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Malaria is a devastating and pervasive infectious disease and continues to be a major global health issue, with over half the world's population being at risk of transmission. In the absence of a suitable vaccine, efforts to eradicate the disease rely heavily on clinically available drugs. Plasmodium falciparum, the deadliest species of malaria, has however become resistant to most conventional antimalarial treatments, resulting in the worldwide search for new, effective drugs. Amongst other requirements, these drugs should target resistant parasitic strains in an attempt to curb the escalation of the disease. In this regard, the incorporation of a metal into the organic framework of a biologically active compound has become an increasingly popular method of enhancing antiplasmodial activity in the drug-resistant parasite strains. Two series of 7-chloroquinoline-1,2,3-triazole ligands, one with the direct attachment of the triazole to the quinoline and one where the two entities are separated by an aminopropyl linker, were synthesised. Coordination of selected ligands with [IrCl(μ-Cl)(Cp*)]₂ yielded six neutral, cyclometallated and two cationic,N,N-chelated iridium complexes. Computational analysis revealed that metal coordination to the quinoline nitrogen occurs first, forming an unstable kinetic product that, upon heating over time, forms the stable, cyclometallated, thermodynamic product. All of the compounds were fully characterised using an array of spectroscopic (¹H, ¹³C{¹H}, ¹⁹F{¹H}, ³¹P{¹H} NMR and FT-IR spectroscopy) and analytical (mass spectrometry and melting point analysis) techniques. Single crystal X-ray diffraction confirmed the proposed molecular structure and a pseudo-tetrahedral geometry around the metal centre for the cyclometallated and monodentate, quinoline nitrogen-coordinated complexes. The ligand series containing the propyl chain linker displayed superior in vitro antiplasmodial activity against the chloroquine-sensitive NF54 strain of P. falciparum in comparison with the series having thetriazole directly attached to the quinoline moiety. Upon complexation with iridium, the activity of selected ligands is significantly enhanced (0.247< IC₅₀ (μM)< 2.34), with some complexes being over one hundred times more active than their respective ligands. For most of these compounds, their antiplasmodial activity is lower in the chloroquine-resistant K1 strain, however, their calculated RI values suggest that they likely only experience mild cross-resistance, not to the same extent of chloroquine. Selected complexes were tested against the healthy, mammalian Chinese Hamster Ovarian (CHO) cell line and were found not to be cytotoxic. They were also determined to be more selective towards the parasite than healthy cells. An “IC₅₀ speed assay” using the three most active complexes against the chloroquine-sensitive NF54 strain found the two neutral, cyclometallated complexes to be fast-acting compounds which reach their lowest IC₅₀ values within 24 hours, while the active cationic complex was determined to be slow-acting, only reaching its lowest IC₅₀ value after 48 hours. To gain insight into the possible mechanisms of action of these compounds, selected ligands and complexes were tested for their ability to inhibit the formation β-haematin(the synthetic form of haemozoin), sinceone of the mechanisms of 7-chloroquinoline-containing compounds is the inhibition of haemozo information. All five of the tested compounds were found to inhibit β-haematin formation to some extent but were, in general, less effective β-haematin inhibitors than chloroquine itself. Interestingly, the aminopropyl-containing cationic complex which displayed the lowest antiplasmodial activity exhibited far greater β-haematin inhibitory activity (IC₅₀ 9.65 μM) than chloroquine(IC₅₀ 65.3 μM).Finally, three of the most active complexes were evaluated for their ability to facilitate transfer hydrogenation, by reducing β-nicotinamide adenine dinucleotide (NAD+) to NADH in the presence of hydrogen source, sodium formate. Through preliminary qualitative and quantitative cell-free experiments, it was found that the two most active neutral, cyclometallated complexes tested may be capable of acting as transfer hydrogenation catalysts while the active, cationic complex tested did not indicate reduction of NAD+ to NADH over 4 hours.

