amorphous. SEM showed that the holey graphenes comprise grains that are very tightly packed and compact. The low-resolution SEM micrographs confirm the XRD results, that the materials are amorphous. TEM analysis confirmed the presence of pores in the holey graphene - hrGOFC0.15, hGOMC0.15, and hrGOOC0.15 layers; therefore, the holey graphenes were successfully synthesized.Item Embargo Design and synthesis of potential chrome-based anti-tuberculosis agents(2025-09-05) Mogolla, Shibe Ncina; Ramaite, I. D. I.; van Ree, T.This dissertation describes the design and synthesis of 4-(4-oxochromen-3-yl)-3,4-dihydropyrimidin-2-one derivatives and the assessment of their biological activity against a strain of the causative agent of TB. In this investigation, two classes of chromone-based compounds were synthesised. Different reactions were exploited to synthesise target compounds. In the first route, a Vilsmeier-Haack reaction was applied to convert the 3,5-disubstituted/unsubstituted 2-hydroxyacetophenones to corresponding 6,8-disubstituted/unsubstituted chromone-3-carbaldehydes. The 6,8-disubstituted/unsubstituted chromone-3-carbaldehydes were oxidized to afford 6,8-disubstituted/unsubstituted chromone-3-carboxylic acids with poor percentage yield 15-28%. Additionally, a second series of compounds were obtained by employing the Biginelli reaction to afford ethyl 6-hydroxy-4-(6-substituted/unsubstituted chromon-3-yl)-2-oxo-6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives with moderate to good percentage yield of 53 – 74%. Ethyl 6-hydroxy-4-(6-substituted/unsubstituted chromon-3-yl)-2-oxo-6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-5-carboxylates were successfully dehydrated to ethyl 4-(6-substituted/unsubstituted chromon-3-yl)-2-oxo-6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives using a Dean-Stark method at 140 °C, purified by recrystallization. All target compounds were purified by recrystallization and flash chromatography, and then characterized using NMR and FTIR, LC-MS and HRMS. After fully characterizing target compounds, they were screened for activity against the Mtb H37Rv clinical strain. Three media were used for screening and MABA was used for quantitative analysis. Unfortunately, all compounds tested were inactive with an MIC value ˃62.5 μM. Ethyl 2-oxo-4-(4-oxo-6-phenyl-4H-chromen-3-yl)-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate with reported MIC of 3.39 μM also did not show any activity. The discrepancies in the results could be due to differences in media used, incubation conditions, bacteria or contamination. Derivatives with 4-substututed phenyl substituents, were insoluble with solubility <5 μM. The OH group was critical for solubility as removing it resulted in poor solubility. Ethyl 4-(6-substituted/unsubstituted chromon-3-yl)-2-oxo-6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives did not show any cytotoxicity against HepG2 cell line, with all compounds showing ˃50 μM toxicity.Item Embargo Application of organic acid functionalized cellulose for batch and aqueous two-phase extraction of sulfonamides from different matrices(2025-09-05) Shikweni, Mbuyelo; Mokgehle, T.; Tavengwa, N. T.; Ndou, D. I.Antibiotics are among the most widely used drugs globally, with fluoroquinolones, macrolides and sulfonamides being commonly prescribed. Sulfonamides, which form the basis of several sulfa drugs, have significant applications in both medicinal and synthetic organic chemistry. While these substances are effective in their intended uses, their negative environmental impact raises serious concerns. Sulfonamides can have toxic effects on aquatic ecosystems, leading to the disruption of microbial communities, bioaccumulation in organisms and the development of antibiotic resistance. To mitigate these effects, cellulose and its functionalized derivatives were investigated for their ability to adsorb sulfonamides from real wastewater, milk and honey samples. To improve adsorption, cellulose was functionalized with oxalic and adipic acid. The resulting sorbents were then analyzed using FTIR, PXRD and SEM techniques. Based on FTIR analysis the optimal reaction time for cellulose functionalized with adipic acid and oxalic acid via hydrothermal treatment in an autoclave was 1 h at a temperature of 50℃. Furthermore, the FTIR data revealed the emergence of ester moieties from the esterification reaction of carboxyl groups in the organic acids and the hydroxyl groups on cellulose. Based on PXRD analysis for the adipic acid functionalized cellulose contained a hybrid of adipic acid and oxalic acid peaks, indicating functionalization of cellulose. Batch adsorption experiments were conducted using sulfonamide based analytical standards: sulfachloropyradazine and sulfabenzamide, to evaluate the adsorption capability of cellulose and its functionalized derivatives at varying temperature, time, and mass of sorbent. The multivariate based optimal conditions for the adsorption of sulfachloropyradazine and sulfabenzamide using cellulose was 25°C, 180 min and 5 mg and with extraction efficiency of 70 and 51%, respectively. The optimal conditions for adsorption of sulfachloropyradazine and sulfabenzamide using oxalic acid functionalized cellulose was 25°C, 30 min and 50 mg with extraction efficiency of 64 and 75%, respectively. Adsorption of sulfachloropyradazine and sulfabenzamide using adipic acid functionalized cellulose was 25°C, 30 min, and 5 mg with extraction efficiency of 70 and 51%, respectively. Although cellulose functionalized with adipic and oxalic acid showed some influence on the adsorption behavior of sulfachloropyridazine and sulfabenzamide, the adsorption of sulfachloropyridazine was slightly reduced from 70% with unmodified cellulose to 64% with the functionalized form. Functionalizing cellulose with adipic and oxalic acid adds carboxyl and hydroxyl groups, enhancing adsorption of sulfachloropyradazine and sulfabenzamide through stronger hydrogen bonding, electrostatic interactions, and possibly π-π stacking, compared to cellulose. Overall, the functionalization of cellulose with these acids is a promising approach for enhancing the adsorption of sulfonamides which could be applied in wastewater treatment.Item Embargo UV-assisted isomerization studies of active compounds in bush tea (Athrixia phylicoides) leaf extracts and investigations of their potential to inhibit acid corrosion of mild steel and zinc(2025-09-05) Ratshikombo, Rinae; Murulana, L. C.; Kabanda, M. M.; Madala, N. E.Corrosion of metals can be controlled by using corrosion inhibitors. Plant metabolites undergo geometrical isomerization under the influence of UV light radiation. The use of corrosion inhibitors is one of the useful methods to reduce or decrease corrosion on metals. While synthetic inhibitors are useful in preventing the corrosion of metals, they can sometimes be harmful and costly. There is an alternative solution in the form of green inhibitors, which can offer the same level of protection at an affordable price. Inhibitors of corrosion are applied to the environment and the metal they protect against deterioration. Considering this information, it is necessary to examine different metals exposed to an acidic environment in the presence and absence of inhibitors. The impact of UV light radiation on bush tea (A. phylicoides) plant extract was investigated for zinc, and mild steel corrosion exposed to 1.5 M hydrochloric and sulphuric acids at 303-333K. This study employs liquid chromatography-mass spectrometry (LC-MS) to investigate the geometric isomerization of compounds within plant extracts, aiming to identify and quantify different isomers and understand the conditions influencing their stability and transformation. Gravimetric analysis (GA), Electrochemical Impedance