Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 02/06 Archiv

Recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) is a morphogen with the ability to induce the formation of cartilage and new bone. In the product currently on the market for some special orthopaedic indications, rhBMP-2 is implanted by invasive surgery in combination with a suitable carrier which enables a sustained release and a prolonged presence of the morphogen at the site of action - prerequisites for an optimal therapeutic effect. The aim of the present work was to develop a sustained releasing “carrier-free”, injectable formulation that overcomes the necessity of invasive surgery and has the potential to expand the indications of rhBMP-2. Based on the principle of controlled precipitation, a microparticulate formulation was developed. Beside physicochemical characterisations of the microparticles, the integrity of rhBMP-2 in the precipitated state and after redissolution was demonstrated and the potential of precipitation to prevent degradation was elucidated. The ability of the microparticle formulation to deliver rhBMP-2 in a sustained manner was tested in-vitro and the efficacy of the aqueous protein suspension to augment bone density was examined in an animal model.

The marine bryozoan Flustra foliacea is known as source of unique brominated indole alkaloids. Flustra alkaloids are structurally related to the highly toxic acetylcholinesterase inhibitor physostigmine which is clinically tested as a possible remedy for Alzheimer's disease. The concentration of those natural products can vary strongly, depending on location and season. Thus, exploration of the total synthesis of the Flustra alkaloids is required for any detailed analysis of their biological activity. As a recent member of the family, we isolated deformyl-flustrabromine (dFBr) which shows promising activity at the nicotinic acetylcholine receptor (nAChR). Deformylflustrabromine may be a biosynthetic precursor of other Flustra alkaloids such as flustraminol A. An efficient first total synthesis of dFBr and three of its congeners has been developed. Key step of the synthesis is the inverse prenylation at the indole 2-position. When treated with tert-BuOCl and prenyl[9-BBN], Nb-Formyl-Nb-methyl-tryptamine cleanly reacts affording the inversely 2-prenylated compound in a yield of 75 %. However, inverse prenylation of the indole 2-position was not suitable for the 6-brominated analog, synthesized via the Batcho-Leimgruber route. The influence of 6-bromination on the reactivity of several indoles was investigated confirming that deactivating effect. For the synthesis of dFBr we had to turn back to non-brominated indoles. Surprisingly good regioselectivity for the indole 6-position was observed on monobromination of the corresponding, 2-inversely prenylated indole precursor with one equivalent of NBS in HOAc/HCO2H (3:1). The product flustrabromine crystallizes as the E-rotamer. Alkaline hydrolysis afforded deformylflustrabromine which was synthesized within four steps and an overall yield of 53 % starting from Nb-methyl-tryptamine. Now, gram quantities of material are accessible for further biological studies. During this study, interesting formation of traces of inversely prenylated THF was observed. This phenomenon has been further studied by performing the actual reaction in the absence of indole derivatives. It was possible to convert unsubstituted tetrahydrofuran to the 2-inversely prenylated compound simply by treatment with NCS and prenyl[9-BBN] at room temperature, in a yield of 88 %. This is a new reaction.

