Chemistry

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Adsorption of pharmaceuticals by nano-molecularly imprinted polymers (nano-MIPs) from wastewater: kinetics, isotherms, and thermodynamics studies.
(2024) Nxumalo, Nonhlazeko Loveday.; Mahlambi, Precious Nokwethemba.; Mahlambi, Mphilisi.; Mngadi, Sihle.; Chokwe, Tlou.
It has been reported that pharmaceuticals are not entirely removed or broken down during the wastewater treatment process, allowing them to escape into effluent water. This stems from the pharmaceuticals widespread use and the inefficient wastewater treatment methods. Therefore, the objective of this study was to develop more effective methods for removing pharmaceuticals from wastewater systems. Adsorption-based pharmaceutical removal is one of the most promising approaches because it is easily incorporated into current water treatment systems. The first part of this work reports on literature studies for recent advancements in the adsorption process involving the incorporation of an artificial molecularly imprinted polymer (MIP), that is an effective molecular receptor that can selectively recognize and remove pollutants. In magnetic solid-phase extraction, dispersive solid-phase microextraction, and solid-phase extraction, MIPs can be used as a selective adsorbent for analyte cleanup and preconcentration. Moreover, MIPs can be produced by combining nanoparticles to develop composite nanomaterials (nanoMIPs). In comparison to conventional bulk adsorbents, the enhanced selective adsorption capacity and kinetics are attributed to the large surface area per unit volume and specific functionality of nanomaterials. Nonetheless, some significant barriers to the application of nanomaterials are their dispersive qualities, difficulty in cycling, and secondary pollution from the loss of adsorbent during treatment. Another way to use nanoparticles for detectability enhancement is to modify the molecularly imprinted polymers chemical or physical characteristics. The nanoparticles' embedding in the MIP enhances the material's surface area or gives the adsorbent new features. This study describes a method for creating reusable, economical, and effective polymer-based silver nanoparticles-adsorbents. Notably, silver nanoparticles have a wide range of applications due to their unique properties which include their large surface area, shape and size. Plant-mediated synthesis plays a significant role in their synthesis. Remarkably, the synthesis of silver nanoparticles from plant extracts is inexpensive, easily scalable, and harmless for the environment. Plant extracts can be used to produce nanoparticles with controlled sizes and shapes. The molecular imprinting technique was used to create species-specific functionalities like carboxylic acid (-COOH) on a polymer surface. MIPs offer several advantages, including large surface area, targeted functionalities for high reactivity, and the ability to minimise nanoparticles from leaking into the surrounding environment when MIP-based adsorbents are being handled. To further comprehend the behaviour of adsorbents and the adsorption process, kinetics, thermodynamics, and isotherm models were explored. The second part of the work involved synthesizing the MIPs for efficient and selective removal of pharmaceuticals from specific groups. All target compounds were employed as multiple templates in a bulk polymerization process carried out at 70 °C to synthesize MIPs. Additional reagents utilized in the synthesis included toluene as a porogenic solvent, ethylene glycol dimethacrylate as cross-linker, 1,1'-azobis-(cyclohexane carbonitrile) as an initiator and 2- vinyl pyridine as functional monomer, respectively. The synthesis of a non-imprinted polymer (NIP) was conducted without templates, using reaction conditions similar to those of MIP. Furthermore, following the synthesis, the polymers were characterized using X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Liquid chromatography-mass spectrometry (LC-MS) was successfully used to develop an analytical method for detection and quantification of the target pharmaceuticals. The method yielded quantification limits of 0.42 to 0.75 mg L-1 and detection limits of 0.14 to 0.25 mg L-1 for the target pharmaceuticals. The synthesized polymer attained maximum matrix-matched adsorption capacities of 3.89, 4.97 and 3.40 mg g-1 for sulfamethoxazole, nevirapine and ibuprofen, respectively within 10 minutes. Competitive adsorption of the target pharmaceuticals demonstrated a link between adsorption and the pharmaceuticals pKa, log Kow, and molecular size. Studies on batch adsorption and kinetics revealed that the binding of pharmaceuticals to the MIP particles suited the pseudo-second order kinetics, leading to various interactions through chemisorption. The data also fitted well in Langmuir isotherm which meant that the target pharmaceuticals adsorption occurred on the homogeneous binding sites of the MIP. Furthermore, the thermodynamic data demonstrated the adsorption process's endothermic and spontaneous nature. Notably, the synthesized MIP was highly selective and its application in environmental studies led to the development of a less expensive analytical method. Moreover, the MIP particles that had been generated were recovered to be reusable up to five cycles with removal efficiency >90%. The third part involved incorporating silver nanoparticles (AgNPs) into MIPs using ibuprofen, nevirapine, and sulfamethoxazole as templates. In this part, starch (St) and macadamia nutshells (MCD) were employed in the synthesis of AgNPs as reducing and stabilizing agents. Following that, each of these AgNPs was incorporated with MIP, and the most effective combination was identified through comparison. The synthesized adsorbents were further optimized for the adsorptive removal of selected target pharmaceuticals. The % removal efficiencies were greater than 70%, indicating that the adsorbents are suitable for use in water treatment processes. The material's adsorption mechanisms and performance were examined through the application of various kinetics and isotherm models. Both the St and MCD-AgNPs experimental data fit to Freundlich and Langmuir adsorption isotherms. However, based on the somewhat higher correlation coefficients, the Langmuir isotherm model provided a better fit. The St/MCD nanoMIPs best suited the Freundlich model, indicating that the adsorption occurred on the multilayer heterogeneous surface. Further, both the St/MCD nanoMIP adsorbents underwent spontaneous, endothermic adsorption, as demonstrated by the thermodynamic data, whereas the behaviour of the kinetics was effectively anticipated by pseudo-second order model, which suggested adsorption through chemisorption. Accordingly, large internal surface area, greater loading capacity, thermal stability, and reusability were among the advantageous properties of the nanoMIPs adsorbent materials. Moreover, both adsorbents showed improved qualities and were highly selective and effective in removing the selected pharmaceuticals in wastewater. As a result, during the course of five adsorption/desorption cycles, the St/MCD nanoMIPs show a removal efficiency of more than 90%. As a result, they demonstrated proficiency in efficient application. The fourth part involved the incorporation of MIP with Platanus acerifolia and Moringa oleifera silver nanoparticles. Using plants to synthesize AgNPs is a more cost-effective and lowmaintenance method; in contrast, using other organisms requires a particular medium and a specific amount of time. Therefore, the leaves of both the platanus acerifolia (PL) and moringa oleifera (MO) served as stabilizing and reducing agents during the synthesis of AgNPs. Each optimized parameter that could influence the adsorption potential, such as temperature, adsorbate concentration, pH, adsorbent dose, and contact time, was examined in relation to the removal effectiveness of the MO/PL nanoMIP adsorbents. These evaluated parameters were optimum at pH 7, concentration of 0.2 mg/L and contact time of 10 minutes for both MO and PL-nanoMIPs, mass dosage of 30 mg and 20 mg, and temperature of 40 and 30 °C for MO and PL-nanoMIP, respectively. Further, the maximum removal efficiencies obtained at these optimum conditions were >97% for both MO-nanoMIP and PL-nanoMIP. The adsorption experimental data for both MO/PL-AgNPs and MO/PL-nanoMIPs nano-adsorbents fitted with the linear Langmuir model which suggests that the binding took place on the homogenous monolayer surface. Additionally, compared to MO/PL-AgNPs, the MO/PL-nanoMIPs adsorption capacities for the target pharmaceuticals were higher, suggesting that the nanoMIPs larger surface areas contribute to their enhanced adsorption capacity. The linear pseudo-second order kinetic model best fitted on MO/PL-nanoMIPs which implied adsorption through chemisorption, whereas the thermodynamic data demonstrated that the adsorption process was endothermic and spontaneous. Moreover, the values of ΔH° for the MO/AgNPs were less than 40 kJ/mol and more than 40 kJ/mol for the MO/PL-nanoMIPs. This therefore confirmed that the MO/AgNPs was dominated by physical adsorption whereas the MP/PL-nanoMIPs was dominated by chemical adsorption. The MO/PL-nanoMIPs confirmed the high efficiency for the removal of target pharmaceuticals in wastewater. Upon recycling the adsorbents for five cycles, it was noted that the MO-nanoMIP adsorbent was effective continued to remove 86.7- 88.8% and 97-98% for PL-nanoMIP even in the fifth cycle. Indeed, the removal of sulfamethoxazole, nevirapine, and ibuprofen by nanoMIP adsorbents has demonstrated the importance of the surface area, structural stability, pore size and the electrostatic interactions brought about by the charges on the nanoMIPs surface. Consequently, among the investigated nanoMIP adsorbents, PL-nanoMIP demonstrated strong adsorption capacities for the targeted pharmaceuticals due to it large surface area and narrow size distribution as compared to the other nanoMIP adsorbents. The usability of plant leaves as a reducing and capping agent for nanoparticles as well as the recycling of nanoMIPs has the potential to transform waste that is no longer useful into valuable pollutants adsorbents. This would solve the problem of waste disposal and have beneficial impacts on the environment pollution and the economy. Notably, the nanoMIPs synthesized in this study are highly selective, reusable adsorbents that are cost effective and environmentally friendly. In contrast, as a substitute for more costly synthetic materials, these nanoMIPs are a promising material for the removal of different classes of pharmaceuticals in wastewater treatment plants and they can possibly be applied on a large scale.
Assessment of antiretroviral drugs uptake by vegetables from contaminated soil and their adsorption by exfoliated graphite in river and wastewater.
(2022) Kunene, Philisiwe Nganaki.; Mahlambi, Precious Nokwethemba.
