Doctoral Degrees (Chemistry and Polymer Science)
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- ItemFundamental Palladium Catalyzed Oxidative Addition Reactions(Stellenbosch : Stellenbosch University, 2023-11-28) Moloto, Bryan Phuti; Esterhuysen, Catharine; Bickelhaupt, F Matthias; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.ENGLISH ABSTRACT: This thesis focuses on investigating fundamental oxidative addition (OA) reactions catalysed by palladium (see Chapter 1). OA, being the first and rate determining step in cross-coupling reactions, is a reaction of vital importance in synthetic chemistry. Palladium-catalysed crosscoupling reactions are widely used in industrial applications, such as in catalytic converters and the synthesis of pharmaceuticals. Besides these applications, palladium is widely used as a versatile catalytic reagent in many different chemical processes. Considering the importance of oxidative addition reactions catalysed by palladium, a deep understanding of the underlying mechanism is crucial to designing new catalysts and improving the existing ones. In a nutshell, the main focus is on understanding the mechanism behind the oxidative addition step and the trends in activation barriers upon variation of either the catalyst or substrate structure. The following summary will discuss only the most important findings from the chapters involved. As explained in Chapter 2, the findings in this thesis were successfully obtained using the Activation Strain Model of chemical reactivity (ASM, discussed in section 2.3) in combination with computations based on Density Functional Theory (DFT) as implemented in the ADF program. The ASM model is a fragment-based approach that characterizes reactions in terms of the rigidity and the bonding capabilities of the original reactants , and the extent to which the reactants must deform along the reaction pathway of a particular reaction mechanism. Thus, the total energy profile of a particular chemical reaction can be decomposed into contributions from the deformation of the reactants (the strain energy) and their mutual interaction (the interaction energy). The interaction energy can then be further decomposed using the canonical energy decomposition analysis (EDA) of ADF into electrostatic interactions, destabilizing Pauli repulsion, and stabilizing orbital interactions. In Chapter 3, with the aim of understanding the underlying mechanism and trends found by the oxidative addition, we detailed our quantum chemical exploration of the palladiummediated activation of C(spn )–X bonds (n = 1–3; X = F, Cl, Br, I) in the archetypal model substrates H3C–CH2–X, H2C=CH–X, and HC≡C–X by a model bare palladium catalyst. First and foremost, we investigated the bond dissociation enthalpies (BDEs) of the bonds to be activated. So, we started from the C(sp3 )–X moving to C(sp2 )–X and then to C(sp)–X bonds for each of the selected set of X atoms above. We found that as we move down group 17, the C(spn )–X bond becomes weaker and as such easier to break. Based on our state-of-the-art analyses, we discovered that as we vary the substituent X, going down Group 17 from X = F to Cl to Br to I on the C(spn )–X substrate, the oxidative addition barriers drastically decrease. This favorable activation barrier stabilization originates from two factors: (i) a less destabilizing activation strain; and remarkably (ii) a more favorable electrostatic attraction between the catalyst and the substrate. When changing the substrate from C(spn )–F to C(spn )– I, consequently, the electrostatic interaction between the catalyst and substrate also becomes more favorable. Iodine, being the largest halogen of the selected substituents, has a more diffuse and electron-rich density and a higher nuclear charge that in turn engage in favorable electrostatic attractions with the palladium nucleus and electron density, respectively. This effect makes the oxidative addition reaction involving the C(spn )–X bond with a larger halogen atom correspond to a more stabilizing interaction and hence lower reaction barrier. Next, in Chapter 4 we have quantum chemically investigated the palladium-mediated activation of HnA–AHn bonds (AHn = CH3, NH2, OH, F) by catalysts PdLn with Ln = no ligand, PH3, (PH3)2. Herein, we found that as we move from C to F along the period, i.e., from H3C– CH3 to H2N–NH2 to HO–OH to F–F, the activation barriers decrease and more interestingly the activation of the F–F bond is even barrierless. As we move from C to F on the selected substrates, the number of the substituents around the A–A bond become less and as such enabling the catalyst to approach the substrate with ease, thereby resulting in a decreasing activation barriers. The causal effects of this barrier stabilizations stem from: (i) a reduced activation strain due to a weaker HnA–AHn bond; (ii) a decreased Pauli repulsion as a result of a difference in steric shielding of the HnA–AHn bond; and (iii) an enhanced backbonding interaction between the occupied 4d atomic orbitals of the palladium catalyst and * acceptor orbital of the substrate. The findings in this thesis have the potential to equip experimentalists with detailed mechanistic insight that can facilitate a deep understanding into the trends in reactivity of palladium-mediated oxidative addition reactions.
