Rozprawy doktorskie na temat „Ruthenium Metal Complexes”

In nature, transition metal containing enzymes display many biologically important, attractive and efficient catalytic oxidation reactions. Many transition metal catalysts have been designed to mimic the predominant oxidation catalysts in nature, namely, the cytochrome P450 enzymes. Ruthenium porphyrin complexes have been the center of this research and have successfully been utilized, as catalysts, in major oxidation reactions, such as the hydroxylation of alkanes. The present work focuses on photocatalytic studies of aerobic oxidation reactions with well characterized ruthenium porphyrin complexes. The photocatalytic studies of aerobic oxidation reactions of hydrocarbons The photocatalytic studies of aerobic oxidation reactions of hydrocarbons catalyzed by a bis-porphyrin-ruthenium(IV) μ-oxo dimer using atmospheric oxygen as the oxygen source in the absence of co-reductants were investigated. The ruthenium(IV) μ-oxo bisporphyrin (3a-d) was found to catalyze aerobic oxidation of a variety of organic substrates efficiently. By comparison, 3d was found to be a more efficient photocatalyst than the well-known 3a under identical conditions. A KIE at 298K was found to be larger than those observed in autoxidation processes, suggesting a nonradical mechanism that involved the intermediacy of ruthenium(V)-oxo species as postulated. The reactivity order in the series of ruthenium(IV) μ-oxo bisporphyrin complexes follows TPFPP>4- CF3TPP>TPP, and is consistent with expectations based on the electrophilic nature of the ruthenium(IV) μ-oxo bisporphyrin species. The trans-dioxoruthenium(VI) porphyrins have been among the best characterized metal-oxo intermediates and their involvement as the active oxidant in the hydrocarbon oxidation have been extensively studied. In addition to the well-known chemical methods, we developed a novel approach for generation of trans-dioxoruthenium( VI) porphyrins with visible light by extension of the known photoinduced ligand cleavage reactions. A series of trans-dioxoruthenium(VI) porphyrin complexes (6a-d) were photochemically synthesized and spectroscopically characterized by UV-vis, and 1H-NMR.

Thesis (Ph. D.)--University of Sydney, 2008.
Includes tables. Includes list of publications: leaves i-ii. Title from title screen (viewed October 30, 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Chemistry, Faculty of Science. Includes bibliographical references. Also available in print form.

Etude de la reactivite d'agregats derives de ru::(3)(co)::(12) stabilises par des coordinats polydentes phosphores et/ou azotes, en vue d'application en catalyse homogene. Les coordinats assembleurs sont appm et diphenylpyridylphosphine. On etudie egalement la reactivite des complexes a coordinats acyle ru::(3)(co)::(9)(c(o) (c::(6)h::(5))) (p(c::(6)h::(5)) (c::(5)h::(4)n))

dinucleares de rutenio que contienen ligandospolypyridyl. Estos complejos se han aplicado para las reacciones catalíticas, tales como la reducción de CO2 y la oxidación del agua y sustrato orgánico. En la primera, las actividades catalíticas hacia la reducción de CO2 se han investigado desde el punto de vista de las propiedades electrónicas y estéricas de los catalizadores, así como su nuclearidad. En el segundo, la aplicación de mono-y dinucleares complejos de Ru-aqua que contienen ligando tridentadoaniónico hacia reacción de oxidación se ha estudiado. Además, una reactividad potencial de dianión molibdato, que puede ser considerado como modelo homogéneo de catalizadores de óxido de metal heterogéneos para la transformación de CO2 se ha estudiado.
This thesis has been focused on the synthesis and characterization of a series of new mono- and dinuclear ruthenium complexes containing polypyridyl ligands. These complexes have been applied for the catalytic reactions, such as CO2 reduction and oxidation of water and organic substrate. In the first, the catalytic activities toward CO2 reduction have been investigated from the viewpoint of electronic and steric properties of the catalysts as well as their nuclearity. In the second, the application of mono- and dinuclear Ru-aqua complexes containing anionic tridentate ligand toward oxidation reaction has been studied. Additionally, a potential reactivity of molybdate dianion, which can be considered as homogeneous model of heterogeneous metal oxide catalysts for CO2 transformation has been studied.

Preparation de 2 macrocycles contenant a la fois des sites chelatants diphenyl-2,9 phenanthroline-1,10 et dialkyl-4,4' ou diaryl-4,4' bipyridine-2,2'. Dans le complexe heterodinucleaire il existe une interaction a l'etat excite entre les 2 metaux