This study was directed toward vegetable uptake of the commonly used antiretroviral drugs (ARVDs), abacavir, nevirapine, and efavirenz. Antiretroviral drugs are used to treat the human immune-deficiency virus (HIV). South Africa (SA) is one of the countries with a high number of infected people on ARV therapy, therefore, the ARVDs are anticipated to be existing at high concentrations in the South African environment than in other countries worldwide. In recent years, the presence of ARVDs in the environment has drawn attention; hence studies have reported their presence in aquatic environments while very few studies have been conducted on their uptake using vegetables. This work was therefore based on the optimization and application of sensitive, simple, cost-effective, and robust techniques for quantifying ARVDs in vegetables. Based on this information, ultrasonic extraction (UE) and microwave-assisted extraction (MAE) were used to isolate target compounds from vegetable samples to the aqueous phase. Dispersive liquid-liquid microextraction (DLLME) and solid-phase extraction (SPE) were utilized to preconcentration and clean up the extracts from UE and MAE, respectively. A liquid chromatography photodiode array detector (LC-PDA) was utilized to detect and quantify the extracted compounds. The UE with and without DLLME cleanup were compared with each other, also, MAE with and without SPE cleanup were compared with each other. The methods comparison was done in terms of their detection (LOD) and quantification limits (LOQ), extraction efficiencies (%Recovery), relative standard deviations (%RSD), and concentrations of ARVDs found in vegetable samples. In comparison of UE and ultrasonic-assisted dispersive liquid-liquid microextraction (UADLLME), the LOD and LOQ obtained ranged between 0.0081 - 0.015 μg/kg and 0.027 - 0.049 μg/kg for UE and 0.0028 -0.0051 μg/kg and 0.0094 - 0.017 μg/kg for UADLLME respectively. High recoveries ranging from 93 to 113% in UE and 85 to 103% in UADLLME with less than 10% RSD in both procedures were obtained. These results indicated that UADLLME is more sensitive than the UE method, although they are both accurate and precise. The UE can be recommended for routine analysis as UADLLME showed the inability to extract analytes from root vegetables. The optimized UE and UADLLME methods were applied to extract ARVDs from vegetables bought from local fruit and veggie supermarket. Vegetables were categorized as root (carrot, potato, and sweet potatoes), leaf (cabbage and lettuce), and fruit (green paper, butternut, and tomato). The target ARVDs were quantified in most samples with concentrations up to 8.18 μg/kg. The concentrations obtained were slightly high in UADLLME than in UE as a result of its high sensitivity. Efavirenz was the most dominant drug, while the potato was the most contaminated vegetable. In the comparison of MAE and MAESPE, the obtained LOD and LOQ ranged from 0.020 to 0.032 μg/kg and 0.068 to 0.109 μg/kg for MAE and 0.019 to 0.066 μg/L and 0.065 to 0.22 μg/L for MAE-SPE. The obtained recoveries ranged from 85 to 103% for MAE and from 82 to 98 % for MAE-SPE, respectively, and the RSDs were all less than 6%. These results showed that both methods have comparable sensitivity; however, the recoveries values for MAE were slightly higher than those obtained in MAE-SPE, which signals MAE’s high accuracy. The optimized MAE and MAE-SPE methods were applied to remove ARVDs in the root (potatoes, onions, and beetroot), leaf (lettuce, and spinach), and fruit (green paper, cucumber, and eggplant) vegetables bought from local fruit and veggie supermarket. The obtained ARVDs concentration range was 1.48 ± 0.5 - 27.9 ± 1.2 μg/kg. The MAE-SPE resulted in low concentration compared to MAE without cleanup. Beetroot exhibited high concentrations of the target ARVDs, while nevirapine was found to have high concentration and as a dominant compound. The results obtained revealed that the vegetables from the studied area are contaminted with ARVDs, which could indicate their possible irrigation with wastewater effluent or the use of sludge as biosolids in the agricultural areas. This is a concern as it leads to unintentional consumption by consumers which could lead to drug resistance by the human body or have human health effects. The study was then expanded by conducting the phytoremediation approach to investigate the uptake of abacavir, nevirapine, and efavirenz by beetroot, spinach, and tomato from the contaminated soil. The three selected vegetable plants were planted and irrigated with ARVDs spiked (at 2000 and 5000 μg/L) water over a period of three months. The optimized UE and LC-PDA methods were used to extract and quantify the selected ARVDs from the target vegetables and soil. The obtained results showed that the studied vegetables have the potential to take up abacavir, nevirapine, and efavirenz from contaminated soil, be absorbed by the root, and translocate to the aerial part of the plants. Abacavir was found at high concentrations to a maximum of 40.21 μg/kg in the root, 18.43 μg/kg in the stem, and 6.77 μg/kg in the soil, while efavirenz was the highest concentrations, up to 35.44 μg/kg in leaves and 8.86 μg/kg in fruits. Spinach root accumulated more ARVDs than beetroot and tomato. The bio-accumulation factor ranged from 2.0-14 μg/kg in beetroot, 3.6 - 15 μg/kg in spinach, and 6 – 10 μg/kg in tomato. The root concentration factor range was 0.047 – 17.6 μg/kg; 0.34-5.9 μg/kg, and 0.14-2.82 μg/kg in beetroot, spinach, and tomato, respectively. The translocation factor range obtained was 0.40 – 38 μg/kg, 0.08 – 19 μg/kg, and 0.14 – 49 μg/kg in beetroot, spinach, and tomato, respectively. However, the accumulation of ARVDs in all studied plants showed that they could be used in phytoremediation. The results obtained in the phytoremediation approach revealed that the utilization of the contaminated water has an influence on the presence ARVDs in vegetables; hence this work also focused on evaluating the exfoliated graphite adsorption of ARVDs in water. Natural graphite was intercalated with acids and exfoliated with thermal shock to obtain the exfoliated graphite. The scanning electron microscopy images showed that the exfoliated graphite had increased c-axis distance between the layers with accordion-like structure which were confirmed by the lower density of exfoliated graphite material (0.0068 gmL-1) compared to the natural graphite (0.54 g mL-1). Fourier Transformed Infrared Spectroscopy results showed the C=C in natural and exfoliated graphite at 1635 cm-1 stretching. The phenolic, alcoholic, and carboxylic groups were observed from 1000 to 1700 cm-1 for the intercalated and exfoliated graphite. The Energy-dispersive X-ray results further confirmed these results, which showed carbon and oxygen peaks in the intercalated and exfoliated graphite spectrum, whereas natural graphite showed only a carbon peak. Raman spectroscopy results showed that the material’s crystallinity was not affected by the intercalation and exfoliation processes as observed from the ratios of the G and D peaks and the G' and D'. Natural, intercalated and exfoliated graphite contained the D, G, D', and G' peaks at about 1350 cm-1, 1570 cm-1, 2440 cm-1, and 2720 cm-1, respectively. The exfoliated graphite material showed the characteristic of a hexagonal phase graphitic structure by (002) and (110) reflections in the X-ray diffraction results. The exfoliated graphite adsorption method was optimized based on the pH of a solution, adsorbent dosage, and adsorption time prior to application to water samples. The optimum pH solution, adsorbent dosage, and adsorption time were 7, 30 mg, 0.01 μg/L, and 30 minutes respectively. The kinetics and isotherm studies were conducted to assess the model that best fit and explain the experimental data obtained. The kinetic model and adsorption isotherm studies showed that the experimental data fit well pseudo-second-order kinetics and is well explained by Freundlich’s adsorption isotherm. The maximum adsorption capacity of the exfoliated graphite (EG) for ARVDs ranges between 1.660-197.0, 1.660-232.5, and 1.650-237.7 mg/g for abacavir, nevirapine, and efavirenz, respectively. These results showed that under proper operating conditions, the EG adsorbent could potentially be applied as a water purifying tool for the removal of ARVDs pollutants.
Comparison of extraction methods efficiency for the extraction of polycyclic aromatic hydrocarbons and phenolics in water matrices, sludge and sediment: sources of origin and ecological risk assessment.
(2023) Ndwabu, Sinayo.; Mahlambi, Precious Nokwethemba.; Malungana, Mncedisi.
Polycyclic aromatic hydrocarbons (PAHs) and phenolic compounds (PCs) are persistent and environmentally toxic compounds. This study therefore aimed to determine the levels of both PAHs and PCs in river water, wastewater, sludge and sediment samples. The evaluation of their origin source and ecological risk was also determined. The status of both these contaminants in South African environment is still not fully investigated, which is a gap this study intended to fill together with previous studies that have been carried-out. The PAHs and PCs were extracted using different extraction methods which include a solid phase extraction (SPE) and dispersive liquid-liquid micro-extraction (DLLME) in water matrices. The microwave assisted extraction (MAE) and Ultrasonication (UE) coupled with either filtering (F) or F + SPE as a clean-up technique was used for extraction of solid samples. The analytes extracted form water or sediment were determined using GC-MS. The PAH %recoveries obtained under optimum conditions in liquid samples were determined to be 72.1 - 118% for SPE and 70.7 – 88.4% for DLLME while the LOD and LOQ were 5.00 – 18.0 ng/L and 10.0 – 44.0 ng/L for SPE while they were 6.00 – 20.0 ng/L and 11.0 – 63.0 ng/L for DLLME. The recovery test for PAHs in solid samples gave a range of 93.7% - 121% for UE and 79.6% - 122% for MAE while the LOD and LOQ ranged from 0.0250 μg/kg to 1.21 μg/kg & 0.0800 μg/kg to 3.54 μg/kg for MAE and from 0.0840 μg/kg to 0.215 μg/kg & 0.0190 μg/kg to 0.642 μg/kg for UE respectively. The LOD and LOQs for PCs in both water and solid matrices were 0.01 – 2.00 μg/L and 0.02 – 6.07 μg/L for SPE, 0.05 – 1.20 μg/kg and 0.17 – 3.17 μg/kg for MAE and 0.09 – 1.33 μg/kg and 0.26 - 3.54 μg/kg for UE correspondingly, their %recovery test gave ranges of 75.2 – 112% (SPE), 80.9 – 110% (MAE) and 79.3 – 119% (UE).The optimization and validation of these methods indicated that they can be used for the extraction of PAHs or PCs in liquid samples, however, SPE when compared to DLLME showed to be more accurate and sensitive. Moreover, in solid samples the clean-up method was a deciding factor, with F + SPE cleaned samples giving higher concentrations of both PCs and PAHs than the filtered ones in both MAE and UE. The concentrations of PAHs ranged from nd (not detected) to 1046 ng/L in river water and nd to 778 ng/L in wastewater samples with naphthalene showing dominance over all other PAHs in both water matrices. The PC concentrations at 4.12 to 1134 μg/L for wastewater and nd to 98.0 μg/L for river water were high but still within the maximum allowable limit except for 2.4-DCP (2.4 dichlorophenol) at Wdv4. The concentrations obtained from F + SPE cleaned samples were higher for both PAHs and PCs with a range from 95.96 to 926.0 μg/kg and 1.30 to 310 μg/kg compared to concentrations from filtered only samples at 21.61 to 380.6 μg/kg and 0.90 to 266 μg/kg respectively. Pyrene showed dominance over all other PAHs in both sludge and sediments while 2.4-DCP and PCP dominated the sludge and sediment samples respectively. PAHs were determined to be of petrogenic (water matrices) and pyrolytic (solid samples) origin and on average posed low (water matrices) and a medium to high (solid matrices) ecological risk. The ILCRderm values at 4.98 x 10-1 and 2.62 x 10-1 (DahA) and 5.92 x 10-2 and 5.34 x 10-2 (PCP) were highfor adults compared to that of children at 1.92 x 10-1 and 1.01 x 10-1 (DahA) and 1.39 x 10-2 and 1.26 x 10-2 (PCP) for both sediment and sludge samples respectively. The low values of ILCRderm for children indicates that the have a high risk exposure even at low concentrations of the contaminants. The findings of this study showed that both areas (uMsunduzi river and Darvill wastewater works (WWW) of interest are polluted with PAHs and PCs therefore, more regulations such as the National Environmental Management: Waste Act (NEMWA) are needed to ensure environmental, human and animal safety.
Construction of functional and robust cobalt phthalocyanines modified electrodes for the electrocatalytic detection of metal-based and pharmaceutically derived pollutants.
(2024) Moodley, Danica.; Booysen, Irvin Noel.; Mambanda, Allen.
Water pollution has become a detrimental global concern in a world that continues to grow through industrialisation, population, and demand in sales from agricultural and pharmaceutical industries. It is therefore imperative for innovative methods of continuous water monitoring to be implemented to avoid the harsh effects that pollution poses to human, animal and environmental preservation. Advances from traditional analytical methods have been made to combat associated drawbacks such as tedious sample preparation, high maintenance costs, and lack of mobility. Electrochemical sensors can be used for the analysis of a vast range of water pollutants while offering on-site, simple analysis and inexpensive fabrication. Metallophthalocyanines have been utilised extensively as electrode modifiers due to their excellent redox properties and stability which can be fine-tuned by alteration of the metal centre and substituents. In addition, thes3e alterations improve selectivity, solubility and immobilisation onto electrode substrates. This research is aimed at the application of gold electrodes modified with CoPc-cou nanoconjugates and CoPc-cou electrospun nanofibers (ENFs) for the electrocatalytic detection of pollutants, paraquat and mercury, in real water samples. Experimental chapter one explores the optimization and application of a gold-modified electrode, CoPc-cou-f-MWCNTs/3-HT|Au, for the electrocatalytic detection of a water pollutant, paraquat (PQ). It was fabricated via a sequential modification procedure entailing the formation of self-assembled monolayers (SAMs) of a nanocomposite comprising of a coumarin tetra-substituted cobalt phthalocyanine (CoPc-cou) and carboxylic acid functionalized multiwalled carbon nanotubes (f-MWCNTs). This was followed by the in-situ immobilization of poly(3-hexylthiophene) ([3-HT]n) through electropolymerisation to render the chemically modified electrode (CME). Subsequently, the CME illustrated enhanced sensitivity towards PQ compared to the bare or CoPc-cou-f-MWCNTs modified electrodes. The CoPc-cou-f-MWCNTs/3-HT|Au electrode displayed a linear PQ detection range of 0.193 – 1000 μM with a limit of detection (LOD) and limit of quantification (LOQ) of 0.193 μM and 0.584 μM, respectively. Comparison between calibration curves for the modified electrode and HPLC-MS illustrates that the former method has a lower but comparable calibration sensitivity for PQ. In addition, this CME could electrocatalytically distinguish PQ within a real water sample collected from the Durban lagoon. Furthermore, the direct recovery of PQ in the lagoon water by the modified Au electrode was found to be 86%, which is lower than the calculated value of 97% obtained by HPLC-MS after rigorous solid-phase microextraction of the analyte. However, the lower percentage recovery could be rationalized by the interference studies. In experimental chapter two fabricated electrospun nanofibers containing CoPc-cou, polyaniline (PANI) and poly-vinyl alcohol (PVA) were used to modify a gold substrate which was subsequently immobilised using a 5% Nafion solution affording the CoPc-cou-ENFs-Nf|Au modified electrode. Comparison of the chemically modified electrode with the bare and other modified electrodes under optimised conditions displayed superior detection of mercury (Hg(II)) attaining a linear range of 10 – 3000 μM and an LOD and LOQ of 0.14 μM and 0.46 μM, respectively. This can be attributed to the affinity between Hg(II) and the mercaptocoumarin substituent (Hg-S) as well as the higher surface area occupied by the ENFs resulting in an increased number of active sites. Furthermore, the chemically modified electrode exhibit selectivity and sensitivity in an interference sample containing multiple heavy metals (Pb2+, Cd2+ and Hg2+). A good percentage recovery of 96% was attained when the CoPc-cou-ENFs-Nf|Au electrode was applied to a real water sample which was comparable to a percentage recovery of 98% which was attained using the ICP-OES to analyse the same water samples.
Derivatised phenanthroline transition metal chelates : targeted chemotherapeutic agents = I-Derivatised phenanthroline transition metal chelates: i-targeted chemotherapeutic agents
(2024) Hunter, Leigh André.; Akerman, Matthew Piers.