Spectroscopy (EIS), and Potentiodynamic Polarization (PDP) were used to study corrosion inhibition, Fourier Transform Infrared Spectroscopy (FTIR) was used to analyze functional groups in the presence and absence of corrosion inhibitors. Contact angle or wettability studies (CA / WS) have been conducted to assess the hydrophobicity or hydrophilicity of the surface. Scanning Electron Microscopy (SEM) and computational studies were employed to gain a deeper understanding of the surface morphology and interactions between the A. phylicoides plant extracts and the metal surface. LC-MS chromatograph shows that the extract undergoes geometric isomerization. The GA, EIS, and PDP tests showed that the extracts were able to reduce the amount of corrosion that occurred on the metal surface. FTIR tests confirmed that the extracts were able to form a protective layer on the metal surfaces, which inhibited the corrosion process. The SEM and computational studies provided additional evidence that the extracts were able to reduce the corrosion rate by forming a protective layer on the metal surfaces. The results of the study showed that the extracts had a strong adhesive capacity and were able to form a stable protective layer on the metal surfaces. This layer was able to resist the corrosive action of the environment and prevent further corrosion. The study also showed that the extracts had good stability and were able to remain intact on the metal surface for a long time.Item Embargo Synthesis, Characterization and Corrosion Inhibition Investigation of substituted triazines on aluminium and mild steel in 1M HCl: Experimental and Theoretical approach(2025-09-05) Tshikhudo, Fulufhelo; Murulana, L. C.; Fernandez, C.; Mnyakeni-Moleele, S. S.; Kabanda, M. M.Corrosion is the natural process through which refined metals are gradually converted to more chemically stable forms such as oxides, hydroxides, or sulphides. This process occurs because metals tend to return to their natural states. Proper selection and use of corrosion inhibitors can greatly extend the lifespan of metal components and reduce maintenance costs. This current study investigates the synthesized substituted triazines, namely 4,6-dichloro-2-morpholine-1,3,5-triazine (DMT), 4.6-dichloro-2-anilino-1,3,5-triazine (DPT), and 4,6-dichloro-N-methylanilino-1,3,5-triazine (DNT) as corrosion inhibitor on aluminium (Al) and mild steel (MS) in 1M hydrochloric acid (HCl). The substituted triazines were successfully synthesized and characterized using Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared (FT-IR) spectroscopy, and liquid chromatography-mass spectrometry (LCMS). Thermogravimetric analysis (TGA) was performed on the DMT, DPT, and DNT inhibitors to determine the degradation temperature. It was observed that the mass loss of DMT, DPT, and DNT begins when the temperature reaches 85.91˚C, 181.007˚C, and 253.82˚C, respectively. Their anti-corrosive effect on Al and MS in 1M HCl was studied at a lower temperature using gravimetric analysis, electrochemical impedance spectroscopy (EIS), potentiodynamic polarization curve (PDP), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDX), and density functional theory approach (DFT). The weight loss measurement was carried out at different temperatures (303 to 323 K) and concentrations from 0.001M to 0.005M of the DMT, DPT, and DNT. The results obtained from the weight loss analysis revealed that the %IE of all the inhibitors is directly proportional to concentration on Al and MS. The highest inhibition efficiency of DMT, DPT, and DNT was observed at a concentration of 0.005M. On Al surface, the %IE of DMT and DPT decreased with increasing temperature, reaching 83.02% and 82.39% at 303 K, respectively. In contrast, DNT showed improved performance with rising temperature, achieving a maximum %IE of 95.02% at 313 K, making it the most effective inhibitor for Al under these conditions. On the MS surface, all three inhibitors exhibited a decrease in %IE with increasing temperature, with values of 93.87% (DMT), 90.20% (DPT), and 87.95% (DNT) at 303 K. The inhibitor adsorption on the Al and MS surface for all the inhibitors obeyed the Langmuir adsorption isotherm. The adsorption isotherm indicates the reaction is spontaneous, and inhibitor molecules adsorb onto Al and MS surface through weak force (Physisorption) and chemical bond (Chemisorption). viii | P a g e Based on EIS results, the Al impedance spectra consist of capacitive loops at a higher frequency and inductive loops at a lower frequency. In contrast, MS consists of a high-frequency capacitive loop. The capacitive loops represent the charge transfer resistance of the corrosion process and double layer. The inductive loops are attributed to the relaxation process in the oxide film covered on the metal surface. The PDP results revealed an increase in Ecorr (a less negative value) was observed with a sustained rise in the DMT, DPT, and DNT concentration. For Al, all inhibitors are either anodic or cathodic inhibitors according to changes in Ecorr and mild steel PDP, revealed that all the inhibitors are mixed typer inhibitors, implying that DMT, DPT, and DNT interfere with both the dissolution of the metal (anodic reaction) and the reduction of oxygen (cathodic reaction). The SEM/EDX confirms that DMT, DPT, and DNT inhibitors formed a protective film on the Al and MS surfaces, protecting them from a corrosive environment. From a water contact angle, the hydrophobicity of the Al and MS surfaces is enhanced in the presence of DMT, DPT, and DNT. The effect of graphene oxide (GO) into DMT, DPT, and DNT inhibitor in 1M HCl solution on MS as corrosion inhibitor was done using EIS and PDP. The modification of GO indicates an increase in the diameter of the Nyquist plot semi-circle and a shift in Ecorr to more negative on the Tafel plot. DFT using the perdew-burke-ernzehof (PBE) in the DMol3 program was used to perform inhibitorAl interactions to estimate the binding energies of the inhibitors on the Al(111) surface. The calculated binding energies value indicates that all inhibitor molecules physically bind on the Al(111) metal surface. For MS, the Perdew–Wang exchange (PW91) was used to perform inhibitorFe interaction. The binding energy calculation values indicate that all inhibitor molecules are chemically adsorbed onto the Fe(100) surface.Item Embargo Investigation of UV-Induced geometrical isomerisation of helichrysum kraussii extracts and their inhibition potentials for acid corrosion of mild steel, zinc and aluminium(2025-05-16) Sithuba, Tshedza; Murulana, L. C.; Kabanda, M. M.; Madala, N. E.Corrosion is the destruction of material due to chemical or electrochemical processes. Corrosion can be controlled by using corrosion inhibitors. Recently, plants have been explored as possible green corrosion inhibitors because they are environmentally friendly, easy to dispose, easily accessible and cheaper to extract or convert to inhibitors. Plant's metabolites or chemical constituents undergo geometrical isomerisation under the influence of UV light radiation. These changes might affect the extract's ability to inhibit corrosion. In this study, the effect of the UV light radiation on the Helichrysum kraussii (H. kraussii) plant extract was investigated through comparison with the non-UV-radiated H. kraussii plant extracts for mild steel, zinc and aluminium metal corrosion in 1.0 M HCl and H2SO4 at 30-60 ℃. This investigation was made possible by using techniques such as gravimetric weight loss analysis, Liquid chromatography-mass spectrometry (LCMS), Fourier transform infrared spectroscopy (FTIR), electrochemical analysis, contact angle, Scanning electron microscopy (SEM), Energy dispersive spectroscopy (EDS), and quantum molecular dynamic simulations. LCMS