One particular aspect of the chemistry of the trifluoromethyl group is its high electron-withdrawing power which reduces the donor properties of normally strong bases. This investigation has been concerned with the chemistry of some phosphines containing this group. For this purpose, substituted phosphines containing methyl or phenyl and trifluoromethyl groups have been prepared. For the study of their donor properties, a series of addition compounds with boron trifluoride, platinum(Il) chloride and nickel(II) salts have been prepared. The reported methods for preparing the methyl-trifluoromethyl-phosphines do not produce a good yield; therefore, an attempt has been made towards a better understanding of the reactions. The phenyl-trifluoromethyl-phosphines have been prepared by reacting trifluoroiodo-methane with a phosphorus compound containing a P-P bond. Thus, a reaction with tetraphenylcyclotetraphosphine gives phenylbistrifluoromethylphosphine and phenyltrifluoromethyl-iodophosphine, and reaction with tetraphenyldiphosphine gives diphenyltrifluoromethylphosphine. The latter has also been prepared by reaction of trifluoroiodomethane with either triphenylphosphine or diphenylchlorophosphine. These new phosphines are colorless liquids (except phenyltrifluoromethyliodophosphine which is reddish-brown) of high boiling point. They are stable in air and cannot be hydrolysed with acid or water, except the iodophosphine C₆H₅CF₃PI, which reacts with water to give phenyltrifluoromethylphosphinic acid, a new oxyacid. Phenylbis-trifluoromethylphosphine can be hydrolysed with aqueous alkali to give fluoroform and phenylphosphonous acid. Diphenyltrifluoromethylphosphine, on the other hand, cannot be hydrolysed by aqueous alkali, but reacts slowly with alcoholic potassium hydroxide to give fluoroform and diphenylphosphinic acid. The phosphines form a further series of new compounds by reaction with halogens. Phenylbistrifluoromethylphosphine reacts with iodine to form trifluoroiodomethane, but forms phenylbistrifluoromethyldibromophosphorane with bromine. This compound also gives phenyltrifluoromethylphosphinic acid on aqueous hydrolysis, as obtained in the case of phenyltrifluoromethyliodophosphine. Besides forming the dibromophosphorane, diphenyltrifluoromethylphosphine is the first trifluoromethyl-phosphine known to form a diiodophosphorane. It is interesting to note that diphenyltrifluoromethylphosphine is difficult to hydrolyse, whereas the phosphoranes can be hydrolysed easily, giving fluoroform and diphenylphosphinic acid. By reaction with methyl iodide, this phosphine also forms a new phosphonium compound, methyldiphenyltrifluoromethylphosphonium iodide, which is readily hydrolysed by cold water with the loss of the trifluoromethyl group. In general, phosphines containing one trifluoromethyl group show similar properties to those of their parent compounds, trimethylphosphine and triphenylphosphine, while those containing two trifluoromethyl groups are very similar in their behaviour to tristrifluoromethylphosphine. The phosphines containing more than one CF₃ group do not form addition compounds with boron trifluoride. The phenyl-trifluoromethyl-phosphines form more stable complexes than the methyl-trifluoromethyl-phosphines. The phosphines containing up to two trifluoromethyl groups form complexes with platinum(II) chloride. A complex with tristrifluoromethylphosphine could not be obtained. Except dimethyltrifluoromethylphosphine, which forms mainly a cis isomer, the other