The derivatisation of 1,10-phenanthroline at the 2-position afforded two classes of compounds with two different bridging groups in this study. The first group comprised two amide-bridged tetradentate N4-donor ligands and were chelated to copper(II), nickel(II) and palladium(II). The ligand chelation occurred with concomitant deprotonation of the amide N-H, resulting in a monoanionic ligand and monocationic complexes when coordinated to the divalent metal ions. The ligands N-(quinolin-8-yl)-1,10-phenanthroline-2-carboxamide, HL1, and N-(pyridin-2-ylmethyl)-1,10-phenanthroline-2-carboxamide, HL2, were characterised by NMR, IR and UV/vis spectroscopy as well as mass spectrometry. The second class of compounds were imine-bridged copper(II) chelates. These chelates were synthesised via a templating condensation reaction between various salicylaldehyde derivates and 1,10-phenanthrolin-2-ylmethanaminium chloride, yielding eight additional copper(II) chelates. The metal chelates were characterised by IR, UV/vis and EPR spectroscopy, and mass spectrometry. HL1, [Cu(L4)(NO3)] and [Cu(L7)](NO3) were further studied by X-ray diffraction. The copper(II) chelates exhibit two different solid-state structures with the nitrate counter ion coordinated to the metal centre in [Cu(L4)(NO3)], but in the outer coordination sphere for [Cu(L7)](NO3). The paramagnetic copper(II) chelates were studied with EPR spectroscopy, which confirmed the square planar coordination geometries of these chelates in solution. The metal chelates were designed to be chemotherapeutic agents, exerting their cytotoxicity through DNA intercalation and, for the copper(II) chelates, DNA cleavage through the catalytic production of ROS. The ability of the copper(II) chelates to catalyse the production of hydroxyl radical in situ in the presence of ascorbic acid and hydrogen peroxide was studied via a hydroxyl radical assay using Rhodamine B as an analogue for the aromatic DNA bases. Competitive binding studies determined the affinity of the metal chelates towards ct-DNA, [Cu(L1)](PF6) has the highest binding constant: 5.91 × 106 M-1. DFT calculations were performed on the ligands and metal chelates to determine the geometry-optimised structures, vibrational frequencies, 1H and 13C NMR chemical shifts and electronic transitions. The B3LYP/6-311G (d,p) level of theory was used for the ligands, copper(II) and nickel(II) chelates and the B3LYP/LanL2DZ level of theory for the palladium(II) chelates. The TD-DFT method was used for the energy calculations. The experimental and calculated results were compared where possible, and a reasonable correlation was found. The cytotoxicity of five amide-based chelates was evaluated against four human cancer cell lines, namely A549, TK-10, HT29 and U251, using an MTT assay. The screened chelates exhibited favourable anticancer activity with the mean IC50 values against the four cancer cell lines ranging from ca. 12 to 35 μM. Importantly, it was found that the combination of the copper(II) ion and the ligand was essential for enhanced cytotoxicity. The complex [Cu(L1)](PF6) was identified as the lead drug candidate based on the high DNA affinity and cytotoxicity. This compound was most cytotoxic towards the glioblastoma cell line U251 with an IC50 value of 7.59 μM. The imine-based chelates were screened against three human cancer cell lines: MDA-MB, HELA, and SHSY5Y, and a healthy human cell line, HEK293. The selectivity index of these chelates for neoplastic versus the healthy cell line was calculated. The imine-based chelates showed a high selectivity towards the triple-negative breast cancer MDA-MB, an order of magnitude more toxic to the tumour cell than the healthy one. This selectivity index is significantly improved over that of cisplatin. A gel mobility shift assay investigated the interactions between the copper(II) chelates and plasmid DNA. The in vivo biodistribution of [Cu(L1)](PF6) was determined using the copper-64 radiolabelled analogue of [Cu(L1)]Cl and microPET-CT scanning. The initial biodistribution studies suggested that the complex has good serum stability and showed that there was no significant accumulation in any organs. The subsequent study involved a xenograft model using the A549 cell line and showed significant uptake and retention of the complex in the tumour. The cytotoxicity of the chelate when synthesised with the non-radioactive isotopes of copper and the uptake of the radiolabelled equivalent in a tumour model suggest that this complex could have application as a “theranostic agent”. Iqoqa. Ukukhishwa kwe-1,10-phenanthroline endaweni ye-2 kunikeze amakilasi amabili enhlanganisela namaqembu amabili ahlukene ukuhlanganisa kulolu cwaningo. Iqembu lokuqala lalihlanganisa ama-amide-bridged tetradentate N4-donor ligands futhi ayenziwe ngethusi (II), nickel (II) kanye ne-palladium (II). I-ligand chelation yenzeke ngokuchithwa okuhambisanayo kwe-amide N-H, okuholela ku-monoanionic ligand kanye ne-monocationic complexes lapho ixhunywe kuma-ion ensimbi e-divalent. Ama-ligands N-(quinolin-8-yl)-1,10-phenanthroline-2-carboxamide, HL1, kanye ne-N-(pyridin-2-ylmethyl) -1,10-phenanthroline-2-carboxamide, HL2, abenophawu lwe-NMR, IR kanye ne-UV/vis spectroscopy kanye ne-mass spectrometry. Ikilasi lesibili lama-compounds bekungama-imine-bridged copper (II) chelates. Lawa ma-chelates ahlanganiswa ngokusabela kokujiya kwesifanekiso phakathi kokuphuma kwe-salicylaldehyde okuhlukahlukene kanye ne-1,10-phenanthrolin-2-ylmethanaminium chloride, ekhiqiza ama-chelate ethusi ayisishiyagalombili (II). Ama-chelates ensimbi abonakala nge-IR, UV/vis kanye ne-EPR spectroscopy, kanye ne-mass spectrometry. I-HL1, [Cu(L4) (NO3)] kanye ne-[Cu(L7)] (NO3) zaphinde zacwaningwa nge-X-ray diffraction. Ama-chelates ethusi (II) abonisa izakhiwo ezimbili ezihlukene zesimo esiqinile ezine-ion yekhawunta ye-nitrate exhunywe esikhungweni sensimbi ku-[Cu(L4) (NO3)]], kodwa kwi-outer coordination sphere ye-[Cu(L7)] (NO3). Ama-chelates e-paramagnetic copper (II) ahlolisiswa nge-EPR spectroscopy, eqinisekisa i-square planar coordination geometries yalawa ma-chelates esixazululweni. Ama-chelates ensimbi ayeklanyelwe ukuba abe ama-chemotherapeutic agents, asebenzisa i-cytotoxicity yawo ngokusebenzisa i-DNA intercalation futhi, kuma-chelates ethusi (II), i-DNA cleavage ngokukhiqizwa okunamandla kwe-ROS. Ikhono le-copper (II) chelates lokugqugquzela ukukhiqizwa kwe-hydroxyl radical in situ lapho kukhona i-ascorbic acid ne-hydrogen peroxide yacwaningwa nge-hydroxyl radical assay kusetshenziswa i-Rhodamine B njenge-analogue yezisekelo ze-DNA enamakha. Izifundo ezibophayo ezincintisanayo zinqume ukuhambisana kwama-chelates ensimbi ku-ct-DNA, [Cu(L1)](PF6) inokuhambisana okuphezulu kakhulu okubophayo: 5.91 × 106 M-1. Izibalo ze-DFT zenziwa kuma-ligands kanye nama-chelates ensimbi ukuze kunqunywe izakhiwo ezilungiselelwe i-geometry-optimized, amaza okudlidliza, amashifu amakhemikhali e-1H kanye ne-13C NMR kanye nokuguqulwa kwe-electronic. Izinga le-B3LYP/6-311G (d,p) lethiyori lasetshenziselwa ama-ligands, ithusi(II) ne-nickel(II) chelates kanye nezinga le-B3LYP/LanL2DZ lethiyori ye-palladium(II) chelates. Indlela ye-TD-DFT isetshenziselwe izibalo zamandla. Imiphumela yokuhlolwa nebaliwe yaqhathaniswa lapho kwenzeka khona, futhi kwatholakala ukuhlobana okunengqondo. I-cytotoxicity yama-chelates amahlanu asekelwe ku-amide yahlolwa ngokumelene nemigqa yeseli yomdlavuza wabantu emine, okuyi-A549, TK-10, HT29 kanye ne-U251, kusetshenziswa i-MTT assay. Ama-chelate ahloliwe abonise umsebenzi omuhle wokulwa nomdlavuza ngamavelu amaphakathi we-IC50 ngokumelene nemigqa yeseli yomdlavuza emine kusukela ku-ca. 12 kuya ku-35 μM. Okubalulekile, kwatholakala ukuthi inhlanganisela ye-ion yethusi (II) kanye ne-ligand yayibalulekile ekuthuthukisweni kwe-cytotoxicity. Inkimbinkimbi [Cu(L1)] (PF6) ikhonjwe njengekhandidethi yesidakamizwa esihamba phambili ngokususelwe ekuhlobaneni okuphezulu kwe-DNA kanye ne-cytotoxicity. Le nhlanganisela ibiyi-cytotoxic kakhulu ibheke kumugqa weseli we-glioblastoma u-U251 onenani le-IC50 elingu-7.59 μM. Ama-chelate asekelwe ku-imine ahlolelwa imigqa emithathu yamangqamuzana omdlavuza womuntu: i-MDA-MB, i-HELA, ne-SHSY5Y, kanye nolayini wamaseli womuntu onempilo, i-HEK293. Inkomba yokukhetha yalawa ma-chelates we-neoplastic ngokumelene nomugqa weseli onempilo ibaliwe. Ama-chelates asekelwe ku-imine abonise ukukhetha okuphezulu kumdlavuza webele we-triple-negative MDA-MB, ukuhleleka kobukhulu obunobuthi obuningi engqamuzaneni yesimila kunaleyo enempilo. Le nkomba yokukhetha ithuthukiswe kakhulu kune-cisplatin. Ukuhlolwa kwe-gel mobility shift assay kuphenye ukusebenzisana phakathi kwe-copper(II) chelates ne-plasmid DNA. I-in vivo biodistribution ye-[Cu(L1)](PF6) inqunywe kusetshenziswa i-analogue ene-radiolabelled ye-copper-64 ye-[Cu(L1)]Cl ne-microPET-CT scanning. Ucwaningo lokuqala lwe-biodistribution luphakamise ukuthi inkimbinkimbi inokusimama okuhle kwe-serum futhi yabonisa ukuthi kwakungekho ukuqoqwa okuphawulekayo kunoma yiziphi izitho. Ucwaningo olwalandela lwaluhilela imodeli ye-xenograft esebenzisa ulayini weseli we-A549 futhi lwabonisa ukuthatheka okubalulekile nokugcinwa kwenkimbinkimbi esimilanjeni. I-cytotoxicity ye-chelate lapho ihlanganiswa nama-isotopes ethusi angewona ama-radioactive kanye nokuthathwa kwe-radiolabelled okulingana nemodeli yesimila kuphakamisa ukuthi le nkimbinkimbi ingaba nesicelo "njenge-ejenti yokwelapha".
Determination of neonicotinoid insecticides in water, soil and sediment samples: acute and chronic risk assessment.
(2022) Ngomane, Nkosinathi Chris.; Mahlambi, Precious Nokwethemba.
Neonicotinoids are a type of insecticides pesticides widely used worldwide as a result of their low vertebrates toxicity, relative environmental stabilities, good bioavailability and high level of selectiveness. These insecticides are commonly employed in agricultural activities, in grass management and horticulture as well as in households to control domestic pet flea. Due to neonicotinoids intensive usage, they are continuously introduced to the water bodies where they can adversely affect the aquatic life and accumulate in sediments. Moreover, they can end up in drinking and unintentionally consumed by human beings resulting to health effects. With this regard, this work reports for the first time on the occurrence of neonicotinoids in sediment, soil tap, sludge, wastewater and river water samples from the province of KwaZulu-Natal. Also, the ecological risk of neonicotinoids in water sources was also assessed for the first time in the samples from this province.The liquid chromatography coupled with a photo-diode array detector (LC-PDA) method was modified and applied for the simultaneous detection of neonicotinoids (clothianidin, thiamethoxam and imidacloprid). Ultrasonic extraction (UE), soxhlet extraction (SE) and solid-phase extraction (SPE) methods were developed and applied for the extraction of nitro-guanidine neonicotinoids in water, soil and sediment samples. The SPE, SE, and UE parameters that influence the recoveries of the analytes were first optimized before application to real samples for the analytes recovery improvement. The SPE was used for the extraction of neonicotinoids in sludge and water samples, while SE and UE were both used to extract soil and sediment samples. The extraction conditions optimized for SPE were conditioning solvent and sample volume. While for the UE were extraction time, extraction solvent, and the solvent volume. And for SE method, extraction solvent and the extraction solvent volume were optimized. The LC-PDA method used for detection was also first optimized to improve peak separation, retention times, detection limits and quantification limits. The optimized parameters for the LC-PDA method were the mobile phase, flow rate, and the PDA detection wavelength. Optimum water recoveries of the neonicotinoids ranged from 79 to 112%. The detection and quantification limits of the analytes in water samples were 0.013 - 0.031 μg/L and 0.041 - 0.099 μg/L, respectively. The obtained analytes concentration ranged from 0.061 - 0.10 μg/L, 0.077- 3.76 μg/L and 0.99 - 15 μg/L in tap, river and wastewater, respectively. Analyte recoveries ranged from 85 - 102% in soil and 92 - 103% in sediment for the ultrasonic extraction method. The neonicotinoid recoveries ranged from 83 to 109% in soil and between 84 to 94% in sediment samples for the Soxhlet extraction method. The method’s detection limits and quantification limits in solid samples ranged from 40 - 80 μg/kg and 140 - 270 μg/kg, respectively. The relative standard deviation was less than 4%. The concentration determined in real environmental samples were 47 to 410 μg/kg in soil and 25 to 410 in sediment. The toxicity studies showed that clothianadin pose a high risk towards daphnia species in the river. Imidacloprid, clothianidin and thiamethoxam posed medium risk against algae, daphnia and fish species in the effluent receiving water bodies. These results imply the necessity to continuously monitor these neonicotinoids in the water sources. In South Africa there is limited data concerning the environmental occurrence of neonicotinoids, therefore this work will contribute towards the information available for the analysis of neonicotinoids. This will assist the policy makers to establish the MRL values that are precise for the African continent.
