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Thiazole derivatives as potential hiv-1 protease inhibitors

  • Authors: Hlongwe, Zola
  • Date: 2021-04
  • Subjects: Gqeberha (South Africa) , Eastern Cape (South Africa) , Enzyme kinetics
  • Language: English
  • Type: Master's theses , text
  • Identifier: http://hdl.handle.net/10948/52116 , vital:43427
  • Description: Series of compounds were screened using Schrodinger suite (Maestro). The DFT calculations were used for geometry optimization of the ligands using the B3YLYP functional and 6-31G basis set, and these structures were used for docking studies. Maestro was used to predict the activity of thiazole derivatives against HIV-1 protease. The range of estimated inhibition constants for these thiazole derivatives (65 nM-5 μM) indicate moderate to weak activity against HIV-1 protease, given that the activity of current protease inhibitors is typically found have experimental inhibition constants around 0.1-2.0 nM. Twenty compounds were selected based on the docking results and they were synthesized and characterized by NMR, FT-IR and elemental analysis. The cytotoxicity studies were done at two different concentrations (100 μM and 10 μM), using the brine shrimp bioassay. All compounds were highly toxic at 100 μM, with the percentage mortality between 20 to 75%. Eight compounds were selected for the enzyme bioassay based on the results obtained from lower concentration (10 μM). In the enzyme inhibition studies, the profile of HIV-1 activity was done at different inhibitor concentrations (800 μM – 10 μM) by measuring the cleavage of the synthetic substrate (Abz-Thr-lle-PNO2Phe=Gln-Arg-NH2) at excitation wavelength of 345/490 nm using fluorescence. Ligands 5 (unsubstituted derivative), 7 (4-nitro derivative) and 16 (4-methoxy derivative) gave percentage inhibition of 39, 45 and 42%, and this activity was very low compared to the activity of the positive control ritonavir (85% enzyme inhibition). Ligands 8 (4-methoxy derivative) and 12 (4-methoxy derivative) gave enzyme inhibition of 70% and 75%. These results suggest that the presence of the methoxy substituents ii increases activity of these compounds against HIV-1 protease. Most of the compounds gave good IC50 values between 12.5-42.7 nM. The bromo-substituted ligand 7 gave the lowest IC50 (12.5 nM). Ligand 11 also gave a good IC50 value of 14.86 nM. The bromo-substituted derivatives showed to be very active compared to other types of thiazole derivatives. Enzyme kinetics were carried out to compare the inhibition constants obtained via computational modelling. Ligand 7 (4-methoxy derivatives) binds better in the active site of HIV-1 protease than other compounds in Class B, with Ki = 50 nM, Km = 23.8 Nm and Vmax = 83.3 nM/min. The unsubstituted (L5), 4-bromo (L7) and 4-nitro (L8) substituted compounds gave inhibition constants of 100 to 112 nM. The in vitro testing yielded higher activity than that determined in silico. , Thesis (MSc) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2021
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  • Date Issued: 2021-04