phosphines, CH₃(CF₃)₂P,C₆H₅(CF₃)₂P, and (C₆H₅)₂ CF₃P form mainly trans isomers. The non-occurrence of the tristrifluoromethylphosphine complex and the production of mainly trans isomers of the above-mentioned phosphines has been interpreted in terms of steric phenomenon. The phosphines containing more than one CF₃ group do not form complexes with nickel(II) salts. The nitrato complexes of trimethylphosphine and dimethyltrifluoromethyl-phosphine are paramagnetic, while the dichloro, dibromo, diiodo, and dithiocyanato complexes are diamagnetic. A correlation of the various properties, for example boiling points and heats of vaporization, has shown that the trifluoromethyl substituted phosphines are not anomalous in the general family of phosphines. An attempt has also been made towards a study of the infra-red spectra of the phosphines and their compounds, and towards a correlation with the spectra of other phosphorus compounds. Finally, an approximate estimate of the "electronegativities" of a wide range of substituted phosphines gives values which are in good agreement with the observed order of reactivities of the phosphines studied, and assists in correctly placing the trifluoromethyl-phosphines in such a range of compounds. ` / Science, Faculty of / Chemistry, Department of / Graduate

Current knowledge of mechanistic organometallic chemistry has resulted largely from the study of mononuclear transition metal complexes. The possibility that different primary organometallic processes involving two or more metal centres may exist has been addressed only recendy. Reactivity studies on a simple, well defined binuclear system ought to provide fundamental insights into the nature of such polynuclear primary processes. The binuclear rhodium hydrides {[R₂P(CH₂)nPR₂]Rh(μ-H)}₂ (R = Pri, n = 2-4, 1a-1c; R = OPri, n = 2, 1d) were thus reacted with a variety of organic compounds in an attempt to define primary processes involving two metal centres. The reactions of 1a-c with dihydrogen proceed rapidly to produce fluxional binuclear tetrahydrides whose structure is dependent on the chelate ring size of the diphosphine ligand. The dihydrides also catalyze the hydrogenation of olefins. Two mechanistic pathways for this cycle are proposed to exist as supported by chemical and kinetic evidence. One utilizes binuclear intermediates, the other mononuclear; the latter predominates in the 1b catalyzed system (chelate ring size of six) while the former is favoured in the cycle mediated by la (chelate ring size of five). The reactions of 1a and 1b with 1,3-dienes led to the solid (X-ray diffraction) and solution state characterization of binuclear complexes incorporating bridging dienyl ligands in the previously unobserved μ-ƞ⁴-ϭ and μ-ƞ³-ƞ³ "partial sandwich" bonding modes. A fluxional process interconverting the two bonding modes was observed spectroscopically in the products of the 1a/butadiene reaction and a model accounting for this is proposed. Labelling and alternate synthetic studies, as well as the observation of an intermediate at low temperature, support a mechanism for these reactions which involves the dehydrogenation of the dihydrides followed by further reaction of [(P₂)Rh]₂ with a second equivalent of diene. Bridging amido hydrides of general formula [(P₂)Rh]₂(μ-NR'CH₂R")(μ-H) are produced in the reactions of 1a and 1d with imines (R'N=CHR"). Mechanistic studies reveal that initial ϭ-donation of the imine lone pair; of electrons to one Rh followed by π-coordination of the C=N bond to the other