Exploring the structure activity relationship of antiplasmodial compounds identified from the MMV Pathogen Box.
(2024) Mafuleka, Sean Manqoba.; Sithebe, Siphamandla.; Veale, Clinton Gareth Lancaster.
Over 200 million new infections are caused by malaria-causing plasmodium species. This results in over 500 000 annual deaths. These deaths are mostly young children under the age of five years. As there is an emergence of resistance to primitive first-line treatments, there is an increasing need for the development of new targets with novel scaffolds. For such advancements, we have to consider the structure-activity of antiplasmodial compounds. The Pathogen Box is a concept modelled on the Malaria Box, except the 400 drug-like compounds it contains are a diverse range of compounds which are active against numerous neglected diseases of interest, and is readily accessible. It unpacks 125 compounds of antiplasmodial activity, a lot of which have been identified from phenotypic screening of the GSK Tres Cantos Anti-Malarial Set (TCAMS). Upon request, select researchers around the globe receive a set of compounds from the Pathogen Box to help in the advancements towards neglected disease drug discovery. In turn, the researchers are requested to present, in the public domain, any data they will have generated in their work within two years. This presents an opportunity for a collaborative space for neglected disease drug research. In this project, compound MMV023227 was found to have promising antiplasmodial activity. We have therefore designed and synthesized some analogues of the hit compound with the purpose of identifying an SAR. We initiated the synthesis of the designed analogues of compound MMV023227 by successfully synthesising the three imidazole compounds that are 2-(3-bromophenyl)-4,5-dimethyl-1H-imidazole (3.1), 2-(3-bromophenyl)-4-methyl-1H-imidazole (3.2), and 2-(3-bromophenyl)-1H-imidazole (3.3) in yields between 33 – 42 %. We moved these compounds towards the desired final compounds through several stages, but we could only go as far as producing compounds N-(2-chlorobenzyl)-3-(1-(ethoxymethyl)-1H-imidazol-2-yl)aniline (3.9), N-(2 chlorobenzyl)-3-(1-(ethoxymethyl)-4-methyl-1H-imidazol-2-yl)aniline (3.10) and N-(2-chlorobenzyl)-3-(1-(ethoxymethyl)-5-methyl-1H-imidazol-2-yl)aniline (3.11) in yields between 7 – 41 %.
Extraction of pesticides using selected analytical methods from soil and maize segments : cumulative and health risks assessment.
(2024) Zondo, Sandisiwe Gladness.; Mahlambi, Precious Nokwethemba.
Increased agricultural operations result in increased usage of various pesticides to safeguard agricultural crops, however this is done without paying attention to the effects of the amounting potential harm both humans and the environment are exposed to. In this present study, a structured study was conducted to investigate the uptake of atrazine, mesotrione, 2,4- dichlorophenoxyacetic acid and glyphosate herbicides from contaminated soil and their translocation into different maize segments. Soil profile and quality of irrigation water were also assessed as they are crucial resources required in agricultural crop production due to their ability to influence the yield and quality of the agricultural products. Various physicochemical parameters were measured in an attempt to monitor the soil profile, irrigation water and maize quality harvested from Buhle farm located in Howick, KwaZulu-Natal Province. The irrigation water physicochemical parameters considered were the pH, electrical conductivity, alkalinity and chloride concentration. The soil physicochemical parameters considered were moisture content, pH, electrical conductivity, texture, total nitrogen as well Mg, Na, K, Zn, Mn, P and N elements. Maize was analysed for nutrition content and medicinal health promoting compounds. Based on the attained results, the soil texture contained high clay content (56.4%), followed by sand (40.6%) and silt (2.98%). The concentrations for total nitrogen, phosphorus and potassium which were translated to high soil fertility were 2700, 19 and 222 mg L-1, respectively. These particular elements are essential for agricultural plantation processes and consequently maize quality and maize yield. The levels of sodium, sodium adsorption ratio and electrical conductivity found in irrigation water were 0.05 mg L-1, 2 and 1.81 μS m-1, respectively. The findings showed that maize harvested from Buhle farm had high starch content of 58.6%. Fibre, protein and fat contents in maize were 23.4, 9.01 and 4.55%, respectively. Furthermore, the total anthocyanin, total flavonoids and total phenolic acid content were 8.5, 49.5 and 100 mg L-1, respectively. High amounts of phenolic acid detected indicated therapeutic ability of the maize since phenolic acids are essential for cancer prevention to the consumer. The presence of anthocyanin, flavonols and phenolic acids in maize crop is associated with its quality that could benefit livestock and human after consumption. The analysis of herbicides in soil and maize samples require sample pre-treatment due to their low concentration and complex matrix hence an ultrasonic extraction, microwave-assisted extraction (MAE), Soxhlet extraction (SE) and QuEChERS methods were investigated. The optimization and application of ultrasonic extraction, MAE, SE and QuEChERS methods were conducted for the effective extraction of pesticides from maize and their corresponding soil samples. The analysis of pesticides (atrazine, glyphosate, 2,4-dichlorophenoxyacetic acid and mesotrione) was done with gas chromatography-flame ionization detector. Factors influencing the efficiency of the extraction methods such as the extraction solvent, extraction time, solvent volume, sample wetting and spiking concentration were assessed. Under the optimum experimental conditions, the relative standard deviation (RSD), coefficient of determination (R2), limit of detection (LOD), limit of quantification (LOQ), and percentage recoveries were the quantitative characteristics of the current methods assessed. All calibration curves showed a high correlation coefficient (R2) ≥0.996, indicating good linearity. The LODs and LOQs ranged between 0.22-0.32 μg L-1 and 2.0-2.9 μg L-1 for SE , 0.1-0.25 μg L-1 and 1.1-2.2 μg L- 1 for MAE, 0.02 – 0.15 μg L-1 and 0.2 - 0.5 μg L-1 for UE and 0.01 – 0.23 μg L-1 and 0.13 – 0.8 μg L-1 for QuEChERS. The maize and soil analytes recoveries for SE, MAE, EU and QuEChERS ranged between 62-80% and 70-81%, 80-98% and 85-101%, 100-104% and 91- 97 % and 94-115% and 92-101%, respectively with the repeatability, articulated as RSD values of which are within the acceptable range as they are lower than 20%. MAE method showed higher sensitivity compared to SE while, UE and QuEChERS both showed high sensitivity for the extraction and quantification of the target analytes at low concentrations found in soil and maize cob. It was observed that 2,4-dichlorophenoxyacetic acid (2.4-D) was least absorbed by the soil, however, all the studied herbicides showed high absorption in the leafy segment of the maize plant due to the high polarity of the leaf cuticle. Glyphosate showed high absorption rate in soil, roots, stalk and leaves while mesotrione was highly absorbed in corn and tassels in all treatments. The absorption rate of analyte increased with increasing growth days. The higher treatment concentration (0.75 g L-1) showed elevated accumulation with the highest concentration (1.02 μg L-1) observed for glyphosate in leaves after 140 days and high mesotrione in corn (0.51 μg L-1) and tassel (0.42 μg L-1) observed after 120 days. Even though all maize treatment showed a pesticide toxicity index (PTI) values of <1, the health risk index (HI) data were below 100% threshold as well indicating no possible health risk linked with the intake of these crops by both adults and children.
Harnessing the power of Microalgae and Daphnia for bioremediation of nutrients, pharmaceuticals, and heavy metals in wastewater.
(2024) Tenza, Ntombiphumile Perceverence.; Mahlambi, Precious Nokwethemba.
Excess nutrients in aquatic ecosystems promote eutrophication, which significantly affects oxygen-dependent organisms. Furthermore, toxic microalgae, such as microcystin, cylindrospermopsis, etc., thrive during eutrophication, releasing poisonous compounds harmful to human health and other aquatic organisms. Pharmaceutical compounds and heavy metals in aquatic environments further exacerbate these global concerns. Thus, addressing such problems is paramount and aligns with Sustainable Development Goals (SDGs) 6 - Clean Water and Sanitation, 12 - Responsible Consumption and Production, and 14 - Life Below Water. Bioremediation of wastewater with biological microorganisms such as microalgae and daphnia provides an excellent solution due to their remarkable properties that enable them to efficiently eliminate many contaminants, including heavy metals, nutrients, and pharmaceuticals. So, this study explored the novel approach to nutrient removal by combining Chlorella spp. and Daphnia magna (D. magna). Chlorella spp. completely removed nitrate and nitrite from wastewater by converting them into compounds like amino acids, proteins, and lipids. When D. magna was employed alone, it faced significant challenges due to the absence of primary producers like bacteria and microalgae, which they mainly feed on. However, combining it with Chlorella spp. proved exceptionally effective, as 100% removal was obtained for nitrate and nitrite, possibly driven by D. magna grazing on Chlorella spp. that had assimilated nitrate and nitrite into their biomass. Challenges arose for ammonia and phosphate removal as they achieved up to 27% removals. This can be ascribed to nutrient release, Chlorella’s saturation capacity, and environmental changes such as pH. For pharmaceuticals, the study successfully developed and validated the LC-PDA method for separating sulfamethoxazole, nevirapine, and efavirenz. The optimum conditions were a mobile phase (90:10% acetonitrile: water with 0.1% formic acid), run time (8 minutes), flow rate (0.4 mL/min), and wavelength (220 nm). The study also developed and validated the solid-phase extraction (SPE) method for extracting analytes of interest in water matrices. The optimum conditions were conditioning solvent (mixture of acetonitrile and methanol in a 70:30 (v/v) ratio), sample volume (50 mL), and pH 7. The study then assessed Chlorella's capacity to remove sulfamethoxazole, nevirapine, and efavirenz. The obtained removal efficiencies for efavirenz, nevirapine, and sulfamethoxazole ranged from 0–60%, 5–51%, and 10–50%, respectively. Furthermore, the results exhibited lower removal efficiency (up to 15%) for higher concentrations (1 and 5 mg/L), whereas lower initial concentrations (0.5 and 0.25 mg/L) showed higher removal rates (up to 60%). Low removals could be due to factors like toxic metabolite accumulation and pharmaceutical toxicity. This study also explored copper, lead, and zinc adsorption capacity on Chlorella spp. biomass. Batch cultures were assessed in triplicate at 150 rpm in an orbital shaker under different biomass dosages, pH levels, contact times, and metal concentrations. The optimum conditions were pH 7, 60 minutes contact time, biomass dosage of 12.5 mg, and 0.5 m/L concentration. The optimal conditions yielded complete removal of lead and zinc, with copper reaching up to 80% removal. The study also assessed the adsorption of target heavy metals employing Freundlich, Langmuir, and Temkin isotherms, with the Langmuir isotherm better fitting copper (R2 = 0.9888) while the Freundlich isotherm best-fitted lead (R2 = 0.976) and zinc (R2 = 0.968). Lead and zinc favoured the pseudo-first-order kinetic model, whereas copper favoured the pseudo-second-order kinetic model. Thermodynamic studies exhibited an endothermic and spontaneous process for copper and zinc. The results of this PhD underscored Chlorella's potential as an environmentally safe and effective option for removing nutrients, pharmaceutical compounds, and heavy metals. Mechanisms for removal included surface adsorption, photodegradation, bioaccumulation, and enzymatic degradation. The Fourier transform infrared spectroscopy (FTIR) confirmed the existence of functional groups like alkene, amide, carbonyl, carboxyl, ethers, hydroxyl, and methyl, which participate in the adsorption of these contaminants through various interactions. Surface morphology analysis through scanning electron microscopy (SEM) shows changes in Chlorella spp. cells after exposure to target compounds (nutrients, pharmaceutical compounds, and heavy metals), suggesting the possibility of interaction that aids their removals. Thus, this study contributed valuable insights for improving wastewater treatment strategies and addressing water scarcity concerns. Additionally, it promotes a circular economy as Chlorella spp. and daphnia biomass can be harvested at the end of the treatment process for diverse uses, including biogas production, organic fertiliser, animal feed, etc. Going forward, future research should focus on optimising bioremediation by exploring different combinations of microalgae and other biological agents to enhance the removal efficiencies of heavy metals and pharmaceuticals. Moreover, genetic modification of Chlorella spp. to improve resilience and uptake capacity is crucial, and integrating advanced monitoring technologies like biosensors are promising directions. In-depth studies on removal mechanisms, such as adsorption, photodegradation, bioaccumulation, and enzymatic degradation, are essential. Also, scaling up to pilot and full-scale applications is crucial for evaluating feasibility and economic viability. Lastly, collaboration with industrial partners and policymakers can help develop regulatory frameworks and incentives. These efforts can advance bioremediation and support global SDGs related to clean water, responsible production, and life below water.
