Holographic Schwinger-Keldysh effective field theories

We construct a holographic dual of the Schwinger-Keldysh effective action for the dissipative low-energy dynamics of relativistic charged matter at strong coupling in a fixed thermal background. To do so, we use a mixed signature bulk spacetime whereby an eternal asymptotically anti-de Sitter black hole is glued to its Euclidean counterpart along an initial time slice in a way to match the desired double-time contour of the dual field theory. Our results are consistent with existing literature and can be regarded as a fully-ab initio derivation of a Schwinger-Keldysh effective action. In addition, we provide a simple infrared effective action for the near horizon region that drives all the dissipation and can be viewed as an alternative to the membrane paradigm approximation.Comment: 43 pages, 3 figures, v2: presentation improved, reference adde

Comparative sequence analysis reveals an intricate network among REST, CREB and miRNA in mediating neuronal gene expression

BACKGROUND: Two distinct classes of regulators have been implicated in regulating neuronal gene expression and mediating neuronal identity: transcription factors such as REST/NRSF (RE1 silencing transcription factor) and CREB (cAMP response element-binding protein), and microRNAs (miRNAs). How these two classes of regulators act together to mediate neuronal gene expression is unclear. RESULTS: Using comparative sequence analysis, here we report the identification of 895 sites (NRSE) as the putative targets of REST. A set of the identified NRSE sites is present in the vicinity of the miRNA genes that are specifically expressed in brain-related tissues, suggesting the transcriptional regulation of these miRNAs by REST. We have further identified target genes of these miRNAs, and discovered that REST and its cofactor complex are targets of multiple brain-related miRNAs including miR-124a, miR-9 and miR-132. Given the role of both REST and miRNA as repressors, these findings point to a double-negative feedback loop between REST and the miRNAs in stabilizing and maintaining neuronal gene expression. Additionally, we find that the brain-related miRNA genes are highly enriched with evolutionarily conserved cAMP response elements (CRE) in their regulatory regions, implicating the role of CREB in the positive regulation of these miRNAs. CONCLUSION: The expression of neuronal genes and neuronal identity are controlled by multiple factors, including transcriptional regulation through REST and post-transcriptional modification by several brain-related miRNAs. We demonstrate that these different levels of regulation are coordinated through extensive feedbacks, and propose a network among REST, CREB proteins and the brain-related miRNAs as a robust program for mediating neuronal gene expression

Synthesis and Characterization of Poly(9,9-Dihexylfluorene-mb-methylene)s

The synthesis and characterization of copolymers possessing exact repeating sequences of 9,9-dihexylfluorene and methylene repeat units are described. Each poly(9,9-dihexylfluorene-mb-methylene) (PFM, mb = multiblock) was synthesized following the assembly of a symmetrically disubstituted monodisperse oligofluorene. Alkyl segments possessing terminal alkene functionality were then coupled at both of the substituted positions on the oligofluorene to give a macromolecular "segmer" compound. Each segmer was polymerized using Acyclic Diene Metathesis (ADMET) and, following post-polymerization hydrogenation, a PFM with an entirely repeating diblock sequence was produced. PFMs possessing 9,9-dihexylfluorene segment lengths of x = 1, 2, 3, 4, 7, or 8 units and methylene segment lengths of y = 10 or 18 units were prepared to give a ten member PFM library. As PFMs have exact chemical compositions and monomer unit sequencing, studies aimed at elucidating solution and bulk phase trends were performed. Spectroscopic characteristics that make polyfluorene-type materials attractive include their generally efficient blue light emission (λmax ~ 448 nm). Successful investigations into the optical tuning of PFMs in solution and in the bulk are described. Additionally, thermal- and photostabilities of PFMs under a variety of conditions are reported and compared to the related homopolymer, poly(9,9-dihexylfluorene) [PDHF]. Compared to PDHF, PFMs display similar, and in some cases superior resistance to photobleaching processes. Additionally, thermal and photostability investigations into keto-induced degradation processes of PFMs suggest that interruption of the fluorene segments with alkyl spacers effectively suppresses intrachain charge migration and interchain Förster energy transfer in the bulk. The rate of PFM, and likewise PDHF degradation was found to be at least partially dependent on the initial state of the sample.Efforts toward the transition metal-catalyzed production of cyclic oligomers are described. Two rigid bifunctional molecules bearing both transition-metal metathesis initiating and terminating groups were prepared. The synthesis and metathesis activity of these compounds are reported