The thesis describes developments in the organometallic chemistry of ruthenium porphyrin complexes, particularly their preparation, characterization and reactivity. Treatment of paramagnetic Ru(rV)(porp)Br₂ species, prepared via the interaction of [Ru(porp)]₂ with HBr in CH₂CI₂, with organolithiums or Grignard reagents yields the corresponding diamagnetic Ru(IV) complexes Ru(porp)R₂, where porp = the 2,3,7,8,12,13,17,18-octaethylporphyrinato dianion(OEP): R = Ph, m-MeC₆H₄, p-MeC₆H₄, p-MeOC₆H₄, p-FC₆H₄, Me, Et; and porp = the 5,10,15,20-tetraphenylporphyrinato dianion(TPP): R = Ph. The spectral analyses (¹H NMR, UV/vis, and mass spectroscopies) of these complexes are fully consistent with the assigned structures, which are further verified by the X-ray crystallographical analyses of Ru(TPP)Br₂ and Ru(OEP)Ph₂. The dimethyl complex Ru(OEP)Me₂ is also formed along with Ru(OEP)(P[sup n]Bu₃)₂ by the reaction of Ru(III)(OEP)(P[sup n]Bu₃)Br and methyllithium, the process involving disproportionation of Ru(OEP)Me(P[sup n]Bu₃). The diamagnetic nature of the Ru(porp)R₂ complexes, as evidenced by their sharp and temperature-independent ¹H NMR chemical shifts, requires that the d⁴-electrons of the Ru(IV) are spin-paired in the lowest, doubly degenerate d[sub xz] and d[sub]yz orbitals; the porphyrin ring current results in upfield shifts for the axial ligand protons with respect to their 'normal' positions. An unusual feature in the Ru(OEP)Ph₂ structure is the considerable distortion of the (Ph)C-Ru-C(Ph) fragment from linearity. The Ru(porp)R₂ complexes are stable as solids and in solution under atmospheric conditions, but the metal-carbon bonds are readily cleaved either by reagents such as protonic acids, carbon monoxide and phosphines, or via thermolysis. A CO insertion product Ru(OEP)Ph(COPh) is observed in solution by ¹H NMR spectroscopy upon the reaction of Ru(OEP)Ph₂ with 1 atm CO in deuterated benzene at room temperature. The anaerobic thermolysis of the Ru(porp)R₂ complexes at 80 - 100°C yields the five-coordinate, low-spin, paramagnetic Ru(porp)R derivatives, and organic products that depend on the nature of the aryl or alkyl moiety R and the solvent The remarkable transformations shown below have been demonstrated, and niechanisms are proposed.[See Thesis for Diagram] The Ru(OEP)Ph complex has been characterized crystallographically and, together with Ru(OEP)Ph₂, these represent the first reported structures involving organoruthenium porphyrins. The temperature-dependent *H NMR shifts for the Ru(OEP)R species establish a single spin state (S = 1/2) over the temperature range studied (-60° to 70°C). Under appropriate conditions in benzene or toluene, the rate-(leternnning step for the thermal decomposition of the Ru(OEP)R₂ species (R = aryl) is the homolytic cleavage of the metal-carbon bond, and the temperature variation data for the rate constant of this step allow for an estimation of the Ru-C bond strength in solution. Such bond energies are critical for a better understanding of homogeneously catalyzed hydrocarbon reactions. Substitution effects on the Ru-aryl bond strengths were studied using four para- and meta-substituted phenyl complexes (p-Me, p-MeO, p-F, and m-Me); the bond energies are in the 29 - 33 kcal/mol range, and a Hammett ρ value of +1.7 describes the rate constant trend for the p-MeO, p-Me and unsubstituted phenyl systems. Because of their ccordinatively unsaturated nature, the Ru(porp)R complexes are very reactive toward reagents. The Ru(OEP)Ph species readily binds a second axial ligand L, such as pyridine or tri-n-butylphosphine, to form a six-coordinate derivative, and temperature variation data for the equilibrium constant for pyridine binding give a solution bond energy of 11.2 kcal/mol for the Ru-N(py) bond. The Ru(OEP)Me species on reaction with L (py or P[sup n]Bu₃) undergoes disproportionation to Ru(OEP)Me₂ and Ru(OEP)L₂. The Ru(OEP)Ph species reacts with carbon monoxide to generate Ru(OEP)(CO)[sub n] (n = 1 or 2). Bromination of Ru(OEP)Ph forms a paramagnetic Ru(IV)(OEP)Ph(Br) intermediate, characterized by ¹H NMR, en route to Ru(OEP)Br₂, while treatment of Ru(OEP)Ph with HX (X = Br, CI) yields the Ru(OEP)X₂ species. Reaction of the Ru(OEP)(X-C₆H₄) complexes (X = H, p-MeO) with in situ-generated phenyl radicals is close to diffusion-controlled (k ≈ (1.4 - 2.0) X 10⁹ M⁻¹h⁻¹ at 60° - 100°C), and leads to the formation of the mixed aryl species Ru(OEP)Ph(p-MeOC₆H₄). Of interest, the photosensitized O₂-oxidation of Ru(porp)R species (R = aryl) yields the μ-oxo dinuclear species [Ru(porp)R]₂O, the metal-carbon bond remaining intact, which is unusual for the interaction of organometallic metalloporphyrins with dioxygen under light.
Science, Faculty of
Chemistry, Department of
Graduate

A theoretical investigation into several reactions is reported, centred around the chemistry, formation, and reactivity of ruthenium vinylidene complexes. The first reaction discussed involves the formation of a vinylidene ligand through non-innocent ligand-mediated alkyne-vinylidene tautomerization (via the LAPS mechanism), where the coordinated acetate group acts as a proton shuttle allowing rapid formation of vinylidene under mild conditions. The reaction of hydroxy-vinylidene complexes is also studied, where formation of a carbonyl complex and free ethene was shown to involve nucleophilic attack of the vinylidene Cα by an acetate ligand, which then fragments to form the coordinated carbonyl ligand. Several mechanisms are compared for this reaction, such as transesterification, and through allenylidene and cationic intermediates. The CO-LAPS mechanism is also examined, where differing reactivity is observed with the LAPS mechanism upon coordination of a carbonyl ligand to the metal centre. The system is investigated in terms of not only the differing outcomes to the LAPS-type mechanism, but also with respect to observed experimental Markovnikov and anti-Markovnikov selectivity, showing a good agreement with experiment. Finally pyridine-alkenylation to form 2-styrylpyridine through a half-sandwich ruthenium complex is also investigated. The mechanism for this process is elucidated, along with a description of the formation of the unexpected experimental deactivation product. Additionally the chemistry and bonding of pyridylidene complexes is also studied.

This thesis reports the design, synthesis, optical resolution of polypyridyl metal complexes and their molecular recognition of DNA. These metal complexes have been synthesised to bind DNA intercalation in a sequence selective manner. Modifications have manipulated the intercalative segments to bind to DNA in a rigid fashion by appending chemical groups directly to the aromatic extensions of the fragment. Also the ancillary non-intercalative ligands comprised of either bidentates or tetradentates, have been specifically chosen to deliver appended groups along the DNA sugar phosphate backbone, for hydrogen bonding and van der Waals interactions. Classical and chromatographic separation methods were investigated to separate the optical isomers of these ruthenium (II) complexes. A liquid recycling chromatography system was most successfully employed. Stereoselective synthesis was also investigated. Ultimately, it has been shown that the systematic modification of simple metal complexes is a useful method in determining the interactions of simple metal for nucleic acids.

