Techn. Hochsch., Diss., 2003--Aachen.

Univ., Diss., 2004--Marburg

Organic light-emitting diode (OLED) technology has found multitudinous applications in the development of solid-state lighting, flat-panel displays and flexible screens. Nowadays, the phosphorescent OLEDs based on metallophosphors can reach sufficiently high efficiencies for practical application. Recently, red, green and blue (RGB) platforms of highly efficient phosphorescent emitters have been achieved and OLEDs TV is now commercialized in the marketplace. However, the design and synthesis of innovative emitter materials play an important role in commercialization of the OLED technology. The basic concept of OLED is herein discussed in chapter 1 putting main focus on phosphorescent iridium(III) complexes. In chapter 2, a series of cyclometalated iridium(III) complexes containing 2-(4-benzylphenyl)pyridine have been synthesized and different electron-donating and electron-withdrawing substituents were attached on the pyridyl ring in the ligand. The device D6 doped with 8 wt% B4 gave the excellent OLED performance with a peak of external quantum efficiency (ext) of 21.4%, power efficiency (P) of 51 lm/W and current efficiencyL) of 76.3 cd/A, which is much higher than that of commercial available fac-Ir(ppy)3 under the same operation condition. These findings draw our attention to the fact that a weak electron-donating benzyl group could alleviate intermolecular aggregation in the solid state, thus improving the device performance. The bulky moiety introduced on 2-phenylpyridine through a CH2 spacer in the ligands could suppress the triplet-triplet annihilation in their metal complexes. Cylcometalating ligands and their respective metal complexes have been fully characterized by 1H and 13C NMR spectroscopy and matrix-assisted laser desorption inoization-time of flight (MALDI-TOF) mass spectrometry. In chapter 3, a series of thiazole-based iridium(III) complexes have been synthesized and characterized. It is considered that the thiazole moiety is infrequently used for organic semiconducting materials. To have a better understanding on this functional unit, different hole-transporting groups (eg, carbazole or fluorene) are attached to the thiazole ring in the cyclometalating ligands in order to tune the HOMO and LUMO levels of the complexes. Device D29 doped with 8 wt% T2 gave the highest L of 35.8 cd/A and ext of 11.1%. This result implied that thiazole moiety is an alternative option to afford a new class of cyclometalating ligands for OLED research. In chapter 4, a series of cationic iridium(III) complexes bearing diimine ligand have been synthesized and characterized. The diimine ligands were decorated with the sterically bulky groups. As self-aggregation could deteriorate the device efficiency, this molecular design strategy can diminish the aggregation-caused quenching problems, which has been supported by the aggregation-induced emission enhancement present in complexes E2 and E3. In Chapter 5, a series of bis-tridentate iridium(III) complexes have been synthesized and characterized. Our challenging is to design two types of tridentate chelates (ie. monoanionic and dianionic ligands) for balancing the charge on the metal center. Besides, these chelates should be a good cyclometallate to coordinate with the iridium metal. Four compounds with different dianionic tridentate chelates were designed to achieve distinct color emission. Compound K4 exhibited extremely high quantum yield of 85.5%. This finding revealed that the metal complex featuring two tridentate chelates is a promising phosphorescent dye in OLED. Lastly, the concluding remarks and the experimental details of all the compounds in the previous chapters were included in Chapters 6 and 7.