The suppressor-of-forked locus of Drosophila melanogaster

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Characterization of the Proteins HPIP and VENTX2 as Novel Regulatory Proteins of Human Hematopoiesis

The hallmark of hematopoietic stem cells (HSC) is their ability of self-renewal and differentiation into multiple hematopoietic cell lineages. Although the molecular network controlling stem cell fate decisions is largely unknown, multiple studies have attributed a key role to transcription factors in this developmental process. In this context the family of homeobox genes was characterized as ‘master genes’ of this early hematopoietic development. The identification of new genes involved in normal and leukemic hematopoiesis and the development of therapies against deregulated processes in hematopoiesis are the major goals in experimental and clinical hematology. . The identification of new genes involved in normal and leukemic hematopoiesis and the development of therapies against deregulated processes in hematopoiesis are the major goals in experimental and clinical hematology. Therefore, the focus of this thesis was the characterization of two novel putative regulatory proteins of early human hematopoiesis, the hematopoietic PBX-interacting protein (HPIP) and the human Vent-like Homeobox gene (VENTX2) and to investigate to the activity of the FLT3 protein kinase inhibitor SU5614 on leukemic blast from AML patient samples. Using complex in vitro assays we analyzed the impact of constitutive expression of HPIP and VENTX2 on stem cell and early human hematopoietic development. To detect clonal progenitor cells primary and secondary colony-forming-unit (CFC) assays were performed. In addition the in vitro equivalent of HSC long-term culture initiating cells were detected with the (LTC-IC) assay. We were able to show that the constitutive expression of HPIP can rapidly lead to increased numbers of cells detected on the level of committed clonogenic progenitor cells and LTC-ICs. In addition, the production of CFC per LTC-IC is markedly enhanced when cord blood (CB) cells are transduced with HPIP as compared to the control. Notably, besides its effect on maintenance of primitive hematopoietic progenitor cells, constitutive expression of HPIP did not block terminal hematopoietic differentiation. Additional we could show that the constitutive expression of HPIP leads to an increase of myeloid cells in transplanted NOD/SCID mice. These data characterize HPIP as a novel regulator of the early human hematopoietic stem cell, demonstrating that its constitutive expression has a notable impact on self renewal and differentiation of human hematopoietic stem cells. In vitro and in vivo analyses shed light on the understanding to the function of the homeobox gene VENTX2. On the level of the most primitive hematopoietic progenitors we could not observe a significant increase in the frequency of HSCs. Furthermore, the number of colonies generated per LTC-IC did not significantly differ between the VENTX2 arm and the control arm. A strong effect was obtained on the level of clonogenic progenitor cells. VENTX2 increased the production of myeloid cells 1.7-fold in comparison to the control. Secondary replating assay confirmed the amplificatory effect of VENTX2 transduced cells in the number of secondary G-CFU indicating that VENTX2 promote myeloid lineage differentiation. Interestingly, on the level of clonogenic progenitors VENTX2 expression resulted in a significantly decreased growth of erythroid colonies by 4.2-fold compared to the control suggesting that constitutive expression of VENTX2 may inhibit early erythroid differentiation. This inhibition did not occur on the level of primitive hematopoietic cells detected by Limiting Dilution LTC-IC assay where VENTX2 increased within a 2.2 fold compared to the control. The observation that VENTX2 overexpression drives CD34+ to differentiate into myeloid lineage was additional proved by in vivo experiments. In NOD/SCID mice VENTX2 induced a 3-fold increase in the proportion of CD15+ mature myeloid cells within the GFP-positive compartment compared to the control. A 7-fold increase was observed in the total of CD38+ GFP+ cells in comparison to the MIG mice control (p<0.01). Furthermore, VENTX2 transduced cells increased the proportion of CD34-CD38+ cells 1.2 fold compared to the control suggesting that VENTX2 expands the compartment of more differentiated progenitors in vitro as well as in the NOD/SCID mouse model. This implicates a amplificatory effect of the VENTX2 expression on differentiated progenitor cells. All together, these data characterize VENTX2 as a novel regulatory protein in human hematopoiesis adding information about the role of non-clustered homeobox genes in early blood development. In an additional project of this thesis, we tested the specificity of the FLT3 protein kinase inhibitor SU5614 on normal and leukemic blasts from patients with acute myeloid leukemia. Here we could demonstrate the efficiency of the compound to eliminate the leukemic stem cell in AML patient samples with mutated as well as non mutated FLT3 receptor. However, our data also point to a considerable toxicity on normal HSC, which should be taken in account in the management of patients with compromised normal hematopoiesis