confirmed the formation of geometrical isomerisation when the H.kraussii extract was exposed to UV radiation. From the gravimetric analysis data, the corrosion rate (CR) was calculated and found to be decreasing with an increase in the concentration of the inhibitor extracts, with the highest concentration (1500ppm) at 30 ℃ having a corrosion rate of 3.92x10-4 and 1.70x10-4 g.cm2.h-1 for UV-radiated and non-radiated extract in 1.0 M H2SO4 for mild steel, respectively. Similar trends have been observed for the zinc and aluminium metals in HCl and H2SO4 solutions. The percentage inhibition efficiency (%IE) was found to increase with the increase in the two extract concentrations in the acidic media. In the presence of non-radiated extract, the % IE for mild steel in 1.0 M HCl was found to be 99.601% for 1500 ppm at 30 ℃. However, in the presence of UV-radiated H. kraussii extract, it was found to be 98.007%. The activation energy (Ea) values were found to increase with an increase in the concentration of both extract inhibitors. This suggests that the corrosion inhibition process of the three studied metals is through physisorption. The values of the change in Gibbs free energy (Δ𝐺𝑎𝑑𝑠𝑜) for both the extracts were found to be negative, indicating that the reaction between the inhibitor molecules and the metal surface was spontaneous. From the electrochemical impedance spectroscopy (EIS), the semi-circle diameter for mild steel and zinc metals and the circle diameter for the aluminium metal in the Nyquist plot was found to increase with an increase in the inhibitor concentration. The charge transfer resistance (Rct) values were found to increase with an increase in the extract inhibitor concentrations. For mild steel in 1.0 M H2SO4, the Rct values ranged between 8.751-26.52 Ωm2 and 10.20-26.41 Ωm2 for the UV-radiated and non-radiated extract, respectively. The introduction of the two extract inhibitors in the HCl and H2SO4 solution managed to reduce the corrosion current density (icorr) for mild steel, zinc and aluminium metals. The icorr values for mild steel in 1.0 M H2SO4 ranged between 397.202 -1395.884 mA.cm-2 and 343.358 – 1572.977 mA.cm-2 for the UV-radiated and non-radiated extracts. FTIR performed on the coated mild steel, zinc, and aluminium surface showed functional groups such as C=C, O-H, and N-H for both extracts, which are known to be functional groups of the most effective corrosion inhibitors. Contact angles were used to study the surface morphology of the metals, and it was observed that introducing the extract inhibitors in aggressive solutions changed the metal's surface from hydrophilic to hydrophobic surface. Computational simulations have been studied to demonstrate the most conceivable adsorption arrangements or configurations between the metal surface and the inhibitor. Parallel configuration of the inhibitor molecules on the metal surface was found to be the best configuration, giving high adsorption energy. SEM showed that introducing the two extract inhibitors in the acidic solution protected the metal surface from developing deep pits caused by the acid attack. EDS showed that corrosion took place on the metal surface and that the extract inhibitors were adsorbed on the metal surface based on the functional groups such as oxygen, calcium and nitrogen obtained on the metal surface. X-ray diffraction showed the presence of oxide on the metal surface confirming that the corrosion process took place. Based on the results obtained, it was found that the non-radiated H. kraussii extract was found to be more effective in inhibiting the corrosion of mild steel, zinc and aluminium metals in 1.0 M HCl and H2SO4 than the UV-radiated H. kraussii extract. This suggests that the UV radiation decreases the inhibition efficiency of the H. kraussii extract as an efficient corrosion inhibitor for mild steel, zinc and aluminium metals in 1.0 M HCl and H2SO4. Therefore, it is recommended that the H. kraussii extract be used only as a corrosion inhibitor for mild steel, zinc, and aluminium metals in 1.0 M HCl and H2SO4 in its original state without being exposed to UV radiation.Item Embargo Computational study of selected antimalarial and anticancer acylphloroglucinols(2025-05-16) Tshilande, Neani; Mammino, Liliana; Ghio, CaterinaMalaria and cancer tend to become drug-resistant few years after a drug is introduced into clinical use. This prompts the search for new molecular structures that are sufficiently different from the drugs for which resistance has developed. Acylphloroglucinols (ACPLs) are natural compounds with several biological activities. They are considered as possible lead structures for developing drugs against degenerative and other diseases. Computational studies are particularly important for biologically active compounds because their activities depend on their molecular properties, and knowing these properties (descriptors) is necessary for drug development. Representative ACPLs with anticancer and/or antimalarial activities were selected and computationally studied in vacuo and in three solvents with different polarities. All the calculations were done with completely relaxed geometry, using the Hartree Fock (HF) and Density Functional Theory (DFT) methods; second-order Moller-Plesset perturbation theory (MP2) calculations were also performed in vacuo. Structure-based virtual screening was used to study the interactions between these molecules and relevant proteins. The conformational studies identified conformational preferences and conformers’ stabilizing factors, among which intramolecular hydrogen bonds (IHBs) have dominant roles. The highest-occupied molecular orbital (HOMO) - lowest-unoccupied molecular orbital (LUMO) energy gap decreases and the dipole moment increases as the medium polarity increases. The solvent effect depends on the conformer type and the solvent polarity. The molecular docking analysis shows that most of these compounds bind well with the selected proteins and highlights the type of molecule-protein interactions for each case. These results indicate that the selected molecules are interesting for further steps in view of their possible development into antimalarial and anticancer drugs.Item Open Access Innovative Extraction and Identification of Rutin Flavonoid from Moringa oleifera Leaves Using UHPLC-qTOF-MS and Computational Metabolomics Tools(2024-09-06) Ndou, Dakalo Lorraine; Madala, N. E.; Tavengwa, N. T.; Ndlala, A. R.Moringa oleifera is a tree that has been studied extensively and it has been found to host a variety of medicinal and nutritional properties. Owing to these properties, it has often been referred to as a ‘miracle tree’. M. oleifera contains a variety of metabolites such as flavonoids, glucosinolates, phenolic acids, tannins, and carotenoids that are responsible for the pharmacological properties of this plant. In this study, the metabolite of interest in M. oleifera was the rutin flavonoid. Rutin has various pharmacological properties and its presence in M. oleifera makes the plant more bioavailable. In this study, the presence of rutin was evaluated in M. oleifera plants in households from different villages within the Vhembe District. The Molecular Networking (MN) approach was utilized to revisit the chemical space of flavonoids in M. oleifera. The aim was to establish the biochemical modifications responsible for the chemical diversity of these compounds, which have been reported to be associated with the purported pharmacological properties of this plant. Modern extraction methods such as ultrasonic-assisted aqueous two-phase extraction (UA-ATPE) and pipette tip micro-solid phase extraction (PT-μSPE) were explored in the extraction of the most bio-available and most sought-after flavonoid, rutin, in M. oleifera leaf extracts. This