published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

The evolution of the present work began with the syntheses of novel bis(alkylimino)acenaphthene (BIAN) ligands. At the outset of this research, despite the presence of dozens of aryl-BIAN ligands in the literature, there were as of yet no reported BIAN ligands bearing alkyl substituents. Given the nearly ubiquitous use of transition metal complexes of alkyl diazabutadiene (DAB) ligands for e.g. catalysis and as ligands for carbene chemistry, interest was generated in developing this emerging field of synthetic chemistry. Initial studies focused on the synthesis of alkyl-BIAN ligands since the traditional synthetic approaches that had been developed for aryl-BIAN ligands were unsuccessful for the alkyl analogues. As an alternate synthetic route, it was decided to employ amino- and imino-alane transfer reagents which had previously proved successful for the conversion of C=O into C=N-R functionalities. While this transfer route had proved successful to synthesize moderate yields of highly fluorinated DAB ligands, it was unknown how or whether this methodology would apply in the case of alkylated BIAN systems. Over the past decade, there has been a surge of interest regarding lanthanide complexes that are capable of undergoing spontaneous electron transfer processes. There are several reports in the literature that describe the ability of Ln(II) ions to undergo spontaneous oxidation, thereby causing one-electron reduction of the coordinated ligand and generally resulting in the corresponding Ln(III) complex. The present work focused on an enhanced understanding of the electronic communication between the lanthanide and the attached ligand. Particular emphasis was placed on defining the resulting oxidation states and the manner in which delocalized electrons of the radical anion species travel over a conjugated system. This fundamental information was gleaned from single-crystal X-ray diffraction studies and magnetic moment measurements that were obtained using the Evans method. Additional insights stemmed from the use of more classical techniques such as IR and NMR spectroscopy. In favorable cases, the presence or absence of spectral peaks can permit assignment of the lanthanide oxidation state. Accordingly, the research plan was to synthesize a series of BIAN-supported decamethyllanthanocene complexes with the goal of learning how to control the spontaneous charge transfer that had been reported in the literature. A longer term goal was to develop a bifunctional ligand of the BIAN type that was capable of accommodating two lanthanide or main group element moieties. Systems with tunable electronic interactions between lanthanide or main group elements are of interest because they offer the prospect of extended delocalization of electron density. Systems of this type have potential applications as e.g. molecular wires and single-molecule magnets. Indeed, such systems have been investigated by using bis(bipyridyl) and bis(terpyridyl) ligands to support two redox-active moieties. However, in the present work, it was recognized that a bifunctional BIAN-type ligand might be of considerable interest as the supporting structure for studying the communication between lanthanide or main group element moieties. A synthesis of variously substituted tetrakis(imino)pyracene (TIP) ligands was therefore undertaken. The flat, rigid nature of the TIP ligands rendered them ideal scaffolds for studying the redox behavior and electronic communication between lanthanide or main group element centers. The new TIP ligand class also proved to be useful for the assembly of the first example of a metallopolymer based on a BIAN-type ligand. / text

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Principles of transition metal electronic structure are presented to enable an understanding of the activation of C-H and C=C bonds by metals. A multitechnique approach utilizing core and valence photoelectron spectroscopies (p.e.s.) and molecular orbital calculations has been used to gain these insights. In the first half of the dissertation three principles are developed: ligand additivity, core-valence ionization correlation, and ring methylation. In the latter half of the dissertation these principles are seen to be crucial for understanding ionization data for the C-H and C=C activated species. Additive (with respect to ligand substitution) electronic effects, including additive core and valence ionization potentials, are shown in the p.e.s. of phosphine substituted molybdenum carbonyls. These additive effects demonstrate that the electronic effects of ligand substitution are predictable from empirical models. The core-valence ionization correlation enables direct comparison of XPS (core) and UPS (valence) ionization data and allows separation of bonding and overlap induced valence shift effects from Coulombic and relaxation shift effects. In the study of trimethylphosphine substituted cyclopentadienylmanganese tricarbonyl complexes, both the ligand additivity and core-valence ionization correlation principles are less valid than for the molybdenum carbonyl complexes because of loss of the very influential carbonyl backbonding. Methylation of the cyclopentadienyl ring in this system adds another independent variable of electronic structure perturbation and enables separation of the one-center and two-center Coulombic contributions to the core shifts. The above principles are used in the later chapters to show that the initial activation of the C-H bond in alkenylmanganese tricarbonyl complexes is dominated by the interaction of the C-H sigma bonding level with empty metal acceptor levels. The activation stops at the agostic stage rather than proceeding to full β-hydribe abstraction because there is, in these molecules, no gain in the number of pi electrons between the allyl and diene hydride endpoints of the abstraction cycle. Activation of the C=C bond in the cyclopentadienylmetal olefins is similar for Co and Rh complexes despite little similarity in the valence ionization spectra. The spectral differences are largely caused by the relaxation energy differences between Co and Rh. These complexes also provide interesting examples of electron delocalization through the metal. Permethylation of the cyclopentadienyl ring shifts the olefin pi ligand ionizations more than the expected Coulombic shift.