Polypyridyl transition metal complexes containing ruthenium, rhodium and iridium centers are mainly studied due to their light absorbing and emitting properties. Lanthanide oxides such as europium oxide absorb light as well and exhibit strong luminescence and long lifetimes. The optical properties of these materials were significant especially in solar energy utilization schemes and optical applications. Energy transfer across a surface is important in several applications including phosphors and biomedical applications. Excited states of metal complexes with a carboxylate-containing ligand such as deeb = diethyl-2,2'-bipyridine-4,4'-dicarboxylate were studied on nanoparticle surfaces. In this work, [Rh(deeb)2Cl2](PF6), [Ir(deeb)2Cl2](PF6) and [Ir(deeb)2(dpp)](PF6)3 were synthesized using the building block approach. The metal complexes were characterized using 1H NMR spectroscopy, mass spectrometry, electronic absorption spectroscopy and electrochemistry. The 1H NMR spectra of the complexes were consistent with those of their ruthenium analogs. Mass spectra contain fragmentation patterns of the (M-PF6)+ molecular ion for [Rh(deeb)2Cl2](PF6) and [Ir(deeb)2Cl2](PF6), and (M-3PF6)3+ molecular ions for [Ir(deeb)2(dpp)](PF6)3. The electronic absorption spectrum of [Rh(deeb)2Cl2](PF6) shows a maximum at 328 nm, which is assigned as 1π→π*transition. The electronic absorption spectrum of [Ir(deeb)2Cl2](PF6) shows maxima at 308 nm and 402 nm, which are assigned as 1π→π* and metal-to-ligand charge transfer transitions, respectively. The [Ir(deeb)2(dpp)](PF6)3 complex exhibits peaks due to 1π→π* transitions at 322 nm and 334 nm. [Rh(deeb)2Cl2](PF6) has emission maxima from the 3LF state at 680 nm and 704 nm for the solid and glassy solutions at 77 K, respectively. [Ir(deeb)2Cl2](PF6) has emission maxima from the 3MLCT state at 538 nm in acetonitrile and 567 nm in the solid state at room temperature, with lifetimes of 1.71 μs and 0.35 μs, respectively. [Ir(deeb)2Cl2](PF6) has an unusually higher quantum yield than analogous compounds. [Ir(deeb)2(dpp)](PF6)3 has emission maxima from the 3IL state at 540 nm in acetonitrile and 599 nm in the solid state at room temperature, with lifetimes of 1.23 μs and 0.14 μs, respectively. Cyclic voltammetry of [Ir(deeb)2Cl2](PF6) and [Ir(deeb)2(dpp)](PF6)3 yield reversible and quasi-reversible couples corresponding to deeb ligand and Ir3+/+reductions, respectively. Attachment of the complexes were conducted by equilibration of complex solutions in acetonitrile with europium oxide nanoparticles. Europium oxide nanoparticles, which were synthesized by gas-phase condensation, have 11-nm diameters and exhibit sharp f-based luminescence in the visible and near IR regions. EDX, TEM, IR and reflectance spectroscopy measurements indicate substantial coating through various modes of attachment of the nanoparticle surface by the metal complexes while retaining the excited state properties of the metal complexes. Surface adsorption studies indicate monolayer coverage of the nanoparticle surface by the metal complexes, consistent with limiting surface coverages of previously reported analogous systems. Eu2O3 nanoparticles modified with [Rh(deeb)2Cl2]+ exhibit minimal to no energy transfer from emission spectra, and a reduction in the lifetime at 77K could be due to the rhodium complex preventing the excitation of Eu3+. Upon attachment of the Ir complexes [Ir(deeb)2Cl2]+ and [Ir(deeb)2(dpp)]3+ on as-prepared nanoparticles, Eu3+ luminescence was observed for nanoparticles modified with iridium complexes at room temperature, which could be due to energy transfer among other possibilities. Efficiencies of 68% and 50%, and energy transfer rate constants of 1.1 x 10-5 and 1.0 x 10-5 were calculated from lifetime data for [Ir(deeb)2Cl2]+ and [Ir(deeb)2(dpp)]3+ on Eu2O3 nanoparticles, respectively. Since iridium complexes are used as components of light-emitting diodes, europium oxide nanoparticles modified with iridium complexes have potential in optical applications which make studies of these compounds interesting.
Master of Science