work has been divided into four experimental chapters. In Experimental Chapter 4, the presence of rutin was evaluated in the leaves of 135 M. oleifera plants from households in different villages within the Vhembe District of Limpopo Province of South Africa. The metabolite extraction was carried out using the conventional liquid extraction method using 80% MeOH and the resulting extracts were analyzed using UHPLC-qTOF-MS. The results from the UHPLC-qTOF-MS showed that only 15 plants produced rutin. This was confirmed using tandem mass spectrometry (MS2) and an authentic standard, which further validated the detected ion as a true representation of rutin. It was concluded that different cultivars of this plant are being grown in various households within the Vhembe District. These differences are expected to result in a negative perception towards Moringa plants, and as such, knowledge of the cultivar-chemical relationship should be made public with the intention to encourage the cultivation of proper plant species. The extraction of rutin from M. oleifera leaves using UA-ATPE was reviewed in Experimental Chapter 5. An ethanol/salt ATPE was formed for the extraction of rutin. Ultrasonication was used to assist in the extraction of rutin from the leaves. Central composite design (CCD) was used to design experiments and two factors which were optimized are ultrasonic time and ultrasonic temperature. The ammonium sulphate ((NH4)2SO4), sodium chloride (NaCl), and magnesium sulphate (MgSO4) salts were used to form the ethanol/salt ATPE two phase system. The resulting Response Surface Model (RSM) was observed to be a linear fit for the ethanol/(NH4)2SO4 and the ethanol/MgSO4 ATPE systems, with R2 values of 0.7339 and 0.5782, respectively, as obtained from the analysis of variance (ANOVA). The ethanol/NaCl ATPE system yielded a quadratic fit with R2 = 0.7865 and was observed to be the best performing in the extraction of rutin from the M. oleifera leaves with optimum extraction at a temperature of 25 ºC and time of 22.5 minutes. Based on multiple reaction monitoring (MRM) through the UHPLC-qTOF-MS technique, the concentration of rutin extracted by the ethanol/NaCl ATPE system was 240 μg L-1. According to ANOVA, temperature (the B-term) was found to be the significant term with a p < 0.0500 that the extraction of rutin through UA-ATPE is temperature-dependent. Therefore, it was concluded that the extraction of rutin from M. oleifera leaves favors low temperatures. The results of the current study further demonstrate the usefulness of simple extraction techniques, such as heated water with additives like salts, as a feasible method to enrich pharmacologically relevant metabolites from plants. This reaffirms traditional protocols that are currently used by communities which include boiling plants in water to extract useful chemical compounds for the treatment of common ailments such as colds and headaches. In Experimental Chapter 6, PT-μSPE was applied in the extraction of rutin from M. oleifera leaves using activated hollow carbon nanospheres (HCNSs) as the sorbent. The activated HCNSs were characterized using FTIR, which confirmed the presence of the functional groups of interest such as OH stretch, -COO- vibration, and C=O stretch. TGA thermogram showed a difference in the thermal stability of the raw and activated HCNSs, proving that the raw HCNSs are more stable than the activated HCNSs, and SEM displayed the difference in the morphology of the raw and activated HCNSs by observing the difference in the coalescence of the material. Parameters such as loading cycles, elution solvent, concentration of rutin, pH, loading volume, and mass of sorbent were optimized. The analysis of the extracts was conducted with a UV-Vis spectrophotometer to ascertain the recovery of rutin. The optimal conditions for rutin recovery using PT-μSPE were determined to be 15 loading cycles, i-PrOH as the elution solvent, a 2 ppm as standard concentration of rutin, a pH of 2, 500 μL as loading volume, and 1.5 mg of sorbent. The LOD, LOQ, and RSD values were found to be 0.604 mg L-1, 1.830 mg L-1, and 3.26%; respectively. It was thus confirmed that the PT-μSPE method is effective in the extraction of rutin even at trace levels based on the low LOD value obtained and the RSD value obtained proved that this method is a reliable pre-concentration technique and is thus repeatable for the analysis of complex samples. Therefore, in cases where some plants produce these compounds in minute concentrations, methods such as this one presented herein can be used to estimate and concentrate the pharmacologically relevant compounds. Molecular networking (MN) was used to study the global metabolic profile of M. oleifera and is outlined in Experimental Chapter 7. Herein, Global Natural Products Social (GNPS) platform was used to generate the MN from the LC-MS data obtained from the methanolic leaf extracts of M. oleifera. The MN was viewed and analyzed using Cytoscape. Through MN, it was observed that M. oleifera contains a variety of metabolites. Other GNPS tools such as network annotation propagation (NAP), DEREPLICATOR, MS2LDA, and MolNetEhancer were further used to compliment the classical MN model. To this end, MS2LDA was used to annotate the flavonoids found within M. oleifera. Kaempferol, quercetin, and isorhamnetin flavonoids were successfully annotated by MS2LDA. Additionally, Chrysin-6,8-C-diglucoside was also annotated and reported for the first time in M. oleifera leaves. The results of this study further suggest MN models as useful tools for chemical exploration, enabling the discovery of new metabolites by leveraging existing knowledge as "chemical charms" to unearth hidden metabolites.Item Open Access Synthesis and application of ion imprinted polymers for selective extraction of metal ions from different matrices(2024-09-06) Masindi, Muphulusi Lizzy; Mudzielwana, R.; Tavengwa, N.Exposure to toxic metal ions such as Zn2+ and Pb2+ can lead to several diseases including cancer on human being. This study aims to synthesize Zn2+and Pb2+ ion imprinted polymers (IIPs) for removal of Zn2+ and Pb2+ from various sample matrixes. Polymerization was achieved by mixing the methacrylic acid (MAA) as a functional monomer, ethylene glycol di-methacrylate (EGDMA) as a cross-linker, azobis (isobutyronitrile) (AIBN) as initiator and methanol as a progen. The temperature was increased to 80 oC while stirring for 7 h. The identical procedure was used to make non- imprinted polymer (NIP), but no template was used. Imprinted polymers were extracted with 2 M HCl for the removal of templates. The point of zero, or pHPZC, was determined and infrared spectroscopy was used to characterize the final products. The results of the Fourier-transform infrared (FTIR) analysis demonstrated the removal of ion templates by broad O-H peak at a wavelength of 3500 cm-1 and pHPZC results revealed that, at acidic solution, the imprinted polymers carried positive charges, and at basic solution pH, the imprinted polymers carried negative charges the PHPZC was found 6.98 and pH level was 7.0. The maximum percentage of Zn2+ removal using the Zn-IIP was found to be 80% when the solution pH of 7.0, adsorbent dose was 5 mg, contact time at 15 min at shaking speed of 100 rpm and initial metal ion concentration of 25 mg/L were used. The adsorption kinetic data corresponded to pseudo-second order reaction kinetics with R2 = 0.99, indicating that the process occurred by chemisorption. The Langmuir isotherm showed an excellent fit with an adsorption capacity of up to 9.03 mg g-1 and R2 = 0.99, implying that adsorption was on a monolayer surface. This study shows that zinc ion imprinted polymer has higher efficiency towards Zn2+ in the solution. The finding indicates that zinc