Design of metal ion-selective reagents for recovery of precious metals

  • Authors: Moleko-Boyce, Pulleng
  • Date: 2019
  • Subjects: Bioinorganic chemistry , Metal complexes Speciation (Chemistry)
  • Language: English
  • Type: Thesis , Doctoral , DPhil
  • Identifier: http://hdl.handle.net/10948/42510 , vital:36664
  • Description: The study is divided into two sections; namely, (1) the design of rhodium(III) specific chelating ligands (tridentate bis-benzimidazole derivatives), and (2) the development of iridium(IV)-specific quaternary diammonium cations with electron donating and electron withdrawing groups. Bis-benzimidazole chelating ligands used were bis((1H-benzimidazol-2-yl)methyl)amine (NNN1), bis((1H-benzimidazol-2-yl)ethyl)amine (NNN2), bis((1H-benzimidazol-2-yl)methyl)sulfide (NSN1) and bis((1H-benzimidazol-2-yl)ethyl)sulfide (NSN2). Quaternary diammonium cations used were tetramethylbenzyl-1,10-diammonium chloride (QuatDMDAMeBnz), tetrabenzyl-1,10-diammonium chloride (QuatDMDABnz), tetratrifluoromethylbenzyl-1,10-diammonium chloride (QuatDMDACF3Bnz) and tetranitrobenzyl-1,10-diammonium chloride (QuatDMDANO2Bnz). For both studies, polyvinylbenzylchloride (PVBC) nanofibers were used as support material. The PVBC nanofibers which were functionalised with bis-benzimidazole derivatives and quaternary diammonium cations, respectively, were investigated for the selectivity for Rh(III) over Ir(III), Pt(II), Pd(II) and Ni(II), and for separation of Ir(IV) from Rh(III), respectively. The sorbent materials were characterised by FTIR, SEM, BET surface area, TGA, EDS and elemental analysis, and the results showed that the functionalization of the sorbent materials was successful.The efficiency of bis-benzimidazole derivatives and quaternary diammonium cations, respectively, were investigated in a column study under dynamic flow adsorption conditions. The adsorption kinetics and isotherms were investigated under batch conditions and fitted on pseudo-first-order and pseudo-second-order model, and Freundlich and Langmuir isotherm, respectively. It was observed that the bis-benzimidazole derivatives showed uptake of [RhCl3(H2O)3], and the loading capacities were observed in the following order; NSN1 (181.06 mg/g) > NSN2 (148.55 mg/g) > NNN1 (131.88 mg/g) > NNN2 (75.87 mg/g). The bis-benzimidazole derivatives preference for metal ions was further investigated with a multi-element solution containing Rh(III), Ir(III), Pt(II), Pd(II) and Ni(II). The bis-benzimidazole derivatives showed the following order of loading capacity: NSN1 (47.28 mg/g) > NSN2 (23.89 mg/g) > NNN1 (17.47 mg/g) > NNN2 (14.91 mg/g) for Rh(III); NSN2 (10.64 mg/g) > NNN2 (6.84 mg/g) > NSN1 (5.74 mg/g) > NNN1 (5.02 mg/g) for Ir(III); NNN2 (33.96 mg/g) > NSN1 (30.95 mg/g) > NSN2 (19.95 mg/g) > NNN1 (14.92 mg/g) for Pt(II); NNN1 (47.94 mg/g) > NNN2 (28.90 mg/g) > NSN1 (16.22 mg/g) > NSN2 (15.83 mg/g) for Pd(II). Bis-benzimidazole derivatives showed no uptake of nickel(II) under these conditions. It was observed the ligand-selectivity order for Rh(III) was similar in both single-element and multi-element studies. This order showed that the bis-benzimidazoles containing a sulfur atom showed a high preference for rhodium(III) compared to Pt(II) which had a high preference for NNN2 as well as Pd(II) which had a high preference for NNN1. Ir(III) generally had a lower preference for the ligands presumably due to its higher kinetic inertness compared with Rh(III). Column sorption of [IrCl6]2- and [RhCl5(H2O)]2- on nanofibers functionalized with diammonium cations was carried out and the loading capacities of [IrCl6]2- were obtained. [RhCl5(H2O)]2- was not adsorbed by the sorbent materials while [IrCl6]2- was loaded onto the column. The loading capacities of [IrCl6]2- with the quaternary diammonium sorbent materials increased in the order of F-QuatDMDAMeBnz (60.29 mg/g) < F-QuatDMDABnz (67.61 mg/g) < F-QuatDMDACF3Bnz (107.59 mg/g) < F-QuatDMDANO2Bnz (140.47 mg/g). The loading capacity for Ir(IV) with quaternary diammonium cationic nanofibers increased with an increase in the electron-withdrawing nature of the quaternizing group. The charge delocalizing ability of the nitrobenzyl group resulted in the best interaction of the diammonium cation with [IrCl6]2-. Batch equilibrium studies were carried out to assess the efficiency of bis-benzimidazole chelating derivatives as adsorbents using a multi-metal solution (Rh(III), Ir(III), Pt(II), Pd(II) and Ni(II)) in 0.5 M HCl. The efficiency of the quaternary diammonium cations was tested using a binary metal solution (Ir(IV) and Rh(III)) in 6 M HCl. The isothermal batch adsorption studies of a multi-metal solution with bis-benzimidazoles derivatives fitted the Langmuir isotherm model which confirmed monolayer adsorption onto a homogeneous surface. The Langmuir isotherm parameter (qe (mg/g)), using functionalized nanofibers, showed the order of NNN2 (128.21 mg/g) > NSN1 (99.01 mg/g) > NSN2 (91.74 mg/g) > NNN1 (84.03 mg/g) for Pt(II); NNN1 (66.23 mg/g) > NNN2 (5.89 mg/g) > NSN1 (1.40 mg/g) > NSN2 (0.59 mg/g) for Pd(II); NSN2 (10.64 mg/g) > NNN2 (6.84 mg/g) > NSN1 (5.74 mg/g) > NNN1 (5.02 mg/g) for Ir(III); NSN1 (140.85 mg/g) > NSN2 (109.89 mg/g) > NNN1 (104.17 mg/g) > NNN2 (91.74 mg/g) for Rh(III). The pseudo-first-order kinetics model was found to be the best fit to describe the adsorption kinetics of all metal ions onto all the sorbent materials. K1 (min-1) value in pseudo-first-order kinetics showed the same order of adsorption as observed in the Langmuir isotherms. The isothermal batch adsorption studies of [IrCl6]2- and [RhCl5(H2O)]2- with quaternary diammonium cations fitted the Freundlich isotherm model and confirmed to be effective for multiple-layered adsorption onto a heterogeneous surface. The Freundlich isotherm parameter (kf (mg/g)) using functionalized quaternary diammonium cationic nanofibers increased in the order of F-QuatDMDANO2Bnz (794.33 mg/g) > F-QuatDMDACF3Bnz (185.35 mg/g) > F-QuatDMDABnz (156.32 mg/g) > F-QuatDMDAMeBnz (112.46 mg/g) for Ir(IV) uptake. F-QuatDMDANO2Bnz resin showed the highest adsorption than that of F-QuatDMDAMeBnz, F-QuatDMDABnz and F-QuatDMDACF3Bnz and this order is similar to what was observed in column studies. The quaternary diammonium cations were shown to have the highest adsorption capacity for Ir(IV) compared with Rh(III). The adsorption of Rh(III) was also observed to increase in the order of F-QuatDMDANO2Bnz (177.83 mg/g) > F-QuatDMDACF3Bnz (40.37 mg/g) > F-QuatDMDABnz (36.98 mg/g) > F-QuatDMDAMeBnz (12.71 mg/g). The pseudo-second-order kinetic model was found to be the best fit to describe the adsorption kinetics of both metal ions onto all the sorbent materials. K2 (g.mg-1min-1) value in pseudo-second-order kinetics showed the same order of adsorption as observed in the Freundlich isotherms. The adsorption studies showed adsorption takes place via chemisorption process. This thesis presents PGMs and iridium-specific materials that could be applied in solutions of secondary PGMs sources containing rhodium, platinum and palladium with bis-benzimidazoles as well as in feed solutions from ore processing with diammonium cations for iridium recovery.
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  • Date Issued: 2019

