Transition metal complexes offer potential alternatives to fluorescent organic compounds in various sensing applications. They show several characteristic properties over organic dyes, such as strong luminescence emission, long emission lifetime and large Stoke shift. Among transition metal complexes, cyclometalated iridium(III) (Ir) complexes are most widely explored for sensing applications, due to their bright and tuneable phosphorescence emission. Up to now, Ir(III) complexes have been successfully applied to detect a range of analytes in environmental and biological systems, such as cations, anion, small molecules and proteins. In this thesis, we deeply explored the capability of Ir(III) complexes to the detection of a range of targets including metal ions, small molecules and biomarkers. Several strategies are used to improve the biocompatibility of Ir(III)-based probes while retaining their desirable characteristics. In chapter 2, we developed a novel Ir(III) complex for the detection of Al3+ with a detection limit of 1 μM. The long lifetime of the complex was harnessed to distinguish luminescence response to Al3+ from autofluorescence in biological samples by TRES experiment, while the probe was also successfully applied for imaging Al3+ in living cells. The results have been published as Chem. Commun., 2016, 52, 3611. In chapter 3, we reported a new reaction-based luminogenic probe for imaging both H2S and hypoxia in living zebrafish. This probe demonstrated their utility for the detection of H2S in solution, living cells and zebrafish model, while it was also capable of discriminating hypoxic from normoxic cells and zebrafish model. The results have been published as Sens. Actuator B-Chem., 2018, 255, 1953. In chapter 4, we conjugated a natural product oridonin to an Ir(III) scaffold for tracking intracellular NF-κB. This complex was successfully applied to track NF-κB translocation induced by TNF-α, without affecting the translocation process. The results have been published as Chem. Eur. J., 2017, 23, 4929. In chapter 5, an Ir(III) scaffold with galactose moiety was designed and synthesized for discriminating ovarian carcinoma cell lines from normal cell lines. This probe can selectively "light up" ovarian carcinoma cells with negligible luminescence in normal cells. The results have been published as Anal. Chem., 2017, 89, 11679. These works have further demonstrated the utility of Ir(III) complex in the monitoring environment and studying biomolecules in living systems. In particular, the conjugation of endogenous molecule galactose or a natural compound oridonin to Ir(III) scaffolds highlights an effective solution to develop biocompatible probes. However, it should be pointed out that there is a need for developing a general strategy to improve the biocompatibility of luminescent Ir(III) complex-based probes, while there is huge potential for incorporating luminescent Ir(III) complexes-based sensing platforms into portable devices, and exploring theranostic probes.

For a long time the forest industry in Sweden has been waiting for nation-wide coverage by the GSM network. However, this has not been realized and therefore this thesis project was initiated, by Holmen Skog, to enable the needed information exchange. This thesis focuses on how to establish a communication system to transfers information to and from the forestry machines, where GSM coverage is not available. This thesis studies several different telecommunication solutions and evaluate an existing communication system called Mobeel. / Under en lång tid har skogsindustrin i Sverige väntat på utbyggnaden av ett rikstäckande GSM-nät. Detta har dock inte ännu realiserats och därför initierades detta examensarbete, av Holmen Skog, där målet är att få till stånd ett tillfredsställande informationsflöde. Denna uppsats fokuserar på hur ett kommunikationssystem ska implementeras för att kunna skicka information till och från skogsmaskinerna där GSM täckningen inte är tillfredsställande. Examensarbetet involverar en studie av olika telekommunikationssystem och en utvärdering av det befintliga systemet Mobeel.

