3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Synthesis and characterisation of novel [PtII(phen)(Ln-κS)2] complexes: exploring rare monodentate coordination of disubstituted acylthioureato ligands(2019) Kangara, Edmore F.This thesis describes a study directed towards the synthesis and full characterization of novel [Pt(phen)(Ln-κS)2] complexes where disubstituted acylthioureato ligands (Ln), (also referred herein as N,N-di(alkyl/aryl)-N’-acylthioureato ligands), coordinate to the platinum(II) metal centre in a monodentate fashion through the sulfur donor atom and establishing the driving factors behind this rare coordination mode. The study included a systematically chosen ligand library where the ligands varied mainly on the electronic influence of acyl substituents balanced with minor steric variations on the amino end of the ligand. [Pt(phen)(Ln-κS)2] complexes were synthesized in excellent yields via a stepwise method where the ligands were first deprotonated using sodium hydride in anhydrous THF and subsequently reacting the resultant solvated salts with the [PtCl2(phen)] precursor under reflux for one hour in a 1:2.2 (precursor/ligand) stoichiometric ratio. The complexes were characterised using FT-IR (ATR) spectroscopy, 1H- and 13C NMR spectroscopy, high-resolution mass spectrometry, UV-vis spectrophotometry, elemental analysis, and single-crystal X-ray diffraction. The complexes were also probed for their solution conformations in correlation with the solid-state structures obtained through single-crystal X-ray diffraction using variable temperature 1H- and 195Pt NMR spectroscopy in order to gain insight into the persistence of intramolecular π-π stacking interactions in solution as a stabilising factor directing the monodentate coordination. This study showed that [Pt(phen)(Ln-κS)2] complexes with acylthioureato ligands bearing aromatic acyl substituents could at least exist in three conformations while complexes with acylthioureato ligands that have non-aromatic acyl substituents could only have one structural conformation at -50 ° C. However, there is no conclusive evidence of the intramolecular π-π stacking interactions in solution at ambient and higher temperatures. Investigations into whether the electronic effects of acyl substituents could influence the nucleophilicity of the other donor sites in the ligands, particularly oxygen, enough to render their reactivity towards platinum(II) ions more preferable was done using conceptual DFT. The study showed that the sulfur donor atom was tenfold more nucleophilic than any other donor atom in the acylthioureato ligands regardless of acyl substituents making it the most probable site to coordinate with platinum(II) ions. Mechanistic insights into how the reaction proceeded were probed through a series of individual experiments that involved the metal precursor, the ligands, the [Pt(phen)(Ln-κS)2] complexes, the byproduct [Pt(phen)(Ln-κO,S)]+ complexes and acids of different degrees of acidity. These experiments showed that the synthetic reaction proceeded most likely via solvolysis of the precursor resulting in a solvento complex and subsequent anation of the solvento complex with disubstituted acylthioureato anions to get [Pt(phen)(Ln-κS)2]. [Pt(phen)(Ln-κS)2] could also be obtained by reacting the cationic byproduct [Pt(phen)(Ln-κO,S)]+ with the ligand after deprotonation with base. It was also shown that the [Pt(phen)(Ln-κS)2] complexes dissociated under different acids resulting in different dissociation products via protonation-anation reactions. The nature of the dissociation products depended on the strength of the acid and the coordinating properties of the acids’ conjugate bases. This coordination mode could be extrapolated to include platinum(II) complexes bearing other co-ligands like bipyridine and triphenylphosphine, however in medium to low yields. A pilot study into the potential antiproliferative activity of [Pt(phen)(L1-κS)2] and [Pt(phen)(L2-κS)2] (where L1 = N,N-di(ethyl)-N’-(1-naphthoylthioureato) and L2 = N,N-di(butyl)-N’-(1naphthoylthioureato) anions) against an A549 lung cancer line showed that these complexes are very active with IC50 values of 6.4 ± 0.9 and 2.4 ± 0.3 μM respectively, killing cancer cells via apoptosis. This study also revealed that these complexes could potentially interact with DNA as a major groove binder. The knowledge obtained through this study should contribute to the fundamental understanding of the coordination chemistry of disubstituted acylthiourea ligands, chemical and physical properties of various platinum(II) complexes bearing disubstituted acylthiourea ligands coordinated in a monodentate fashion and explore possible applications in the fight against cancer.Item Synthesis and spectroscopic characterization of soluble mixed-ligand diruthenium complexes: potential application as anti-cancer agents.