ion imprinted polymer has high adsorption efficiency of 94.00 (mg/g) in removing zinc ion from the honey sample. The removal of Pb (II) from wastewater using Pb (II) IIP was found to be 90%. Further the re-usability study was evaluated 7 times and the adsorption efficiency was high at 90%, for this study the waste material can be beneficial for reused. The functional groups of both the imprinted polymer and the non-imprinted polymer were characterized by FTIR, and the point of zero charge was determined using the optimum conditions of 50 mg adsorbent dose, initial solution pH 9, and 15 min contact time. The adsorptive nature of the IIP and NIP was evaluated by means of Langmuir and Freundlich isotherms. The Langmuir adsorption isotherm modelled the data better, as shown by the Langmuir and Freundlich correlation coefficients of 0.999 and 0.975, respectively. An inventive answer has evolved in the form of ion-imprinted polymer, which was produced using the molecular imprinting approach as a basis. Higher selectivity coefficients have been demonstrated by IIPs compared to non-imprinted polymers.Item Open Access Synthesis of novel 2-thiohydantoin derivatives as potential anti-diabetic drugs(2024-09-06) Tshishonga, Unarine; Mnyakeni-Moleele, S. S.; Bvumbi, M. V.Thiohydantoin is a hydantoin with one carbonyl group replaced with a thiocarbonyl group. In this study five series (glycinates, alaninates, butanoates, vallinates and norvalinates) of thiohydantoin derivatives (21a-v) were successfully synthesized and characterized using known analytical characterization techniques. The synthesis of these compounds followed four reaction steps using conventional methods from step one with nucleophilic substitution to Knoevenagel condensation reaction as the final step. All twenty two compounds were obtained in good to excellent yields and were subjected to in vitro screening for their inhibitory activity against α-glucosidase. Among the five series of thiohydantoin derivatives, the alaninate derivative 21f exhibited the highest inhibition at both concentrations of 65 μM and 130 μM, with values of 71.13±0.61 and 64.20±0.54, respectively. The glycinate derivative 21j exhibited the highest inhibition of 60.95±1.07 at 130 μM, while butanoate derivatives showed a consistant moderate inhibition. Only compound 21z exhibited concentration-dependent trends of moderate inhibition on the norvallinates derivatives and the vallinates exhibited negligible inhibition.Item Open Access Synthesis, photoisomerization and antimalarial activities of cinnamoyl chloroquinoline hybrids(2024-09-06) Nemudzivhadi, Anza Imanuel; Bvumbi, M. V.; Mnyakeni-Moleele, S. S.The primary aim of this project was to synthesize a series of cinnamoyl chloroquinoline hybrids employing a technique of molecular hybridization. Cinnamoyl chloroquinoline hybrids are compounds with the heteroaromatic core of amino-7-chloroquinoline, linked to differently substituted cinnamic acid groups by flexible primary diamines. In this study, three series (n=2, 3 and 6) of nineteen cinnamoyl chloroquinoline hybrids 18-36 were successfully synthesized by modifying known conventional methods with yields ranging from 24-74%. The structures of synthesized compounds were characterized by a combination of 1H NMR, 13C NMR, HRMS and IR analysis. Hybrids 18-36 were found to isomerize when exposed to light to form mixture of cis and trans isomers. Through chromatographic mass spectrometry (LC-MS), these isomers were studied and LC-Q-TOF-MS/MS analyses of the photo-products revealed the emergence of cis isomer which eluted before its synthesized trans counterpart, suggesting a reduced polarity. The polarity of the compounds was significantly influenced by the nature of the substituents attached to the phenyl ring. Electron-withdrawing groups such as Cl, NO2, and F increased polarity in contrast to electron donating group OCH3 which reduced polarity. The concept of photoisomerization of cinnamoyl chloroquinoline hybridswere validated by the measurement of the transformation of trans to cis isomers using 1H NMR. Compounds 18-36 were tested against wild-type drug-sensitive strain (NF54) and multidrug-resistant isolate (K1) of the human malaria parasite Plasmodium falciparum. Compounds with longer alkyl carbon chain linkers demonstrated greater antiplasmodial activity compared to those with shorter chain linkers. The in vitro studies revealed that compound 32 showed the most potent activity (in vitro 50% inhibitory concentration, 0,012 μM for strain NF54 and 0,009 μM for strain K1 and resistance index of 0.717 as a potential antimalarial agent. Other compounds (compounds 34 and 35) also showed moderate activity against a CQ-sensitive strain (NF54) and superior activity against a CQ-resistant strain (K1) of Plasmodium falciparum.Item Open Access Risk assessment of the possible contamination of trace metals in fish samples from Lake Kariba, Zambia(2024-09-06) Poopedi, Phaphadi Maxwell; Tavengwa, Nikita T.; Chimuka, LukeExposure to inorganic endocrine disrupting chemicals (EDCs) has been linked to cause carcinogenic and mutagenic effects on human health and aquatic species. Trace metals in food are widely acknowledged as a public health concern yet largely ignored in many African nations where legislation is not yet fully implemented. Thus, the study aimed to extract and determine the toxic levels of inorganic EDCs of interest at certain doses and possible health risk associated with metal ions in fish sold in the open markets from Siavonga, Lake Kariba (Zambia). Sampling was done for two consecutive years, 2021 and 2022. Two fish species, which constitute Lake Kariba, were sampled; the bream (Oreochromis mortimeri) and Kapenta (Limnothrissa miodon): Firstly, twenty-eight fresh Kariba bream (Oreochromis mortimeri), five sun-dried Kariba bream (Oreochromis mortimeri) and five batches of sun-dried Kapenta (Limnothrissa miodon) were sampled from Lake Kariba open market. Secondly, six fresh Kariba bream (Oreochromis mortimeri), five sun-dried Kariba bream (Oreochromis mortimeri) and five batches of sun-dried Kapenta (Limnothrissa miodon), were purchased in an open market in Siavonga. Fish muscle tissues were excised to analyze trace metal ions before being digested using a microwave digestion system and analyzed using ICP-OES and MS. Eleven trace elements: Aluminum (Al), Arsenic (As), Cadmium (Cd), Chromium (Cr), Copper (Cu), Iron (Fe), Lead (Pb), Manganese (Mn), Mercury (Hg), Selenium (Se) and Zinc (Zn) were analyzed in fish muscle tissues (epaxial and hypaxial myomers). The results showed that the mean metal concentration for the first sampling was not significantly higher ( > 0.05) than the mean concentration for the second fish sampling, except for sun-dried Kapenta. The first sampling collected in November (2021) revealed that the fish collected on a Zambian open market contained higher levels of Cr, Mn and Fe ranging from 6.50±3.30 to 101.40±22.69 mg kg-1 in sun-dried bream. At the same time, sun-dried Kapenta contained high levels of Cr, Mn, Fe, As and Al ranging from 0.49±0.05 to 160.72±132.60 mg kg-1. In contrast, fresh bream contained high levels of Cr, As and Mn ranging from 13.99±7.96 and 22.30±12.20 mg kg-1. Compared to the second sampling around August (2022) they revealed high levels of Cr, Mn, As, Se and Fe ranging from 0.15±0.07 to 110.6±63.82 mg kg-1 in Sun-dried bream. In contrast, sun-dried Kapenta contained high levels of Cr, Mn, As, Se, Fe and Zn levels ranging from 0.78±0.03 to 187.8±58.59 mg kg-1. In comparison, fresh bream contained high Cr, Mn, As, Se and Fe ranging from 0.26±0.16 to 163.00±68.41 mg kg-1. The obtained results showed that the concentrations of metals exceeded the recommended maximum permissible limits proposed by the Joint Food and Agricultural Organization