Biologically many disease states lead to changes in expressed proteins. Therefore, "system changes" that occur must be considered in any treatment for the disease. This new approach to drug design and discovery would be particularly applicable to the diseases that involve adaptive changes in the central nervous system, such as neuropathic pain. There is growing evidence that drugs behave differently in pathological states than in normal states, thus preventing their effectiveness in pathological disease states. Therefore, a new paradigm for drug design is needed. In recent years, the melanocortin-4 receptor (MC4R) found in the spinal cord and CNS has received growing attention as a therapeutic target. MC4R based agonist ligands produce anti-opioid effects, and researchers have shown that an antagonist of the MC4R can produce pronounced anti-allodynic effect. Opioid receptors have been the central and most efficacious targets sought after for relieving neuropathic pain. In our new approach, single peptide molecules are designed to interact with opioid receptors as an agonist, and as an antagonist at the MC4 receptor. For the treatment of pain, a series of linear and cyclic peptides based on the overlapping pharmacophores of endogenous melanocyte stimulating hormone and opioid ligands are designed through computational aided molecular modeling and synthesized. Throughout the studies the opioid pharmacophore is maintained towards the N-terminal while melanocortin pharmacophore is maintained towards the C-terminal. Cyclization of peptides has been the central synthetic feature in designing the bifunctional ligands. The use of microwave has been shown to be very efficient in cyclizing the peptides. Solvent, reagent, power and temperature conditions are established for the microwave application in aiding the macromolecules for cyclizing their side chain termini.

The experimental work conducted in this thesis was aimed at determining the thermodynamic quantities associated with the formation of complexes formed between various metal ions and KELEX 100, a ligand which is used commercially for liquid - liquid extraction. In order to accomplish this, the beats of protonation of the ligand KELEX 100 were determined calorimetrically at 25°C in a partially aqueous medium of75% (v/v) l,4-dioxane and at an ionic strength of 0.1 mol dm·3• Extraneous heat effects that usually accompany complex formation were accounted for by measuring each heat contribution separately. The complexation of the lead (II), cadmium (II) and nickel (II) ions with KELEX 100 was studied in 75%(v/v) l,4-dioxane medium. The enthalpies of complexation were measured calorimetrically and calculated using the program LETAGROP KALLE. These results were combined with the values of the Gibbs free energies available in the literature for these systems to yield the entropies of complexation. In all calorimetric determinations a constant ionic strength of 0.1 mol dm'3 and a temperature of 25°C was maintained. The calculated enthalpies and entropies are discussed in terms of a number of factors that affect the thermodynamics of the systems. These factors include the structure of the ligand molecule, the nature of the donor atoms, the degree of substitution on the ligand and the properties of the metal atom such as charge and size, and the nature of the solvent. The cumulative enthalpies and entropies of formation of the metal-ligand complexes are favourable, Le. complexation is accompanied by a decrease in enthalpy and an increase in entropy. However, the enthalpy changes contribute more to the stability of the complexes and hence are the driving forces for complex formation. In the case of the Cd(II) ion, the enthalpy and entropy changes are similar. The cumulative enthalpies of formation increase (Le., become more exothermic) in the order: Ni > Pb > Cd while the reverse order is found for the entropies of formation. The smaller enthalpy change for the Cd(II) complex is possibly due to the weak interaction between the 'soft' Cd(II) ion and the 'hard' KELEX 100 ligand while the decrease in entropy for the Ni(II) may be due to the loss of fewer solvent molecules from the Ni(II) hydration sphere on complexation with the ligand. The stepwise entropy and enthalpy changes for the formation of the ML+ complexes are dependent on the ionic radius of the metal ion. However, no linear correlations exist between the cumulative entropy or enthalpy changes of formation of the ML complexes and the size of the metal ion. The stepwise and cumulative enthalpies of formation appear to be largely independent of steric effects of the bulky alkyl substituent on the KELEX 100 ligand. The increased steric hindrance of the substituent decreases the cumulative entropy change for the formation of the Ni(II) complexes. However, in the case of the Pb(II) complexes, steric effects do not appear to affect the cumulative entropies of complex formation. / Thesis (M.Sc.)-University of Natal, 1995.