Role of alternative splicing in neurogenic commitment

To form complex organisms characterized by different tissues with specialized functions, cells must acquire distinct identities during development. Yet, all the cells of an organism are equipped with the same genomic information. Elucidating the mechanisms that regulate the determination of a cell identity, i.e. the cell-fate commitment, is a main purpose in developmental biology. Numerous studies focused on genes that are activated or repressed at each stage of differentiation, identifying several key regulators of development. However, this approach ignores the transcript variability derived from alternative splicing, the transcriptional process by which different gene coding segments, i.e. exons, are combined giving rise to multiple transcripts and proteins from the same gene. With the advent of novel sequencing technologies, it is becoming clear that alternative splicing is widespread in higher organisms, regulates several processes and presents tissue- and cell-specificity. In mammals, the brain shows the highest degree of alternative splicing, with neurons expressing a high variety of splice variants. In this project I investigated whether and how alternative splicing could regulate cell-fate determination in the context of the embryonic development of the mouse neocortex, a highly complex structure presenting several different neuronal subtypes generated at specific time points. For this purpose, I analyzed transcriptome data of cells of the neurogenic lineage isolated from the developing mouse neocortex at subsequent stages of differentiation. I showed that the expression pattern of the proteins regulating splicing, i.e. the splicing factors, changes during neocortical development. By employing several bioinformatic tools, I described the splicing profile that characterizes each differentiation stage and, for the first time, I identified the splicing events that mark cell-fate commitment to a neurogenic identity. Alternative splicing mostly involved genes with a role in nervous system development, cell growth and signaling, mainly leading to the production of alternative protein isoforms. Splicing choices taken during the neurogenic commitment were kept throughout neurogenesis. Thus, exons that start to be included during cell-fate determination are always included in post-mitotic neurons. Exons gained during neurogenic commitment were characterized by strong features in their upstream intron, presented a general short length with an overrepresentation of microexons in the 3-27 nucleotides length range and showed an enrichment for binding motifs of the neural splicing factor nSR100. In vivo manipulation in the embryonic mouse neocortex highlighted isoform-specific effects on neocortical development, strongly suggesting a causal relationship between alternative splicing choices and cell-fate commitment. Moreover, the higher cell-specificity offered by the present dataset, compared to similar studies, allowed a better understanding of previously identified splicing events that characterize the nervous system and the relationships between neural-specific splicing factors.:Table of Contents Abstract I Zusammenfassung III Table of Contents V List of Figures VII List of Tables IX Abbreviations X Gene abbreviations XII 1 Introduction 1 1.1 Neurogenesis during embryonic development 2 1.1.1 Formation and patterning of the neural tube 2 1.1.2 Neural progenitors in the dorsal telencephalon 6 1.1.3 Neurogenesis 8 1.1.4 Regulation of neurogenesis 10 1.1.5 A novel tool to investigate cell-fate determination in the central nervous system: the Btg2RFP/Tubb3GFP mouse line 13 1.2 Alternative splicing: an additional level of genomic regulation 15 1.2.1 The splicing reaction 16 1.2.2 What makes splicing alternative? 18 1.2.3 Regulation of alternative splicing 19 1.2.4 The challenge to detect splicing 23 1.2.5 New sequencing technologies reveal a high transcriptome complexity 29 1.2.6 Splicing in nervous system development 31 1.2.7 Aims of the project 36 2 Materials and methods 38 2.1 Materials 38 2.1.1 Bacteria, cells, mouse strains 38 2.1.2 Vector 38 2.1.3 Primers 38 2.1.4 Chemicals and buffers 41 2.1.5 Antibodies 42 2.1.6 Kits and enzymes 42 2.2 Methods 43 2.2.1 Animal experiments 43 2.2.2 Molecular biology 44 2.2.3 Immunohistochemistry 46 2.2.4 Bioinformatics 47 3 Results 53 3.1 Splicing factors are differentially expressed during neurogenic commitment and neurogenesis 53 3.2 Detection of alternative splicing 55 3.2.1 Isoform-switching 55 3.2.2 Exon usage and splicing events 57 3.3 Validation 62 3.3.1 The isoform switching method has a poor validation rate 62 3.3.2 Analysis at the exon level has a high rate of validation 65 3.4 Pattern and representation of splicing events 67 3.4.1 Splicing choices during neurogenic commitment define the splicing profiles of neurons 67 3.4.2 Splicing events: microexon inclusion characterizes neurogenic commitment 69 3.5 Alternative splicing changes the protein output of genes involved in neurogenesis 75 3.5.1 Spliced genes are involved in neurogenesis and signaling 75 3.5.2 Impact of alternative splicing on the proteome 77 3.6 Splicing regulation: neural exon features and splicing factor binding 79 3.6.1 Included neural exons are short and preceded by strong exon-definition features 79 3.6.2 Early included exons are enriched for nSR100 binding sites 85 3.7 The Btg2RFP/Tubb3GFP mouse line outperforms previous models for the study of cell-type-specific splicing in the brain 88 3.8 In vivo manipulation of splice variants 90 4 Discussion 94 4.1 The combination of different bioinformatic approaches allows an accurate identification of splicing events at the exon-level 95 4.2 Splicing choices during neurogenic commitment establish a neural signature characterized by microexon inclusion 97 4.3 Splicing during neocortical development leads to the generation of alternative protein isoforms in genes involved in neurogenesis and signaling 98 4.4 Neural exons are short and present strong features facilitating inclusion 101 4.5 Neural exons are prevalently regulated by nSR100 during neurogenic commitment 102 4.6 In vivo overexpression of splice variants highlights isoform-specific functions in neurogenic commitment 105 4.7 Concluding remarks and future perspectives 108 5 Supplementary figures 110 6 References 118 Acknowledgments 137 Anlange I 138 Anlange II 13