The development of palladium nanoparticles for radiopharmaceutical application

  • Authors: Gandidzanwa, Sendibitiyosi
  • Date: 2019
  • Subjects: Nanotechnology , Nanostructures Nanofluids
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: http://hdl.handle.net/10948/42163 , vital:36631
  • Description: The dissertation describes an in-depth synthesis and optimisation of palladium(0) nanoparticles of three distinct size ranges, respective capping agents, and cellular uptake studies using a non-toxic concentration (10 μM), laying a foundation for the design of palladium-based folate receptor-targeted theranostic nanoradiopharmaceutical. In the preliminary selection to determine the optimal diamines for the study, ethylenediamine, hexamethylenediamine, 1,10-diaminodecane, 1,12-diaminododecane, 1,4- diaminobenzene, 4,4’-ethylenedianiline, 1,2-diphenyl-1,2-diaminoethane, and tetraaminophthalocyanine were employed. The characterisation of the nanoparticles obtained from the in situ reduction of palladium(II) salt at room temperature by either 1,2,3- trihydroxybenze (pyrogallol), citric acid, sodium metabisulphite, sodium borohydride, hydrazine hydrate, or formaldehyde was performed. Ethylenediamine and sodium borohydride were found to be the best diamine capping and reducing agent, respectively. Systematic investigations determined that the nanoparticle synthesis was dependent on various reaction parameters: such as reaction temperature, time, reductant reducing power, and capping agents. The parameters effects on the nanoparticle size, morphology, shape, stability, crystallinity, and surface charge were investigated. The optical properties, elemental composition, functional group, concentration and molecular weight for the synthesised nanoparticles or conjugates were determined. These properties were analysed using Ultraviolet–visible spectroscopy (UV-Vis), high resolution transmission electron microscopy (HRTEM) coupled with selective area electron diffraction (SAED) and energy dispersive X-ray spectroscopy (EDS), X-ray powder diffraction (XRD), zeta potential (ZP), dynamic light scattering (DLS), elemental analysis (EA), 1H and 13C-nuclear magnetic resonance (1H- and 13CNMR), Fourier-transform infrared spectroscopy (FTIR), inductively coupled plasma-optical emission spectroscopy (ICP-OES), and liquid chromatography-mass spectroscopy (LC-MS). The in vitro cytotoxicity, cell uptake, and internalisation studies of palladium nanoparticles (10 μM) ranging in size and different types of capping agent were performed using three breast cancer cell lines: MDA-MB-468 , MCF-7 and MDA-MB-231 , and a non-tumorigenic MCF-10A breast cell line. The cell uptake and internalisation were investigated using ICP-OES and TEM. A high dependence between reduction rate and concentration of palladium precursor was observed for the room temperature synthesis of palladium nanoparticles, and the employed synthesis procedure will be applied to the hot palladium isotope (109Pd). A facile, green, aqueous synthesis route for palladium nanoparticles at room temperature was developed, and the synthesised nanoparticles indicated narrow size distributions. A concentration dependence between cytotoxicity and palladium nanoparticles was observed, with lower concentrations (10 μM) exhibiting minimal cytotoxicity relative to higher concentrations (100 μM). The cellular uptake of palladium nanoparticles was found to be concentration, folate-receptor, capping agent, and cell line proliferation-dependent. Well-defined, monodispersed, and negatively charged folate-ethylenediamine and folate-phthalocyanine capped palladium nanoparticles were taken up by cells, with higher nanoparticle internalisation in folate receptor positive tumorigenic cells relative to folate receptor negative non-tumorigenic cells. It can be concluded that palladium(0) nanoparticles can be synthesised from the reduction of palladium(II) by sodium borohydride at room temperature. The folate-conjugated palladium nanoparticles are non-cytotoxic at 10 μM and were successfully optimised and selectively delivered to folate receptor-positive breast cancer cells (MDA-MB-231 and MCF-7) relative to non-tumorigenic breast cells (MCF-10A) and folate receptor negative cancer cells (MDA-MB-468).
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  • Date Issued: 2019

The synthesis, characterization, and application of peptide-capped magnetite nanoparticles for the targeting of cancer cells

  • Authors: Hickson, Matthew Victor
  • Date: 2019
  • Subjects: Nanomedicine -- Research , Nanostructured materials Cancer -- Alternative treatment
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: http://hdl.handle.net/10948/40172 , vital:35965
  • Description: In this study, a comparative analysis was performed upon three co-precipitation techniques for the synthesis of capped magnetite nanoparticles as to optimize the approach to the highest quality nanoparticles. Three techniques were applied whereby the capping agent either introduced before the stage of nanoparticle precipitation, simultaneously to the stage of precipitation, or after the stage of precipitation. The resultant nanoparticles were tested in terms of their size, dispersity, crystallinity, and magnetic characteristics. The three techniques gave nanoparticles of varying sizes and characteristics. Out of the three synthetic techniques, the post precipitation introduction method gave the highest quality nanoparticles in terms of size distribution, crystallinity and magnetic character. Three novel peptides were synthesized, incorporating amino acids to varying degrees. Structure was confirmed via IR and NMR spectroscopy. The peptides were studied potentiometrically to explore their acid nature and were explored computationally as to discern possible modes of interaction with the nanoparticles. These three peptides were further used in the capping of magnetite nanoparticles. For this set of nanoparticles, a higher synthesis temperature and larger iron content were used as to obtain larger nanoparticles. For the capping procedure, the post precipitation technique was used due to its previous positive results, once again yielding high quality nanoparticles with low size dispersity, high crystallinity, and high magnetic saturations. The nanoparticles were also seen to display positive zeta potentials, which are beneficial for cellular interactions. The peptides and peptide-capped nanoparticles were tested for biological activity against the healthy MCF-10A and cancerous MCF-7 cell lines. The MTT assay displayed increased proliferation for both the cell lines treated with the nanoparticles, while the peptide treatments decreased the MCF-10A cell lines proliferation and increased the MCF-7 proliferation. TEM analysis displayed nanoparticles in the cellular sections. An ICP-OES analysis on the cells showed that the capped nanoparticles of similar zeta potentials were seen to be taken up excessively by cells as compared to the uncapped. The nanoparticles of lower zeta potentials but higher L-glutamine content were taken up to a lesser degree.
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  • Date Issued: 2019