The use of transition metals in synthesis is an incredibly useful tool for organic chemists. Co-ordination of a metal can occur with most function groups in some manner resultingin dramatic changes in the reactivity. Decarboxylative cross-couplings provide a new route to the construction of C–C bondswithout the necessity of costly organometallic precursors. Similarly C–H activationprovides an environmentally and economically desirable method to cross-couplingproducts, and this can be facilitated by the presence of ortho-directing groups. Thedecarboxylative coupling of carboxylic acids, combined with carboxylate directed C–Hactivation has been investigated to demonstrate ortho-arylation and acylation of benzoicacids. In doing so the different functionality of the carboxylate group is demonstrated inone process. Following this, a mild ZnEt2 mediated 1,5-substituted 1,2,3-triazole formation reactionhas been investigated. Significantly, this method is compatible with many differentsubstrates including halides, esters, nitriles, ketones and amides which have proven to beincompatible with analogous Mg or Li methods. The resultant heteroaryl zinc can beutilised further in cross-coupling reactions, or with other electrophiles, enabling theformation of a wide range of substituted triazoles.

This project was focused on the synthesis and reactivity of rare-earth nbutyl complexes of the formula [CpMe2M(μ-nBu)]2 (where M = Y, Dy). Dysprosium was used as it has a large magnetic moment which is favourable for producing single molecule magnets (SMMs). Yttrium was used as a diamagnetic analogue to examine the reactivity of [CpMe2Y(μ- nBu)]2 in solution, and provide further characterisation of isolated complexes with NMR spectroscopy. Another goal of the project was to establish the reactivity of [CpMe2M(μ- nBu)]2 with respect to the commonly used alkylating reagent nbutyllithium (nBuLi). It was found that the nbutyl complexes are remarkably stable in solution and the solid state, allowing for the synthesis to be scaled up and for the nbutyl complexes to be used as starting materials. The reactivity of [CpMe2M(μ- nBu)]2 towards ferrocene was investigated. The product was a ferrocenyl-bridged dimer of the formula [CpMe2M(μ-(C5H4)FeCp)]2 resulting from a single deprotonation of ferrocene. The reactivity of [CpMe2M(μ- nBu)]2 towards N-heterocyclic carbenes (NHCs) was also investigated. No reaction occurred between [CpMe2Y(μ- nBu)]2 and 1,3-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr), a reaction did occur between [CpMe2Y(μ- nBu)]2 and 1,3-bis-(tert-butyl)imidazol-2-ylidene (ItBu) but no crystalline product could be obtained. [CpMe2M(μ- nBu)]2 reacts with 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) to form a monomeric, benzyl tethered carbene complex [CpMe2M(IMes’)]. An ortho-methyl group on one of the mesityl substituents is deprotonated generating an asymmetric functionalised carbene. A control experiment between CpMe3M (M = Dy, Y) and IMes resulted in the formation of the abnormal, rearranged carbene complexes [CpMe3M(aIMes)]. C6H6. Structural analysis revealed a very short C-H---π interaction between neighbouring molecules. The mechanism of carbene rearrangement was probed by 1H NMR spectroscopy (M = Y). Magnetic susceptibility measurements revealed that [CpMe2Dy(μ- nBu)]2, [CpMe2Dy(μ-(C5H4)FeCp)]2, [CpMe2Dy(IMes’)] and [CpMe3Dy(aIMes)]. C6H6 are not SMMs. [CpMe2M(μ- nBu)]2 activates sulfur and selenium to form hexanuclear clusters of the formula [CpMe10M((E3)2E2] (M = Dy, Y; E = S, Se). [CpMe10M((S3)2S2] is an SMM with an energy barrier to magnetisation reversal, Ueff, of 73 cm-1. The analogous selenium cluster could be characterised by single crystal X-ray diffraction however separation from unreacted selenium proved difficult without using coordinating solvent. Extraction of [CpMe10Y((Se3)2Se2] with THF resulted in the crystallisation of the ion pair [CpMe2Y(THF)3][{CpMeY(Se2)}6Se] and [{CpMe2Y(THF)}(µ-Se2)]. A trimetallic dysprosium coordination complex containing a hexaazatrinapthalene (HAN) bridging ligand is reported. Magnetic measurements on [{(thd)3Dy}3HAN] (Dy3HAN) show that it is an SMM in zero field and two magnetic relaxation mechanisms are present. An optimised DC field of 1 kOe allowed for better resolution of the two relaxation processes and an energy barrier for each process could be extracted. The Ueff barriers are 42 and 52 cm-1. Ab initio theoretical analysis revealed the magnetic anisotropy axes are nearly collinear precluding the presence of a toroidal magnetic moment. The ground state of Dy3HAN was found to be frustrated.