Reactions of unsaturated hydrocarbons catalysed by transition metal compounds

A range of different heterogeneous catalysts for the isomerisation of ortho-xylene have been prepared and evaluated. These included commercially-available samples, supported metal catalysts and zirconia-based catalysts. The greatest activity was seen for the former, which was found also to be active for a number of related reactions. Zirconia-based catalysts, in particular sulphated zirconia, gave significant activity. It was possible to prepare a catalyst to give 9.5% conversion of ortho-xylene per gram of catalyst with good selectivity to the meta isomer. The catalyst was prepared in two ways, either by the action of ammonium sulphate on "zirconium hydroxide", a hydrated zirconia precursor, or by precipitation from a sulphuric acid-containing solution of zirconium (IV) propoxide. The factors in the synthesis procedure which affect the catalytic performance of the catalyst were investigated. These included choice of reagents, preparative method and calcination procedure. This information was used to prepare an 'idealised' catalyst, which showed activity for a number of reactions of commercial interest. A range of different aminophosphine complexes based on the reaction of a N,N'- substituted diamine with chlorodiphenylphosphine have been prepared for subsequent study as ligands in complexes active in homogeneous catalysis. Palladium and platinum complexes of the type [(diaminodiphosphine)MCl(_2)] have also been prepared and characterised. A number of x-ray diffraction analyses have been performed, which along with other data has allowed the solid state and solution structures to be discussed. The relative reactivities of the ligands have been determined by reactions with manganese pentacarbonyl bromide and also with palladium dichloride complexes. This depends largely on the steric requirements of the ligand in question. The potential of these ligands in catalysis has been evaluated by the performance of their platinum dichloride complexes in the tin (II)-promoted hydroformylation of styrene, and their palladium acetate complexes for the methoxycarbonylation of ethene