Molecularly imprinted polymeric materials for adsorptive removal of nitrogen compounds from fuel oils

  • Authors: Abdul-Quadir, Muhammad Sabiu
  • Date: 2018
  • Subjects: Polymerization , Organonitrogen compounds Nitrogen compounds
  • Language: English
  • Type: Thesis , Doctoral , DPhil
  • Identifier: http://hdl.handle.net/10948/23426 , vital:30542
  • Description: The deleterious effects of refractory polyaromatic hydrocarbons found in fuels such as organonitrogen compounds (quinoline, carbazole and its alkylated derivatives) are such that they emit NOx to the environment when combusted, thereby reducing air quality. These compounds also deactivate the catalyst used during fuel refinement and in catalytic converters of cars. Hydro-denitrogenation (HDN), a process currently being employed in petroleum refineries to eliminate organonitrogen compounds in fuels, is limited in treating these refractory compounds. Hence, this thesis describes the use of two separate complimentary approaches for the removal of organonitrogen compounds in fuel such as oxidative denitrogenation and adsorptive denitrogenation. The catalyzed oxidation of fuel oil model nitrogen containing compound, quinoline to quinoline N-oxide, was conducted under batch and continuous flow microreactor at 70°C by using tert-butylhydroperoxide (t-BuOOH) as oxidant and silica supported V2O5 as catalyst, followed by the selective adsorption of the quinoline N-oxide. An overall conversion of 62% quinoline N-oxide was observed. Quinoline-N-oxide in model fuel was absorbed by employing synthesized molecularly imprinted 2,6-pyridine-polybenzimidazole (2,6-PyPBI) nanofibers, 86% of quinoline-N-oxide was removed to give an adsorption capacity (qe) of 4.8 mg/g. DFT calculations to study the interactions of quinoline-N-oxide vs 2,6-PyPBI indicated that: (i) hydrogen bonding (through amino group of 2,6-PyPBI and oxygen atoms of the quinoline-N-oxide), (ii) pi-pi stacking and (iii) extensive number of van der Waals interactions took place. Several oxygenates from N-compounds were produced, thus, complicating the fuel matrix. Therefore, there is a need to move towards adsorptive denitrogenation. Poly-2-(1H-imidazol-2-yl)-4-phenol (PIMH) imprinted microspheres was prepared by suspension polymerization using 2-(2’-hydroxy-4-ethenylphenyl) imidazole as a functional monomer and ethylene glycol dimethacrylate as a crosslinker in the presence of various organonitrogen compounds (templates) to produce 2-(2’-hydroxy-4-ethenylphenyl) imidazole (PIMH). Imprinted microspheres show selectivity for various target model nitrogen-containing compounds with adsorption capacities of 6.8 ± 0.2 mg/g, 6.3 ± 0.3 mg/g and 5.8 ± 0.3 mg/g for quinoline, pyrimidine and carbazole, respectively. Adsorption selectivity increased in the order of quinoline (αi-r = 136.9) ˃ pyrimidine (αi-r = 126.2) ˃carbazole (αi-r = 86.3), when naphthalene was selected as a reference compound. Though, imprinted microspheres displayed excellent nitrogen compound removal both in model and real fuel, there was a need to improve the adsorbent adsorption capacity for N-compounds in fuel through the fabrication of imprinted nanofibers. Molecularly imprinted poly-2-(1H-imidazol-2-yl)-4-phenol nanofibers was prepared by electrospinning of 2-(2’-hydroxy-4-ethenylphenyl) imidazole (PIMH) in the presence of various organonitrogen compounds. These imprinted nanofibers show selectivity for various target model nitrogen-containing compounds with adsorption capacities of 11.7 ± 0.9 mg/g, 11.9 ± 0.8 mg/g and 11.3 ± 1.1 mg/g for quinoline, pyrimidine and carbazole, respectively. Adsorption selectivity increased in the order of pyrimidine (αi-r = 258.8) ˃ quinoline (αi-r = 235.5) ˃ carbazole (αi-r = 168.2). It further displayed excellent nitrogen removal in real fuel. The use of polybenzimidazole (PBI) nanofibers showed selective adsorption of organonitrogen compounds as imprinted sorbent also displayed high selectivity for their target model nitrogen-containing compounds with adsorption capacities of 11.4 ± 0.4 mg/g, 11.9 ± 0.2 mg/g and 10.9 ± 0.7 mg/g for quinoline, pyrimidine and carbazole respectively. Adsorption selectivity increased in the order of pyrimidine (αi-r = 241.5) ˃ quinoline (αi-r = 237.6) ˃ carbazole (αi-r = 170). Thermodynamic parameters obtained from isothermal titration calorimetry (ITC) revealed that quinoline-PIMH/PBI and pyrimidine-PIMH/PBI interactions are exothermic in nature, while carbazole-PIMH/PBI is endothermic in nature. DFT calculations indicated that π-π interactions/stacking and hydrogen bond interactions took place between N-compounds (carbazole, quinoline and pyrimidine) and adsorbent (PIMH and PBI). A significant reduction in the quantity of nitrogen containing compounds in hydrotreated fuel was observed (peak area reduction) when adsorbents (PIMH and PBI) was employed, however, the complex nature of organonitrogen compounds in fuel complicate the structure/function approach on MIPs for targeting these unwanted compounds.
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  • Date Issued: 2018