Major intrinsic proteins (MIPs) are an ancient family that were found in various bacteria, fungi, amphibians, plants and animals. They are collectively called aquaporins (AQPs) because some members were found to transport water, and others were shown to be permeable to small uncharged molecules such as glycerol, urea, ammonium, or formamide. In the crop plant maize, 34 cDNA sequences encoding putative AQPs had been previously identified. They include 13 plasma membrane intrinsic proteins (ZmPIPs), 13 tonoplast intrinsic proteins (ZmTIPs), 5 NOD26-like intrinsic proteins (ZmNIPs) and 3 small basic intrinsic proteins (ZmSIPs). Environmental cues such as increased salt concentration or nutrient deprivation affect root hydraulic conductivity. To examine an implication of AQPs in these processes, the expression of the maize MIP gene family was analyzed by a ZmMIP DNA array that harbored gene-specific sequences as targets for hybridization. Eleven ZmPIP and 5 ZmTIP members were detected in roots of 11 day-old seedlings grown in hydroponic culture. Members of the other two subgroups were expressed weakly. ZmPIP1-1, ZmPIP1-5, ZmPIP2-1, ZmPIP2-4, ZmPIP2-5, ZmPIP2-6, ZmTIP1-1, ZmTIP2- 1, ZmTIP2-2 and ZmTIP2-4 had the high abundance. Six day-old maize primary roots were further dissected to investigate the spatial expression pattern. High abundance of all detected ZmMIP members were observed in the elongation zone (3-10 mm) and root hair zone (10-20 mm), but less transcripts were detected in the root tip (0-3 mm) and mature zone (50-60 mm). Thus, the expression of aquaporins correlated with the region of enhanced water uptake. Analysis of aquaporin expression of longitudinally separated primary roots showed that higher transcription of ZmPIP1-1, ZmPIP1-5, ZmPIP2-1, ZmPIP2-4, ZmPIP2-5, ZmTIP1-1, ZmTIP2-2 and ZmTIP2-4 in cortex than in stele tissue. There was no difference of ZmPIP1-2 and ZmPIP2-6 transcript between cortex and stele. This indicated that aquaporin-mediated cellular pathway through cortex tissue played an important role for root water transport involving the identified isoforms. Maize seedlings responded differentially to 100 vs. 200 mM NaCl treatments. Leaf water content was rapidly and persistently reduced after application of 200 mM NaCl in contrast to 100 mM NaCl. The stress hormone abscisic acid (ABA) strongly accumulated in roots after 2 h; it stayed at a highly elevated level for 48 h after addition of 200 mM NaCl, but ABA rapidly declined close to control levels in plants treated with 100 mM NaCl. The transcriptional responses of ZmMIP genes were also different in both szenarios. Two hours after addition of 100 mM, but not of 200 mM NaCl, two highly expressed plasma membrane isoforms ZmPIP1-1 and ZmPIP2-4 were transiently induced. In addition, the most highly expressed maize PIP gene in roots, ZmPIP1-5, showed a weak, yet significant induction. None of the ZmTIP genes was altered. The specific and transient induction was interpreted as a measure to enhance water uptake when plants were just regaining the capability of water uptake. In contrast, multiple ZmPIP and ZmTIP genes were specifically E. Summary 95 reduced by 200 mM NaCl after 24 h. After 48 h, deregulations were overridden in both cases indicating homeostasis. One µM ABA exogenously applied to the roots transiently induced ZmPIP2-4 similar to 100 mM NaCl as well as ZmPIP1-2. Previously, an increase in hydraulic conductivity had been observed upon ABA application. One hundred µM ABA, a high concentration frequently used in other studies, lead to a complete, possibly non-specific repression of all detected ZmPIP and ZmTIP genes after 24 h. It is inferred that the early induction of ZmPIP2-4 by NaCl may be mediated by ABA, whereas other regulations are probably ABA-independent. Furthermore, transcriptional repression of aquaporins could be involved in the reduction of water permeability after treatment with 200 mM NaCl, but not after milder salt stress. Aquaporin abundance was also investigated at the protein level in total microsomal fractions using antisera detecting ZmPIP2-3 and ZmPIP2-4 as well as the ZmPIP1 subgroup. Apparently, the protein level of aquaporins was not correlated to the transient changes in mRNA abundance. This may point to a real discrepancy of mRNA and protein levels. Alternatively, other detected isoforms, which were not altered, might obviate the resolution of changes, or a possible membrane translocation was not resolved when using microsomal fractions. Phosphorylation of aquaporins has been reported as another possible mechanism to regulate aquaporins. However, with respect to NaCl and ABA treatments no alterations in the degree of phosphorylation could be detected in this study, which, however, could not discriminate between different isoforms. Finally, the implication of AQPs in changes of hydraulic conductivity provoked by K+- and NO3 --deprivation was examined in a preliminary study. K+-deficiency reduced four ZmPIP and three ZmTIP members. This could be related to a reduced cellular water transport through roots as well as the retarded growth although overall water flux was increased. Surprisingly, ZmPIP1-5 and ZmTIP1-1 was specifically repressed after N-deprivation. This change may indicate that these isoforms are primarily involved in the transcellular water flow that is reduced under N-limitation; yet at the same time enhanced root growth is possible, which involves other isoforms that were not affected in this instance.