Electrochemical behavior of mono- and bimetallic chromiumtricarbonyl and cationic manganesetricarbonyl of fluxional dibenzo[a,e]cyclooctatetraene (DBCOT) complexes were studied via cyclic voltammetry over a range of scan rates (20 – 2000 mV/s) and temperatures (0 °C and 25 °C). The presented work displays electrochemical reduction mechanisms associated with eight-membered ring coordinated M(CO)3 systems that undergo rapid ring inversion in solution. The electrochemical studies of these complex systems exhibit comparitively similar behaviors, which suggest relatively undifferentiated mechanisms. Slight differences between the chromium and isoelectronic cationic manganese are seen in their chemical reactions in solution and the potential at which they reduce. The significance of the electrochemical studies of these complexes are justified by their potential contribution to nanotechnology considering the possibility of generating a cylindrical nanostructure containing the tub-shaped eight-membered ring ð-coordinated M(CO)3 system. The high probability of a haptotropic shift to the eight-membered ring upon reduction could prove to be beneficial to electrocatalysis.

Mono- and dinuclear chromiumtricarbonyl and manganesetricarbonyl complexes of dibenzo[a,e]cyclooctatetraene (DBCOT) were synthesized and characterized. In the bis(chromiumtricarbonyl)DBCOT synthesis, the main product was the syn,anti isomer where the two Cr(CO)3 moieties coordinate to opposite faces of the DBCOT backbone. This complex exhibits three dynamic processes in solution. A ring inversion of the organic skeleton occurs while the two chromiumtricarbonyl moieties undergo tripod rotation. This is the first study where eight-membered ring inversion is studied for a pi-coordinated metallic system. The rate of inversion at various temperatures was determined by 1H NMR line shape analysis at two different field strengths (300 and 600 MHz). Compared with other cyclooctatetraene compounds reported, there is a large positive entropy of activation and a relatively high enthalpy of activation in this system. DFT calculations, using the B3LYP/6-31G** basis set, were performed to gain a better understanding of the experimental results. It is proposed that free rotation of both Cr(CO)3 groups in the planar transition state are responsible for the large entropy of activation for ring inversion in hexahapto,hexahapto-dibenzo[a,e]cyclooctatetraene-syn,anti-bis(tricarbonylchromium). The relatively large enthalpy of activation is due to a stabilizing interaction between the endo carbonyl groups on the syn-Cr(CO)3 and the remote arene. In the monometallic DBCOT complexes, the metal can either be inside or outside the tub conformation. Interestingly, the crystal structures show opposite orientations for the isoelectronic chromium and manganese systems. The Cr(CO)3 group is positioned anti relative to the DBCOT backbone while the Mn(CO)3+ is syn. It should be noted that the optimized gas phase geometries obtained through DFT calculations agree with the crystallographic results. Electrochemical studies were performed to investigate the change in redox behavior associated with coordination of mono and bis-chromium units to the DBCOT backbone. Four new organometallic crystal structures are reported in this dissertation. Different tripod orientations, DBCOT backbone angles, and metal orientation relative to the interior of the organic skeleton are found. C-H...O, C-H...pi, and charge assisted C-H...F hydrogen bonding interactions were observed in the solid state packing. The structural motifs found suggest these complexes could serve as organometallic synthons in supramolecular chemistry.

CdSe quantum dots produced by organometallic synthesis are useful as tunable emitters for photonic devices and as multi-colored protein markers for biomedical imaging, applications requiring bright and narrow emission. A diffusion-limited model helped monitor growth rates via photoluminescence and absorbance spectroscopy, in order to characterize synthesis kinetics in stearic acid, dodecylamine, and in trioctylphosphine oxide. The nucleation rate increased with Se concentration, while the growth rate followed the Cd concentration. Emission peak widths, emission redshift rates, nanocrystal growth rates, and reactant concentrations all decreased to a minimum when emission reached the critical wavelength, at a reaction completion time, tc. The temperature dependence of 1/tc and of redshift rates followed Arrhenius behavior governed by activation energies, which were tailored by the choice of solvent. Synthesis in solvents, such as stearic acid, with lower activation energies produced faster initial nanocrystal growth and longer critical wavelengths. The highest photoluminescence quantum yield was generally at wavelengths shorter than the critical wavelength, when moderate growth rates enabled surface reconstruction while precursors were still available. / Ph. D.