Synthesis of folate-conjugated palladium nanoparticles

  • Authors: Xolo, Luthando
  • Date: 2018
  • Subjects: Nanotechnology , Nanostructured materials Complex compounds
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: http://hdl.handle.net/10948/36442 , vital:33943
  • Description: In this study, the synthesis of two new folate-conjugated palladium (Pd) nanoparticles was carried out. This was done via two steps; firstly, the synthesis of palladium nanoparticles (PdNPs) capped with 4-aminothiophenol (4-Atp) and secondly, they were conjugated to the folate to form Folate-4Atp-PdNPs. All the above were characterized by using Fourier Transform Infrared spectroscopy (FTIR) which confirmed the formation of the targeted product (PdNPs-4-Atp-folate) as well as the 2-Aet linked with folate product (2-Aet-folate). The optical properties of the products formed were characterized further by using UV-Vis spectroscopy and Photoluminescence (PL). The size and shape of the nanoparticles were obtained by Transmission Electron Microscopy (TEM). The FTIR confirmed the formation of desired nanoparticles (Fa-4Atp-PdNPs), with peak of C=O stretching vibration at 1659 cm-1. The UV-Vis showed absorption peaks at 236 nm and 285 nm which was due to n-π* and π-π* transitions. The nanoparticles also showed excitation and emission peaks at 360 nm and 455 nm from the PL when excitation wavelength was set at 270 nm. The methanol soluble nanoparticles had an average size of 36 nm while the water-soluble nanoparticles were 4 nm in size. The HRTEM also showed the methanol nanoparticles were amorphous while the water-soluble nanoparticles were crystalline. The work reports on comparison of the methanol-soluble and water-soluble nanoparticles size distribution and the effect of capping agent used on the nanoparticles.
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  • Date Issued: 2018

Vanadium-based catalysts for oxidation of organosulfur compounds: synthesis, catalysis and mechanistic studies

  • Authors: Dembaremba, Tendai , Ogunlaja, Adeniyi
  • Date: 2018
  • Subjects: Organosulfur compounds
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: http://hdl.handle.net/10948/30248 , vital:30909
  • Description: A series of oxidovanadium(IV) complexes based on the ligand, 2-(2’-hydroxyphenyl)imidazole, with substituent groups of different electronegativities on the phenolic para position, were successfully synthesized, characterized and investigated for their catalytic activities in the oxidation of dibenzothiophene (DBT), a typical refractory sulfur compound found in fuel. It was observed from catalytic oxidation studies that the presence of an electron withdrawing group on the phenolic para position of the ligand results in higher catalytic activity. SC-XRD data and DFT studies were used to explain the trends in activity observed. The highest activity was observed with 6.5 nmol of the nitro derivative catalyst [VO(PIMNO2)2] when 100% of 100 mg (0.543 mmol) of DBT was converted to its sulfone derivative dibenzothiophene sulfoxide (DBTO2) using 2.0 mL (1.05 mmol) of t-BuOOH. Potential to immobilize the complex catalysts was demonstrated through the synthesis of oxidovanadium(IV) copolymer nanofibers. The oxidovanadium nanofibers were successfully employed in the oxidation of sulfur compounds in a real fuel sample (diesel 500) which were then removed through solvent extraction using acetonitrile to give clean fuel. SC-XRD, EPR and UV-Vis spectroscopy were instrumental in providing insight into the mechanism of the catalyzed reaction. Vanadium oxides were also investigated as a cheaper alternative for the catalytic oxidation reaction. Phases of different vanadium oxides were synthesized by calcining NH4VO3 in air at different temperatures with an intention to investigate them for their catalytic activities. The catalyst obtained from calcination at 600⁰C was predominantly the orthorhombic phase of V2O5. Potential to immobilize the vanadium oxides was demonstrated using a silica support where NH4VO3 was impregnated onto silica and calcined in air at 600⁰C. The catalyst showed good potential in the oxidation of DBT to DBTO2, with 10 mg (43.9 μmol) of catalyst successfully converting 100% of 100 mg (0.543 mmol) DBT to DBTO2 using 2.0 mL (1.05 mmol) of t-BuOOH. The catalyst was also employed for a real fuel sample (diesel 500) with good results. The mechanistic aspects of vanadium oxides were also investigated in this study.
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  • Date Issued: 2018

Benzoyl isothiocyanates derived ligands as potential HIV-1 protease inhibitors and their reactions with gold ions