precedes formal insertion of the C=N bond into Rh-H. This proposal is consistent with the results of labelling and kinetic studies, but the crux of its support lies in the spectroscopic observation of two intermediates en route to the product amido hydrides. The specific synthesis of cationic μ-ƞ²-ϭ imine complexes closely related to one of the proposed intermediates in the reaction was carried out to confirm the plausibility of such an intermediate. Reaction of the amido hydrides with dihydrogen was slow in producing free amine and the hydrogen adducts of 1a or 1d, precluding the use of these dihydrides as catalyst precursors in the homogeneous hydrogenation of imines. Reaction of 1a and 1d with nitriles (R"'C=N) produces μ-alkylideneimido hydride complexes of general formula [(P₂)Rh]₂(μ-N=CHR'")(μ-H). One derivative (P₂, R = Pri, n = 2; R"' = CH₃) has been characterized by X-ray crystallography. Further reaction of these complexes with dihydrogen yield the amido hydrides [(P₂)Rh]₂(μ-NHCH₂R"')(μ-H). No intermediates in these reactions were observed, precluding meaningful mechanistic proposals for this stepwise reduction of nitriles as mediated by two metal centres. / Science, Faculty of / Chemistry, Department of / Graduate

This project involved utilising the Brønsted basic nature of polar organometallic compounds DyCp3 and [Fe{N(SiMe3)2}2], to deprotonate organic compounds that contain an acidic H-N bond to form low co-ordinate compounds that can then aggregate together to form polynuclear cage compounds. Using DyCp3 in a reaction with BtaH, a dimer formed, [(η5-Cp)2Dy(µ-Bta)]2. This dimer is a single-molecule magnet. [(η5-Cp)2Dy(µ-Bta)]2 was compared to a previously reported compound [(η5-Cp)2Dy{µ-N(H)pmMe2}]2 which, despite having a similar structure to [(η5-Cp)2Dy(µ-Bta)]2, is not a SMM. Synthesis of a chlorine- bridged dimer [(η5-Cp)2DyCl(THF)]2 and subsequent magnetic measurements confirmed that [(η5-Cp)2DyCl(THF)]2 is a SMM. Removal of the THF ligand from [(η5-Cp)2DyCl(THF)]2 was achieved via sublimation. The product of this sublimation was a mixture of two different polymorphs of the same compound, [(η5-Cp)2DyCl]2 and [(η5-Cp)2DyCl]∞. [(η5-Cp)2DyCl]2 was shown to be a SMM, and [(η5-Cp)2DyCl]∞ was shown to display SMM behaviour. [(η5-Cp)2DyCl]∞ had the largest energy barrier to relaxation of magnetisation for any known homospin dysprosium(III) compound. Using [Fe{N(SiMe3)2}2] in a reaction with HppH resulted in the formation of [{Fe{N(SiMe3)2}(hpp)2}2Fe]. [{Fe{N(SiMe3)2}(hpp)2}2Fe] displayed anti-ferromagnetic exchange between the iron(II) centres which resulted in a ground spin state of S = 2. Reacting [Fe{N(SiMe3)2}2] with BtaH resulted in the formation of [{(Me3Si)2NFe}4Fe(Bta)6]. Despite repeated attempts [{(Me3Si)2NFe}4Fe(Bta)6] could not be re-synthesised. An alternative “one pot” synthetic method was attempted, this resulted in the formation of [Fe{N(SiMe3)2}2(LiBta)]2. The structure of [Fe{N(SiMe3)2}2(LiBta)]2 was described using ring-ladder principles and magnetic studies revealed weakly anti-ferromagnetically coupled iron(II) centres which displayed a large zero-field splitting. Extension of the one-pot synthetic route to the use of tin halides was conducted. Using SnCl2 in the one-pot synthetic route resulted in the formation of [{(Me3Si)2N}8Sn8Li8Cl4(Bta)12]. Whilst using SnBr2 resulted in the formation of the compound [{(Me3Si)2N}8Sn8Li8Br4(Bta)12]. The charge separated compound [{(THF)2Li(Bta)}3{Li(THF)}]2[SnI4] was the result of using SnI2 in the one-pot method.