Mechanistic Investigations of the Direct Arylation of Pyridine N-oxides with Bromoarenes and Structure-Reactivity Relationship of Aryl Palladium Complexes in Transmetalations with Organoboron Compounds

Reaktionsgeschwindigkeiten der katalytischen Reaktionen zwischen Pyridin-N-Oxiden und Bromaromaten: Die direkte Arylierung von 4-substituierten Pyridin-N-oxiden mit Bromaromaten ergibt Arylpyridin- N-oxide in Ausbeuten von 70-80%. Jedoch ergeben analoge Arylierungsreaktionen zwischen 2-Brompyridinen und Pyridin-N-oxiden, welche elektronschiebende Substituenten tragen, Kreuzkupplungsprodukte in niedrigeren Ausbeuten von 23-49%. Hingegen bilden Arylierungen von Pyridin-N-oxiden, welche elektronziehende Substituenten tragen, mit 2-Brompyridinen die Pyridin- N-oxidprodukte in 70% Ausbeute. Frühere Berichte über den Mechanismus erklären nicht diese Substratabhängigkeit, weshalb die Geschwindigkeiten der Substratverbräuche und Produktbildungen für die Reaktionen von fünf 4-substituierten Pyridin-N-oxiden mit 2-Brompyridin und Brombenzol bestimmt wurden. Die Reaktionen mit beiden Arylhalogeniden zeigten, dass elektronarme Pyridin- N-oxide eine höhere Reaktivität gegenüber C-H-Aktivierung aufweisen und bilden das Kreuzkupplungsprodukt schneller als elektronreiche N-oxide. Als Nebenreaktion wurde eine konkurrierende Homokupplung des Arylhalogenids identifiziert, wodurch 2,2ʹ-Bipyridin bzw. Biphenyl gebildet wird. Wo die Ausbeute des Kreuzkupplungsprodukts niedrig war, ergab die Homokupplung des 2-Brompyridins Bipyridin in bis zu 35% Ausbeute. Die Homokupplung von Brombenzol zu Biphenyl wurde in signifikant niedrigeren Ausbeuten von <10% beobachtet. Im Vergleich zum Brombenzol, wurde eine schnellere Verbrauchsrate mit 2-Brompyridin beobachtet und dessen Ursprung dem konkurrierenden Homokupplungsmechanismus zugeschrieben. Als zusätzliche Nebenreaktion wurde die Homokupplung des Pyridin-N-oxidsubstrats identifiziert. Homokupplungsprodukte des Arylhalogenids und des Pyridin-N-oxids wurden in jeder Reaktionen in ähnlichen Ausbeuten erhalten, was darauf hindeutet, dass beide Nebenreaktionen durch miteinander verbundene Redoxzyklen ablaufen. Potentiell inhibierende Effekte durch die stickstoffhaltigen Verbindungen, welche in der Reaktionsmischung vorhanden sind, wurden untersucht. Mit der Zugabe von Pyridin, Bipyridin oder Bipyridin-N-oxid wurden langsamere Bildungsgeschwindigkeiten der Kreuzkupplungsprodukte beobachtet. Jedoch sanken die Ausbeuten nicht signifikant, was ausschließt, dass die Inhibierung durch das Substrat oder durch das Produkt für das Absenken der Ausbeuten in Reaktionen mit 2-Brompyridin verantwortlich ist. Synthese und Reaktivität von Arylpalladiumkomplexen in der direkten Arylierung von Pyridin-N-Oxiden: Um die Reaktivität von Arylpalladiumkomplexen in der direkten Arylierung von Pyridin-N-oxiden zu untersuchen, wurden die vorgeschlagenen Intermediate synthetisiert. Ein 6-tert-Butyl- 2-pyridylpalladium(II)bromidkomplex, welcher ein P(t-Bu)3-Ligand trägt, wurde synthetisiert und mittels Röntgenstrukturanalyse charakterisiert, was einen ungewöhnlichen η2-C,N-Bindungsmodus des Pyridylliganden aufdeckte. Zum Vergleich wurde ein 3-Methylphenylpalladium(II)komplex, an dem P(t-Bu)3 gebunden ist, synthetisiert. Nach dem Erhitzen bildete der Pyridylkomplex das Bipyridinhomokupplungsprodukt