and World Health Organization (FAO/WHO) Expert Committee on food for fish consumption. However, fish were safe from adverse health effects due to Hg not being detected in fish sampled. The pollution index was assessed to determine the extent of pollution. The estimated daily intake (EDI) for all metals were higher than the provisional tolerable daily intakes (PTDI) recommended by FDA for both adults and children. Target hazard quotients (THQ) and hazard indices (HI) was higher than 1, indicating health risks from a non-carcinogenic lifetime of fish consumption. The lifetime average daily dose (LADD) was used to estimate the incremental lifetime cancer risk (ILCR). All metals were lower than 1×10 4 except for fresh bream 2021 for both children and adults, indicating a carcinogenic risk of 1 in 10,000 from consumption of Kapenta and Kariba bream from Lake Kariba in a lifetime. This raises concern over an adverse health effect on the consumption of fish consisting of excess trace metals. Long-term exposure to trace metals through fish consumption poses potential non-carcinogenic and carcinogenic health risks to the residents and suggests possible adverse health effects.Item Open Access Synthesis of sulfonylthioureas containing two carbon linker as potential antidiabetic drugs(2024-09-06) Mbhokazi, Tiyisela Nyeleti; Mnyakeni-Moleele, S. S.; Bvumbi, M. V.Target compounds (18a-s) from the series (morpholine, piperidine, N-methylaniline, 2,6-dimethylaniline and diethylamine) of novel sulfonylthioureas were designed and synthesized over three reaction steps using different appropriate synthetic methods. Nucleophilic substitutions were employed in order to incorporate amines, three different carbon linkers between amines and sulfonylthioureas moiety. Furthermore, nucleophilic substitution reaction was used to incorporate appropriate substituted isothiocynates as the final main step. Compounds (18a-s) were obtained in good to excellent yields and were characterized using a combination of 1H NMR, 13C NMR, IR and HRMS analysis. Compounds (18a-s) were evaluated for their antidiabetic activity against α-glucosidase and α-amylase. The in vitro screening results showed that most compounds had little to moderate activity against α-amylase at the concentrations of 60μM, 120μM and 240μM. When compounds were tested against α-glucosidase, they showed little to moderate antidiabetic activity at the concentrations of 60μM and 120μM but exhibited significant anti-diabetic activities at 240μM. Compounds that have a phenyl group substituent (18j, 18m, 18q, 18r and 18s with inhibition 70.21±5.97, 78±3.03, 76.33±2.03, 69.55±4.11 and 84.67±3.34 respectively at 240 μM) and a methyl group substituent (18q-s) exhibited stronger inhibition activity.Item Open Access Novel thiazolidinedione derivatives as corrosion inhibitors for mild steel and zinc in 1 M HCI(2024-09-06) Dube-Johnstone, Nhlalo M.; Murulana, L. C.; Mnyakeni-Moreele, S. S.Corrosion inhibition studies on mild steel (MS) and zinc in 1 M HCl were carried out at four temperatures (303.15 K, 313.15 K, 323.15 K, and 333.15 K) using eight novel thiazolidinedione derivatives (TZDs) codenamed: A1, A2, A3 (alaninates), B1, B2 (butanoates), G1, G2, and G3 (glycinates). After synthesis, the TZDs were characterized using nuclear magnetic resonance (NMR) spectroscopy. Specifically, two NMR techniques were employed: proton NMR (1H NMR) at 400MHz and carbon 13 NMR (13C NMR) at 100MHz. After characterization, five experimental techniques were employed to investigate the corrosion inhibition potential of the TZDs: weight loss (WL) analysis, potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS) and Fourier transform infrared spectroscopy (FTIR). The adsorption of the TZDs onto both metals was found to be best modelled by the Langmuir adsorption isotherm. Thermodynamic data showed that all TZDs adsorbed spontaneously onto both metal surfaces, transitioning from mixed type adsorption to chemisorption with an increase in temperature. However, WL analysis percentage inhibition (%IEWL) and activation energy (Ea) data showed that all TZDs adsorbed onto zinc via chemisorption. Data obtained from PDP analysis showed that the TZDs inhibit corrosion on MS at both anodic and cathodic sites, with a prevalence of cathodic action. However, on zinc, all TZDs inhibit corrosion exclusively at anodic sites. Data from EIS analysis showed that the adsorption of the TZDs onto both metals is a charge transfer driven process. The significantly depressed semi-circles obtained from zinc EIS data shows that capacitance plays much less of a role relative to MS, explaining the much lower phase shift (n) values obtained. Spectra obtained from FTIR analysis show that carbonyl, amine, nitro, aliphatic and aromatic functional groups all take part in the formation of an adsorption film on both metal surfaces.Item Open Access Evaluating the potential of the membrane technology for copper recovery from effluents and wastewater generated at copper mines and processing facilities in South Africa(2023-10-05) Ramabulana, Mpho; Ramaite, I. D. I.; Bazhko, O.Membrane separation is a well-known and widely used method in water treatment. It finds applications in mining and metallurgical processes and offers many potential benefits to the mining industry, such as significant water recovery from mine wastewater, excellent metal upgrades, and reagent recycling from process streams. This study evaluated membrane technology for the recovery of copper and recycling clean water from an aqueous effluent stream generated from copper mines. The copper content in the test work was 639 mg/L copper (Cu) in a synthetic solution and 427 mg/L copper in a real solution. Seven commercial flat sheets (FS) membranes were tested at a laboratory scale, and at the pilot scale, one spiral-wound membrane was tested. The performance of membranes was assessed, as well as the effect of various process parameters. It was demonstrated that nanofiltration (NF) technology could be effectively used to treat wastewater generated by copper mines. Five of seven evaluated membranes (AMS A3011, A3012, A3014, B4021, and DOW N90) were found to reject >90% of copper into the concentrate at operating pressure of 20, 30, and 40 bar at ambient temperatures. In all the evaluated membranes the following was observed; o An increase in the operational pressure increased operational flux; o However, as pressure and temperature increased, the rejection of copper and other metals decreased. During the optimisation of DOW N90 operational parameters, the following trends were identified: o Operational pressure is required as it improved operational flux, increased the rejection of copper, and minimized flux depreciation with time. o The temperature had a negative impact on flux; however, the optimum operating temperature has to be found because copper rejection can be compromised at higher temperatures. The DOW NF90, which was tested on a pilot rig, was also found to be suitable for treatments of the diluted copper solution, with a high copper rejection achieved. And a permeate recovery of 53.64% was achieved, but this value can be improved by increasing copper in the concentrate for further recovery.Item Open Access Synthesis of Novel 6, 8-Distributed-Chromone-3-Carboxamides and their evaluation as potential anti-tuberculosis agents(2023-10-05) Malusela, Thisundiwi; Ramaite, I. D. I.; Puka, L. R.This project focusses on the synthesis of novel 6,8-disubstituted-chromone-3-carboxamides and their evaluation as potential anti-tuberculosis agents. In this study, four 3-iodo-5-substituted-2-hydroxyacetophenones (58A-D) and three 3-bromo- 5-substituted-2-hydroxyacetophenones (63A-C) were successfully synthesized from 5- substituted-2-hydroxyacetophenones (57A-D). The Vilsmeier-Haack reaction was used to synthesize the 8-iodo-6-substituted-chromone-3-carbaldehydes and 8-bromo-6-substitutedchromone- 3-carbaldehydes from the 3-iodo/bromo-5-substituted-2-hydroxyacetophenones. These compounds were treated with sodium chlorite and sulfamic acid to afford corresponding chromone-3-carboxylic acids. Recrystallization with either ethanol or methanol was used to purify the synthesized compounds. All compounds were synthesized in good to excellent yields. The yields of the 3- iodo-5-substituted-2-hydroxyacetophenones (58A-D) ranged from 55 - 75 %, the 3-bromo-5- substituted-2-hydroxyacetophenones (63A-C) were synthesized with yields from 66 - 87 %, the percentage yields are significantly different probably because different methods were used. The yields of the 8-iodo-6-substituted-chromone-3-carbadehydes (59A-D) ranged from 78 – 90 %, the 8-bromo-6-substituted-chromone-3-carbaldehydes (64A-C) with yields from 85 - 87 %, 8-bromo-6-substuted-chromone-3-carboxylic acids from 47 – 52 %, and chromone-3- carboxylic acid afforded a yield of 57 %. 