The principal organometallic products resulting from the reactions of Na[(ƞ⁵-C₅H₄R)Cr(CO)₃] (R = H or Me) with allyl chlorides in THF are the green, dimeric [(ƞ⁵-C₅H₄R)Cr(CO)₃]₂ complexes (51-67% yields). The red organometallic by-products usually formed during these conversions are novel (ƞ⁶-6-alkenylfulvene)Cr(C0)₃ complexes (5-8% yields) which have been characterized completely by conventional spectroscopic methods. Dark green [W(N0)₂Cl₂]n may be synthesized in high yields by two preparative methods. The first method involves treatment of WCl₆ in CH₂Cl₂ with an excess of NO, and it proceeds via the isolable intermediate complexes, dark violet c̲i̲̲s̲-W(N0)₂Cl₄ and bright green f̲a̲c̲-W(NO)₃Cl₃. The second method involves controlled reaction of W(CO)₆ with two equivalents of ClN0 in CH₂Cl₂. It is initiated by traces of oxidant and probably proceeds via a catalytic, radical-chain mechanism that is described. If either reaction is effected in the presence of two equivalents of CH₃CN, then yellow-green W(N0)Cl₃(CH₃CN)₂ is the only nitrosyl-containing product formed. Polymeric [W(N0)₂Cl₂]n may be cleaved by a variety of Lewis bases, L, and (n̲-Bu)₃Sn(C₅H₅) to form W(N0)₂Cl₂L₂ (L = phosphine, phosphite, CH₃CN, etc.) and CpW(N0)₂Cl (Cp - ƞ⁵-C₅H₅), respectively, in good yields. The synthesis of the electron-rich nitrosyl complexes CpM(NO)L₂ (M = Cr, Mo, or W; L = P(0Me)₃, PMePh₂, P(n̲-Bu)₃, SbPh₃ or 1/2 (dppe)) is described. They are preparable in moderate to high yields by the reduction of the iodo dimers [CpM(NO)In]₂ (M = Cr, n = 1; M = Mo or W, n = 2) with sodium amalgam in THF ln the presence of the appropriate Lewis base, L, and they exhibit metal-dependent trends in vNO (Cr » Mo > W), δ ³¹P (Cr > Mo » W), and ²J₃₁p (Cr < Mo < W). These reduction reactions proceed via a number of transient intermediates, some of which are isolable. A unified mechanism for these reductive syntheses is proposed. The novel complexes, CpMo(NO)(ƞ⁴-trans-diene) (diene = acyclic conjugated diene) and CpMo(NO)(ƞ⁴-c̲i̲s̲-2,3-dlmethyl-butadiene)t are preparable in moderate yields by the reduction of [CpMo(NO)I₂]₂ with sodium amalgam in THF in the presence of the appropriate diene. The reaction between [CpMo(NO)I₂]₂ and C₄H₆•Mg•2(THF) results in the formation of a green, isolable oligomeric complex CpMo(NO)I(ƞ³-C₃H₄R) (where R = CH₂MgI and the nitrosyl oxygen acts as a Lewis base towards Mg) that can be hydrolyzed to CpMo(NO)I(ƞ³-C₄H₇) or converted to CpMo(NO)(ƞ⁴+-t̲r̲a̲n̲s̲-C₄H₆). These diene complexes have been fully characterized by conventional spectroscopic techniques (extensive ¹H and ¹³C NMR spectra being particularly informative) and by single-crystal X-ray structural determinations of CpMo(NO)(ƞ⁴-t̲r̲a̲n̲s̲-2,5-dimethyl-2,4-hexadiene) and CpMo(N0)(ƞ⁴-c̲i̲s̲-2,3-dimethyl-butadlene). A molecular orbital rationale for the structural and spectrocopic properties and relative stabilities of these c̲i̲s̲- and t̲r̲a̲n̲s̲-diene complexes is then presented. / Science, Faculty of / Chemistry, Department of / Graduate

The oxidative cleaving of a rhenium–rhenium bond by bromine in binuclear Fischer carbene complexes proves to be an effective method to prepare mononuclear bromido-carbene complexes. The reaction of mono- and dilithiated thieno[2,3-b]thiophene ([2,3-b]-TT) and thieno[3,2-b]thiophene ([3,2-b]-TT) with Re2(CO)10 afforded dirhenium nonacarbonyl ethoxycarbene complexes (2.1 and 2.5) and the tetrarhenium bis(ethoxycarbene) complexes (2.2 and 2.6) from the dilithiated thiophene substrates featuring bridging thiophene linkers. Rhenium–rhenium bond cleavage by bromine of the monocarbene complexes yielded the scarce class of mono-rhenium bromido-carbene complexes (2.3 and 2.7), while the corresponding reaction of the biscarbene tetrarhenium carbonyl complex of [2,3-b]-TT afforded the cleaving of both metal–metal bonds to give the novel dirhenium biscarbene dibromido complex with a thienothiophene spacer (2.4). A new indirect aminolysis route is described to prepare the chlorido dimethyl- aminocarbene complex (2.8), with unexpected cleavage of the Re–Re bond. Spectroscopic, structural and electrochemical methods are employed to investigate the structural and electronic effect of the