nahezu quantitativ, wohingegen der Phenylkomplex das Biphenylhomokupplungsprodukt, sowie den protodemetallierten Aromaten und das reduktiv eliminierte Arylhalogenid (Verhältnis 3:4:1) ergab. Der Phenylkomplex wies einen exponentiellen Zerfall des Startmaterials auf (t1/2 = 15 Minuten bei 80 °C), wohingegen die Zersetzung des Pyridylkomplexes erst nach einer Induktionsperiode, bei der die Bildung einer anionischen 2-Pyridylpalladatspezies beobachtet wurde, auftrat. Die unabhängige Synthese der anionischen Spezies und die Bestimmung dessen Einfluss auf die Reaktion deuteten an, dass es die Zerfallsreaktion katalysiert. Ein 2-Pyridyl-N-oxidpalladium(II)komplex, bei dem ein zyklometallierter Phosphinligand und ein stabilisierender PEt3-Ligand gebunden sind, wurde mit einem Methyl- oder einem Trifluoromethylsubstituenten am Pyridyl-N-oxidliganden synthetisiert. Die Komplexe reagierten mit einem 2-Pyridyl- oder Phenylpalladiumkomplex bei Raumtemperatur oder niedriger und bildeten kreuzgekuppelte Arylpyridin-N-oxidprodukte. Die Bildung des Bipyridin-N,Nʹ-dioxids über Homokupplung des Pyridyl-N-oxidkomplexes wurde zwar beobachtet, jedoch aber nur bei höheren Temperaturen. Die Homokupplungen der Arylpalladiumkomplexe und Pyridyl- N-oxidpalladiumkomplexe waren signifikant langsamer als eine Kreuzkupplungsreaktion zwischen den Komplexen. Transmetallierung zwischen Arylpalladiumkomplexen und Organoborverbindungen: In Suzuki-Miyaura-Kreuzkupplungsreaktionen wird angenommen, dass der Transmetallierungsschritt entweder zwischen einer anionischen Boronatspezies und einem Palladiumkomplex mit einem Halogenidliganden (Boronat-Mechanismus) oder zwischen einer neutralen Organoborspezies und einem hydroxidgebundenem Palladiumkomplex (Oxo-Palladium-Mechanismus) stattfindet. Um die Transmetallierung zu untersuchen, wurde ein Satz von dimeren bromidverbrückten P(o-tol)3- palladium(II)komplexen, welche 4-substituierte Arylliganden tragen, synthetisiert und in guten Ausbeuten erhalten. Der Austausch des Bromids mit Hydroxid lieferte die analogen hydroxidgebundenen Arylpalladium(II)dimere. Untersuchungen des Transmetallierungsschritts sind oft auf Grund der Löslichkeit der anionischen Organoboronatspezies eingeschränkt. Eine anionische Boronatspezies, welche als Gegenion Tetrabutylammonium tragen, wurde hergestellt und zeigte eine ausreichende Löslichkeit in organischen Lösungsmitteln, wie THF und DCM. Erste Experimente, welche den Transmetallierungsschritt untersuchen, wurden durchgeführt anhand von Konkurrenzexperimenten zwischen acht 4-substituierten Arylpalladiumkomplexen und einer Organoborspezies. Die relativen Reaktionsgeschwindigkeiten der substituierten Palladiumkomplexe wurden für den Boronat- und den Oxo-Palladiummechanismus bestimmt. Lineare Hammett- Korrelationen ergaben ρ = +0.81 für die Reaktionen zwischen bromidverbrückten Palladiumkomplexen und einem anionischen Boronat, und ρ = +0.52 für die Reaktion zwischen hydroxidverbrückten Palladiumkomplexen und einer neutralen Boronsäure. Eine positive Reaktionskonstante kennzeichnet einen Anstieg in der Reaktivität der elektrophileren Arylpalladiumkomplexe. Der Vergleich der ρ-Werte zeigt an, dass bromidgebundene Arylpalladiumkomplexe leicht empfindlicher gegenüber Substitutionsmuster sind als ein hydroxidgebundener Arylpalladiumkomplex