- ItemDeveloping marker technologies to probe complex polymers and products(Stellenbosch : Stellenbosch University, 2022-11) Liprini, Marehette Suzanne; Van Reenen, Albert; Lutz, Marietjie; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.ENGLISH ABSTRACT: Fluorescent imaging has proven to be a valuable tool across a wide variety of applications. It can help with detecting, locating and observing the interactions between different molecules. This study used fluorescence to evaluate interactions, provide detection and trace different components within complex polymer systems. Cellulose nanowhiskers (CNW) were isolated and characterized, then labelled using fluorescent labelling with fluorescein 5(6)-isothiocyante (FITC) and rhodamine B (RhB). The attachment of the fluorescent dyes was easily observed with fluorescence microscopy. Fluorescently labelled cellulose nanowhiskers (CNW) were incorporated into different crystalline fractions of two different types of polypropylene impact copolymers (CMR 648 and CMR 348). This part of the study focused on the visually assessing the interactions between the different crystalline fractions within polypropylene impact copolymers. The different fractions of the copolymers were first evaluated in the form of solvent-cast films. The solvent-cast films showed strong associations between the 30 oC fraction and the 60 oC fraction, as well as between the 60 oC fraction and the 80 oC fraction. The fluorescent images showed no strong association between the 30 oC fraction and the 80 oC fraction in the absence of the 60 oC fraction. The fraction interactions were also evaluated after mechanical agitation in the melt, followed by injection moulding. The injection-moulded samples showed the same interactions visually as observed with the solvent-cast films. The visual assessment after extracting the labelled 30 oC fraction and 60 oC fraction also showed that the labelled CNW did not migrate out of the fractions into which they were incorporated. The next section of this study focused on the detection of fluorescently labelled markers within paint samples. CNW labelled with fluorescent dyes were incorporated into two types of paint. The paint films were evaluated with confocal fluorescence microscopy and the different paint samples could be identified. The fluorescent markers could still be detected within the paint films even after accelerated weather testing by implementing confocal fluorescence microscopy (CFM), lambda scanning, and unmixing. The last part of the study focused on the release of ethyl formate from different polymer films of polylactic acid (PLA) and polyethylene glycol (PEG). The intrinsic fluorescence associated with the ethyl formate precursor, PLA and PEG was used to track the release of the ethyl formate after exposure to humidity and humidity with citric acid. The release could easily be tracked visually with CFM.
- ItemBonding interactions in congested molecules: a study of the interatomic forces and the molecular electrostatic potential(Stellenbosch : Stellenbosch University, 2022-09) von Berg, Stuart Raymond Colenzo; Dillen, Jan; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.ENGLISH ABSTRACT: The purpose of this research is to apply the quantum theory of atoms in molecules (QTAIM) to the molecular electrostatic potential (MEP) field and use the topology of the MEP to determine whether a stabilising interaction occurs between two hydrogens in a congested molecule. A method for comparing bond strength using the ratio of the nuclear and electronic components of the MEP is developed and applied to the congested molecules. The MEP ratio was used to associate the bond strength of the hydrogen-hydrogen interaction in congested molecules to that of a hydrogen bond between water molecules. Despite this result, analysis of the electron density, laplacian and kinetic energy created an equally compelling argument against the interaction being stabilising.