different conjugation pathways in the different thienothiophenyl carbene substituents, and the replacement of the rhenium pentacarbonyl fragment with a bromido ligand. Nucleophilic attack on the central sulphur of dithieno[2,3-b;3ˈ,2ˈ-d ]thiophene ([2,3-b;3ˈ,2ˈ-d]-DTT) by n-BuLi opened the central thiophene ring and afforded, after subsequent reaction with Cr(CO)6 and alkylation with [Et3O][BF4], a series of mono- and biscarbene complexes containing a 3,3ˈ- dithienyl backbone with a SBu substituent (3.1-3.4). Repeating the reaction with diisopropylamine as the nucleophile, led to a dihydrodesulphurization reaction with ring-opening of the central thiophene ring of [2,3-b;3ˈ,2ˈ-d]-DTT and elimination of the sulphur atom. Subsequent reaction with n-BuLi or LDA, Cr(CO)6 and [Et3O][BF4] afforded 3,3ˈ-dithienyl monoand biscarbene complexes (3.8 and 3.9). In both instances the α,αˈ-dithienothiophene biscarbene complex (3.5) was observed spectroscopically but not isolated. By using α,αˈ- dibromodithieno[2,3-b;3ˈ,2ˈ-d]thiophene as substrate, improved yields of the targeted mono- and biscarbene complexes of [2,3-b;3ˈ,2ˈ-d]-DTT (M = Cr, W) could be obtained. The biscarbene complexes were unstable in the reaction mixture but in the case of tungsten could be isolated after in situ aminolysis with dimethylamine. The use of KHMDS as base converted Cr(CO)6 to K[Cr(CO)5(CN)] and after reaction with [2,3-b;3ˈ,2ˈ-d]-DTT and subsequent alkylation with [Et3O][BF4], afforded the chromium tetracarbonyl carbene complex of [2,3-b;3ˈ,2ˈ-d]-DTT (3.7). Two ([3,2-b]-TT) and three annulated thiophenes ([2,3-b;3ˈ,2ˈ-d]-DTT and dithieno[3,2-b;2ˈ,3ˈ- d]thiophene ([3,2-b;2ˈ,3ˈ-d]-DTT)) were employed as building blocks to synthesize chelated mononuclear biscarbene and dinuclear tetracarbene complexes. The electronic properties of the annulated thienylene chelated carbene complexes are investigated by cyclic voltammetry experiments and compared to non-chelated mono-carbene complexes of the Fischer-type. Density functional theory (DFT) calculations are used to assign the redox events and to probe the extent of electron delocalization as well as the possibility of electronic (intramolecular metal-metal) communication as a result of intervalence. The differences of these electronic properties in the conjugated chelated carbene complexes are compared to chelated carbene compounds without a linear conjugated pathway. The transfer of thiophene and [2,3-b]-TT Fischer carbene complexes into the coordination sphere of Pt(II) complexes by transmetallation was applied to prepare new cis-Pt(II) biscarbene complexes of the Fischer-type. Numerous reagents (two Pt(II) precursors and a range of varying monocarbene complexes), solvents and reaction conditions were studied for the transmetallation. Mostly neutral mononuclear Pt(II)-biscarbene complexes were obtained (5.2, 5.7, 5.9a/b and 5.12a/b). In the case of 5.9 and 5.12, two geometric stereoisomers of the cis-Pt-biscarbene complexes are observed, respectively. An insoluble cationic Pt triscarbene complex (5.12d) is indicated for the reaction with dimethylaminecarbene complexes. The stability and reactivity of the novel Pt(II) Fischer multicarbene complexes were investigated. The performance of 5.2 and 5.7 as (pre)catalysts in the model catalytic alkyne hydrosilylation reactions are evaluated as a new application for this class of compounds. / Thesis (PhD (Chemistry)) University of Pretoria 2020. / Chemistry / PhD (Chemistry) / Restricted

There is a high demand for the development of processes for the conversion of ubiquitous molecules into industrially useful commodities. Transition metal catalysts are often utilized for the activation and functionalization of small organic molecules due to their diverse nature and proven utility with a myriad of chemical transformations. The functionalization of methane (CH4) and dinitrogen (N2) to methanol (CH3OH) and ammonia (NH3) respectively is of particular interest; however, both methane and dinitrogen are essentially inert due to the inherit strength of their bonds. In this dissertation a series of computational studies is performed to better understand the fundamental chemistry behind the functionalization of