(2018) Mashiloane, KaraboThree mixed-ligand metal-metal bonded complexes containing one unsymmetrical anionic bridging ligand were successfully synthesized and characterized as to their electrochemical and spectroscopic properties. The investigated mono-substituted diruthenium complexes have the general formula, Ru2(OAc)3(L)Cl, where OAc = acetate anion and L = anilinopyridinate bridging ligand (ap, 2-Meap, 2-Fap). UV/Visible spectroscopy studies reveal that the investigated diruthenium complexes exist in the forms Ru2(OAc)3(L)Cl and [Ru2(OAc)3(L)]+ in solution. The two forms are observed as a split band in the 500 – 700 nm visible region. A collapse of one band is seen upon reaction of the complexes with excess halide (Cl-, Br-) indicating an equilibrium shift towards the neutral species in solution, whereas a reaction with AgBF4 precipitates the chloride as the AgCl salt, leaving only the cationic species in solution. Electrochemical characterization of the mixed-ligand diruthenium complexes conclusively reveals a stable Ru25+ oxidation state in all three complexes. Upon an applied potential in a non-coordinating solvent, each complex undergoes a reversible one-electron oxidation and reduction process accessing the Ru26+, and Ru24+ oxidation states respectively. The treatment of human breast adenocarcinoma MCF-7 cells with these water-soluble complexes results in a less than 50 % cell survival. This demonstrates significance of solubility in the development of metallodrugs for cancer treatment.Item The selective complexation of metal ions by ligands bearing cyclohexyl substituents(1991) Croft, Graeme John BruceThe addition of cyclohexyl substituents to existing ligands was investigated for its potential use as a factor in ligand design for achieving high specificity for particular metal ions, (Abbreviation abstract)Item Palladium (II) and iron (II) complexes derived from pyridyl-imine ligands as catalyst precursors for 1-hexene oligomerization and norbornene polymerization(2017) Khuzwayo, Pamela ZanelePyridyl-imine ligands L1-L4 were prepared by condensation of pyridine-2-carboxyaldehyde with an appropriate amine. Characterization by NMR spectroscopy, infrared spectroscopy, mass spectrometry and elemental analysis confirmed successful preparation in yields of 64-88%. These ligands were used to prepare Pd(II) complexes C1-C4, from PdCl2(CH3CN)2 and the corresponding pyridyl-imine ligand. 1H-NMR, 13C-NMR, FT-IR, mass spectrometry and elemental analysis confirmed coordination. Attempts to prepare target Fe(II) complexes C5-C8 by reacting the ligands with anhydrous FeCl2 were unsuccessful. Infrared data suggested coordination of ligands to the Fe centre, however mass spectrometry and elemental analysis data revealed that target complexes were not obtained. Pd(II) complexes C1-C4 were evaluated as catalyst precursors for 1-hexene oligomerization and norbornene polymerization using methylaluminoxane (MAO) as co-catalyst. The oligomerization of 1-hexene was investigated in a neat reaction media at various Al:Pd ratios. All investigated complexes were found to be inactive for the oligomerization of 1-hexene. From 1H-NMR spectroscopy and GC-MS analysis it was observed that the product distribution was mainly a mixture of 2-hexene and 3-hexene isomers. Parameters such as temperature and time did not have any significant influence towards the productivity of 1-hexene oligomers. Norbornene polymerization studies were carried out with Pd(II) complex C4 in toluene at room temperature. This complex was found to exhibit good activity for norbornene polymerization, producing a vinyl bicyclic polymer, confirmed with infrared and solid state 13C-NMR spectroscopy. Increasing the amount of co-catalyst (MAO) and temperature did not have any significant influence on