- ItemPolymer-coated magnetic nanoparticles and polymer nanoparticles for the treatment of Mycobacterium tuberculosis (Mtb)(Stellenbosch : Stellenbosch University, 2022-04) Smit, Marica; Lutz, Marietjie; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.ENGLISH ABSTRACT: Tuberculosis (TB) can be classified as a neglected disease where an estimated one fourth of the world’s population could be infected with Mycobacterium tuberculosis (Mtb) in the form of latent TB. Combinations of three or more anti-tuberculosis (anti-TB) drugs are required during a long treatment period (between 6 months and 2 years) to effectively eliminate Mtb. The long treatment duration with concentrated anti-TB drugs has lead to side-effects, low patient adherence and resulting possible drug resistance. Orally administered anti-TB drugs have difficulty effectively reaching the lung and alveolar macrophages. Concentrated anti-TB drugs are thus orally administered daily in tablet form but anti-TB drug loaded polymer nanoparticles could possibly prevent rapid drug degradation via sustained release. There is thus a need to decrease the necessary concentration of the administered anti-TB drugs, which could be achieved via pulmonary inhalation which directly treats TB in the lungs. Polymer coated superparamagnetic iron oxide nanoparticles (SPMNs) could possibly enable targeted drug delivery via injection. The nanoparticles can be controlled with an external magnetic field to Mtb infected areas, followed by drug release from the anti-TB drug loaded polymer coating. In this thesis, biocompatible polymers namely chitosan, carrageenan, alginate, dextran sulfate and poly(lactide-co-glycolide) (PLGA) were utilized for anti-TB drug loading. Quaternary ammonium chitosan (CS-qC12) and quaternary ammonium poly(styrene-alt- maleic anhydride) (SMI-qC12) were also synthesized due to the known improvement in antimicrobial activity and mucoadhesion, due to the quaternary ammonium functional groups, compared to pristine chitosan and poly(styrene-alt-maleic anhydride). Several commonly administered anti-TB drugs such as isoniazid (INH), rifampicin (RIF), ethambutol (EMB), streptomycin (STM), ethionamide (ETA) and ofloxacin (OFX) were utilized for anti-TB drug loading. Chitosan (CS) based anti-TB drug loaded nanoparticles were synthesized via ionic gelation where polymer and anti-TB drug is dissolved, followed by the addition of crosslinking agent or polymer to prepare the nanoparticles (distributing anti-TB drug throughout the polymer matrix). PLGA nanoparticles were prepared via an “oil-in-water” emulsion followed by solvent evaporation. Sustained drug release (aqueous acetic acid solution, pH 5, UV-Vis spectrophotometry) over 7 days was seen for all the drug loaded nanoparticles, except with ofloxacin loading. The SPMNs were produced via co-precipitating with Fe2+ and Fe3+ in one step (CS SPMNs and CS-qC12 SPMNs) or two steps (chitosan-alginate-carrageenan (CS-Al-Car) SPMNs and chitosan-dextran sulfate (CS-DS) SPMNs). PLGA SPMNs and SMI-qC12 SPMNs were synthesized by activating the pristine iron oxide nanoparticles with oleic acid and (3-aminopropyl)triethoxysilane (3-APTES), respectively, before polymer coating. The polymer coated SPMNs were ex situ drug loaded by dispersing the SPMNs in anti-TB drug solution. Sustained drug release over 8 days was observed for the INH, ETA and RIF loaded polymer coated SPMNs. The resazurin microtiter assay (REMA) against TB mimic Mycobacterium Smegmatis (M. Smeg) was utilized to quantify the antimicrobial activity, via minimum inhibition concentration (MIC) determinations. The CS-DS nanoparticles were determined to be the optimal drug carrier with lower MIC values (CS-DS-OFX = 0.2441 μg/mL) compared to the free drugs (OFX = 0.5859 μg/mL).
- ItemSynthesis and characterization of fluorous-stabilized metal nanoparticles for evaluation in fluorous biphasic catalysis(Stellenbosch : Stellenbosch University, 2022-04) Hensberg, Joshua; Malas-Enus, Rehana; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.ENGLISH ABSTRACT: A fluorous biphasic approach as a green strategy for the facile recycling and re-use of expensive catalysts, has been probed. A series of fluorous-stabilized Au NPs were successfully synthesized using a micelle-template strategy. The strategy entailed modifying a hydrophilic G3-DAB PPI-NH2 dendrimer to include peripheral palmitoyl groups yielding an amphiphilic unimolecular micelle (referred to as the modified dendrimer in this work). The modified dendrimer was characterized by FT-IR spectroscopy and 1H NMR spectroscopy; and displayed complete solubility in CHCl3. Using the modified dendrimer as a template, organic- soluble Au DENs were prepared by the encapsulation of Au ions into the interior of the dendrimer, followed by reduction. These Au DENs were extracted from the organic phase into a fluorous phase (S1 or S2) with the use of fluorous ligands (L1 and L2). This extraction step was found to be the most challenging and much effort was placed on optimizing the extent of extraction into the fluorous phase. In instances incorporating high Au quantities, little