methane and the activation of dinitrogen in a homogeneous environment. A catalytic cycle is proposed for the oxy-functionalization of methane to methanol. The cycle consists of two key steps: (1) C-H activation across a metal-alkoxide bond (M-OR), and (2) regeneration of the M-OR species through an oxy-insertion step utilizing external oxidants. The C-H activation step has been extensively studied; however, the latter step is not as well understood with limited examples. For this work, we focus on the oxy-insertion step starting with a class of compounds known to do C-H activation (i.e., Pt(II) systems). Computational studies have been carried out in an attempt to guide experimental collaborators to promising new systems. Thus, the majority of this dissertation is an attempt to extend transition metal mediated C-O bond forming reactions to complexes known to perform C-H activation chemistry. The last chapter involves a computational study of the homogeneous cleavage of N2 utilizing iron-?-diketiminate fragments. This reaction has been studied experimentally, however, the reactive intermediates were not isolated and the mechanism of this reaction was unknown. Density functional theory (DFT) calculations are carried out to elucidate the mechanism of the reductive cleavage of N2 via the sequential addition of iron- ?-diketiminate fragments to N2 to form a bis-nitride (N3-) intermediate. The role of potassium promoters on the dinitrogen and bis-nitride species is also investigated.

Values of thermodynamic equilibrium constants were obtained by potentiometric measurements with a Beckman Model GS pH meter in aqueous solutions for the following reactions: 1. The step-wise dissociation or protons from CH_3CHNH_3COOH^+ and C_6H_5CH_2CHNH_3COOH^+ at 0, 10, 20, 30, and 40°C. 2. The step-wise formation of bis-alamino copper(II) and bis-phenylalanino copper(II) at o, 10, 20, 30, and 40°C. 3. The step-wise formation of tris-acetylacetonato iron(III) at 30°C. Enthalpy and entropy changes were calculated for the reactions in 1 and 2, above, from the temperature dependence of the equilibrium constants. Measurements were made and data obtained for the reactions in 3 at several different ionic strengths, metal ion concentrations, and pH values. It was found that the addition of a phenyl group to alanine lowers the pK of dissociation of both protons from the acid species of the amino acid. This is attributed to the attraction which the phenyl group has for electrons. The same effect caused the log K of the first step-wise chelate of copper(II) to be lower with phenylalanine than with alanine. The second step-wise chelate of copper(II) with phenylalanine, however, has a higher log K value than the equivalent alanine chelate. This shows that the phenyl group influences the electronegativity of the copper(II) ion in the first chelate. The calculated formation constants of tris-acetylacetonato iron(III) were independent of metal ion concentration and ionic strength but increased as the pH of the measurements decreased. This was attributed to hydrolysis of the iron(III) ion. It was shown that at least qualitative measurements of equilibrium constants maybe made at pH values as low as 1.5 with a Beckman Model GS pH meter. There was no measurable increase in the proton concentration when Fe^+++ was added to solutions containing glycine or alanine. It was concluded from this that chelation does not occur to any great extent between Fe^+++ and these amino acids, although it has recently been reported in the literature that strong chelates are formed between Fe^+++ and simple amino acids. It is possible that complexes, but not chelates, are formed in the reactions of F^+++ with simple amino acids. The reaction of dilute perchloric acid with certain metal ions produces a small amount of Cl^-, indicating that an oxidation-reduction reaction occurs between the perchlorate ion and the metal ion. It was previously thought that dilute perchloric acid is not an oxidizing agent. Most of the calculations necessary in processing the data obtained were programmed for the IBM 650 computer.

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.

No description available.

No description available.