  • Authors: Odame, Felix
  • Date: 2016
  • Subjects: HIV (Viruses) -- Enzymes Enzyme inhibitors -- Research , Pharmaceutical chemistry Biochemistry
  • Language: English
  • Type: Thesis , Doctoral , DPhil
  • Identifier: http://hdl.handle.net/10948/33228 , vital:32585
  • Description: The synthesis and evaluation of benzoyl isothiocyanate derivatives as potential HIV-1 protease inhibitors is presented. The ligands were first designed to fit the protease active site using Autodock 4.2. The design was based on the deNOVO method of drug design in which the active site coordinates from the crystal structure of protease bound to ritonavir was used. An attempt to access the scaffolds designed initially led to the formation of 2,2,4-trimethyl 2,3-dihydro-1H-1,5-benzodiazepin-5-ium isophthalate and 2-2-(3-methylphenyl-1Hbenzimidazole which could not be converted to the desired intermediate. A further attempt led to formation of amino acid and amino acid ester derivatives of benzoyl isothiocyanates which have been fully characterized and the reasons why the desired intermediates were not readily accessible explained. Scaffolds based on the benzoyl isothiocyanate derivatives of structurally diverse diamines were then screened. Sixty compounds have been synthesized and fully characterized using elemental analysis, spectroscopy, GC-MS and twenty-six crystal structures have been discussed. The DFT transition state studies of 11-phenyl- 1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), N-(1Hbenzimidazol-2-yl)benzamide (21), 3-(1,3-benzothiazol-2-yl)-1-(benzoyl)thiourea (23), and N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (39), have been carried out and their detailed density functional theory reaction mechanism have be computed. The Bernly algorithm was used in the determination of saddle points (transtions states), and the intrinsic reaction coordinates leading to the determination of intermediates were traced and optimized to a global minimum or in some cases a local minimum was obtained. The cell viability tests of diamine derivatives which was done by exposing white blood cells to the compounds (inhibitors) at 37 °C and a pH of 7.4 showed that 1-(4-bromobenzoyl)-3-[2- ({[(4-bromophenyl)formamido]methanethioyl}amino)phenyl]thiourea (46), 1-(3-chloro benzoyl)-3-[2-({[(3-chlorophenyl)formamido]methanethioyl}amino)phenyl]thiourea (48), 1- (3-bromobenzoyl)-3-[2-({[(3-bromophenyl)formamido]methanethioyl}amino)phenyl] thiourea (49) and 3-benzoyl-1-(4-{[(phenylformamido)methanethioyl]amino}butyl)thiourea (54), in that group of compounds were cytotoxic with EC50 values of 17.04 ± 9.75 μM, 69.20± 38.16 μM, 35.90 ± 20.55 μM and 68.37 ± 26.45 μM, respectively. 4-Bromo-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (32), 4-methoxy-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene]benzamide (33) and 3-chloro-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (37) were also cytotoxic giving EC50 values of 45.47 ± 21.92, 45.09 ±13.79 and 74.94 ± 13.17 μM, respectively. 3-(1,3-Benzothiazol-2-yl)-1-(3-bromobenzoyl)thiourea (31) and 3-(1,3-benzothiazoyl-2-yl)-1-(4-nitrobenzoyl)thiourea (30) derivatives were also found to be cytotoxic with EC50 values of 1.207 ± 0.58 and 24.08 ±13.14 nM, respectively. 11-(4-Chlorophenyl-1,8,10, 12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (12), 11-(4-methoxyphenyl)-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,9,1-pentaene-13-thione (14), and 11-phenyl-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), were found to be cytotoxic giving EC50 values of 0.152 ± 0.051, 37.96 ± 21.87 and 5.28 ± 2.95 μM, respectively. In the enzyme inhibition studies compound 49 gave a percentage inhibition of 97.03 ± 10.61% at 100 μM, but the fact that it is cytoxic might make it less useful, whilst compounds 19 and 16 had a percentage inhibition of 59.57 ± 13.59% (4-nitro derivative) and 79.97 ± 11.97% (3-nitro derivative) respectively at 100 μM of inhibitor and 20 μM of enzyme (HIV-1 protease). The results suggests that the presence of the nitro group at position 3 (16) and 4 (19) leads to an increase in activity against HIV-1 protease.
  • Full Text:
  • Date Issued: 2016

Development of Palladium selective reagents and materials

  • Authors: Moyo, Cyprian Bertrand
  • Date: 2016
  • Subjects: Palladium Palladium compounds -- Industrial applications Chemistry, Inorganic
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: http://hdl.handle.net/10948/12231 , vital:27046
  • Description: The adsorption and separation of Pd(II) from Pt(IV), Ir(IV) and Rh(III) by silica microparticles functionalized with triethylenetetramine (TETA), 2-(2-aminoethylthio)ethanamine (NSN) and 2-(2-(2-aminoethyl)ethylthio)ethanamine (NSSN) in 1 M hydrochloric acid medium was investigated by continuous column studies. The functionalized sorbent materials were characterized by microanalysis, SEM-EDS and FT-IR. Palladium selectivity of the sorbent materials was achieved by stripping of rhodium, iridium and platinum chlorido species with 0.5 M of NaClO4 in 1 M HCl while [PdCl4]2 was eluted with 3% w/v thiourea. The desorption efficiency of thiourea was confirmed by the SEM-EDS analysis of the materials after Pd(II) elution. Palladium loading capacity of the sorbents were in the order S-NSSN (23.85 mg/g) > S-NSN (12.70 mg/g) > S-TETA (4.97 mg/g). The extraction patterns on the sorbent materials were explained by considering the coordination chemistry of the ligand with [PdCl4]2ˉ and ionic interactions of [PtCl6]2ˉ and [IrCl5(H2O]ˉ. The square planar complexes, [Pd(HNSSNH)Cl2]Cl2 and [Pd(NSNH)Cl2][PdCl4]2, were isolated, analyzed by spectroscopy and single crystal X-ray, whereas evidence of the fraction of Pd(II)-TETA complex was obtained by HPLC studies. This provided proof of the inner sphere coordination mechanism as the mode of interaction of these ligands with [PdCl4]2ˉ. Trace amounts of Brˉ anions in ligands resulted in the inadvertent isolation of bromide coordinated Pd(II) NSN and NSSN complexes. The ion-pair salts of [TETAH4]4+ with [PtCl6]2ˉ, [IrCl6]3ˉ and [RhCl6]3ˉ were also isolated and characterized by microanalysis and IR to further explain the extraction patterns.
  • Full Text:
  • Date Issued: 2016