Adhäsionsvorgänge von Leukozyten spielen eine wichtige Rolle bei den verschiedensten biologischen Prozessen. Die Adhäsionsinteraktionen können Signalkaskaden aktivieren, die Funktionen wie die Zellmigration, Proliferation und Reifung von T-Lymphozyten steuern. Die Zellen des Immunsystems müssen schnell auf körperfremde Eindringlinge reagieren können und Adhäsionsvorgänge zwischen Zellen bzw. zwischen Zellen und der extrazellulären Matrix effektiv regulieren. Um jeden Infektionsherd im Körper zu erreichen, benutzen die Immunzellen die Lymph- und Blutbahnen, können diese Systeme aber verlassen (Diapedese) und durch Gewebe migrieren. Am Infektionsort interagieren die Immunzellen mit infizierten Zellen und starten Vernichtungsprogramme. Weiterhin präsentieren antigenpräsentierende Zellen im Lymphknoten ihre Antigene vorbeiziehenden T-Zellen, die bei korrekter Antigenerkennung zu T-Effektorzellen proliferieren. Bei all diesen regulierten Adhäsionsreaktionen spielen besonders die Integrine eine große Rolle. Von besonderem Interesse ist hierbei das Heterodimer LFA-1 (CD11a/CD18). LFA-1 wird nur auf Leukozyten exprimiert und bindet an die Liganden ICAM-1,-2,-3 der Immunglobulinsuperfamilie. Die kontrollierte Adhäsion bzw. Deadhäsion von Leukozyten bedarf einer spezifischen Regulation des LFA-1-Integrins und die Aufklärung der molekularen Grundlagen dieser Vorgänge ist von großem Interesse. Die LFA-1-vermittelte Zelladhäsion kann über den intrazellulären Guanin-Nukleotid-Austauschfaktor Cytohesin-1 aktiviert werden. Die Aktivierung wird dabei u.a. über Inositid-abhängige Membranrekrutierung von Cytohesin-1 kontrolliert. In dieser Arbeit wurde ein mit Cytohesin-1 interagierendes Protein, CYTIP, identifiziert, welches durch Cytokine in hämatopoetischen Zellen vermehrt exprimiert wird. CYTIP interagiert über seine „coiled-coil“-Proteininteraktionsdomäne direkt mit der N-terminalen „coiled-coil“-Domäne von Cytohesin-1 und inhibiert vollständig die Zelladhäsion auf Integrinliganden. Aufgrund der zwei Proteininteraktionselemente („coiled-coil“-Domäne, PDZ-Domäne) stellt CYTIP ein Adaptermolekül dar, um verschiedene Signalkomponenten in einem Multiproteinkomplex zu koppeln. CYTIP (Cytohesin-1 interacting protein) stellt eine neue Molekülklasse dar, die durch direkte Interaktion mit Cytohesin-1 die LFA-1 vermittelte Zelladhäsion negativ regulieren kann.