the activity and monomer conversion. However, increasing reaction time was observed to have a significant influence on the activity.Item A molecular mechanics study for selective complexation of metal ions in medical applications(1994) Chantson, Tracy, ElizabethMolecular mechanics calculations are used to interpret and predict metal ion discrimination by coordinating ligands. Of particular interest are chelates exhibiting characteristics that Single them out for potential medical application; Selectivity patterns for several series of ligands are investigated with the help of strain energy profiles as a function of metal-donor atom bond distance. Ligands include simple; open-chain oxygen- and nitrogen-donors ana triaza- and tetraazamacrocyeles. Results are compared with X-ray crystallographic and solution data. Factors such as chelate ring size, conformational flexibility and preferred metal coordination geometry are found to influence metal specificity. Addition of pendent donor groups to macrocyoles leads to rigid structures and selectivity predictions according to cavity size. Interpretation of specific. metal ion recognition by polyetner antibiotics is attempted. Structural and steric factors are probed as possible determinants of metal choice. both covalent and ionic bonding models are explored. The covalent approach results in predictions of metal selectivity which correlate with mown selectivity patterns. Unfortunately, inability to optimise force field parameters in the ionic bonding approach forced us to abandon this model. The main force field used is the TRIPOS (1992,1993) force field. It performs well in calculations involving a univariate scanning technique but has to be modified to obtain reasonable structure reproduction with the large antibiotics, Errors in thermodynamic data predictions are obtained, nonbonding parameters have yet to be properly parameterized and the allocation of partial atomic charges warrants closer examination . All of these factors contribute to the poor performance of the force field when ionic interactions between metal and donor atoms of the polyethers are assumed.Item The CIS influence of the corrin ring in cobalt corrins(2016) Ghadimi, NafiseIt is well-established that there is electronic communication between the equatorial and axial ligands in the cobalt corrins. It can therefore be anticipated that the electronic structure of the corrin ligand will affect the chemistry of the axial coordination sites of Co(III) in these complexes. To probe this cis-influence the electronic structure of the corrin was perturbed by substituting the H atom at C10 by Br (which is π electron-donating towards the corrin) in aquacobalamin ([H2OCbl]+), and by NO2 (which is strongly electron-withdrawing) and NH2 (which is strongly electron-donating) in aquacyanocobester ([ACCbs]+). The first part of this study was dedicated to aqua-10-bromocobalamin ([H2O-(10-Br)Cbl]+) and the second part to aquacyano-10-nitrocobester ([AC-(10-NO2)Cbs]+) and aquacyano-10-aminocobester ([AC-(10-NH2)Cbs]+). The successful synthesis of [H2O-(10-Br)Cbl]+, was verified by ESI-MS, 1H and 13C NMR, uv-vis spectroscopy and XRD. The stability constants for the substitution of coordinated H2O by a series of anionic (N3 –, NO2 –, SCN–, SO3 2–) and neutral N-donor ligands (imidazole, DMAP) were obtained for [H2OCbl]+, [H2O-(10-Br)Cbl]+ and [H2O-(10-Cl)Cbl]+ under the same conditions. Substitution of the C10 H by Cl or Br favours the coordination of anionic ligands, but discriminates against the binding of neutral N-donor ligands. The anionic ligands bind more strongly to [H2O-(10-Br)Cbl]+ than to [H2OCbl]+ with log K values between 0.05 and 0.62 (average 0.33) larger. Conversely, neutral ligands bind less strongly to [H2O-(10-Br)Cbl]+ than to [H2OCbl]+ with log K values between 0.29 and 0.36 (average 0.33) smaller. DFT (BP83/TZVP) calculations were used to rationalise these observations. When H is changed to Cl or Br, the metal ion becomes less positive. When the β ligand changes from a neutral to an anionic ligand, the partial charge on the C10 substituent becomes more negative. Replacing C10 H by Cl or Br discriminates against a neutral ligand because of the greater electron richness of the metal. If the ligand is an anion, however, the charge donation can be accepted by delocalisation