A series of mononuclear complexes of general formula [M(η5-C5Me5)Cl3-n(pzH)n](n-1)+ (n = 1,2) has been prepared as a result of an investigation of the reactivity of pyrazole with rhodium and iridium cyclopentadienyl and pentamethyl-cyclopentadienyl precursors. These complexes are discussed in terms of the dynamic processes that are exhibited in the 1H NMR experiment and in terms of their use as precursors to dimeric species. Dinuclear complexes of formula [M(η5-C5R5)Cl(μ-pz)]2 containing pyrazolyl bridges have been prepared from the mononuclear compounds and from the chloro-bridged dimers of formula [M(η5-C5R5)Cl2]2 by treatment with triethylamine, but not from the dipyrazole iridium cation [Ir(η5-C5Me5)Cl(pzH)2]+ 26 which has been found to be unreactive to this type of symmetrical dimer formation: the low reactivity is attributed to a relative non-lability of the pyrazole groups. The dimeric complexes have been shown to undergo a core conformational change upon chemical reduction or halide abstraction. The chair conformation of the pyrazolyl bridged complex [Rh(η5-C5ME5)Cl(μ-pz)]2 38 has been proven crystallographically. Chloride abstraction from 38 yields the binuclear product [(Rh(η5-C5ME5)(μ-pz))2(μ-Cl)]BF4 46 which is bridged by two pyrazolyl and one chloride ligand and has been structurally characterized by X-ray diffraction to contain a boat conformation for the pyrazolyl framework. Reduction of either 38 or the C5H5 analogue 40 results in the metal-metal bonded dinuclear complexes [Rh(η5-C5ME5)(μ-pz)]2 48 and 49. The C5H5 complex 49 has been crystallographically determined to possess the boat conformation. The reactivity of the metal-metal bonded products has been investigated: one and two fragment addition is discussed and a number of oxidative addition products have been structurally characterized. The mononuclear dipyrazole iridium cation 26 which contains non-labile pyrazole groups is utilized to prepare mixed-metal and mixed-oxidation state dimers with the formula [Ir(η5-C5Me5)Cl(μ-pz)MLn]. The synthesis and potential for further investigation of these complexes is discussed. / Graduate

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A variety of mononuclear alkene complexes, [Ir{ArNC(NR2)NAr}(cod)], and dicarbonyl complexes, [Ir{ArNC(NR2)NAr}(CO)2] (where R = Me or Et; Ar = Ph, 4-MeC6H4, 4-MeOC6H4, 2,6-Me2C6H3 or 2,6-iPr2C6H3; and cod = 1,5-cyclooctadiene), were synthesized from the neutral N,N-dialkyl-N',N"-diarylguanidines via deprotonation and transmetalation. These complexes were fully characterized by spectroscopic techniques and single-crystal X-ray diffraction. The single-crystal structure determinations show the guanidinato(1—) ligands coordinate the low valent d8 iridium(I) center in an N,N'-chelating binding mode, and the C—N bond lengths indicate a high degree of π-electron delocalization over the CN3 core. The 13C NMR chemical shifts of the alkene carbon atoms in the IrI(cod) complexes and the average CO stretching frequencies for the IrI(CO)2 complexes suggest that the guanidinato ligands function as stronger donors than related monoanionic, bidentate nitrogen-donor ligands. Intermediates in the reactions of the [Ir{ArNC(NR2)NAr}(cod)] complexes with O2 were identified and characterized as (alkene)peroxoiridium(III) species, [Ir{ArNC(NR2)NAr}(cod)(O2)], using multi-dimensional NMR and IR spectroscopy. The (alkene)persulfidoiridium(III) intermediate [Ir{PhNC(NMe2)NPh}(cod)(S2)] was identified and characterized in the reaction of [Ir{PhNC(NMe2)NPh}(cod)] with S8. It was determined that these intermediates are able to transfer oxygen or sulfur to simple organic molecules such as PPh3. The self-decay of the (alkene)peroxoiridium(III) intermediates leads to C—O bond formation and alkene oxidation, and upon addition of excess cod release of 4-cycloocten-1-one was observed. In addition, a mononuclear alkene complex, [Ir{PhNC(Me)NPh}(cod)], and a dinuclear tetracarbonyl complex, [{Ir(CO)2}2{π-PhNC(Me)NPh-κN:κN'}2], with an amidinato ligand, were synthesized and characterized. In the reaction of the IrI(cod) complex with O2, the corresponding (alkene)peroxoiridium(III) intermediate [Ir{PhNC(Me)NPh}(cod)(O2)] was observed. The reactivity of this intermediate and its decay products is similar to that of [Ir{ArNC(NR2)NAr}(cod)(O2)], with the formation of 4-cycloocten-1-one being observed upon addition of cod. Mononuclear (alkene)rhodium(I) complexes, [Rh{PhNC(NMe2)NPh}(cod)] and [Rh{PhNC(Me)NPh}(cod)], and a dinuclear complex, [{Rh(nbd)}2{π-PhNC(NMe2)NPh-κN:κN'}2], were synthesized and characterized (where nbd = norbornadiene or bicyclo[2.2.1]hepta-2,5-diene). Investigation of the reactivity of these complexes with O2 show they react very slowly or not at all.

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.