1H NMR, 13C NMR and FTIR spectroscopic techniques were used to characterize synthesized compounds and also confirmed by melting points for compounds reported in literature.Item Open Access Synthesis of novel-6.8-disubstituted-chromone-2-carboxylic acid derivatives and their biological evaluation as potential antimalarial agents(2023-10-05) Mabasa, Nyiko Samuel; Ramaite, I. D. I.; Tavengwa, N. T.Malaria is a mosquito vector-borne disease caused by a female anopheles mosquito belonging to a plasmodium genus, affecting more than 500 million people per annum. There are five plasmodium genus responsible for causing malaria, but four of them are responsible for causing human malaria. The most common one to cause malaria in Africa is P.Falciparum. The most commonly used drugs for malaria are quinine derivatives and artemisinin derivatives which are both derived from traditional plants. Malaria parasites have become resistance to almost all the currently used drugs. In this project different synthetic approaches were used to prepare novel chromone derivatives. This study was focused on the synthesis of various 6.8-substituted-chromone-2-carboxylic acids (41) derivatives from the corresponding 5-substituted-2-hydroxyacetophenones (38). The first step included the introduction of iodine on the 5-subsituted-2-hydroxyacetophenones (38) to give 5-substituted-3-iodo-2-hydroxyacetophenones (39A-D). The same step was repeated but with bromine to give 5-substituted-3-bromo-2-hydroxyacetophenones (39E-H). The 3.5-disubstituted-2-hydroxyacetophenones (39A-H) underwent condensation with diethyl oxalate and sodium ethoxide to form ethyl-6.8-disubstituted-chromone-2-carboxylates (40A-H), which was converted to the corresponding 6.8-disubstituted-carboxylic acids (41A-H). Attempted conversion of the acids to the corresponding carboxamides 43 via the carbonyl chloride intermediates (42A-D) was unsuccessful. The percentage yield of synthesized 3.5-disubstituted-hydroxyacetophenones (39A-H) ranged between 46-82 %, whilst those of ethyl-6.8-disubstituted-chromone-2-carboxylates (40A-H) intermediates ranged between 44-95 %. The yields of synthesized 6.8-disubstituted-chromone-2-carboxylic acids (41A-H) ranged between 48-98 % while the corresponding acids chlorides (42A-D) ranged between 44-60 %. Our attempted synthesis of 6.8-disubstituted-chromone-2-carboxamides (43) was unsuccessful. Compounds (39-43) were purified by recrystallization and characterized using NMR and FTIR spectroscopic techniques.Item Open Access Phytochemistry and biological studies of constituents from Breonadia Salicina (VAHL) Hepper and J. R. I. Wood(2023-10-05) Tlhapi, Bafedile Dorcas; Ramaite, I. D. I.; Van Rhee, T.; Anokwuru, C. P.Breonadia salicina (Vahl) Hepper and J.R.I. Wood is a tree used widely to treat numerous infectious diseases in South Africa and other African countries, and ethnopharmacological studies have shown a number of biological activities of the crude extracts. Furthermore, phytochemical studies have indicated that the stem bark is rich in tannins, and alkaloids have been isolated from the twigs and leaves. However, few studies have correlated the phytochemistry to the physiological activties. This study aimed to explore the phytochemistry of B. salicina using a metabolomic approach and correlating the phytochemistry to the biological activities for possible drug development. Samples of B. salicina were collected at Fondwe, Limpopo Province, South Africa. Phytochemical studies followed a metabolomics approach, with repeated column chromatography and preparative thin-layer chromatography yielding a number of pure compounds. Antimalarial and antitrypanosomal activities of the crude extracts, pure compounds, fractions, and seasonal samples were evaluated using the parasite lactate dehydrogenase (pLDH) and Trypanosoma brucei assays, respectively. Furthermore, the antioxidant activities of the crude extracts, fractions and pure compounds were evaluated using DPPH (2,2-diphenyl-1-picrylhydrazyl) and reducing power assays. The antimycobacterial activities of the crude extracts and fractions were determined against Mycobacterium tuberculosis (H37RvMA strain), and anti-diabetic activities of the crude extracts were determined using α-amylase and α-glucosidase inhibition assays. The anti-inflammatory activities of the crude extracts were assessed using the Griess assay, while the in vitro toxicology of the crude extracts was evaluated using cell toxicity, NucRed nuclei dye, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Hoechst 33342/Propidium iodide (PI) dual staining assays. Eight compounds (bodinioside Q, 5-O-caffeoylquinic acid, D-galactopyranose, hexadecane, kaempferol 3-O-(2’’-O-galloyl)-glucuronide, lupeol, palmitic acid, and sucrose) were isolated for the first time from the root, stem bark, and leaf extracts of B. salicina, while 51 compounds were tentatively identified from the crude extracts, fractions and seasonal samples by UPLC-QTOF-MS and 1H-NMR spectroscopy. The aligned UPLC-QTOF-MS data were analysed chemometrically to determine the chemical variability of the crude extracts of the roots, stem bark, and leaves collected during four different consecutive seasons. The principal component analysis (PCA) model, hierarchical cluster analysis (HCA) and partial least square discriminant analysis (PLS-DA) were constructed. These indicated the presence of two main clusters related to the different parts of the plant (root, stem bark, and leaf). In the antiplasmodial activity, three fractions collected in the first year affected the viability of Plasmodium falciparum, with viabilities of 16.16 ± 8.63 %, 27.01 ± 4.47 % and 31.07 ± 6.71 %; and IC50 values of 2.19 ± 0.09 μg/mL, 1.91 ± 0.05 μg/mL and 3.02 ± 0.08 μg/mL, respectively, at a concentration of 10 μg/mL. However, all the tested crude extracts and fractions collected in the first year contained potent antiplasmodial activities at a concentration of 50 μg/mL. Furthermore, the dichloromethane leaf extract collected in the second year in autumn, winter, spring and summer displayed high activities, with viabilities of 18.57 ± 1.99 %, 32.07 ± 4.91 %, 38.11 ± 5.07 % and 20.21 ± 5.19 % at a concentration of of 50 μg/mL with IC50 values of 7.90 ± 0.06 μg/mL, 18.15 ± 0.07 μg/mL, 19.40 ± 0.06 μg/mL and 15.26 ± 0.05 μg/mL at a concentration of 300 μg/mL, respectively. The pure compounds, including kaempferol 3-O-(2"-O-galloyl)-glucuronide (1) and palmitic acid (8), caused a significant decrease in parasite viability at a concentration of 50 μg/mL, with viabilities of 29.37 ± 1.29 % and 24.97 ± 5.21 %; and IC50 values of 9.06 ± 0.036 μg/mL and 6.792 ± 0.046 μg/mL at a concentration of 200 μg/mL. In the antitrypanosomal test, the crude