Transition metal complex, especially iridium(III) complex, possesses substantial advantages in sensing applications. To date, a series of iridium(III) complex-based chemosensors and biosensors have been constructed for the detection of a wide range of biologically important analytes, including ions, small molecules, amino acids, peptides and proteins. Chapter 1 provides an overview of the general synthetic routes and properties of iridium(III) complexes. General strategies for the development of iridium(III) complex-based chemosensors and the utilization of iridium(III) complex as a DNA probe in biosensors are also reviewed. Chapter 2 describes the application of an iridium(III) complex as a switch "on-off-on" chemosensor for the detection of both exogenously supplied and endogenously generated sulfide ion in vitro, in cellulo and in vivo. The optimized probe (1-Fe 3+), which coordinates Fe 3+ ion to an iridium(III) complex, could achieve a limit of detection (LOD) of sulfide ion down to 2.9 µM and establish a linear detection range from 10 to 1500 µM. While 1-Fe 3+ did not show any luminescence response in vitro under a high concentration of thiols, it exhibited a significant luminescence enhancement when the concentration of thiols was perturbed in cellulo and in vivo. This phenomenon can be explained by the presence of cystathionine gamma-lyase (CGL) and cystathionine beta synthase (CBS) in cellulo that could catalyze the conversion of the hydrogen sulfide (H 2 S) precursors, including cysteine and glutathione (GSH), into H 2 S. The results of this work have been published in a peer-reviewed scientific journal (Biosens. Bioelectron, 2017, 94, 575). Chapter 3 discusses the adaptation of an oligonucleotide-based Vascular endothelial growth factor 165 (VEGF 165) biosensor on a portable microfluidic device. An iridium(III) complex with an extensive conjugation system was used as a long- lived and red-emitting G-quadruplex probe. The polypropylene (PP)-based suspended-droplet microfluidic chip allows easy sample introduction, flexible sample volume range and valve-free manipulation of a stepwise reaction. We successfully assembled all the required components, including a ultraviolet (UV) lamp, a filter, a rotatable sample holder and a detector, into a portable box. The device could achieve a LOD of VEGF 165 down to the picomolar level, which is comparable to the results of a conventional fluorometer. The results of this work have been published in a peer-reviewed scientific journal (Dalton Trans., 2019, 48, 9824) The integration of graphene oxide nanomaterial to an oligonucleotide- based isothermal signal amplification system is presented in Chapter 4. Strand displacement amplification (SDA) could substantially amplify the signal from the target Hepatitis B virus (HBV) gene, while the electron accepting graphene oxide could effectively quench the emission of iridium(III) complex and enlarged the luminescence fold-enhancement of the system. The system could achieve a LOD for the HBV gene down to the picomolar level and was selective for the wild-type HBV gene over the single-base mutated HBV gene. The operation mechanism and the important rules for the formation of a stable split G-quadruple are detailed in this chapter. The results of this work have been submitted to a peer-reviewed scientific journal. In Chapter 5, the adaptation of SDA on an exonuclease III-assisted amplification (EXO) as a quadruple-cycle phosphorescence amplification system is reported. A systematic three-round structural optimization campaign was performed for the first time to iteratively improve the G-quadruplex selectivity of a large pool of iridium(III) complex. The proof-of-principle application of a self-assembly tetrahedron nanostructure (TNS)-based aptasensor was demonstrated using a cancer biomarker mucin 1 as the target analyte. This TNS-based aptasensor revealed a 57% higher luminescence enhancement compared to the conventional dsDNA aptasensing approach. The results of this work will be submitted to a peer-reviewed scientific journal upon completion of mechanism studies. Chapter 6 summarizes the properties, advantages, improvements and potentials for the developed iridium(III) complex-based sensors

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.