There are various strategies in the treatment of cancer including surgical excision, radiotherapy, chemotherapy and immunotherapy. Chemotherapy offers the distinct advantage of systemic distribution, with the potential to reach primary tumours as well as metastases. A significant drawback of the vast majority of chemotherapeutic agents is their lack of specificity for cancer cells as well as poor tumour penetration, meaning that cells distal to blood vessels receive an inadequate dose and remain viable. There is an imperative need for the development of anti-tumour drugs which exhibit good tumour penetration and distribution with minimal systemic toxicity. Tumour activated prodrugs (TAPs) are one of the main strategies now employed in antitumour drug development, and involve administering an inert, less toxic form of a particular drug which is then selectively transformed into its toxic version by the body in the vicinity of the tumour.1 In this study, TAPs which contain a matrix-metalloproteinase II (MMP-2) specific peptide cleavage sequence were synthesised. There is significant evidence that there is increased expression of MMP-1, -2, -3, -7, -9, -13, -14 in both primary tumours and metastases, and that there is a positive correlation between high levels of MMP expression and poor patient prognosis.2 In this work, recombinant DNA techniques were used to visualise the expression of MMP-2 and MMP-9 in vitro. Plasmid constructs in which MMP-2 and MMP-9 were fused to the AmCyan fluorescent protein gene were generated for insertion into a mammalian transfection vector. Transfection into three cell lines that exhibited different levels of MMP-2 and MMP-9 expression was evaluated by measuring the fluorescence emission in the 480 – 550 nm range. The results demonstrated potential for monitoring MMP expression and secretion in monolayer and 3D cell culture by transfection with MMP-fluorescent protein plasmid vectors. However, employing AmCyan as the fluorescent protein resulted in an unexpected interaction with the riboflavin component of cell culture media whereby fluorescence emission could not be observed in the 500 - 550 nm range as expected. The use of other fluorescent proteins should also be pursued, as well as the use of cell-culture media which is riboflavin-free. In order to evaluate the potential of targeting MMP-2 overexpression in solid tumours for selective activation of a TAP, a series of model fluorophore-peptide substrates were investigated in cell monolayers and 3D multicellular tumour spheroids. The target compound DDDDK(FITC)DIPVSLRSK(RhB) (4.8) contained a tetra-aspartate (DDDD) uptake-blocking group designed to prevent influx of the compound into the cell prior to activation by MMP-2 cleavage. Additionally the fluorescein isothiocyanate and rhodamine B fluorophores we attached to the peptide on opposing sites of the MMP-2 cleavage site, facilitating visualisation of the intact peptide as well as the post-cleavage fragments. LC-MS studies showed that in the absence of the uptake-blocking group K(FITC)DIPVSLRSK(RhB) (4.5) is almost entirely cleaved into its respective fragments K(FITC)DIPVS (4.6) and LRKS(RhB) (4.7) after 24 hours. LC-MS results also showed that the uptake-blocking group slows cleavage of the peptide, a trait which was also observed in fluorescence confocal microscopy. K(FITC)DIPVSLRSK(RhB) (4.5) and DDDDK(FITC)DIPVSLRSK(RhB) (4.8) were tested in DLD-1 cell monolayers in the absence of MMP-2 activity. After 4 hours K(FITC)DIPVSLRSK(RhB) (4.5) was found to have entered the cells intact and undergone a small degree of cleavage, while DDDDK(FITC)DIPVSLRSK(RhB) (4.8) did not enter cells intact, and instead only a very minor amount of intracellular fluorescence in the red channel was visible, indicative of non-specific cleavage. In the presence of MMP-2, less uptake of the intact K(FITC)DIPVSLRSK(RhB) (4.5) peptide was observed and instead discreet localised fluorescence was observed in the red and green channels, suggesting that cleavage was occurring in the extracellular space. This result was also observed, but to a lesser degree, for DDDDK(FITC)DIPVSLRSK(RhB) (4.8). These compounds were then also tested in multicellular tumour spheroid models, where the intact peptide K(FITC)DIPVSLRSK(RhB) (4.5) underwent cleavage in the surrounding media, resulting in sequestration of the LRSK(RhB) (4.7) fragment by the outermost cells, preventing it from penetrating further into the spheroid. Contrastingly, the slower cleavage of DDDDK(FITC)DIPVSLRSK(RhB) (4.8) improved the distribution of fluorescence in the red channel, having allowed the intact peptide to diffuse further into the spheroid before cleavage and cellular uptake of the LRSK(RhB) (4.7) fragment. These results confirmed the importance of the uptake-blocking group for ensuring delivery of the payload to the less accessible regions of solid tumour. Overall, this work demonstrated the potential of using an MMP-2 specific cleavage sequence for the selective delivery of chemotherapeutic agents to solid tumours, and as such a series of cytotoxin-peptide substrates containing the MMP-2 specific cleavage sequence were synthesised. The cytotoxic compounds investigated were the platinum(IV) complex cis, cis, trans-acetato[(1R,2R)-cyclohexane-1,2-diamine-N,N’]succinatooxalatoplatinum(IV) and ruthenium(II) complex [(4-methyl-4'-carboxy-2,2'-bipyridine)bis(4,4'-di-tert-butyl-2,2'-bipyridine)]ruthenium(II) hexafluorophosphate. The cytotoxic properties of library of platinum(IV)-peptide conjugates were tested, with none of the peptide-Pt(IV) conjugates possessing IC50 values similar to the free platinum(II) precursor. The intact DIPVSLRSK(Pt) (5.8) peptide is slightly less toxic than its post-cleavage fragment LRSK(Pt) (5.7) in the absence of MMP-2, but the IC50 of DIPVSLRSK(Pt) (5.8) is almost identical to LRSK(Pt) (5.7) in the presence of MMP-2, suggesting that MMP-2 is contributing to the activation and subsequent cytotoxicity of the compound. In both cell lines, the conjugate which contains the uptake-blocking group DDDDGDIPVSLRSK(Pt) (5.9) is not cytotoxic, proving that incorporation of the tetra-aspartate moiety can modify the activity of these compounds. Platinum accumulation studies in cell monolayers did not show a significant difference between the levels of intracellular platinum following incubation with LRSK(Pt) (5.7), DIPVSLRSK(Pt) (5.8), and DDDDGDIPVSLRSK(Pt) (5.9). However, no platinum was detected in the hypoxic/necrotic regions or periphery of spheroids treated with LRSK(Pt) (5.7) and DDDDGDIPVSLRSK(Pt) (5.9) when analysed by SRIXE mapping. After observing the poor spheroid penetration of the hydrophilic platinum(IV)-peptide compounds, the substitution of the cytotoxic platinum(IV) complex for a ruthenium(II)-bipyridyl complex saw an improvement in spheroid penetration. Peptide conjugation of the ruthenium(II) complex improved the cellular uptake of the ruthenium(II) and fluorescence confocal microscopy of LRSK(Ru) (5.10) showed that the compound was localised in the cytoplasm, while little of the free complex [Ru(tBu2bpy)2(HOOC-4’-CH3bpy)]2PF6 (5.6) was observed inside cells. This increase in uptake is likely to have contributed to the increased cytotoxicity of the compound, reducing the IC50 value by a factor of 2.

