Doctoral Degrees (Chemistry)

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Browsing Doctoral Degrees (Chemistry) by Author "Brink, Alice"

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    ItemOpen Access
    A crystallographic and mechanistic investigation of rhenium (I) tricarbonyl complexes as model radiopharmaceuticals
    (University of the Free State, 2011-11) Brink, Alice; Roodt, Andreas; Visser, Hendrik G
    English: Rhenium(I) and technetium(1) tricarbonyl complexes hold significant potential as model radiopharmaceuticals which could be utilized as therapeutic and imaging agents. 99mTechnetium in particular, is one radionuclide which is used in more than 80% of radiopharmaceuticals as a diagnostic agent. The biodistribution of a potential radiopharmaceutical can in principle be manipulated by the coordination of a biologically active molecule to the radionuclide. The principle aim of this study was to gain further insight into the chemistry, coordination and kinetic behaviour of fac-[M(CO)3+ (M = Tc, Re) complexes. With this idea in mind, a range of salicylidene ligands, SaIH, were synthesised according to the Schiff-base reaction. These organic ligands were synthesized as potential bifunctional chelators between the tricarbonyl radionuclide and the biologically active directing molecule. The ligands contain various amine compounds which were coordinated to the imine nitrogen atom on the salicyclidene "backbone". The imino substituents consisted of aromatic, aliphatic and biologically active moieties with varying steric, electronic and biological properties and included amines such as m-toluidine, 3-methylbutylamine, aniline, histamine, tryptamine, tyramine etc. The ligands were characterized via NMR and IR spectroscopy. A single crystal X-ray diffraction study of the ligands was reported and revealed the various orientations of the substituents relative to the salicylidene backbone. The reported X-ray crystallographic structure determinations included the following ligands: 2-(m-tolyliminomethyl)phenol, 5- methyl-2-(m-tolyliminomethyl)phenol, 4-fluoro-2-(m-tolyliminomethyl)phenol, 2-(4-nitrophenyliminomethyl) phenol, 2-[(4-hydroxyphenyl)iminomethyl]-5-methylphenol, 2-[(2- imidazol-4-yl)ethyliminomethyl]-5-methylphenol, 2-[(2-indol-3-yl-ethyl)iminomethyl]-5- methylphenol, 2-(9-ethylcarbazol-3-yliminomethyl)-5-methylphenol, 2-[2-(4-hydroxy- phenyl)ethyliminomethyl]-5-methylphenol, 5-methyl-2-(1,2,4-triazol-3-yliminomethyl)-phenol. A further important part of this investigation was concerned with the synthesis and evaluation of the solid state characteristics of the SalH ligands coordinated to the rhenium(I) metal centre. The advantage of the fac-[M'(CO)3(S)3]+complex (M = Tc or Re; S = H20 or other coordinated solvents) is the high stability of the classic low spin d6 [M(CO)3]+ core in water and the potential of exchanging the labile solvent ligands. The SalH bidentate ligands were bonded to the fac-[M(CO)3]+ core according to the [2+1] approach, thus leaving an 'open' third position occupied by either a solvent or by a neutral monodentate ligand. The complexes were also characterized via NMR and IR spectroscopy. The solid state behaviour of these fac-[Re(Sal)(CO)3(S)] complexes were investigated by X-ray crystallography, and included the complexes: fac-[Re(Sal-mTol)(CO)3(HOCH3)], fac-[Re(Sal- Ph)(C0)3(HOCH3)],fac-[Re(Sal-pTol)(CO)3(HOCH3)],fac-[Re(Sal-CyHex)(C0)3(HOCH3)], fac-[Re(Sal-3MeBu)(CO)3(HOCH3)], fac-[Re(Sal-Ph)(CO)3(NCsHs)], fac-[Re(Sal- 3MeBu)(CO)3(NCsHs)], fac-[Re(5Me-Sal-Hist)(CO)3], fac-[Re(5Me-Sal-Trypt)(CO)3 (NCsHs)], fac-[Re(5Me-Sal-Carba)(CO)3(NCsHs)], fac-[Re(5Me-Sal-mTol)(C0)3(HOCH3)], fac-[Re(5Me-Sal-3Me2Bu)(CO)3(HOCH3)]. The coordination geometry around the Re(l) metal centre in the crystal structures was a distorted octahedron. The imino substituents crystallize in similar orientations despite various steric sizes, while the bond angles and lengths were not significantly affected by the different nitrogen-coordinated substituents. The study of the solid state coordination of the complexes was further supplemented with a theoretical DFT (density functional theory) study for specifically the 2-(mtolyliminomethyl) phenol, 5-methyl-2-(m-tolyliminomethyl)phenol, 2-(9-ethylcarbazol-3- yliminomethyl)-5-methylphenol,fac-[Re(Sal-mTol)(CO)3(S)],fac-[Re(Sal-Ph)(COh(S)],fac- [Re(5Me-Sal-Carba)(CO)3(S)] compounds. The comparison between the optimised structure and the crystal data reveal small differences, illustrating that predictions can be made in terms of the coordination