Reactivity of metals tethered to metal-organic frameworks

The reactivity of solid-state materials differs from those in solution or gaseous states due to structure, surface and transport effects. While the reactivity of metal complexes in solution have been well explored, the study of well-defined solid-state metal complexes has been stymied by difficulties in characterisation and poor stability. Metal-organic frameworks (MOFs) provide a promising platform for the site-isolation, characterisation and reaction of such complexes. The controlled delivery of CO gas from photoactivated Mn(I) carbonyl complexes is desired for medical and chemical synthesis applications. A fac-tricarbonyl Mn(I) complex was tethered to the bis-pyrazole coordination site of L’ in MnMOF, [Mn3L2L’] (H2L = 4,4'-{methylenebis(3,5-dimethyl-1H-pyrazole-1,4-diyl)}dibenzoic acid), and found to undergo a series of solvent-induced isomerisations. The photoactivated decarbonylation pathway for MnMOF[Mn(CO)3X]Y (X,Y = Br- or solvent) was studied, involving the stepwise loss of the carbonyl ligands, with di- and mono-carbonyl intermediates observed by IR spectroscopy and photocrystallography. Exposure to environmental oxidising agents resulted in a proposed final Mn(II) decarbonylation product, which formed a Mn(II) carbonyl species when exposed to CO gas. MnMOF[Mn(CO)3X]Y was used as an ex-situ light-triggered source of CO gas for aminocarbonylation reactions, achieving high yields with low excesses of CO. Two other Mn(I) carbonyl metalated MOFs, UiO-67-bpy and DUT-5-bpy, were likewise tested, and achieved high yields, although with different efficiencies. This demonstrated the influence of structure, topology and particle size on the effectiveness of these CO sources. To examine the former, MnMOF was structuralised from sacrificial sol-gel-derived manganese oxide templates. The template structure was found to influence the kinetics of formation and macrostructural properties of the MOF crystals. Inorganic azides may react photochemically through a range of mechanisms, including the formation of highly reactive nitrene intermediates. As such, they are useful synthetic or catalytic intermediates. An azidocarbonyl Mn(I) molecular complex dissolved in tetrahydrofuran or dichloromethane was found to form a bridging isocyanate complex upon irradiation with light, while the same complex isolated within MnMOF showed different reactivities at different temperatures in the presence of a coordinating solvent. Isocyanate was formed at room temperature for bulk, matrixisolated samples, and at 190 K in a single crystal. At lower temperatures, decarbonylation occurred without formation of a nitrene. The site-isolation of palladium catalysts in MOFs has allowed for improved reactivities and selectivities, but few of these complexes have been structurally characterised through single-crystal X-ray diffraction techniques. Palladium halide complexes were tethered to MnMOF by post-synthetic metalation, but further investigations were hindered by the lability of the complexes and their propensity to form of pore-bound species, in addition to ligand-bound species, resulting in unpredictable metalation efficiencies. Finally, silver coordination polymers have demonstrated antibacterial behaviour, but the properties controlling their activity are not well understood. The dissolution behaviour of a sub-set of four silver coordination polymers, chosen to probe the relative impacts of coordination chemistry and topology, revealed that metal-ligand bond strength has the greatest impact on controlling silver ion release. The formation of composite materials with organic polymers attenuated the release of silver ions in waterwith the more water permeable polymer, polycaprolactone, allowing for greater silver release than polyethylene. All four coordination polymers showed antibacterial activity, albeit to different extents. For the reactions of metal complexes tethered to MOFs to be studied, the retention of long-range order and complex stabilities are the major barriers to characterisation. Judicious choice of a MOF host which permits changes in the coordination sphere of the metal, without loss of crystallinity, and site-isolation mitigates some of these challenges. In this work, it has been observed that environmental parameters such as temperature, light and exposure to air and moisture, all affect the reactions of metals tethered to MOFs. In addition, structural parameters of topology, morphology and structuralisation affect the utility of these materials