methanol leaf extract, dichloromethane leaf extract, and two fractions attained in the first year strongly affected the viability of trypanosomes at the tested concentration of (50 μg/mL), with a viability of 6.74 ± 0.06 %, 6.38 ± 2.15 %, 7.78 ± 0.08 % and 5.05 ± 0.35 %; and IC50 values of 11.4 ± 0.42 μg/mL, 10.6 ± 0.07 μg/mL, 2.0 ± 0.09 μg/mL and 7.1 ± 0.14 μg/mL at a concentration of 300 μg/mL, respectively. Furthermore, the crude methanol leaf extract collected in the second year in autumn, spring and summer displayed higher activities, with viabilities of 5.84 ± 0.38 %, 26.66 ± 3.91 % and 9.05 ± 0.80 % at a concentration of 50 μg/mL; and IC50 values of 12.0 ± 0.36 μg/mL, 5.2 ± 0.74 μg/mL and 10.6 ± 0.07 μg/mL at a concentration of 300 μg/mL, respectively. However, the crude dichloromethane leaf extract collected in the second year in autumn, winter, spring and summer displayed higher activities, with viabilities of 3.50 ± 0.59 %, 4.13 ± 0.06 %, 29.47 ± 1.25 % and 3.85 ± 0.10 % at a concentration of 50 μg/mL; and IC50 values of 4.6 ± 1.82 μg/mL, 5.1 ± 0.30 μg/mL, 5.1 ± 0.72 μg/mL and 4.0 ± 0.08 μg/mL at a concentration of 300 μg/mL, respectively. The isolated compounds, including bodinioside Q (4), kaempferol 3-O-(2"-O-galloyl)-glucuronide (1), lupeol (2), and palmitic acid (8), exhibited antitrypanosomal activity with viabilities of 12.99 ± 0.53 %, 20.38 ± 2.35 %, 5.46 ± 0.04 %, and 5.83 ± 0.28 % at a concentration of 20 μg/mL; and IC50 values of 4.0 ± 0.09 μg/mL, 1.1 ± 0.22 μg/mL, 4.2 ± 0.27 μg/mL and 5.7 ± 0.09 μg/mL, respectively; On the other hand, the reference drug pentamidine showed an IC50 of 10.2 ± 0.07 μg/mL. The anti-oxidant assays revealed that the crude stem bark extract had the highest DPPH free radical scavenging activity, with an IC50 of 41.7263 ± 7.6401 μg/mL. Furthermore, the crude root extract had the highest reducing power with an IC0.5 of 0.1481 ± 0.1441 μg/mL. In the antimycobacterial activity test, none of the tested plant samples produced significant antimycobacterial activity at a concentration of 90 μg/mL. All the samples produced a MIC value of >62.5 μg/mL against 7H9_ADC_GLU_TW, 7H9_ADC_GLU_N_TW and 7H9_ADC_GLY_TW media. Furthermore, the crude stem bark and root extracts showed very strong antidiabetic activity at the lowest tested concentration of 62.5 μg/mL, with an inhibition of 74.53 ± 0.737 % and 79.1 ± 1.494 % against α-amylase enzyme. However, for the α-glucosidase inhibition assay, the crude stem bark and root extracts showed complete inhibition at the lowest tested concentration of 31.3 μg/mL at 98.20 ± 0.15 % and 97.98 ± 0.22 %. The crude dichloromethane leaf extract showed a decrease in nitrite concentration at the highest concentration of 200 μg/mL, with a cell viability of 79.06 ± 1.88 %, indicating anti-inflammatory activity. The crude stem bark, root and methanol leaf extracts were not cytotoxic against Vero cells at the concentrations of 15.125 μg/mL, 31.25 μg/mL, 125 μg/mL and 250 μg/mL. Furthermore, none of the extracts were cytotoxic at the following concentrations: 50 μg/mL, 100 μg/mL and 200 μg/mL, against RAW 264.7 macrophages. However, the crude stem bark and root extracts showed cytotoxic effects against Vero cells at 250 μg/mL.Item Open Access Experimental and theoretical studies of the inhibition potential of Lippia javanica plant extracts for the corrosion of aluminium, mild steel, and zinc metals in acidic medium(2023-10-05) Nesane, Tshimangadzo; Murulana, L. C.; Kabanda, M. M.; Madala, N. E.Corrosion is a natural phenomenon considered a chemical and an electrochemical process of metals interacting with the surrounding corrosive environment. Inhibition is a preventive measure used by corrosion engineers to reduce the effects of corrosion on metals, the environment, society, and the economy. The current study investigates the use of the Lippia javanica plant as an ecofriendly green inhibitor for mild steel (MS), aluminium (Al), and zinc (Zn) corrosion in a 1 M HCl environment. The leaf extracts were prepared by the Soxhlet extraction method using methanol, ethanol, and acetone as solvents. The leaf extracts of L. javanica were characterized using Fouriertransform infrared spectroscopy (FT-IR) and Liquid chromatography-mass spectrometry (LC/MS) analysis. The inhibitory potential of L. javanica extracts was established by performing weight loss measurements, electrochemical methods such as potentiodynamic polarization (PDP), and electrochemical impedance spectroscopy (EIS) techniques. The weight loss assessment was carried out at different temperatures (303 to 333 K) and varying concentrations of the extracts from 200 to 800 ppm. The technique was also used to determine the stability of the extract with varying immersion times. Weight loss measurements showed that the inhibition efficiency increased with increasing concentration of the extracts up to 800 ppm for all three metals. Increasing the temperature of the corrosive environment resulted in a decrease in the inhibition efficiency of Al and MS corrosion, with that of Zn increasing with temperature. The variation of inhibition efficiency with time showed a similar trend, with the protective efficiency of Al and MS decreasing with time and Zn increasing with immersion time. Increasing Zn’s inhibition efficiency with temperature and immersion time implies a chemical protection mode. The reduction in the inhibition efficiency with temperature and immersion time for Al and MS suggests a physical protection mode. According to EIS measurements, the extracts adsorb onto Al, Zn, and MS surfaces to create a protective coating with pseudo-capacitive properties. The only component of the Zn and MS Nyquist plots in the high frequency was a capacitive loop, but the Al plots also showed an inductive loop at a lower frequency. The higher frequency loop represents the resistance for the charge transfer during the corrosion process. In contrast, the lower frequency loop represents the relaxing of hydrogen ions and the adsorption of corrosive chloride ions onto the oxide film. The PDP results revealed that for Al and MS, the three extracts had a similar impact on both the anodic and cathodic half-reactions. In contrast, both half-reactions were affected for Zn, but the cathodic area was more significantly impacted. Undulation Tafel curves for MS and Zn were observed with and without the extracts; however, a longer passive region was detected for Al, particularly in the presence of the plant extracts. The investigational extracts function as mixed-type corrosion inhibitors for Al, Zn, and MS, as indicated by the control of both the anodic and cathodic areas with the introduction of the extracts. Among the many plotted isotherms for the three extracts on the metal surfaces, the Langmuir adsorption isotherm was determined to be the best-fit isotherm. The isotherm confirmed the mechanism of adsorption, which was a mixed-type adsorption for Al, Zn, and MS. Spectroscopy studies revealed that the interaction of the three extracts with Al, Zn, and MS resulted in the formation of metal-inhibitor complexes, which slowed the corrosion process. Scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS) studies demonstrated that L. javanica leaf extracts form a protective film on Al, Zn, and MS surfaces, protecting them from the corrosive environment. Theoretical simulations showed that the primary extract constituent (verbascoside) had binding energy greater than 13 kcal/mol on the surfaces of Zn(110), Al(111), and Fe(110). The high binding energy indicates a mixed-type binding process that includes chemisorption and physisorption. All corrosion experiments revealed that the three extracts exhibited superior inhibition performance for all the three metals studied with comparable results in 1 M HCl corrosive solution.