of the bidentate ligands to the rhenium metal centre utilising DFT techniques. A kinetic study of substitution of the coordinated solvent ligand of fac-[Re(Sal)(CO)3(S)] complexes was done. The following complexes were evaluated: fac-[Re(SalmTol)( CO)3(HOCH3)], fac-[Re(Sal-pTol)(CO)3(HOCH3)], fac-[Re(Sal-Ph)(CO)3(HOCH3)], fac-[Re(Sal-3MeBu)(CO)3(HOCH3)], fac-[Re(Sal-CyHex)(CO)3(HOCH3)] for entering ligands 3-chloropyridine, pyridine, 4-picoline and 4-dimethylaminopyridine in methanol as solvent. The rates were quite fast and varied from seconds to minutes under the conditions studied. Only one reaction was observed under dry conditions. The Sal-Re ligand systems allowed the unique opportunity to confirm non-associative behaviour since for selected ligands, pyridine and DMAP, limiting kinetic profiles were obtained; clear evidence of either I or D intimate mechanisms. An interchange dissociative (Id) mechanism was proposed for the substitution reaction with positive activation entropy and enthalpy values. An in vitro cancer screen was conducted on selected non-coordinated ligands and fac- [Re(Sal)(CO)3(S)] complexes in a 3-ce]] line panel consisting of TKlO (renal), UACC62 (melanoma) and MCF7 (breast) cancer cells using a Sulforhodamine B (SRB) assay. No significant cell activity was found but limited cell growth inhibition was observed.
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    ItemOpen Access
    Structural and reactivity study of rhodium(i) carbonyl complexes as model nano assemblies
    (University of the Free State, 2015-07) Pretorius, Carla; Roodt, Andreas; Brink, Alice
    This study focussed on the investigation of different β-diketonato ligands in coordination to rhodium(I). Square planar [Rh(O,O’-Bid)(CO)2] complexes have been shown to effectively facilitate metallophilic interactions between rhodium(I) centres in the construction of infinite one- dimensional metal chains in the solid-state. The classification of these systems as forming nano- wired assemblies has led to similar systems finding wide application in electronic and optical technologies. The study was focused on investigating the effect of an altered rhodium(I) environment on the metallophilic interactions and subsequent one-dimensional chains formed in the solid-state. These modifications were initiated by using a range of different coordinating β-diketonato ligands to induce either electronic or steric changes to the rhodium(I) centre. To this end, a range of rhodium(I) complexes were synthesized and characterized by IR, UV/Vis and NMR spectroscopy. Single crystal X-ray diffraction was used in the solid-state structure determinations of these complexes showing significant changes in the Rh···Rh distances in each rhodium(I) complex. It also provided valuable information with regards to how the molecules are arranged along these one-dimensional chains. Rh···Rh distances ranging from 3.134(3) Å to 3.617(3) Å were found in the solid-sate for the range of rhodium(I) complexes with the distances correlating to the UV/Vis absorption profile of each complex. A preliminary substitution reaction and equilibrium study was undertaken to further evaluate how changes at the rhodium(I) centre could affect the reactivity of the rhodium(I) complexes. An important equilibrium was shown to participate in the reaction using 31P NMR and UV/Vis spectroscopy. In this investigation it was seen that using second-order rate constants to describe the reactivity of the complexes correlated to the pKa values of the uncoordinated β-diketone ligands with an increased rate in substitution associated with a lower pKa of the free ligand. 103Rh NMR chemical shifts of the rhodium(I) complexes were also found to correlate to the pKa values of the free ligands as well as highlighting the electronic environment experienced by the metal centre. This provided an effective measure of how electronic changes to the rhodium(I) centre could affect the Rh···Rh interactions of the solid-state structures as well as the physical properties of the compounds. The study concluded with a comparison of all the parameters by which the rhodium(I) complexes were evaluated to assess how changes induced by using different coordinating β-diketonato ligands influence the one-dimensional chains constructed via metallophilic interactions as well as physical properties such as the colour exhibited by the bulk material. These parameters included pKa, UV/Vis absorbance properties, IR, 103Rh NMR, reactivity (k12 constants), Rh···Rh distances and the torsion angles of the assembled molecules.