Identification of alpha-glucosidase inhibitors in indigenous plants used for diabetes.
(2024) Ngcobo, Nkosinathi Khulekani.; van Heerden, Fanie Retief.; Rasalanavho, Muvhango.
Diabetes, a global health concern, is a metabolic disorder with a broad range of micro and macro complications. There is still a need to develop new diabetic therapies. Hence, there is a resurging interest in isolating bioactive compounds with antidiabetic activity. One of the therapeutic therapies is the inhibition of α-glucosidase, an enzyme located in the digestive tract that facilitates the hydrolysation of carbohydrates into glucose. Plant-derived compounds and their derivatives have played a significant role in developing numerous drugs, such as the antidiabetic drug metformin. With the intention to advance and explore new plant-derived compounds that can potentially be developed into new biologically active drugs that will be used to treat diabetes, several Indigenous South African species traditionally used to treat diabetes were selected for investigation. These plants were Bulbine frutescens (L.) Willd., Carpobrotus dimidiatus (Haw.) L.Bolus, Cassia abbreviata Oliv. subsp. beareana (Holmes) Brenan, Gomphocarpus tomentosus Burch. subsp. tomentosus, Maerua angolensis DC. subsp. angolensis, Merwilla plumbea (Lindl.) Speta, Pappea capensis Eckl. & Zeyh, Sclerocarya birrea (A.Rich.) Hochst. subsp. caffra (Sond.) Kokwaro, Senegalia mellifera (Vahl) Seigel & Ebinger subsp. detinens (Burch.) Kyal. & Boatwr., Senna italica Mill. subsp. arachoides (Burch.) Lock, Tabernaemontana elegans Stapf, and Ziziphus mucronata Willd. subsp. mucronata. Lead-like extracts were prepared for all the plant species, and the extracts were subjected to in vitro enzyme inhibition studies. The extract of S. birrea was selected for further investigation since it demonstrated the highest inhibitory activity against α-glucosidase. An active fraction of S. birrea stem bark was subjected to LC-MS analysis, and five compounds were identified in the extracts. Preparative chromatography was used to isolate four compounds: catechin, β-sitosterol, β-sitosterol glucopyranoside, and stigmasterol. Of the isolated compounds, only catechin showed reasonable inhibition of α-glucosidase.
Identification of steroidal glycosides from South African Hyacinthaceae species.
(2022) Msomi, Nomzamo.; van Heerden, Fanie Retief.
Steroidal glycosides isolated from natural products have shown great bioactivity and anticancer potential. Previous studies showed that the Ornithogalum genus of Hyacinthaceae family is one of the sources of steroidal glycosides with vast structural diversity. Therefore, in search of cytotoxic steroidal glycosides from South African species, two Ornithogalum plant species were investigated. Phytochemical investigation of Ornithogalum saundersiae Baker bulbs afforded three undescribed steroidal glycosides namely 3-[(β-D-glucopyranosyl)oxy]-22-[α-L-rhamnopyranosyL-(1→2)-β-D-glucopyranosyl)oxy]-16,23-epoxy-23-(2-methyL-1-propenyl) cholestane triglycoside (170), (171), and (172). LC-MS-MS study conducted on bulb crude extract revealed a significant number of unidentified compounds. Liver cell viability assays on O. saunderisae crude extracts and isolated compounds reveal moderate cytotoxicity effects for 171 (IC50 = 25 µg/mL) and 172 (IC50 = 115 µg/mL). Negligible effects were shown for compound 170. Phytochemical investigation of Albuca batteniana Hilliard & B.L.Burtt. resulted in the isolation of one previously known compound named 3-O-β-D-glucopyranosyL-β-sitosterol (175) exhibiting some cytotoxic effects on liver cells (IC50 =275 µg/mL). All the structures of isolates were elucidated by extensive spectroscopic analysis.
Metallophthalocyanine-based electrochemical sensors for accurate qualitative and quantitative analysis of emerging pollutants in water resources.
(2024) Shoba, Siyabonga Blessing.; Booysen, Irvin Noel.; Mambanda, Allen.
Water is a precious resource and safeguarding it from pollution is paramount to ensure the well-being of both the environment and human health. Emerging contaminants such as pharmaceuticals and heavy metals pose significant threats, necessitating vigilant monitoring and appropriate action. Traditional laboratory-based analytical techniques like Gas Chromatography, ICP-OES and HPLC have been instrumental in quantifying pollutants. However, their high operational costs, maintenance requirements and the need for specialized personnel limit their widespread use, especially in resource-constrained countries. Electrochemical sensors have emerged as a promising solution. They provide real-time, portable and cost-effective options for on-site detection of pollutants in water. Current advancements in electrochemical sensors are centred around achieving selective detection using chemical modifiers, all while maintaining electrocatalytic sensitivity and reproducibility. These sensors can be tailored to target specific contaminants, making them highly efficient tools for monitoring water quality and ensuring the sustainability of this invaluable resource. In the first experimental chapter, a glassy carbon electrode (GCE) was modified by an asymmetric metallophthalocyanine (MPc) complex, A3B-CoPc-flav (where A = flavonyloxy substituent and B = an alkynyloxy substituent/molecular mast). The modification of an electrode was achieved via electrochemical grafting followed by clicked chemistry between the diazonium-functionalized GCE and the a-CoPc-flav3 to afford the GCE|clicked-a-CoPc-flav3. The chemically modified electrodes (CME) were utilized as electrocatalytic detectors for dopamine (DA) under optimized conditions. The response of the GCE|clicked-a-CoPc-flav3 was linear in the concentration range of 2 μM to 14 μM, attaining limits of detection and quantification of 0.311 and 0.942 μM, respectively, and high reproducibility (%RSD of 2.25%, N = 3). Interference studies were conducted, revealing a marginal shift in the DA peak potential in the presence of interfering substances. Despite this shift, the peak current intensity of DA remained largely unaffected, affirming the selectivity and accuracy of the CME. The analytical capabilities of the CME were further assessed using real water samples. The obtained percentage recoveries of (97.1%) of DA by the GCE|clicked-a-CoPc-flav3 and the well-established HPLC-MS method (113%) are both within the acceptable range of 80-120%. In the second experimental chapter, a platinum electrode (Pt) was modified via the electropolymerization of polypyrrole (PPy) after its co-electrodeposition of tetra-[4-((1H benzotriazole)methoxy)phthalocyaninato]cobalt(II) (CoPc-Bzt). The electrodeposition of CoPc-Bzt was performed in 1:1 DMF/acetonitrile containing 1 M tetrabutylammonium hexafluorophosphate (NBu4PF6) electrolyte over 20 cycles using cyclic voltammetry to afford a Pt|PPy/CoPc-Bzt (Bzt = benzotriazole). The resultant CME was prone to fouling by the analyte of interest, mercury(II). Due to fouling the differential pulse anodic stripping voltammetry (DPASV) was used to detect Hg(II) using the Pt|PPy/CoPc-Bzt within 10 μM to 100 μM linear range. The LOD and LOQ were found to be 3.11 and 10.00 μM, respectively. Interference studies illustrated that the detection capabilities of the CME were not affected by the presence of other heavy metal cations. The analytical performances of Pt|PPy/CoPc-Bzt (97.4%) and Inductively coupled plasma – optical emission spectroscopy (ICP-OES) (112.3%) are both within the acceptable range of 80-120%. In the third experimental chapter, the Pb electrocatalytic sensing capability of a gold electrode modified via the adsorption of electrospun nanofibers (ENFs) and Nafion (Nf) as an annealed conductive top-layer was evaluated. The fabricated ENFs comprised of a core polymeric nanocomposite of tetra-4-(3-oxyflavonephthalocyaninato)cobalt(II) (CoPc-flav), the carboxylic acid functionalized multiwalled carbon nanotubes (f-MWCNTs) and polyaniline (PANI) encapsulated in a polyvinyl acetate (PVA) ENFs. The resultant CME, Au|ENFs-1-Nf was not prone to fouling as was found when using the bare and the other constructed CMEs whose signal stabilities were compromised by background electrolyte currents. The Au|ENFs-1-Nf electrode could detect the Pb(II) cations in a reproducible manner (%RSD of 3.92%, N = 3) ranging from 8 to 125 μM, and limits of detection and quantification of 0.51 and 1.55 μM were obtained, respectively. However, the interference studies illustrated that the detection capabilities of the CME are severely compromised by the presence of other heavy metal cations. The analytical performance of the CME rendered a comparable percentage recovery (103%) with that of the ICP-OES (115%). In the fourth experimental chapter, the nanofabrication and characterization of new conductive materials, PANI-CoPc-fur (1) ((PANI = polyaniline and CoPc-fur = tetra-4-(2-furanmethylthiophthalocyaninato)Co(II)) and PANI-CoPc-fur-f-MWCNTs (2) are reported. Subsequently, an electrospun nanofiber (ENF) composite was fabricated where the core comprised of 2 that was encapsulated with a PVA shell. The resultant nanoconjugate, ENFs-2 was adsorbed on a glassy carbon electrode (GCE) followed by the immobilization of a permeable adhesion top layer of Nafion (Nf) to render the chemically modified electrode, GCE|ENFs-2-Nf. The classical physical properties of the electron-mediating layer for the CME synergistically aided in promoting its electrocatalytic activities. Consequently, the CME showed greater anodic and cathodic cyclic voltammetry (CV) peak currents compared to the bare GCE and other modified electrodes, indicating its higher sensitivity to acetaminophen (APAP), an emerging water pollutant of concern. Limits of detection and quantification (LOD and LOQ) values for APAP attained by squarewave voltammetry (SWV) were lower compared to those acquired using other electrochemical techniques. The detection of APAP at the GCE|ENFs-2-Nf attained by squarewave voltammetry (SWV) was linear from 10 to 200 μM of APAP and was reproducible (%RSD of 3.2%, N = 3). The respective calculated LOD and LOQ values of 0.094 and 0.28 μM were lower compared to those acquired using other electrochemical techniques. Analysis of APAP in the presence of commonly associated interferences metronidazole (MTZ) and dopamine (DA) illustrated a significant separation between the SWV peak potentials of APAP and MTZ, whereas there was some degree of overlap between the SWV current responses of APAP and DA. The analytical performance of the GCE|ENFs-2-Nf rendered a comparable percentage recovery (103.8%) with that of liquid chromatography–mass spectrometry (LC–MS) (106%). Iqoqa. Amanzi