or no extraction was observed and was ascribed to the larger size of the Au DENs making phase transfer more unlikely. It was identified that for the formation of small, uniform Au DENs, it was necessary that we identify the maximum quantity of Au ions which could be encapsulated by the dendrimer. Failure to determine this value could lead to overloading the dendrimer and subsequent reduction would form DSNs. For the purposes of this research, it was critical to prepare organic DENs and prevent the formation of DSNs, therefore an additional study was executed to identify the endpoints in a series of UV-Vis spectrophotometric titrations involving the dendrimer and metal salt being investigated. In the study, two dendrimers were investigated and included an unmodified, hydrophilic G3-DAB-PPI-NH2 dendrimer and the aforementioned modified dendrimer. The metal loading capacities of these dendrimers were determined for a range of metal ions in triplicate, which include; Cu(II), Ni(II), Co(II), Zn(II), Cd(II), Pb(II), Ru(III), Rh(III), Pd(II), Pt(II) and Au(III). The results showed that the unmodified dendrimer, in most cases, housed fewer metal ions in comparison to the analogous modified dendrimer. This was attributed to the improved solubility of the modified dendrimer in organic solvents. This, in effect, causes the loading interaction to be driven by solubility differences between the hydrophilic interior of the modified dendrimer and the hydrophobic solvent as opposed to fixed stoichiometric ratios. Subsequently, eight unique, spherical, monodisperse and small fluorous-stabilized Au NPs were generated and characterized by UV-Vis spectroscopy, TEM and ICP-OES analysis. Systems incorporating both L1 and L2 as the fluorous stabilizer were produced. Moreover, the use of perfluoro-1,3- dimethylperfluorocyclohexane (S2) provides smaller fluorous-stabilized Au NPs in comparison to the use of perfluoromethylcyclohexane (S1) in the extraction step. It was found that an increase in temperature during the extraction did not aid it but instead promoted the oxidation of the NPs or accelerated agglomeration in the organic phase. Thus it was discovered that the extraction of the organic soluble DENs into the fluorous phase was highly dependent on their size which in turn was dependent on the outcome of the reduction step. An alternative novel synthetic method (called the direct method) was designed and optimized for the preparation of fluorous-stabilized Au NPs stabilized by L1. Not only did this method offer a significantly reduced preparation time, but it also entailed a fluorous-aqueous biphasic reduction to yield the fluourous-stabilized Au NPs. Furthermore, it was shown by way of this method that it was possible to tailor different sizes of NPs by varying the Au: L1 ratio. It was found that increasing the quantity of ligand to gold resulted in smaller fluorous-stabilized Au NPs. The ratios of Au: L1; with Au = 1 eq. and L1 = 0.28 eq.; 0.56 eq.; 1.12 eq. and 2.24 eq. yielded Au NPs of sizes; 43.4 ± 22.2 nm, 17.8 ± 13.7 nm, 11.8 ± 15.8 nm and 2.0 ± 0.3 nm, respectively. From this work, it has been shown that a simple strategy exists to produce fluorous-stabilized Au NPs within 3 h at ambient temperatures using L1. Other attempts were made with the use of other fluorous ligands such as L2, L3 and L4. In these cases, no fluorous-stabilized Au NPs were attained. Ten fluorous-stabilized Au NP catalyst systems were prepared using both methods, using varying ratios of Au: L1 or L2, in S1 or S3, respectively. These systems were assessed as catalysts in the biphasic catalytic oxidation of 1-octene under the optimized catalytic reaction conditions. It was found that all the fluorous-stabilized Au NPs which were examined in these aforementioned experiments, were active in the fluorous biphasic catalytic oxidation of 1-octene. Not only this, but even after recycling up to five times, the catalyst continued to show steady activity and always performed better than the blank reaction (without catalyst) in terms of % conversion of substrate. There appeared to be a distinct relationship between the average particle diameter (nm) of the Au NPs in the system and the conversion of 1-octene. This was demonstrated for JHD12 and JHD16 which comprised the largest NPs and afforded the lowest conversions of 1-octene in relation to the other catalyst systems tested at this constant metal loading (Cf (Au)) of 5 × 10-7 mol/mL and optimized experimental conditions. Although not tested at the same metal loading as the other catalyst systems, JHD15, was found to be the most active catalyst. This is because the catalyst was tested at a concentration ten times less than all the other catalysts and still provided a higher conversion of 1-octene. The high activity was attributed to the size of the Au NPs of JHD15 which were 2.0 ± 0.3 nm being much smaller than those associated with the other catalyst systems. GC-FID was employed to quantify the relevant chemical species after the catalysis runs. The recyclability and re-use of the catalysts was also investigated. In each case the epoxy product was the major product.