The development of transition metal complex-based luminescent probes and theranostic have recently aroused tremendous interest for labelling and detecting environmental contaminants and cellular biomarkers, particularly in the use of real- time diagnosis and treatment of disease. Reasons behind include the unique photophysical properties of transition metal complexes, particularly in the properties of their long-lived and environmentally sensitive emission, which can be easily fine-tuned via the modification of the metal center and auxiliary ligand of the metal complex to achieve the desired emissive characteristics. In Chapter 2, a series of luminescent iridium(III) complexes were introduced and their synthesis and evaluation on their ability to interact with hydroxide (OH- ) ion in semi-aqueous media at ambient temperature were discussed. Upon addition of OH- ion, a nucleophilic aromatic substitution reaction takes place at the bromine groups of the N^N ligand of iridium(III) complex 2.1, resulting in the generation of product with a yellow-green luminescence. Complex 2.1 showed a 35-fold enhancement in emission signal at pH 14 when compared to neutral pH, and the detection limit for OH- ions was found to be 4.96 μM. Complex 2.1 exhibited high sensitivity and selectivity, long-lived luminescence and impressive stability. Additionally, practical application of complex 2.1 was demonstrated to be able to detect OH- ions in simulated wastewater. In Chapter 3, a series of luminescent iridium(III) complexes were introduced and their design and evaluation on their affinity to detect oxalyl chloride ((COCl)2) at ambient temperature were discussed. In the presence of (COCl)2, a double amidation reaction takes place at the diamino functionality of complex 3.1, leading to the switching-on of a long-lived red luminescence with 9-fold enhancement in emission signal. Complex 3.1 exhibited high sensitivity and selectivity and the detection limit for (COCl)2 was found to be 32 nM. Additionally, complex 3.1 can be used to detect (COCl)2 using a simple smartphone, which allows the detection to be a real-time one. iii In Chapter 4, a dual-functional luminescent probe and inhibitor was designed for the in-situ monitoring of neuraminidase (NA) using a structure-based molecular design strategy. The candidate iridium(III) complexes 4.1a-4.1d were synthesized by grafting an oseltamivir moiety as a binding unit onto signaling iridium(III) precursors, generating probes that allowed for the simultaneous inhibition and sensing of NA. Complexes 4.1a-4.1d showed strong yellow or red luminescence in aqueous buffer containing 0.5% acetonitrile in response to NA. In particular, complex 4.1d exhibited enhanced inhibition against NA compared to the FDA-approved antiviral drug, oseltamivir. Moreover, complex 4.1d also displayed a long-lived lifetime, large Stokes shift, and high quantum yield, allowing its luminescence output to be distinguished in the presence of an interfering auto- fluorescent background. We have successfully developed the first dual-functional molecule 4.1d for the in-situ inhibition and detection of NA, which provides the possibility for the in-field simultaneous therapy and monitoring of influenza infection. In Chapter 5, a general strategy was introduced for the development of a long- lifetime iridium(III) theranostic by grafting a well-known inhibitor as a "binding unit" onto an iridium(III) complex precursor as a "signaling unit". To further optimize their emissive properties, the effect of imaging behavior was explored by incorporating different substituents onto the parental "signaling unit". This design concept was validated by a series of tailored iridium(III) theranostic 5.2a-5.2h for the visualization and inhibition of EGFR in living cancer cells. By comprehensively assessing the theranostic potency of 5.2a-5.2h in both in vitro and in cellulo contexts, probe 5.2f containing electron-donating methoxy groups on the "signaling unit" was discovered to be the most promising candidate theranostic with desirable photophysical/chemical properties. Probe 5.2f selectively bound to EGFR in vitro and in cellulo, enabling it to selectively discriminate living EGFR- overexpressing cancer cells from normal cells that express low levels of EGFR with an "always-on" luminescence signal output. In particular, its long-lived lifetime enabled its luminescence signal to be readily distinguished from the interfering iv fluorescence of organic dyes by using time-resolved technique. Complex 5.2f simultaneously visualized and inhibited EGFR in a dose-dependent manner, leading to a reduction in the phosphorylation of downstream proteins ERK and MEK, and inhibition of the activity of downstream transcription factor AP1. Notably, complex 5.2f is comparable to the parental EGFR inhibitor 5.1b, in terms of both inhibitory activity against EGFR and cytotoxicity against EGFR- overexpressing cancer cells. This tailored dual-functional iridium(III) theranostic toolkit provides an alternative strategy for the real-time and personalized diagnosis and treatment of cancers. Chapter 6 discusses the challenges and future inspirations for the development of iridium(III) complex-based luminescent probes and theranostic