awumthombo oyigugu futhi ukuwavikela ekungcoleni kubaluleke kakhulu ukuze kuqinisekiswe inhlalakahle yakho kokubili imvelo nempilo yabantu. Ukungcola okuvelayo okufana nemithi kanye nezinsimbi ezisindayo kubangela izinkinga ezinkulu, okudinga kuqashelwe kakhulu kanye nesinyathelo esifanele. Izindlela ezijwayelekile zokuhlaziya ezenziwa ezindaweni zokuhlaziya, ezifana nokuhlaziya igesi, i-ICP-OES ne-HPLC zibe nesandla ekulinganiseni izinto ezingcolisayo. Nokho, izindleko zokusebenza eziphezulu, izidingo zokunakekela kanye nesidingo sabasebenzi abakhethekile kunciphisa ukusetshenziswa kwazo ngokusabalele, ikakhulukazi emazweni anezinsizakusebenza ezigqozayo. Ukusebenzisa imishini ekwazi ukuhlonza ingozi kwaletha isixazululo esithembisayo. Imishini lena yaletha isixazululo sangempela, esiphathekayo futhi akubizi kakhulu ukutholwa kokungcola emanzini. Ukuthuthuka kwemishini yesimanje ekwazi ukuhlonza ingozi isebenzisa amakhemikhali ukukwazi ukuhlonza ingozi, ngenkathi kudingeka ukuthi kwayona inakekelwe ukuze ihlale iphilile. Le mishini ingenziwa ngendlela efanele ukuze ikwazi ukubhekana ngqo nokungcola okuthile, okungenza ibe amathuluzi asebenza kahle kakhulu ukuqapha izinga lamanzi nokuqinisekisa ukusimama kwalo mthombo wempilo obaluleke kangaka. Esigabeni sokuqala sokuhlola, iglassy carbon electrode (GCE) yashintshwa nge-asymmetric metallophthalocyanine (MPc), A3B-CoPc-flav (lapho A = iflavonyloxy substituent kanye no-B = i-alkynyloxy substituent/mast molecular). Ukuguqulwa kwe-electrode kwenziwa esifundweni sogesi kubhekwa ukuhleleka kwezakhi phakathi kwediazonium-functionalized GCE kanye ne-a-CoPc-flav3 ukuze kusetshenziswe i-GCE|clicked-a-CoPc-flav3. Ama-electrode ashintshwe amakhemikhali (CME) asetshenziswa njengezihlonzi zogesi zedopamine (DA) ngaphansi kwezimo ezithuthukisiwe. Impendulo ye-GCE|clicked-a-CoPc-flav3 yayiqondile ebangeni lika-2 μM kuya ku-14 μM, ifinyelela imikhawulo yokuhlonza kanye nomthamo we-0.311 kanye no-0.942 µM, ngokulandelanayo, kanye nokuphindaphindeka okuphezulu (%RSD ka-2.25%), N = 3). Izifundo ngemishini ekwazi ukuhlonza inkinga, zaveza ukuguquguquka okuncane kwamandla aphezulu e-DA ebukhoneni bezinto eziphazamisayo. Naphezu kwalolu shintsho, ukuqina kwamanje okuphezulu kwe-DA kusalokhu kungathinteki, okuqinisekisa ukukhetha kanye nokunemba kwe-CME. Amakhono okuhlaziya e-CME abuye ahlolwa kusetshenziswa amasampula angempela amanzi. Amaphesenti atholakele (97.1%) e-DA nge-GCE|clicked-a-CoPc-flav3 kanye nendlela esungulwe kahle ye-HPLC-MS (113%) kokubili kungaphakathi kwebanga elamukelekayo lika-80-120%. Esigabeni sesibili sokuhlola, i-electrode yeplathinamu (Pt) yashintshwa ngemishini yepolypyrrole (PPy) ngemva kokuhlanganiswa kwayo kwetetra--[4-(1H-benzotriazole)(imethoxy)iphthalocyaninato]icobalt(II) (CoPc- Bzt). Imishini ye-CoPc-Bzt yenziwe ngo-1:1 DMF/acetonitrile equkethe oku-1 M kwetetrabutylammonium hexafluorophosphate (NBu4PF6) yemishini engaphezu kwemijikelezo engama-20 kusetshenziswa indlela ebhaka amakhemikhali, ivoltammetry ayizindilingana ukuze kutholakale i-Pt|PPy/CoPc-Bzt (Bzle = benzotriazo). Umphumela we-CME wawuncike kokuhlolwayo, imekhyuli (II). Ngenxa yokonakala yokunyakaza okwehlukile kwe-anodic stripping voltammetry (DPASV) yasetshenziswa ukuze kutholwe i-Hg(II) kusetshenziswa i-Pt|PPy/CoPc-Bzt ngaphakathi kobubanzi bomugqa obuyi-10 µM ukuya e-100 µM. I-LOD ne-LOQ kutholwe kuku-3.11 kanye ne-10.00 µM, ngokulandelanayo. Ucwaningo lokungenelela lubonise ukuthi amandla okwenziwa e-CME awazange athintwe ukuba khona kwamanye amamolekhyuli ensimbi esindayo. Ukuhlaziya ukusebenza kwe-Pt|PPy/CoPc-Bzt (97.4%) kanye neplasma ehlanganiswe emachotsheni – nge-optical emission spectroscopy (ICP-OES) (112.3%) kokubili kungaphakathi kwebanga elamukelekayo lama-80-120 amaphesenti. Esigabeni sesithathu sokuhlola, ikhono le-Pb yemishini ekwazi ukuhlonza ingozi ye-electrode yegolide elungiswe ngokufaka i-electrospun nanofibers (ENFs) kanye neNafion (Nf) njengesendlalelo esiphezulu esisebenzayo iye yahlolwa. Ama-ENF akhiwe ahlanganisa ipolymeric nanocomposite eyinhloko yetetra-4-(3-oxyflavonephthalocyaninato)icobalt(II) (CoPc-flav), isimuncwane sekhabhoni esisebenza ngemultiwalled carbon nanotubes (f-MWCNTs) kanye nepolyaniline (PANI) efakwe kwipolyvinyl i-acetate (PVA) ENFs. Umphumela we-CME, Au|ENFs-1-Nf awuzange uthembakale njengoba kwatholakala lapho kusetshenziswa ama-CME angenalutho namanye akhiwe ukuqina kokuhlonza kuye kwaphazanyiswa amaza imishini engemuva. Imishini ehlonza inkinga ye-Au|ENFs-1-Nf i-Pb(II) ngendlela ekwazi ukukhiqizwa kabusha (%RSD ka-3.92%, N = 3) kusukela kokuyi-8 kuye e-125 µM, kanye nemikhawulo yokutholwa nokulinganisa okuyi-0.51 noku-1.55 µM zatholwa, ngokulandelana. Kodwa-ke, izifundo zokungenelela zibonise ukuthi amandla okuzakhela e-CME asengozini enkulu ngokuba khona kwamanye amamolekhyuli ensimbi esindayo. Ukusebenza kokuhlaziya kwe-CME kuveze amaphesenti aqhathaniswayo (103%) nalokhu kwe-ICP-OES (115%). Esigabeni sesine sokuhlola, inanofabrication kanye nokuhlukaniswa kwezinto ezintsha zokuqhuba, i-PANI-CoPc-fur (1) ((PANI = polyaniline ne-CoPc-fur = tetra-4-(2-furanmethylthiophthalocyaninato)Co(II)) kanye ne-PANI- I-CoPc-fur-f-MWCNTs (2) ibikwa ngokulandelayo, inhlanganisela ye-electrospun nanofiber (ENF) yakhiwe lapho ingqikithi ehlanganisa i-2 ehlanganiswe negobolondo le-PVA, i-ENFs-2 yakhangiswa ngengilazi icarbon electrode (GCE) okulandelwa ukuvalwa kongqimba oluphezulu olunamathelayo lwe-Nafion (Nf) ukuze kunikezwe i-electrode eguquliwe ngamakhemikhali, i-GCE|ENFs-2-Nf amandla ekukhuthazeni imisebenzi yayo yemishini. Ngenxa yalokho, i-CME ibonise ukuphakama okukhulu kwe-anodic necathodic cyclic voltammetry (CV) uma kuqhathaniswa ne-GCE engenalutho namanye ama-electrode ashintshiwe, okubonisa ukuzwela kwayo okuphezulu kwe-acetaminophen (APAP), ukungcola kwamanzi okuvela ukukhathazeka. Imikhawulo yokutholwa nokulinganisa (i-LOD ne-LOQ) amanani e-APAP atholwe ngesquarewave voltammetry (SWV) ibiphansi uma iqhathaniswa naleyo etholwe kusetshenziswa amanye amasu imishini yamakhemikhali. Ukutholwa kwe-APAP ku-GCE|ENFs-2-Nf etholwe ngesquarewave voltammetry (SWV) bekuwumugqa osuka e-10 ukuya ema-200 µM ye-APAP futhi ibikwazi ukukhiqizwa kabusha (%RSD yoku-3.2%, N = 3). Amanani alandelanayo abaliwe e-LOD nawe-LOQ ayi-0.094 kanye nayi-0.28 µM abephansi uma kuqhathaniswa nalawo atholwe kusetshenziswa ezinye izindlela zemishini yamakhemikhali. Ukuhlaziywa kwe-APAP phambi kokuphazamiseka okuvame ukuhlotshaniswa nemetronidazole (MTZ) kanye nedopamine (DA) kubonise ukwehlukana okukhulu phakathi kwamandla aphezulu e-SWV e-APAP kanye ne-MTZ, kuyilapho kube khona izinga elithile lokushayisana phakathi kwezimpendulo zamanje ze-SWV ze-APAP ne-DA. Ukusebenza kokuhlaziya kwe-GCE|ENFs-2-Nf kuveze amaphesenti aqhathaniswayo (103.8%) nalokho kweliquid chromatography–mass spectrometry (LC–MS) (106%).
Phytochemistry of some South African medicinal Rubiaceae and Curtisiaceae species.
(2024) Moyo, Prince Nqaba.; van Heerden, Fanie Retief.
The investigation began by identifying which taxonomic groups from southern Africa are most prominently featured in ethnopharmacological practices. This involved collecting data from ethnopharmacological surveys and performing statistical analyses. Over-represented southern African taxa and the concept of over-represented genera are presented for the first time. The families and genera with the highest margins of over-representation were found to be Loganiaceae and Albizia in southern Africa as a whole and Sapotaceae and Solanum in South Africa. The families and genera with the highest margins of over-representation across disease categories are Ebenaceae and Albizia, Canellaceae and Dicoma, Combretaceae and Pterocelastrus, Ebenaceae and Bersama, Francoaceae and Erythrina, and Aristolochiaceae and Strychnos for plants used in the treatment of STIs, febrile and mosquito-vector diseases, microbial infections, pain, skin conditions, and female sexual/reproductive problems, respectively. The Rubiaceae family was found to be one of the 25 most over-represented taxonomic groups in Southern Africa. Plants in the family were targeted for investigation due to the availability of plant material. The study focused on the phytochemical investigations of three southern African medicinal plants, Coddia rudis (E.Mey. ex Harv.) Verdc., Keetia gueinzii (Sond.) Bridson and Curtisia dentata (Burm.f.) C.A.Sm. The ethnopharmacology and phytochemistry of the Rubiaceae species were first reviewed. The review was intended to be comprehensive, recording and discussing the notable findings of investigations on Rubiaceae species. Hundred and thirteen Rubiaceae species with ethnobotanical applications. Thirty-five species have nutritional applications. Twenty-three out of 34 anti-inflammatory and analgesic species, 17 out of 31 anti-viral and anti-bacterial species, and 13 of 27 Rubiaceae species used for sexual and reproductive problems have not undergone preparative phytochemical analysis. Only 52 southern African Rubiaceae were found to have undergone bioactivity investigations. Two hundred and thirty-three isolated compounds have been reported from 39 Rubiaceae species of southern Africa. Coddia rudis and Keetia gueinzii were selected based on proximal availability in the Pietermaritzburg region. Curtisia dentata was chosen due to findings during the review that plants in the Cornales order (of which C. dentata is a member) produce iridoid glycosides similarly to the Rubiaceae family members. The study yielded eleven bioactive known compounds. Gardenoside, geniposidic acid, and astragalin were isolated from C. rudis leaves and kaempferitrin was isolated from K. gueinzii leaves. Phlorizin and (-)-epicatechin were isolated from C. dentata bark, and loganic acid, secologanoside, geniposide, juglalin, and sweroside were isolated from C. dentata leaves. The study represents the first report of the isolation of these compounds from the species in question. The isolation of phlorizin, a known diuretic with anti-diabetic activities, supports the use of the C. dentata bark to treat diabetes in traditional medicine. Furthermore, obtaining juglalin, which has been reported to inhibit the senescence of dermal fibroblast cells, corroborates the application of the plant in the treatment of various skin conditions. The results of the study are consistent with findings reported in literature that show the presence of biologically active iridoid glycosides in Rubiaceae and Cornales species.
Removal of antiretrovirals using low-cost adsorbents: adsorption kinetics, adsorption isotherms and thermodynamics studies.
(2023) Simelane, Lindokuhle Anele.; Mahlambi, Precious Nokwethemba.; Rochat, Sebastien.; Baker, Ben.