This thesis is based on the past three years of research work including synthesis, characterization of three series of iridium(III) complexes and one series of ruthenium(II) complexes, and their comparative bio-applications of DNA-binding, cell morphology, cytotoxicity, mitochondrial membrane potential, cellular uptake and distribution. Chapter 1 introduces the background and recent studies of transition-metal complexes as biosensors and anti-tumor medicines. Their structure related properties of cytotoxicities, cellular uptake and distributions were also discussed. In chapter 2, five iridium(III) complexes Ir4: [Ir(4-mpp)2DPPZ]+, Ir7: [Ir(4-mpp)2BDPPZ]+, Ir8: [Ir(4-mpp)2MDPPZ]+, Ir115: [Ir(pp)2DBDPPZ]+ and Ir139: [Ir(dpapp)2DBDPPZ]+ were synthesized and characterized. The crystals of complex Ir139 were successfully cultured and analyzed by X-ray crystallography. The HOMO and LUMO energy gaps of complexes Ir4, Ir7 and Ir8 were obtained. The smaller the energy gap is the larger the Stokes shift will be. The DNA binding properties of Ir4, Ir7 and Ir8 were studied to acquire their binding constants and quenching constants. All the five complexes were cultured with hepatocellular carcinoma cell (hep-G2) in different concentrations for cell morphologies and MTT assays. The IC50 values were calculated and the structure-activity relationship (SAR) was discussed. Properties of Ir115 and Ir139 for photodynamic therapy under the visible light were studied, and moderate light-enhanced cytotoxicities were discovered. The live and dead cell assay and mitochondrial transmembrane potential (ΔΨM) testing were performed and a similar cytotoxicity order to IC50 values was obtained. Some interesting interactions between complex and calcein or propidium iodide (PI) dye were observed and discussed. Cellular uptake and distribution assay showed that the fluorescence of iridium complex was closely related to its toxicity. The obvious cellular uptake at 4 ℃ indicated that all the complexes could transfer into cell through a passive transport mode of facilitated diffusion without the consumption of ATP. The greatest change in uptake intensity of Ir115 implied that the ATP could assist the transport of Ir115 at 37.5 ℃. The efficiency of uptake and distribution of complexes in paraformaldehyde (PFA) fixed cells was found to be strictly related to their size and the hydrophobicity. The rigidity of dipyrido[3,2-a:2',3'-c]phenazine based bipyridine ligands in this chapter contributed to the main cytotoxcities of those iridium complexes. Most of the iridium complexes in chapter 2 have similar structures to their classic ruthenium analogues while their activities have largely improved due to the higher cellular uptake and more biocompatibility. Chapter 3 presented five iridium complexes with rotatable 1H-imidazo [4,5-f] [1,10] (phenanthroline) based bipyridine ligands, which are Ir79: [Ir(pp)2MTPIP]+, Ir80: [Ir(pp)2EIPP]+, Ir116: [Ir(piq)2APIP]+, Ir119: [Ir(piq)2PPIP]+ and Ir134: [Ir(iqdpba)2PPIP]+. Cell morphology and proliferation assay, MTT assay indicated that most of them were not quite toxic for hep-G2 cell lines except for Ir116 which contained an amino group and was assumed to be very active to the carboxyl group in the protein residues in cells. Under the irradiation of visible light, Ir80 and the Ir119 were found to be quite photo-toxic with the light IC50 value of 8.08 μM and 6.14 μM respectively. They could become the potential candidates for the promising drugs of photo-dynamic therapy. The cytotoxicities of those five complexes were further investigated by the live and dead assay using calcein AM (acetoxymethyl) and propidium iodide (PI) double stain method. JC-1 aggregates observation and analysis in the mitochondrial transmembrane potential (ΔΨM) testing proved the lower cytotoxicities of those five complexes than those in chapter 2. Fluorescence and cytotoxicity relationship (FCR) was also uncovered in chapter 3 in which the stronger macromolecular binding to complex could lead to its higher fluorescence intensity. Without the metabolic activity and the assistance of ATP at low temperature of 4 ℃, little Ir80 and Ir134 were found in cells, and the moderate uptake for Ir79 and higher volume of Ir116 and Ir119 were detected. A novel strategy of cold-shock enhanced cellular uptake pathway was discovered in Ir119 and its cold-shock caused cytotoxicity would be further evaluated. The volumes of uptake for those complexes in paraformaldehyde fixed cells were all very low due to their higher hydrophilicity and lower structural rigidity than those in chapter 2. Chapter 4 reported the investigation of six iridium complexes of Ir105: [Ir(4-mpp)2CDYP]+, Ir107: [Ir(piq)2CDYP]+, Ir108: [Ir(3-mpp)2CDYP]+, Ir123: [Ir(4-mpp)2CDYMB]+, Ir125: [Ir(piq)2CDYMB]+ and Ir133: [Ir(dpapp)2CDYMB]+ with rotatable 5H-cyclopenta[2,1-b:3,4-b']dipyridin Schiff-base ligands. Most of them were rather toxic to hep-G2 cell lines from the MTT assay, cell morphology and proliferation assay due to the Schiff-base N^N ligands. Those rotatable Schiff-base ligands seemed to have more cytotoxicity than the flexible 1H-imidazo[4, 5-f] [1, 10](phenanthroline) ligands in chapter 3. The planar and rigid structure of piq C^N ligands in Ir107 and Ir125 were supposed to contribute to the highest cytotoxicity in chapter 4. The dead (red PI) to live (green calcein) cell area ratios and the ΔΨM assay were in accordance with the cytotoxocity sequence in MTT assay. Most of the complexes in chapter 4 demonstrated characteristics of one kind of programmed cell death (PCD), namely apoptosis and the typical features of another cell death mode of oncosis including cellular dwelling and cytoplasm vacuolation have been discovered from Hep-G2 cell lines in the incubation with Ir107. The JC-1 aggregates have disappeared when the two most toxic complexes Ir107 and Ir125 were cultured with the cells at 5 μmol/L, indicating the ΔΨM lost repidly under the damage of iridium complexes. All the complexes were distributed in the cellular nuclei when the incubation time reached 120 minutes at the concentration of 20 and 40 μmol/L. The positive correlation in the fluorescence and cytotoxicity relationship (FCR) were also discovered in chapter 4. The luminescence intensity sequence of the complexes from the cellular uptake and distribution has almost the same order as the previous toxicity results. The two most toxic complexes of Ir107 and Ir125 were found to have the two highest fluorescent intensities inside cells at 4 ℃. Most complexes in this chapter could easily distribute in the fixed cellular nuclei except for Ir125 and Ir133 owing to their large and hydrophobic structures. Generally, the uptake of complexes in paraformaldehyde fixed cells was higher than the live cells at 4 ℃ according to their passive transport mode. Although the simple Schiff base ligands of CDYP and CDYMB in this chapter were rotatable and flexible similar to the 1H-imidazo[4, 5-f][1, 10](phenanthroline) based bipyridine ligands in chapter 3, the cytotoxicities of complexes were much higher than those in chapter 3. The former chapters implied that effective uptake of complexes in nuclei were the results of the cytotoxicities which damaged the integrity of nuclear envelope and leaked into the nucleoplasm. We assumed that there could be another explanation in chapter 4 that the complexes transferred into the nuclei through the nuclear pore on the nuclear envelope and accumulated in the nucleolus, and therefore, triggered the apoptosis of cells. This kind of evidence was discovered for the two most toxic complexes Ir107 and Ir125 that could enter into cellular nuclei when the cell looked quite healthy. There would be another possiblilty that the Schiff base could interrupt the function of intracellular hydrolase enzymes. Chapter 5 compared the properties of five ruthenium(II) complexes of Ru2: [Ru(bpy)2DBDPPZ]2+, Ru7: [Ru(bpy)2MTPIP]2+, Ru8: [Ru(bpy)2EIPP]2+, Ru15: [Ru(phen)2BPDC]2+ and Ru24: [Ru(phen)2CDYMB]2+ with the ligand DBDPPZ from chapter 2, MTPIP and EIPP from chapter 3, CDYMB from chapter 4 and BPDC with two carboxyl groups. Those two positively charged ruthenium complexes indicated very low cytotoxicities from the cell morphology assay and MTT assay. No typical features of cellular apoptosis such as round and shrank cells were observed. However, the light IC50 value of Ru8 was excitingly obtained to be 2.33 μM upon the irradiation of 465 nm which was found to be one of the most promising drugs for photodynamic therapy (PDT) in his thesis. Charge and property relationship (CPR) was discovered to be the most decisive factor in the cytotoxicities of iridium and ruthenium complexes in this thesis which was also supported by a few of the independent literature papers mentioning high cytotoxicity of one positively charged ruthenium complex or low toxicity of two positively charged iridium complex. The DBDPPZ and CDYMB ligands in the ruthenium complexes Ru2 and Ru24 did not add into their cytotoxicity but those ligands greatly enhanced the toxicities of iridium complexes. The calculation of both area and number ratios of dead to live cells stained by the PI and calcein dyes indicated the lowest dark cytotoxicity among the ruthenium complexes could be Ru8 while the Ru24 and Ru7 were more toxic than others. Active JC-1 aggregates were maintained in the cell mitochondria and did not greatly diminish with the increasing concentration of ruthenium complexes. The two positive charges were found to play the important role in the poor cellular uptake of all the ruthenium complexes and the large size of phen ligand further prevented the uptake of Ru24 and reduced its toxicity. The Ru2, Ru7 and Ru8 were found to distribute in fixed cells with much higher luminescence intensities than their corresponding iridium complexes of Ir115, Ir79 and Ir80 with the same N^N ligand respectively which were assigned to be the two positive charges in those ruthenium complexes. The facilitated diffusion was found to be the main passive transport for the five ruthenium complexes in HepG2 cells at 4 ℃ when the ATP functions were considered to be largely inhibited. The low temperature cellular uptake has the similar trend of the cytotoxicities of the five complexes, indicating the structures of complexes were decisive in the process of facilitated diffusion. The enormous difference of cellular uptake and distribution in the fixes cells remind us the normal protocol before the cell-image pictures of fluorescence inverse microscopes (FIM) or confocal laser scanning microscope (CLSM) should be cancelled or very cautiously handled when the luminescent metal complexes were applied. In chapter 6, the further structure-activity relationship (SAR) was discussed based on the different C^N, N^N ligands and metal cores from the previous chapters. The overall research scheme, results and significance were summarized. Highlights were listed and future research plan was also proposed. At last, Chapter 7 described briefly the experiment protocols and supplementary information for the former chapters.