The development of transition metal complex-based luminescent probes and theranostic have recently aroused tremendous interest for labelling and detecting environmental contaminants and cellular biomarkers, particularly in the use of real- time diagnosis and treatment of disease. Reasons behind include the unique photophysical properties of transition metal complexes, particularly in the properties of their long-lived and environmentally sensitive emission, which can be easily fine-tuned via the modification of the metal center and auxiliary ligand of the metal complex to achieve the desired emissive characteristics. In Chapter 2, a series of luminescent iridium(III) complexes were introduced and their synthesis and evaluation on their ability to interact with hydroxide (OH- ) ion in semi-aqueous media at ambient temperature were discussed. Upon addition of OH- ion, a nucleophilic aromatic substitution reaction takes place at the bromine groups of the N^N ligand of iridium(III) complex 2.1, resulting in the generation of product with a yellow-green luminescence. Complex 2.1 showed a 35-fold enhancement in emission signal at pH 14 when compared to neutral pH, and the detection limit for OH- ions was found to be 4.96 μM. Complex 2.1 exhibited high sensitivity and selectivity, long-lived luminescence and impressive stability. Additionally, practical application of complex 2.1 was demonstrated to be able to detect OH- ions in simulated wastewater. In Chapter 3, a series of luminescent iridium(III) complexes were introduced and their design and evaluation on their affinity to detect oxalyl chloride ((COCl)2) at ambient temperature were discussed. In the presence of (COCl)2, a double amidation reaction takes place at the diamino functionality of complex 3.1, leading to the switching-on of a long-lived red luminescence with 9-fold enhancement in emission signal. Complex 3.1 exhibited high sensitivity and selectivity and the detection limit for (COCl)2 was found to be 32 nM. Additionally, complex 3.1 can be used to detect (COCl)2 using a simple smartphone, which allows the detection to be a real-time one. iii In Chapter 4, a dual-functional luminescent probe and inhibitor was designed for the in-situ monitoring of neuraminidase (NA) using a structure-based molecular design strategy. The candidate iridium(III) complexes 4.1a-4.1d were synthesized by grafting an oseltamivir moiety as a binding unit onto signaling iridium(III) precursors, generating probes that allowed for the simultaneous inhibition and sensing of NA. Complexes 4.1a-4.1d showed strong yellow or red luminescence in aqueous buffer containing 0.5% acetonitrile in response to NA. In particular, complex 4.1d exhibited enhanced inhibition against NA compared to the FDA-approved antiviral drug, oseltamivir. Moreover, complex 4.1d also displayed a long-lived lifetime, large Stokes shift, and high quantum yield, allowing its luminescence output to be distinguished in the presence of an interfering auto- fluorescent background. We have successfully developed the first dual-functional molecule 4.1d for the in-situ inhibition and detection of NA, which provides the possibility for the in-field simultaneous therapy and monitoring of influenza infection. In Chapter 5, a general strategy was introduced for the development of a long- lifetime iridium(III) theranostic by grafting a well-known inhibitor as a "binding unit" onto an iridium(III) complex precursor as a "signaling unit". To further optimize their emissive properties, the effect of imaging behavior was explored by incorporating different substituents onto the parental "signaling unit". This design concept was validated by a series of tailored iridium(III) theranostic 5.2a-5.2h for the visualization and inhibition of EGFR in living cancer cells. By comprehensively assessing the theranostic potency of 5.2a-5.2h in both in vitro and in cellulo contexts, probe 5.2f containing electron-donating methoxy groups on the "signaling unit" was discovered to be the most promising candidate theranostic with desirable photophysical/chemical properties. Probe 5.2f selectively bound to EGFR in vitro and in cellulo, enabling it to selectively discriminate living EGFR- overexpressing cancer cells from normal cells that express low levels of EGFR with an "always-on" luminescence signal output. In particular, its long-lived lifetime enabled its luminescence signal to be readily distinguished from the interfering iv fluorescence of organic dyes by using time-resolved technique. Complex 5.2f simultaneously visualized and inhibited EGFR in a dose-dependent manner, leading to a reduction in the phosphorylation of downstream proteins ERK and MEK, and inhibition of the activity of downstream transcription factor AP1. Notably, complex 5.2f is comparable to the parental EGFR inhibitor 5.1b, in terms of both inhibitory activity against EGFR and cytotoxicity against EGFR- overexpressing cancer cells. This tailored dual-functional iridium(III) theranostic toolkit provides an alternative strategy for the real-time and personalized diagnosis and treatment of cancers. Chapter 6 discusses the challenges and future inspirations for the development of iridium(III) complex-based luminescent probes and theranostic