The current study was directed to the synthesis and application of low-cost adsorbent for the removal of antiretroviral drugs (ARVDs) such as nevirapine, abacavir and efavirenz in wastewater samples. The study involved the modification and application of liquid chromatography photo diode array (LC-PDA) for the detection of the ARVDs of interest. The good separation of ARVDs was achieved using a gradient elution 50 % ACN: 50 % H2O (0-2 minutes), 70 %ACN: 30 % H2O (3-20 minutes).The macadamia nutshells, Platanus acerifolia leaves (London plane) were explored as easily accessible and eco-friendly adsorbents. The single synthetic route and high surface area of the polymer of intrinsic microporosity number-1(PIM-1) were the distinct properties that were ideal for exploring this adsorbent for removal of ARVDs in wastewater samples. The adsorbents were synthesized and characterized using Fourier transform infrared spectroscopy (FTIR),Scanning electron microscopy (SEM), Brunauer Emmett Teller (BET), Powder X-ray diffraction (PXRD). The results obtained from macadamia nutshell and Platanus acerifolia adsorbent for FTIR characterization were functional groups such O-H, C=O and C=C and many others whereas Platanus acerifolia adsorbent had additional N-H from in addition to one obtained in macadamia adsorbent. The PIM-1 showed CN, C=O and C-H functional groups. SEM showed rod-folded structure and flaky-folded structure for macadamia nutshell adsorbent and Platanus acerifolia leaves adsorbent respectively, whereas PIM-1 exhibited microporous to mesoporous pore on adsorbent surface. The BET showed a surface area, pore diameter and pore volume of 0.1180 m2/g, 27.98 nm, and 8.3×10-5 cm3/g for macadamia nutshells adsorbent and 1.14 m2/g, 0.0024 cm3/g and 4.09 nm for Platanus acerifolia leaves adsorbent. The PIM-1 had a surface of 557.39 cm2/g, pore volume 0.4123 cm3/g and pore diameter 2.96 nm. The PXRD of macadamia and Platanus acerifolia adsorbents had native crystalline cellulose structure whereas PIM-1 had an amorphous material. These characterization results indicated that the adsorbents have the potential to efficiently remove the ARVDs from in contaminated wastewater. Prior to the application of adsorbents, parameters such as adsorption time (5-240 minutes), solution pH (2-10), initial concentration (0.2-2 mg/L), adsorbent mass dosage (0.2-10 mg) and adsorption temperature (15-40°C) were investigated to access the removal efficiency of all the synthesized adsorbents on their ability to remove ARVDs in wastewater samples. Under optimum conditions the adsorption was conducted using 10 mg of the adsorbent in 10 mL wastewater sample spiked at a concentration 1.0 mg/L, at a pH of 7 and stirred at 150 rpm at 30°C. These conditions yielded a removal efficiency greater than 80 %, 90 % and 86 % using macadamia nutshells, Platanus acerifolia leaves and PIM-1 adsorbent, respectively in all ARVDs of interest. The study of adsorption kinetics, adsorption isotherms and thermodynamic model was essential for designing an efficient adsorption process to remove ARVDs which are pollutants of emerging concern. The results obtained showed that pseudo-second-order model well defined the kinetic data, and the adsorption isotherms was well fitted in Langmuir isotherm and adsorption process was exothermic in nature for macadamia nutshells and Platanus acerifolia leaves adsorbent. For PIM-1 adsorbent, the pseudo-second-order was dominant, and the adsorption isotherm was well defined by Freundlich model. Thermodynamic parameters showed that the adsorption was thermodynamically favored, spontaneous, and exothermic in nature. The adsorbents were then applied under optimum conditions and the amount adsorbed of ARVDs from wastewater samples were 94.41, 88.84 and 83.06 mg/g for nevirapine, abacavir and efavirenz respectively for macadamia nutshell adsorbent. For Platanus acerifolia leaves adsorbent, 97.56, 84.75 and 81.56 mg/g amount adsorbed of nevirapine, abacavir and efavirenz. On the other hand, PIM-1 adsorbent had an adsorption capacity of 83.65, 93.83 and 94.56 mg/g amount for nevirapine, abacavir and efavirenz, respectively. Overall, the macadamia nustshells, Platanus acerifolia leaves and PIM-1 adsorbents have illustrated to be efficient and cost-effective adsorbents for removal ARVDs in wastewater samples. However, the two agricultural adsorbents, macadamia nutshell and Platanus acerifolia leaves adsorbents could be highly recommended since their usage is able to reduce land and water pollution which is compromises water quantity which is already at stake across the globe.
Structure-activity relationships of novel anti-diabetic ruthenium compounds : synthesis, characterization, mechanistic and in vitro studies.
(2024) Makanyane, Madikoloha Daniel.; Booysen, Irvin Noel.; Mambanda, Allen.
Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder which is globally responsible for millions of fatalities per year. Management of T2DM typically involves orally administered anti-hyperglycaemic drugs in conjunction with dietary interventions. However, the current conventional therapy seems to be largely ineffective as patients continue to develop complications such as cardiovascular diseases, blindness and kidney failure. Existing alternative treatment entails the administration of organic therapeutic pharmaceuticals, but these drugs have various side effects such as nausea, headaches, weight gain, and respiratory and liver damage. Transition metal complexes have shown promise as anti-diabetic agents owing to their diverse mechanisms of activity. In particular, selected ruthenium compounds have exhibited intriguing biological behaviours as Protein Tyrosine Phosphatase (PTP) 1B and Glycogen Synthase Kinase 3 (GSK-3) inhibitors, as well as aggregation suppressants for the human islet amyloid polypeptide (hIAPP). The introduction chapter served as a survey on studies pertaining to ruthenium compounds as metallo-drugs for T2DM. Herein, we also provide perspectives on directions to fully elucidate in vivo functions of this class of potential metallopharmaceuticals. More specifically, there is still a need to investigate the pharmacokinetics of ruthenium drugs in order to establish their biodistribution patterns which will affirm whether these metal complexes are substitutionally inert or serve as pro-drugs. In addition, embedding oral-administered ruthenium complexes into bio-compatible polymers can be a prospective means of enhancing stability during drug delivery. This chapter was concluded with a descriptive rationale of the research study as well as specifying the specific research aims and objectives. Our prior studies have illustrated that the uracil ruthenium(II) diimino complex, [Ru(H3ucp)Cl(PPh3)] (1) (H4ucp = 2,6-bis-((6-amino-1,3-dimethyluracilimino)methylene)pyridine) displayed high hypoglycaemic effects in diet-induced diabetic rats. To rationalize the anti-diabetic effects of 1 in the first experimental chapter, three new derivatives have been prepared, cis-[Ru(bpy)2(urdp)]Cl2 (2) (urdp = 2,6-bis-((uracilimino)methylene)pyridine), trans-[RuCl2(PPh3)(urdp)] (3), and cis-[Ru(bpy)2(H4ucp)](PF6)2 (4). Various physicochemical techniques were utilized to characterize the structures of the novel ruthenium compounds. Prior to biomolecular interactions or in vitro studies, the stabilities of 1 – 4 were monitored in anhydrous DMSO, aqueous phosphate buffer containing 2% DMSO, and dichloromethane (DCM) via UV-Vis spectrophotometry. Time-dependent stability studies showed ligand exchange between DMSO nucleophiles and chloride co-ligands of 1 and 3, which was suppressed in the presence of an excess amount of chloride ions. In addition, the metal complexes 1 and 3 are stable in both DCM and an aqueous phosphate buffer containing 2% DMSO. In the case of compounds 2 and 4 with no chloride co-ligands within their coordination spheres, high stability in aqueous phosphate buffer containing 2% DMSO was observed. Fluorescence emission titrations of the individual ruthenium compounds with bovine serum albumin (BSA) showed that the metal compounds interact non-discriminately within the protein's hydrophobic cavities as moderate to strong binders. The metal complexes were capable of disintegrating mature amylin amyloid fibrils. In vivo, glucose metabolism studies in the liver (Chang) cell lines confirmed enhanced glucose metabolism as evidenced by the increased glucose utilization and glycogen synthesis in liver cell lines in the presence of complexes 2 – 4. The second experimental chapter, reports on the formation and characterization of new diamagnetic ruthenium uracil mono-imine compounds: [(η6-p-cymene)RuII(L)Cl] (L = urpda = 5-((pyridin-2-yl)methyleneamino)-6-aminouracil) for 1, urdpy = 6-amino-1,3-dimethyl-5-((pyridin-2-ylmethylene)amino)uracil) for 2 or urqd = 5-((quinolin-2-yl)methyleneamino)-6-aminouracil) for 3); cis-[RuII(L)(bipy)2] (L = urpy = 5-((pyridin-2-yl)methyleneamino)uracil) for 4 and H2dadp = 5,6-diaminouracil for 5); trans-[RuII(L)(PPh3)Cl2] (L = urpda for 6) are described. Various physicochemical techniques were utilized to characterize the structures of the novel ruthenium compounds. Furthermore, the DPPH and NO radical scavenging capabilities of metal complexes (2 – 10) were investigated. UV-Vis spectrophotometry data of the time-dependent (for 24 h) studies show that 4 and 5 are stable in aqueous phosphate buffer containing 2% DMSO. Similarly, the stabilities of 1 - 3 and 6 monitored in chloro-containing and non-coordinating solvent dichloromethane show that they are kinetically inert, whereas, in a high nucleophilic environment, the chloride co-ligands of 1 - 3 and 6 were rapidly substituted by DMSO. In contrast, the substitution of the labile ligand of the complexes by DMSO molecules from its solution with a high chloride content was suppressed. Solution chemical reactivities of the different metal complexes were rationalized by density functional theory computations. Furthermore, the binding affinities and strengths between BSA and the respective metal complexes were monitored using fluorescence spectroscopy. Mutually, these metal complexes showed comparable capabilities of denaturing mature BSA aggregates which was established by fluorescence spectroscopy and Transmission Electron Microscopy (TEM). The final experimental chapter entails the encapsulation of the ruthenium complexes 1 - 10 into separate organic chitosan (CS)-polyvinyl alcohol (PVA) blends and the subsequent nanofabrication of their electrospun nanofiber (ENF) conjugates, Ru-CS-PVA ENFs. Intravenous injections of insulin can be regarded as a primitive method for Diabetes Mellitus management which characteristically leads to patients developing insulin resistance while oral-administered anti-diabetic organodrugs such as Metformin have exhibited low bio-availability and typically induce gastrointestinal (GI) side-effects. Although the intravenous injections of selected metal compounds in Streptozocin (STZ)-diabetic results have delivered promising results, limited work has been done to evaluate their efficiencies during oral administration. Herein, the fabricated chitosan (CS)-polyvinyl alcohol (PVA) electrospun nanofibers (CS-PVA ENFs) of the leading insulin-enhancing ruthenium complex 1, cis-[Ru(bipy)2(H4ucp)](PF6)2 and its analogs: 2 – 10. The Ru-CS-PVA ENFs nanocomposites were characterized by using (SEM-EDX), powder X-ray diffraction, and FTIR spectroscopy. The Ru-CS-PVA ENF nanohybrids exhibited randomly oriented fiber mat morphology with mean diameters in the range of 118 - 280 nm. Metal-based drug release kinetics of 1 - 10 from the ENF polymer matrix were measured spectrophotometrically at pH 1.5 and 7.4, respectively. Electronic spectral trends and data analysis over a 24-hour data collection period reveals variable dissolution rates with first-order rate (kobs) constants ranging from 0.0146 to 2.74 μM h-1 with accompanying hyperchromism effects between 5.69 to 37.6% at a pH of 1.5 while at a pH of 7.4, kobs value limits were 0.0104 and 3.89 μM h-1 rendering corresponding 19.14 and 87.32% hypochromic shifts. The release kinetics data of 1 - 10 were spontaneously released into the aqueous media from the Ru-CS-PVA ENFs, with the highest and releasing rates recorded for complexes 8 and 4, respectively.
Syntheses of (pyridyl) pyrazine carboxamide palladium(II) complexes, their DNA/BSA interactions, and cytotoxicity studies.
(2023) Mvelase, Sabathile Thandeka.; Ojwach, Stephen Otieno.