This thesis reports on the synthesis, characterisation, enantiomeric resolution, 1H NMR structural study and physical evaluation of a series of certain bidentate ligand metal complexes, where ‘L-L’ denotes the ancillary bidentate ligand and ‘intercalator’ indicates the intercalating bidentate ligand. The L-L series varies in size and shape. Results of many tests and projects conducted are explained in detail.
Master of Science (Hons)

This thesis is based on the past three years of research work including synthesis, characterization of three series of iridium(III) complexes and one series of ruthenium(II) complexes, and their comparative bio-applications of DNA-binding, cell morphology, cytotoxicity, mitochondrial membrane potential, cellular uptake and distribution. Chapter 1 introduces the background and recent studies of transition-metal complexes as biosensors and anti-tumor medicines. Their structure related properties of cytotoxicities, cellular uptake and distributions were also discussed. In chapter 2, five iridium(III) complexes Ir4: [Ir(4-mpp)2DPPZ]+, Ir7: [Ir(4-mpp)2BDPPZ]+, Ir8: [Ir(4-mpp)2MDPPZ]+, Ir115: [Ir(pp)2DBDPPZ]+ and Ir139: [Ir(dpapp)2DBDPPZ]+ were synthesized and characterized. The crystals of complex Ir139 were successfully cultured and analyzed by X-ray crystallography. The HOMO and LUMO energy gaps of complexes Ir4, Ir7 and Ir8 were obtained. The smaller the energy gap is the larger the Stokes shift will be. The DNA binding properties of Ir4, Ir7 and Ir8 were studied to acquire their binding constants and quenching constants. All the five complexes were cultured with hepatocellular carcinoma cell (hep-G2) in different concentrations for cell morphologies and MTT assays. The IC50 values were calculated and the structure-activity relationship (SAR) was discussed. Properties of Ir115 and Ir139 for photodynamic therapy under the visible light were studied, and moderate light-enhanced cytotoxicities were discovered. The live and dead cell assay and mitochondrial transmembrane potential (ΔΨM) testing were performed and a similar cytotoxicity order to IC50 values was obtained. Some interesting interactions between complex and calcein or propidium iodide (PI) dye were observed and discussed. Cellular uptake and distribution assay showed that the fluorescence of iridium complex was closely related to its toxicity. The obvious cellular uptake at 4 ℃ indicated that all the complexes could transfer into cell through a passive transport mode of facilitated diffusion without the consumption of ATP. The greatest change in uptake intensity of Ir115 implied that the ATP could assist the transport of Ir115 at 37.5 ℃. The efficiency of uptake and distribution of complexes in paraformaldehyde (PFA) fixed cells was found to be strictly related to their size and the hydrophobicity. The rigidity of dipyrido[3,​2-​a:2',​3'-​c]phenazine based bipyridine ligands in this chapter contributed to the main cytotoxcities of those iridium complexes. Most of the iridium complexes in chapter 2 have similar structures to their classic ruthenium analogues while their activities have largely improved due to the higher cellular uptake and more biocompatibility. Chapter 3 presented five iridium complexes with rotatable 1H-imidazo [4,5-f] [1,10] (phenanthroline) based bipyridine ligands, which are Ir79: [Ir(pp)2MTPIP]+, Ir80: [Ir(pp)2EIPP]+, Ir116: [Ir(piq)2APIP]+, Ir119: [Ir(piq)2PPIP]+ and Ir134: [Ir(iqdpba)2PPIP]+. Cell morphology and proliferation assay, MTT assay indicated that most of them were not quite toxic for hep-G2 cell lines except for Ir116 which contained an amino group and was assumed to be very active to the carboxyl group in the protein residues in cells. Under the irradiation of visible light, Ir80 and the Ir119 were found to be quite photo-toxic with the light IC50 value of 8.08 μM and 6.14 μM respectively. They could become the potential candidates for the promising drugs of photo-dynamic therapy. The cytotoxicities of those five complexes were further investigated by the live and dead assay using calcein AM (acetoxymethyl) and propidium iodide (PI) double stain method. JC-1 aggregates observation and analysis in the mitochondrial transmembrane potential (ΔΨM) testing proved the lower cytotoxicities of those five complexes than those in chapter 2. Fluorescence and cytotoxicity relationship (FCR) was also uncovered in chapter 3 in which the stronger macromolecular binding to complex could lead to its higher fluorescence intensity. Without the metabolic activity and the assistance of ATP at low temperature of 4 ℃, little Ir80 and Ir134 were found in cells, and the moderate uptake for Ir79 and higher volume of Ir116 and Ir119 were detected. A novel strategy of cold-shock enhanced cellular uptake pathway was discovered in Ir119 and its cold-shock caused cytotoxicity would be further evaluated. The volumes of uptake for those complexes in paraformaldehyde fixed cells were all very low due to their higher hydrophilicity and lower structural rigidity than those in chapter 2. Chapter 4 reported the investigation of six iridium complexes of Ir105: [Ir(4-mpp)2CDYP]+, Ir107: [Ir(piq)2CDYP]+, Ir108: [Ir(3-mpp)2CDYP]+, Ir123: [Ir(4-mpp)2CDYMB]+, Ir125: [Ir(piq)2CDYMB]+ and Ir133: [Ir(dpapp)2CDYMB]+ with rotatable 5H-cyclopenta[2,1-b:3,4-b']dipyridin Schiff-base ligands. Most of them were rather toxic to hep-G2 cell lines from the MTT assay, cell morphology and proliferation assay due to the Schiff-base N^N ligands. Those rotatable Schiff-base ligands seemed to have more cytotoxicity than the flexible 1H-imidazo[4, 5-f] [1, 10](phenanthroline) ligands in chapter 3. The planar and rigid structure of piq C^N ligands in Ir107 and Ir125 were supposed to contribute to the highest cytotoxicity in chapter 