The development of amine-based extractants for separation of base metals in a sulfate medium

  • Authors: Magwa, Nomampondo Penelope
  • Date: 2015
  • Subjects: Extraction (Chemistry) , Sulfates , Ligands , Benzimidazoles , Infrared spectroscopy , Nuclear magnetic resonance spectroscopy , Metal ions , Metals
  • Language: English
  • Type: Thesis , Doctoral , PhD
  • Identifier: vital:4559 , http://hdl.handle.net/10962/d1020010
  • Description: Tridentate benzimidazole-based ligands, bis((1H-benzimidazol-2-yl)methyl)sulfide (BNSN) and bis((1H-benzimidazol-2-yl)methyl)amine (BNNN), along with dinonylnaphthalene sulfonic acid (DNNSA) as a synergist, were investigated as potential selective extractants for Ni2+ from base metals in a solvent extraction system using 2-octanol/Shellsol 2325 (8:2) as diluent and modifier. However, extraction studies show a lack of pH-metric separation of the later 3d metal ions with bis((1-octylbenzimidazol-2-yl)methyl)sulfide (BONSN) and bis((1- decylbenzimidazol-2-yl)methyl)amine (BDNNN) as extractants, but extractions occurred in the low pH range with an opportunity for back extraction. This investigation suggested that tridentate ligands (at least those of the nature investigated here) are not feasible extractants for separation of base metal ions due to their lack of stereochemical “tailor-making.”
  • Full Text:
  • Date Issued: 2015

Development of styrene based imprinted sorbents for selective clean-up of metalloporphyrins in organic media

  • Authors: Awokoya, Kehinde Nurudeen
  • Date: 2014
  • Language: English
  • Type: text , Thesis , Doctoral , PhD
  • Identifier: http://hdl.handle.net/10962/54521 , vital:26580
  • Description: Most crude oils contain traces of vanadium and nickel complex with porphyrins (VTPP and NTPP) within their asphaltene fraction. Although these metals are only present in trace quantities, they have a significant and detrimental impact on the refining process by degrading the quality of intermediate and end products. Therefore, their selective removal is highly desirable. This thesis presents the development of nickel porphyrin, nickel vanadyl porphyrin imprinted nanofibers and vanadyl porphyrin imprinted polymer (MIP) particles for application as selective sorbents. Computational model based on the combination of molecular dynamics simulations and quantum mechanics was successfully applied to the styrene functional monomer selection. The particle was prepared by bulk polymerization and the nanofibers by a novel approach combining molecular imprinting and electrospinning technology. The morphologies, thermal stabilities and porosities of the imprinted sorbents were studied using SEM, TGA, and BET nitrogen gas adsorption. Chloroform was found to swell the polymer particles to a higher degree than methanol and acetonitrile. The adsorption characteristics of the imprinted sorbents best fitted with Freundlich isotherm model. The imprinted sorbents recorded high extraction efficiencies (EEs) of > 99 % in selectively extracting the metalloporphyrins. The impact of the template on the affinity of recognition for NTPP was evaluated. The results showed that the NTPP adsorption capacity increased as the molar ratio of NTPP to styrene was increased from 1:1 to 3:1. The optimal ratio of template to functional monomer which yielded the best specific affinity and highest recovery (99.9 %) was 3:1. The effects of trifluoroacetic acid (TFA), dichloromethane (DCM), dimethyl sulphoxide (DMSO), pentane (PEN) on electro-spinnability of the polymer solutions and the morphological appearance of the nanofibers were investigated. The imprinted nanofibers exhibited the same selectivity specialism for both NTPP and VTPP. A remarkable stability in relation to reusability was observed when imprinted nanofibers were used, as they could be reused nine times without incurring any significant loss in removal efficiency. The results were validated by analysing a certified reference material. The imprinted sorbents were therefore found to be selective sorbents that are well suited for handling trace metals in organic media.
  • Full Text:
  • Date Issued: 2014

The development of functionalized electrospun nanofibers for the control of pathogenic microorganisms in water.