no / Several Ru-arene and Ir–Cp* complexes have been prepared incorporating (N,N), (N,O) and (O,O) coordinating bidentate ligands and have been found to be active against both HT-29 and MCF-7 cell lines. By incorporating a biologically active ligand into a metal complex the anti-cancer activity is increased.

Yes / This report presents a new library of organometallic iridium(III) compounds of the type [Cp*IrCl(L)] (Cp*=pentamethylcyclopentadienyl and L=a functionalized β‐ketoiminato ligand) showing moderate to high cytotoxicity against a range of cancer cell lines. All compounds show increased activity towards colorectal cancer, with preferential activity observed against the immortalized p53‐null colorectal cell line, HCT116 p53‐/‐, with sensitivity factors (SF) up to 26.7. Additionally, the compounds have excellent selectivity for cancerous cells when tested against normal cell types, with selectivity ratios (SR) up to 35.6, contrary to that of cisplatin, which is neither selective nor specific for cancerous cells (SF=0.43 and SR=0.7–2.3). This work provides a preliminary understanding of the cytotoxicity of iridium compounds in the absence of p53 and has potential applications in treatment of cancers for which the p53 gene is absent or mutant.

No description available.

The complex [IrH(COD)(PMe3)3][Cl]2o2HCl was prepared by the reaction between [Ir(COD)(PMe3)3]Cl and HCl gas in methylene chloride. The product precipitated from the solution and is soluble in polar solvents such as water, acetonitrile, and acetone. [IrH(COD)(PMe3)3][Cl]2o2HCl undergoes reaction in water to form fac-IrCl3(PMe3)3. Also, other [IrH(COD)(PMe3)3][X]2 salts were prepared with X being PF6, OTF, or BF4. It was determined that each salt retained a certain amount of excess acids and [IrH(COD)(PMe3)3][OTF]HOTf was the most stable in the solvent acetonitrile while [IrH(COD)(PMe3)3][PF6]2 showed signs of reaction in acetonitrile after 4 hours. The dicationic salts were also reductively deprotonated by DMSO to form the Ir(I) starting material. Finally a slow equilibrium was noted for [IrH(COD)(PMe3)3][BF4]2 in water by the observation of the reductive deprotonation product. The grignard reaction was employed to synthesize Ir(CH3)3(PMe3)3. IrCl3(PMe3)3 reacts with methyl grignard in THF/Benzene to form fac-Ir(CH3)3(PMe3)3. Only the facial isomer of this reaction was observed and the product was soluble in nonpolar solvents. Acidolysis was utilized to synthesize fac-IrCH3Cl2(PMe3).3 from the reaction between Ir(CH3)3(PMe3)3 and 2 equivalents of HCl. Ir(III) methyl dications have also been synthesized by the reaction of 2 equivalents triflic acids with fac-Ir(CH3)3(PMe3)3. The product of the reaction, mer-IrCH3(OTf)2(PMe3)3 was used to study the insertion of alkynes into the Iridium methyl bond. IrHCl2(PMe3)3 was synthesized by the careful acidolysis of IrH2Cl(PMe3)3 using 1 equivalent of HCl. IrH(OTf)2(PMe3)3 was also synthesized by the metathesis of IrHCl2(PMe3)3 with 2.04 equivalents of silver triflate. The product of that reaction, IrH(OTf)2(PMe3)3, has been used to form dimers and trimers of styrene via catalysis and to isomerize alkene alcohols to aldehydes. IrH(OTf)2(PMe3)3 was also used as a polymerization initiator for vinyl and allyl ethers. / Ph. D.