4. The dead (red PI) to live (green calcein) cell area ratios and the ΔΨM assay were in accordance with the cytotoxocity sequence in MTT assay. Most of the complexes in chapter 4 demonstrated characteristics of one kind of programmed cell death (PCD), namely apoptosis and the typical features of another cell death mode of oncosis including cellular dwelling and cytoplasm vacuolation have been discovered from Hep-G2 cell lines in the incubation with Ir107. The JC-1 aggregates have disappeared when the two most toxic complexes Ir107 and Ir125 were cultured with the cells at 5 μmol/L, indicating the ΔΨM lost repidly under the damage of iridium complexes. All the complexes were distributed in the cellular nuclei when the incubation time reached 120 minutes at the concentration of 20 and 40 μmol/L. The positive correlation in the fluorescence and cytotoxicity relationship (FCR) were also discovered in chapter 4. The luminescence intensity sequence of the complexes from the cellular uptake and distribution has almost the same order as the previous toxicity results. The two most toxic complexes of Ir107 and Ir125 were found to have the two highest fluorescent intensities inside cells at 4 ℃. Most complexes in this chapter could easily distribute in the fixed cellular nuclei except for Ir125 and Ir133 owing to their large and hydrophobic structures. Generally, the uptake of complexes in paraformaldehyde fixed cells was higher than the live cells at 4 ℃ according to their passive transport mode. Although the simple Schiff base ligands of CDYP and CDYMB in this chapter were rotatable and flexible similar to the 1H-imidazo[4, 5-f][1, 10](phenanthroline) based bipyridine ligands in chapter 3, the cytotoxicities of complexes were much higher than those in chapter 3. The former chapters implied that effective uptake of complexes in nuclei were the results of the cytotoxicities which damaged the integrity of nuclear envelope and leaked into the nucleoplasm. We assumed that there could be another explanation in chapter 4 that the complexes transferred into the nuclei through the nuclear pore on the nuclear envelope and accumulated in the nucleolus, and therefore, triggered the apoptosis of cells. This kind of evidence was discovered for the two most toxic complexes Ir107 and Ir125 that could enter into cellular nuclei when the cell looked quite healthy. There would be another possiblilty that the Schiff base could interrupt the function of intracellular hydrolase enzymes. Chapter 5 compared the properties of five ruthenium(II) complexes of Ru2: [Ru(bpy)2DBDPPZ]2+, Ru7: [Ru(bpy)2MTPIP]2+, Ru8: [Ru(bpy)2EIPP]2+, Ru15: [Ru(phen)2BPDC]2+ and Ru24: [Ru(phen)2CDYMB]2+ with the ligand DBDPPZ from chapter 2, MTPIP and EIPP from chapter 3, CDYMB from chapter 4 and BPDC with two carboxyl groups. Those two positively charged ruthenium complexes indicated very low cytotoxicities from the cell morphology assay and MTT assay. No typical features of cellular apoptosis such as round and shrank cells were observed. However, the light IC50 value of Ru8 was excitingly obtained to be 2.33 μM upon the irradiation of 465 nm which was found to be one of the most promising drugs for photodynamic therapy (PDT) in his thesis. Charge and property relationship (CPR) was discovered to be the most decisive factor in the cytotoxicities of iridium and ruthenium complexes in this thesis which was also supported by a few of the independent literature papers mentioning high cytotoxicity of one positively charged ruthenium complex or low toxicity of two positively charged iridium complex. The DBDPPZ and CDYMB ligands in the ruthenium complexes Ru2 and Ru24 did not add into their cytotoxicity but those ligands greatly enhanced the toxicities of iridium complexes. The calculation of both area and number ratios of dead to live cells stained by the PI and calcein dyes indicated the lowest dark cytotoxicity among the ruthenium complexes could be Ru8 while the Ru24 and Ru7 were more toxic than others. Active JC-1 aggregates were maintained in the cell mitochondria and did not greatly diminish with the increasing concentration of ruthenium complexes. The two positive charges were found to play the important role in the poor cellular uptake of all the ruthenium complexes and the large size of phen ligand further prevented the uptake of Ru24 and reduced its toxicity. The Ru2, Ru7 and Ru8 were found to distribute in fixed cells with much higher luminescence intensities than their corresponding iridium complexes of Ir115, Ir79 and Ir80 with the same N^N ligand respectively which were assigned to be the two positive charges in those ruthenium complexes. The facilitated diffusion was found to be the main passive transport for the five ruthenium complexes in HepG2 cells at 4 ℃ when the ATP functions were considered to be largely inhibited. The low temperature cellular uptake has the similar trend of the cytotoxicities of the five complexes, indicating the structures of complexes were decisive in the process of facilitated diffusion. The enormous difference of cellular uptake and distribution in the fixes cells remind us the normal protocol before the cell-image pictures of fluorescence inverse microscopes (FIM) or confocal laser scanning microscope (CLSM) should be cancelled or very cautiously handled when the luminescent metal complexes were applied. In chapter 6, the further structure-activity relationship (SAR) was discussed based on the different C^N, N^N ligands and metal cores from the previous chapters. The overall research scheme, results and significance were summarized. Highlights were listed and future research plan was also proposed. At last, Chapter 7 described briefly the experiment protocols and supplementary information for the former chapters.