  • Authors: Kleyi, Phumelele Eldridge
  • Date: 2014
  • Subjects: Electrospinning , Nanofibers , Pathogenic microorganisms , Pathogenic microorganisms -- Detection , Drinking water -- Microbiology , Water quality -- Measurement , Imidazoles , Spectrum analysis , Anti-infective agents , Polymerization
  • Language: English
  • Type: Thesis , Doctoral , PhD
  • Identifier: vital:4497 , http://hdl.handle.net/10962/d1013134
  • Description: The thesis presents the development of functionalized electrospun nylon 6 nanofibers for the eradication of pathogenic microorganisms in drinking water. Imidazole derivatives were synthesized as the antimicrobial agents and were characterized by means of NMR spectroscopy, IR spectroscopy, elemental analysis and X-ray crystallography. The first set of compounds (2-substituted N-alkylimidazoles) consisted of imidazole derivatives substituted with different alkyl groups (methyl, ethyl, propyl, butyl, heptyl, octyl, decyl and benzyl) at the 1-position and various functional groups [carboxaldehyde (CHO), alcohol (CH2OH) and carboxylic acid (COOH)] at the 2-position. It was observed that the antimicrobial activity of the compounds increased with increasing alkyl chain length and decreasing pKa of the 2-substituent. It was also observed that the antimicrobial activity was predominantly against a Gram-positive bacterial strains [Staphylococcus aureus (MIC = 5-160 μg/mL) and Bacillus subtilis subsp. spizizenii (MIC = 5-20 μg/mL)], with the latter being the more susceptible. However, the compounds displayed poor antimicrobial activity against Gram-negative bacterial strain, E. coli (MIC = 150- >2500 μg/mL) and did not show any activity against the yeast, C. albicans. The second set of compounds consisted of the silver(I) complexes containing 2-hydroxymethyl-N-alkylimidazoles. The complexes displayed a broad spectrum antimicrobial activity towards the microorganisms that were tested and their activity [E. coli (MIC = 5-40 μg/mL), S. aureus (MIC = 20-80 μg/mL), Bacillus subtilis subsp. spizizenii (MIC = 5-40 μg/mL) and C. albicans (MIC = 40-80 μg/mL)] increased with the alkyl chain length of the 2-hydroxymethyl-N-alkylimidazole. The third set of compounds consisted of the vinylimidazoles containing the vinyl group either at the 1-position or at the 4- or 5- position. The imidazoles with the vinyl group at the 4- or 5-position contained the alkyl group (decyl) at the 1-position. For the fabrication of the antimicrobial nanofibers, the first two sets of imidazole derivatives (2-substituted N-alkylimidazoles and silver(I) complexes) were incorporated into electrospun nylon 6 nanofibers while the third set (2-substituted vinylimidazoles) was immobilized onto electrospun nylon 6 nanofibers employing the graft polymerization method. The antimicrobial nylon nanofibers were characterized by IR spectroscopy and SEM-EDAX (EDS). The electrospun nylon 6 nanofibers incorporated with 2-substituted N-alkylimidazoles displayed moderate to excellent levels of growth reduction against S. aureus (73.2-99.8 percent). For the electrospun nylon 6 nanofibers incorporated with silver(I) complexes, the levels of growth reduction were >99.99 percent, after the antimicrobial activity evaluation using the shake flask method. Furthermore, the grafted electrospun nylon 6 nanofibers showed excellent levels of growth reduction for E. coli (99.94-99.99 percent) and S. aureus (99.93-99.99 percent). The reusability results indicated that the grafted electrospun nylon 6 nanofibers maintained the antibacterial activity until the third cycle of useage. The cytotoxicity studies showed that grafted electrospun nylon 6 nanofibers possess lower cytotoxic effects on Chang liver cells with IC50 values in the range 23.48-26.81 μg/mL. The thesis demonstrated that the development of antimicrobial electrospun nanofibers, with potential for the eradication of pathogenic microoganisms in water, could be accomplished by incorporation as well as immobilization strategies.
  • Full Text:
  • Date Issued: 2014

An investigation into the antidiabetic and catalytic properties of oxovanadium(IV) complexes

  • Authors: Walmsley, Ryan Steven
  • Date: 2012
  • Subjects: Hypoglycemic agents Ligands (Biochemistry) Complex compounds Potentiometry Proton transfer reactions Stability Imidazoles Vanadium catalysts
  • Language: English
  • Type: Thesis , Doctoral , PhD
  • Identifier: vital:4320 , http://hdl.handle.net/10962/d1004978
  • Description: In part 1 of this thesis, the antidiabetic activity of a series of novel oxovanadium(IV) complexes was investigated. A range of bidentate N,O-donor ligands, which partially mimic naturally occurring bioligands, were prepared and reacted with the vanadyl ion to form the corresponding bis-coordinated complexes. Initially, 2-(2ˊ-hydroxyphenyl)-1R-imidazoline (where R = H, ethyl and ethanol) ligands were prepared. The aqueous pH-metric chemical speciation was investigated using glass electrode potentiometry which allowed for the determination of protonation and stability constants of the ligands and complexes, respectively. The species distribution diagrams generated from this information gave an indication of how the complexes might behave across the broad pH range experienced in the digestive and circulatory systems. This information was used to create an improved 2nd generation of ligands that were constructed by combining the imidazole and carboxylic acid functionalities. These corresponding bis[(imidazolyl)carboxylato]-oxovanadium(IV) complexes displayed a broader pH-metric stability. Both sets of complexes improved glucose uptake and reduced coagulation in vitro. In part 2 of this thesis, a range of homogeneous and heterogeneous oxovanadium(IV) catalysts were prepared. Firstly, Merrifield beads were functionalized with ligands from Part 1 and then reacted with vanadyl sulfate to afford the corresponding heterogeneous catalysts. These displayed promising catalytic activity for the peroxide facilitated oxidation of thioanisole, styrene and ethylbenzene as well as the oxidative bromination of phenol red. Smaller imidazole-containing beads with higher surface areas than the Merrifield beads were prepared by suspension polymerization. These beads similarly demonstrated excellent catalytic activity for the oxidation of thioanisole and were highly recyclable. In attempt to increase the exposed catalytic surface area, while retaining the ease of separation achieved in the before mentioned systems, micron to nano sized electrospun fibers containing coordinating ligands were fabricated. The corresponding oxovanadium(IV) functionalized fibers were applied to the oxidation of thioanisole using a continuous flow system. The flexible and porous nature of the fiber mats was well suited to this approach. After optimization of the reactant flow rate and catalyst amount, near quantitative (> 99%) oxidation was achieved for an extended period. In addition, leaching of vanadium was mitigated by modification of the attached ligand or polymer material.
  • Full Text:
  • Date Issued: 2012
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