Chapter 1 reviews the coordination behaviour of the 6-diphenylphosphino-2,2'-bipyridine, 6-anilino-2,2'-bipyridine, 2,2'-bipyridyl-6-one, 6-N-methylanilino-2,2'-bipyridine, 6-piperidyl-2,2'-bipyridine and 2-(phenylamino)-1,10-phenanthroline ligands. These ligands are all tridentate and contain well established chelating fragments viz., 2,2'-bipyridine and 1,10-phenanthroline. Thus the review of their coordination provides insight into the expected coordination of the 2-diphenylphosphino-1,10-phenanthroline (Ph2Pphen) ligand. The synthesis and characterisation of this ligand is described in Chapter 2. Chapter 3 describes the synthesis and characterisation of a range of Ph2Pphen ligand-bridged dicopper(l) complexes. It has been shown that Ph2Pphen reacts with a suitable copper(l) precursor, [Cu(MeCN)4]+, to form the versatile dinuclear [Cu2(u-Ph2Pphen)2(MeCN)2]2+complex cation containing two bridging Ph2Pphen ligands; the structure of the SbF6 salt of this complex has been determined X-ray crystallographically. This complex possesses labile acetonitrile ligands which have been substituted by a variety of neutral and anionic ligands. Complexes prepared this way include [Cu2(u-Ph2Pphen)2(u-CI)]+, [Cu2(u-Ph2Pphen)2(u-I)]+, [Cu2(u-Ph2Pphen)2(py)2]2 +, [Cu2(u-Ph2Pphen)2{u-S2CN(Et)2}]+, [Cu2(u-Ph2Pphen)2(n-bipy)]2+ and [Cu2(u-Ph2Pphen)2(n-phen)]2+. X-ray structure determinations have been completed for [Cu2(u-Ph2Pphen)2{u-S2CN(Et)2}]+ and [Cu2(u-Ph2Pphen)2(n-bipy)]2+. The X-ray crystal structures of these ligand-bridged complexes confirm that the phosphorus atom coordinates to one copper atom while the phenanthroline fragment chelates to the other copper atom with the result that each metal atom has a tetrahedral geometry. Chapter 4 reviews the synthesis and characterisation of palladium and platinum complexes of the 2-diphenylphosphino-1, 10-phenanthroline (Ph2Pphen) ligand. The comproportionation reaction with Pd(II) and Pd(0) afforded the dinuclear complex [Pd2(u-Ph2Pphen)2](BF4)2. The reaction of Ph2Pphen with platinum resulted in ill-defined products that could not be isolated and characterised. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1998

A series of novel Bis 2,2':6',2″-terpyridinyl ligands, linked through a flexible alkyl chain situated at the 4' position, were synthesised and characterised by microanalysis, FTIR, NMR, UV-Visible spectroscopy, and MS-ToF. Single crystals of all the ligands were obtained, of which one has been published, one has been submitted for publication and one is in preparation for publication. These ligands were then coordinated to platinum(II) and characterised, including ¹⁹⁵Pt NMR spectroscopy. A detailed kinetic study involving the substituting the chloride co-ligand with the following nucleophiles thiourea, 1,3-dimethyl-thiourea and 1,1,3,3-tetramethyl-thiourea was conducted using stopped-flow techniques. An associative reaction mechanism was suggested for the pendant ligand substitution and the following trend in reactivity was observed: L2-Ptα > L3-Ptβ > L1-Ptχ. UV-Visible absorption spectra were recorded on sequentially diluted solutions of the ligands (in chloroform), and the platinum complexes (in water). These spectra obeyed the Beer-Lambert law. The values of the molar absorption coefficients at the wavelengths of maximum absorption for the ligands followed the trend L1 < L2 < L3, whilst for the complexes the trend was L1-Pt < L3-Pt < L2-Pt. It has been concluded that at low concentrations L2-Pt and L3-Pt undergo intramolecular folding. Variable temperature and variable concentration NMR spectroscopic studies were performed on all three complexes. At higher complex concentrations intermolecular self-association takes place for L2-Pt and L3-Pt but not for L1-Pt. The reactivity of the complexes is predominately determined by their structural conformations in solution. At low concentrations the L1-Pt complex remains in its linear conformational state, whilst the L2-Pt and L3-Pt complexes undergo intramolecular folding with the formation of an axial Pt—Pt bonded and π—π stacked dinuclear platinum terpyridine centre. The latter is believed to be more active in the substitution reaction than the original mononuclear centre. The reasons for the folding and self-association in the L2-Pt and L3-Pt systems are related to the steric crowding and stress in the spacer region of the folded or self-associated complexes. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2012.

Poly(azolyl)borate ligands have proven to be extremely popular ligands since their introduction by Trofimenko in the late 60´s. The basic skeleton of these ligands involves usually three heterocycle units linked to a central boron apex via the azole nitrogen atoms. These ligands have been applied in diverse research areas such as homogeneous catalysis, materials science and bio-inorganic chemistry. More than 2000 papers, including books and reviews regarding the properties of these compounds, have been published. However, only a few synthetic methods for the preparation of such ligands have been reported and only a few examples of chiral borate-centred ligands are known. This thesis deals with the development of a novel synthetic route to tripodal borate ligands using B(NMe2)3 as the boron source. The mechanism of the reaction of this borane with azole heterocycles has been established by exploring the reactivity of a range of azoles. One of the major features of this new synthetic protocol is that it allows the formation of chiral tripodal ligands where the chiral groups are located either at the forth position at the boron atom or at the azole heterocycles. Coordination studies of the ligands have been undertaken and the metal complexes have been studied by a combination of spectroscopic and X- ray diffraction techniques. Preliminary application of the most representative ligands in the Asymmetric Transfer Hydrogenation (ATH) of prochiral ketones has been undertaken in collaboration with Prof. Dieter Vogt at the Technical University of Eindhoven.