Macrocyclic ligand-complexed transition metal-oxo intermediates are the active oxidizing species in a variety of important biological and catalytic oxidation reactions. Many transition metal catalysts have been designed to mimic the predominant oxidation catalysts in Nature, namely the cytochrome P450 enzymes. Ruthenium porphyrin complexes have been the center of the research and have successfully been utilized, as catalysts, in major oxidation reactions such as the hydroxylation of alkanes. This study focuses on kinetic and photocatalytic studies of oxidation reactions with wellcharacterized high-valent ruthenium-oxo porphyrin complexes. The trans-dioxoruthenium(VI) porphyrins have been among the best characterized metal-oxo intermediates and their involvement as the active oxidant in the hydrocarbon oxidation have been extensively studied. Following the literature known methods, a series of trans-dioxoruthenium(VI) porphyrin complexes (3a-b) were synthesized and spectroscopically characterized by UV-vis, IR and lH-NMR. In addition to the well-known chemical methods, we developed a novel photochemical approach for generation of trans-dioxoruthenium(VI) porphyrins with visible light. The fast kinetic study of two-electron oxidations of para-substituted phenyl methyl sulfides by these dioxoruthenium(VI) species was conducted by using stopped-flow spectroscopy. Results showed that the decay of trans--dioxoruthenium(VI) porphyrins in the presence of reactive sulfides follows a biexponential process. The reactivity order in the series of dioxoruthenium complexes follows TPFPP> TPP> TMP, consistent with expectations based on the electrophilic nature of high-valent metal-oxo species. Moreover, the sulfoxidation reactions are 3 to 4 orders of magnitude faster than the well-known epoxidation reactions. In addition, several ruthenium porphyrins were used as the catalysts in the competitive oxidation reactions to identify the kinetically competent oxidants during catalytic turnover conditions. The photocatalytic studies of aerobic oxidation reactions of hydrocarbons catalyzed by a bis-porphyrin-ruthenium(lV) fl-OXO dimer using atmospheric oxygen as oxygen source in the absence of co-reductants were investigated as well. The ruthenium(lV) fl-OXO bisporphyrin (6a) was found to catalyze aerobic oxidation of a variety of organic substrates efficiently. By comparison, 6a was found to be more efficient photocatalyst than the well-known 3a under identical conditions. A KIE at 298K was found to be larger than those observed in autoxidation processes, suggesting a nonradical mechanism that involved the intermediacy of ruthenium(V)-oxo species as postulated.

Metal-organic frameworks (MOFs) have been extensively studied because of their amazing applications in gas storage, purification, photocatalysis, chemical sensing, and imaging techniques. Ruthenium polypyridyl complexes have been broadly considered as photosensitizers for the conversion of solar energy and photoelectronic materials. With this aspect, we have synthesized three new ruthenium polypyridyl based MOFs ([Ru(H2bpc)Cu(bpc)(Hbpc)2(H2O)]·5H2O (1), [Ru(H2bpc)(Fe(bpc)(Hbpc)2(H2O)2]·6H2O (2) and [Ru(H2bpc)Ni(bpc)(Hbpc)2(H2O)2]·6H2O (3)) from ruthenium(III) chloride, bpc (2,2’- bipyridine-4,4’-dicarboxylic acid) ligand, and 3d M(II) metal ions (M(II)= Cu(II), Fe(II), Ni(II)). These MOFs were synthesized under hydro or solvothermal conditions by using water, ethanol or methanol as solvents. The crystal structures of the new compounds contains zigzag chains of [Ru(bpc)3]n- complex ions linked by Cu, Fe or Ni complex ions individually. Above synthesized crystal structures were characterizing by single-crystal Xray and powder X-ray diffraction strategies, UV-vis and IR spectroscopy. Thermal properties were determining by thermogravimetric analysis. Magnetic properties were also studied.

This thesis reports the design, synthesis, optical resolution of polypyridyl metal complexes and their molecular recognition of DNA. These metal complexes have been synthesised to bind DNA intercalation in a sequence selective manner. Modifications have manipulated the intercalative segments to bind to DNA in a rigid fashion by appending chemical groups directly to the aromatic extensions of the fragment. Also the ancillary non-intercalative ligands comprised of either bidentates or tetradentates, have been specifically chosen to deliver appended groups along the DNA sugar phosphate backbone, for hydrogen bonding and van der Waals interactions. Classical and chromatographic separation methods were investigated to separate the optical isomers of these ruthenium (II) complexes. A liquid recycling chromatography system was most successfully employed. Stereoselective synthesis was also investigated. Ultimately, it has been shown that the systematic modification of simple metal complexes is a useful method in determining the interactions of simple metal for nucleic acids.
Doctor of Philosophy (PhD)

This thesis reports on the synthesis, characterisation, enantiomeric resolution, 1H NMR structural study and physical evaluation of a series of certain bidentate ligand metal complexes, where ‘L-L’ denotes the ancillary bidentate ligand and ‘intercalator’ indicates the intercalating bidentate ligand. The L-L series varies in size and shape. Results of many tests and projects conducted are explained in detail.

The study of normal N-heterocyclic carbenes (NHCs), which probably represent one of the most important families of ligands in organometallic chemistry and homogeneous catalysis, has indubitably led to the usage of other related ligands beyond di-amino carbenes. So far, such species are only marginally used as ligands due to their relative novelty and stability. The following chapters describe the exciting journey into the development of new synthetic accesses of various abnormal, remote N-heterocyclic, mesoionic and carbocyclic carbene transition metal complexes. The uses of a number of these ruthenium- and copper-based complexes as catalysts in several applications are also disclosed. Halfway between the study of the electronic effect of mixed NHC/phosphite ruthenium in olefin metathesis reactions (Chapter 1) and NHC copper-catalysed transformations (Chapters 5 and 6), resides the core of this dissertation that links the book end chapters. Indeed, the NHC-Cuᴵ transfer or “transmetalation” reaction is disclosed as a powerful and reliable tool to access new transition metal catalysts in a relatively general manner. The syntheses of a series of various non-conventional NHC-Cu complexes as precursors for the transmetalation reaction are also described in Chapter 2. The dissertation finally closes with some preliminary results on what represents the first experimental and theoretical evidence for the mechanism of the NHC transfer by transmetalation. The exploration of the reaction by exchange from copper to platinum has begun to reveal what was so far unknown through the isolation of reactive intermediate species formed during the process.

On etudie la reactivite chimique de complexes polyhudrures de ruthenium apres activation thermique ou photochimique. Certains complexes pentamethylcyclopentadienyl sont egalement prepares et etudies en spectroscopie rmn du proton

Synthese de complexes hydruro a coordinat dppm : ph::(2) pch::(2) pph::(2). L'etude de la reactivite de certains complexes comme rurhh::(2)cl(cod) (dppm)::(2), conduit a la preparation de nouveaux hydrures dont on etudie les structures