onto the C10 substituent. The reaction kinetics of the substitution of H2O in [H2O-(10-Br)Cbl]+ were determined for the ligands N3 – and imidazole and were compared with values available for [H2OCbl]+ and [H2O-(10- Cl)Cbl]+. The results showed that both N3 – and imidazole react more slowly with [H2O-(10- Br)Cbl]+ than with [H2OCbl]+, consonant with the previous observations for [H2O-(10-Cl)Cbl]+. Although ΔH‡ values are smaller, they do not compensate for significantly more negative values of ΔS‡, indicative of a transition state that occurs earlier along the reaction coordinate in [H2O- (10-Br)Cbl]+ and [H2O-(10-Cl)Cbl]+ whereas the transition state occurs later along the reaction coordinate with [H2OCbl]+. It is argued that this is a consequence of the lower charge density on the metal, making it a better electrophile both towards the incoming and the departing ligand. Dicyano-10-nitrocobester ([DC-(10-NO2)Cbs]) and dicyano-10-aminocobester ([DC-(10- NH2)Cbs]) were synthesised from dicyanocobester [DCCbs] by established methods and converted to the aquacyano form so that the thermodynamics and kinetics of the substitution of coordinated H2O by a variety of ligands could be investigated. The stability constants for the substitution of coordinated H2O by a number of neutral (imidazole, DMAP, methylamine) and anionic (N3 –, NO2 –, SCN–, SO3 2–, CN–) ligands were determined for [ACCbs]+, [AC-(10-NO2)Cbs]+ and [AC-(10-NH2)Cbs]+ in 50% isopropanol. The soft anions (SO3 2– and CN–) bind better to the softer Co(III) metal centre in [AC-(10-NH2)Cbs]+ and [ACCbs]+ than in [AC-(10-NO2)Cbs]+ and the converse is true for the hard anions (N3 –, NO2 – and SCN–). The case is less clear for the N-donor ligands; DMAP clearly has a higher affinity for [AC-(10- NH2)Cbs]+ and [ACCbs]+ than for [AC-(10-NO2)Cbs]+, but there is little discrimination in the case of imidazole and methylamine. This implies that the affinity of the metal for an exogenous ligand depends on the electron density at the metal centre. DFT calculations showed that as the C10 substituent is changed from NH2 to H to NO2, the charge density on the metal centre decreases and the metal becomes harder. The kinetics of the substitution of H2O by CN– in [ACCbs]+, [AC-(10-NO2)Cbs]+ and[AC-(10- NH2)Cbs]+ in 50% isopropanol were determined. The results showed that the substitution of coordinated H2O proceeded with biphasic kinetics and through a dissociative interchange (Id) mechanism where there is nucleophilic participation of the entering ligand in the transition state. The slower phase corresponds to the substitution of coordinated H2O trans to OH– in the aqua hydroxo species, which, together with the dicyano species, is inevitably present in solutions of [ACCbs]+, and the faster phase corresponds to the substitution of the coordinated H2O trans to CN– in the aquacyano species. The difference in rate of the reaction of the [AC-(10-Z)Cbs] (Z = H, NH2 and NO2) was not very large, the ratio between the largest (for Z = H) and the smallest (for Z = NO2) is just over 40, and does not follow the electron donor properties of Z. This is misleading, however, because of a compensation effect between ΔH‡ and ΔS‡. As values of ΔH‡ become smaller, which causes an increase in the reaction rate, ΔS‡ becomes less positive (or more negative), which causes a decrease in the reaction rate. Hence, comparing rate constants at any particular temperature is not very informative and the compensation effect masks the very significant differences in the reactivity of the metal ion towards the entering CN– ligand. The compensation effect is attributed to the position of the transition state along the reaction coordinate, which depends on the charge density on the metal ion. Indeed, if all three reactions had the same value of ΔS‡ then the values of the rate constant would be in the approximate ratio 109:106:1 for Z = NH2, H and NO2, respectively. This study shows that how profoundly the perturbation of the electronic structure of the corrin affects the thermodynamic and kinetic properties of the Co(III) ion, and provides further evidence that the unusual chemistry of Co(III) in the cobalt corrins is a consequence of the cis-influence of the equatorial macrocyclic ligand.Item Studies on hemin and cobalt corrinoids in aqueous solution(2015-01-13) Campbell, Vivien Mary