Reaction of pyrazine-2,3-dicarboxylic acid with a respective amine in the presence of triphenyl phosphite afforded the corresponding carboxamide ligands: [N2, N3-bis(pyridin 2-yl)pyrazine2,3-dicarboxamide] (L1), [N2, N3-bis(6-methylpyridin-2-yl)pyrazine-2,3-dicarboxamide] (L2), [N2,N3-bis(4-methylpyridin-2-yl)pyrazine-2,3-dicarboxamide] (L3), and [N2, N3bis(quinoline-8-yl)pyrazine-2,3-dicarboxamide] (L4). Treatments of the corresponding (pyridyl)pyrazine carboxamide ligands with [PdCl2(NCCH3)2 afforded new mononuclear and dinuclear palladium(II) complexes with a general formula, [Pd2(L1)2Cl2] (Pd1), [Pd2(L2)2Cl2] (Pd2), [Pd2(L3)2Cl2] (Pd3) and [Pd(L4)Cl] (Pd4). The identities and coordination nature of the palladium(II) complexes were established through a combination of characterization techniques such as NMR, FT-IR spectroscopy, mass spectrometry, elemental analysis, and single X-ray crystallography. The molecular structures of the dinuclear Pd1 and Pd3 complexes reveal that the two (pyridyl) pyrazine carboxamide ligands coordinate with the palladium atom via one arm, while the other arm remains non-coordinating. The ligands are bridged by two palladium atoms to form dinuclear palladium(II) complexes. While one ligand coordinates to the palladium in a bidentate fashion via the nitrogen atoms of the pyrazine and amide groups, the other ligand unit coordinates to the palladium through the pyridine nitrogen atom to give two ligand units and two palladium atoms in the complex coordination sphere. On the other hand, ligand L4 binds to palladium atom in a tridentate fashion via the pyrazine, amide, and pyridine nitrogen atoms to give complex Pd4 as a mononuclear species. The interaction of the palladium complexes (Pd1-Pd4) with calf thymus DNA (CT-DNA) was monitored using UV-Vis, and fluorescence spectroscopy. Absorption spectroscopic studies revealed that complexes Pd1-Pd4 interact with CT-DNA via intercalative mode, and the computed intrinsic binding constant (Kb) values range from (4.28-13.12) x 106 M-1. In addition, Ksv values of (1.82-28.41) x 106 M-1 and KF values of (1.01-53.44) x 104 M-1 determined in competitive binding studies confirmed the intercalative binding mode. The interaction of the complexes with CT-DNA decrease in the order of Pd3 > Pd2 > Pd1 > Pd4. Furthermore, bovine serum albumin (BSA) interaction was evaluated using fluorescence studies and the results revealed the existence of a static quenching mechanism with bimolecular constant, kq range of (0.66-13.99) x 1014 M-1 s-1. The Ksv values of (1.48-29.67) x 106 M-1 and KF values of (0.10-16.10) x 105 M-1 confirmed the interaction between BSA and palladium complexes. The interaction follows this order Pd2 > Pd1 > Pd3 > Pd4, which is inconsistent with the CT-DNA trend. In general, ligands bearing electron-donating methyl groups (L2 and L3) contributed to higher binding constants in their respective complexes Pd2 and Pd3 compared to the unsubstituted complex Pd1. In addition, the mononuclear complex Pd4 showed the weakest interactions with both the DNA and BSA, pointing to some beneficial effects of increased metal atoms in the complexes. The cytotoxic effect of the ligands L1-L3 and complexes Pd1-Pd4 were examined against a human breast cancer cell line (MCF-7) using 3-(4,5-Dimethyl-2thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. In general, the ligands displayed poor cytotoxicity L1 (IC50 > 400 μM), L2 (IC50 = 182.4 μM), L3 (IC50 = 80.2 μM), when compared to their respective palladium(II) complexes Pd2 (IC50 = 154.9 μM), Pd3 (IC50 = 230.1 μM). Complexes Pd1 (IC50 = 11.4 μM), and Pd4 (IC50 = 61.5 μM) displayed high and moderate cytotoxic activity which was attributed to the planarity of the complexes.
Synthesis and the application of molecularly imprinted polymers as solid-phase extraction and dispersive solid-phase extraction sorbents in the extraction of antiretroviral drugs in water.
(2022) Xolo, Thabiso.; Mahlambi, Precious Nokwethemba.
A multi-template molecularly imprinted polymer was synthesized, characterized, and applied to real water samples for the specific extraction of antiretroviral drugs (ARVDs), abacavir, nevirapine, and efavirenz. A MIP was synthesized by bulk polymerization at 60 ºC using abacavir, nevirapine and efavirenz (templates), 2-vinylpyridine (functional monomer), 1,1’- azobis-(cyclohexanecarbonitrile) (initiator), ethylene glycol dimethacrylate (cross-linker) and toluene: acetonitrile (9:1, v/v) (porogenic solvent mixture) for 16 hours. The temperature was then increased to 80 ℃ for 24 hours to ensure complete polymerization. The synthesized MIP was washed with acetic acid: acetonitrile (1:9, v/v) via soxhlet extraction until all three ARVDs were undetected in the washing solvent using high performance liquid chromatography coupled with a photo-diode array detector. A non-imprinted polymer (NIP) was synthesised using the same reagents and quantities except for the templates. Both MIP and NIP were characterized using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electron microscope (SEM), N2 physisorption analysis, and elemental analysis. The FTIR results showed that the polymers were similar in structure and BET showed that they were mesoporous. The SEM showed that the MIP surface was rougher when compared to the NIP and characterization with TGA showed that they were both thermally stable. The synthesized MIP was used to study its adsorption kinetics and isotherms. Kinetics modelling revealed that the Pseudo-second-rate order kinetics was the best fitting model with correlation coefficient of 1 compared to Pseudo-first-rate order kinetics which had a correlation efficient of 0.81-0.983 for all target analytes. The best fitting adsorption isotherm was the Freundlich model with a correlation range of 0.9451-0.986 for compared to the Langmuir model which had correlation efficient of 0.6692-0.93390.0198-0.6782 for all target analytes. The traditional solid phase extraction and the MIP-based solid phase extraction methods were applied in distilled water samples spiked with 1 mg.L-1 of ARVDs and recoveries obtained were ranging from 91.68-94.59% and 97.20 to 99.68%, respectively. The MIP-based dispersive solid phase extraction method was successfully optimized with recoveries ranging from 100.28% to 102.60% for all three analytes. Selectivity studies were conducted using both the NIP and MIP with lamivudine and diclofenac as competitors. The recoveries obtained for the MIP ranged between 92% to 98% for the target analytes while they were 63% to 79% for competitors. These results showed good selectivity and strong affinity of the polymer towards the target analytes than the competitors. This is justified by the presence of imprinted recognition sites that have the same functional groups, size, and shape as the target analytes/templates hence recoveries were low for competitors. The MIP was more selective towards analytes of interest compared to the NIP (recoveries ranged from 87.9% to 91%) for the analytes of interest which indicates successful imprinting on the MIP. Reusability studies showed that the MIP can be reused for up to 8 cycles with recoveries above 92% for all target analytes. The developed, adopted, and validated methods were then applied to wastewater, tap water and river water samples from around KwaZulu-Natal. The concentrations obtained for abacavir, nevirapine and efavirenz were 10.65-295.90 μg.L-1 in wastewater, 1.95-13.15 μg.L-1 in river water, and 2.17-6.27 μg.L-1 in tap water. Efavirenz was the most dominant and consistently detected ARVD in all samples. The MIP-DSPE was the most sensitive and selective extraction technique compared to SPE and MIP-SPE. Umhlathuzana and Amanzimtoti were the most ARVD’s polluted wastewater treatment plants, whilst Northern wastewater water works was the least polluted. Camps Drift was the most ARVD’s polluted sampling point in Msunduzi river. Napierville and Scottsville showed the most contaminated tap water samples from suburbs around Pietermaritzburg.
Synthesis elaboration of fragments that potentially inhibit the HOP-HSP90 protein-protein interaction.
(2024) Molefe, Patience Snenhlanhla Sthembile.; Sithebe, Siphamandla.; Veale, Clinton Gareth Lancaster.
Heat Shock Protein 90 (HSP90) is a molecular chaperone that mediates the stability and maturation of many important proteins for oncogenesis. There is an overexpression of the Heat Shock Protein 70/Heat Shock Protein 90 Organising Protein- HSP90 (HOP-HSP90) protein-protein interaction (PPI) complex in tumour tissues unlike in healthy cells. This PPI complex of HSP90 displayed a potential druggable target because of the crucial role it plays in cancer development. However, the challenge is the development of HOP-HSP90 PPI inhibitors. The literature showed the activity of valsartan (27) for the inhibition of HOP-HSP90 PPI as it entails the features of ortho-biphenyl tetrazole fragments that were obtained from the Structural-Binding Relationship (SBR) of the active fragments using fragment-based drug discovery (FBDD). These fragments bound to the tetratricopeptide repeat 2A (TPR2A) domain of HOP and inhibited the PPI of HOP-HSP90. As a result, this study aimed to synthesise and assay ortho-biphenyl tetrazole fragments as inhibitors of HOP-HSP90 for novel anticancer inhibitors, triple-negative breast cancer (TNBC). Valsartan (27) and its analogues were synthesised following reported procedures and modified methods. A series of 13 ortho-biphenyl tetrazole desired fragments were successfully synthesised using a Suzuki-Miyaura cross-coupling reaction and [3 + 2] cycloaddition of nitrile with sodium azide. The cross coupling of 2-iodobenzonitrile or 2-(2-bromophenyl) acetonitrile with para-substituted phenylboronic acid was conducted using different substrates including Cl, Br, F, CH3, CF3, H, and OCH3. Cycloaddition was done after the cross-coupling to skip the protection step of the tetrazole. With the desired ortho-biphenyl tetrazole fragments in hand, the PPI inhibition activity was evaluated at different concentrations from 0 mM to 2.0 mM. It is interesting to observe that some of these fragments showed PPI activity at different concentrations including compounds 76, 80, 82, 83 and 84. No activity was observed following the incorporation of the benzylic carbon. The data presents the successful lead optimisation for the development of HOP-HSP90 novel PPI inhibitors for the treatment of TNBC.
Synthesis of ketones through aerobic transition metal-catalyzed cross-coupling of thioesters.
(2021) Mthombothi, Zabenguni Zakithi.; Sithebe, Siphamandla.
Asymmetric diaryl ketones are an important class of compounds in organic chemistry due to their presence in natural products, synthesis, cosmetics as well as in biological active compounds. The aim of this project was to expand the scope of thiophilic metal carboxylates catalysts that can be applied to the aerobic Liebeskind-Srogl cross coupling reaction between various thioesters and phenylboronic acids. Thioesters bearing electron neutral, withdrawing and donating groups were successfully synthesized in yields ranging from 35 to 54%Xcv. The electron neutral thioester was used in the optimization of the aerobic Liebeskind-Srogl reaction and CuMeSal proved to be the most effective catalyst in this protocol. CuMeSal was applied in the aerobic synthesis of the asymmetric diaryl ketones bearing a wide range of functional groups including CF3, SMe, OMe and F yielding up to 65% in 24hrs. Aerobic Liebeskind-Srogl cross-coupling reaction was applied in the successful synthesis of chalcones, through the coupling of commercially available phenylboronic acids with previously synthesised thioesters catalysed by CuMeSal in DMF for 24hrs,furnishing desired products in poor to excellent yields 26-89%.
Synthesis, characterization and substitution reaction studies of pyridyl N,N’-bidentate palladium(II) complexes. A kinetic and mechanistic study.
(2023) Mjwara, Pinky Ncomela.; Sithebe, Siphamandla.; Papo, Tshephiso Rose.
The influence of structural as well as electronic properties of bidentate N,N chelates with different substituents on the mononuclear Pd(II) complexes were investigated. The complexes were synthesized and characterized by various spectroscopic methods such as 1H & 13C NMR, FT-IR, LC-MS, CHN and single x-ray crystallography. For the first set of complexes (Chapter 3), we studied the unexplored kinetics and mechanistic behaviour of N,N’-pyridyl Pd(II) complexes, viz. dichloro-(N-((pyridin-2-yl)methyl)aniline)palladium(II) (PdL1), dichloro-(4-fluoro-N-((pyridin-2-yl)methyl)aniline)-palladium(II) (PdL2), dichloro-(4-bromo-N-((pyridin-2-yl)methyl)aniline)-palladium(II) (PdL3), dichloro-(4-methoxy-N-((pyridin-2-yl)methyl)aniline)-palladium(II) (PdL4) and dichloro-(4-ethyl-N-((pyridin-2-yl)methyl)aniline)-palladium(II) (PdL5). The substitution behaviour of coordinated chloride atoms by three bio-relevant thiourea nucleophiles, viz. thiourea (TU), N,N’-dimethylthiourea (DMTU) and N,N,N’,N’-tetramethylthiourea (TMTU), of different steric demands was studied in a 0.1 M solution of ultra-pure water under pseudo-first order conditions. The reactions were studied as a function of concentration and temperature using standard Stopped-Flow and UV-Vis spectrophotometric technique. The substitution of the chloride atoms from the Pd metal by thiourea nucleophiles was a two-step reaction where the chloride trans to the pyridine ligand was substituted first, since the pyridine has a stronger trans effect compared to the amine group. The reactivity of mononuclear Pd(II) complexes containing bidentate N,N’-donor ligands with different substituents depends on the electronic effects of the complexes. The reactivity of the complexes increased with the presence of electron withdrawing substituents and decreased when an electron donating group was attached on the para position of the aniline moiety. The electron withdrawing groups influence the pull of electrons from the electron deficient amine that is coordinated to the metal center which results in the loss of electron density from the ligand moiety and increases the electrophilicity of the metal center and thus the substitution reaction. The reactivity of the nucleophiles depends on steric effects, with the bulky TMTU being the least reactive. The negative entropies and second order kinetics for all the substitution reactions support an associative mode of substitution mechanism. DFT calculations were performed to account for the observed reactivity of all the complexes studied. For the second set of novel Pd(II) complexes (Chapter 4), viz. bis[N-(4-bromophenyl)pyridine-2-carboxamidato] Palladium (Pd1) and Palladium(II) [N-(4-bromophenyl)-2-pyridinecarboxamide), pyridine chloride (Pd2), crystals were obtained and the structures were studied. Pd1 crystallizes in the monoclinic crystal system and in the P21/c space group, and Pd2 crystallizes in the orthorhombic system, with the space group Pbca.

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