Erstes Ziel der vorliegenden Arbeit war eine Validierung dieses zweikammerganzkörperplethysmographischen Tiermodells durch Kontrollexperimente mit bereits etablierten Asthmamitteln durchzuführen und zu prüfen, ob und in welchem Maße Ergebnisse des Meerschweinchenmodells auf die Anwendung am Menschen übertragbar waren. Im Einzelnen waren die Bedingungen der Sensibilisierung der Versuchstiere gegen Hühnereiweiß (Ovalbumin), die optimalen Allergendosen, effektivere Sensibilisierungsmethoden, Art und Dauer der Allergen empfindlichen Phase, eine mögliche Re-Sensibilisierung oder Tachyphylaxie Effekte bei wiederholter Allergenexposition, eine evtl. Saisonabhängigkeit der Sensibilisierung bzw. der allergischen Reaktion bei Meerschweinchen und andere Möglichkeiten z. B. mit Histamin, eine bronchiale Hyperreagibilität bei Meerschweinchen zu provozieren, zu prüfen. Als nächstes war die neue Untersuchungsmethode an bekannten Asthmamitteln zu validieren, was mit den Bronchodilatatoren Fenoterol und Theophyllin sowie den Entzündungshemmern Budesonid, Methylprednisolon – Glukokortikoide - und Montelukast, einem Leukotrien-Antagonisten, geschah. Schließlich musste geprüft werden, ob sich die Methode zum Screenen von Pflanzenextrakten bei der Suche nach neuen antiasthmatischen Arzneistoffen eignete. Hierzu wurden Extrakte aus Picrorhiza kurroa und Acetosyringenin (ein Acetophenon, das chemisch strukturverwandt zum Pflanzeninhaltstoff Androsin ist und laut frühere Untersuchungen ausgeprägte antiasthmatische Wirkung besitzt) und 3 Drogen aus der traditionellen iranischen und südamerikanischen Volksmedizin (Angurate, Caiophora sepiara und Wascha aus Dorema ammoniacum) getestet. Die vorgelegten Untersuchungsergebnisse belegen, dass das plethysmographische Zweikammer- Tiermodell in der jetzt vorliegenden von uns validierten und standardisierten Methode an Ovalbumin-sensibilisierten Meerschweinchen geeignet ist, nicht nur die antiasthmatische Wirksamkeit von synthetischen Arzneistoffen zu bestätigen bzw. zu überprüfen, sondern auch Pflanzenextrakte und daraus isolierte Wirkstoffe auf ihr mögliches antiasthmatisches Wirkpotential hin zu untersuchen. Die antiasthmatische Wirksamkeit untersuchter bekannter in der Humanmedizin eingesetzter Antiasthmatika korrelierte eindeutig mit den Ergebnissen in unseren Tiermodellen. Die Methode ist sowohl für die Suche nach neuen Wirkstoffen als auch für die Wirkkontrolle in Industriebetrieben geeignet.

Aim of the study: I. Salicylate and heme oxygenase-1: The adhesion molecule P-selectin has been shown to be a major determinant of inflammatory responses. Different pharmacological agents including salicylate have been shown to inhibit IL-4-induced P-selectin expression in endothelial cells. Mechanisms responsible for P-selectin inhibition, however, are as yet not very well known. In the present work we confirmed this finding and aimed to elucidate the events leading to this inhibition. II. Metalloporphyrins and caspases: Apart from the beneficial effects of HO-1 on inflammatory processes, HO-1 is known to provoke anti-apoptotic effects. Metalloporphyrins are heme-analogous and are thus able to inhibit the activity of the heme-converting enzyme HO-1. Therefore, they are widely used and accepted tools in research investigating functional aspects of HO-1. In studies concerning the anti-apoptotic features of HO-1, different metalloporphyrins are often employed to either stimulate HO-1-expression or inhibit its activity. Apoptotic cell death is then quantified with various assay methods, such as the measurement of caspase-3-like activity. In an approach to determine potential anti-apoptotic features of ASA-induced HO-1 we observed contradictory results in a respective experimental setting. This led to the hypothesis that metalloporphyrins exert actions other than their well-known HO-1-dependent effects. Therefore, the second part of this work deals with the specificity of metalloporphyrins. Aim of the study was to find the cause for these contradictory results and further investigate a potential effect of the metalloporphyrins on caspase activity.

Oxidation reactions of sugars to their corresponding lactones and the selective oxidation of a secondary alcohol of sugar substrates to keto-sugars using transition metal catalysis were investigated. Research results demonstrate that Shvo’s hydrogen-transfer catalyst, [(η4-C4Ph4CO)(CO)2Ru]2, selectively oxidized unprotected sugars to δ-lactones under very mild conditions. This is the first method to synthesize δ-D-galactonolactone, the first oxidation product of the 3rd most abundant sugar. δ-D-Galactonolactone was fully characterized by conformational analysis through NMR experiments and computational methods. We propose that in aprotic, anhydrous solvents the δγ lactone rearrangement mechanism proceeds via a bicyclic transition state. The oxidation of alicyclic vicinal diols to α-hydroxy ketones was investigated as a model system for the selective oxidation of a secondary hydroxyl group in sugar substrates to keto-sugars. The challenge was to develop a method that allows selective oxidation, yet prevents over-oxidation to the dione or dicarboxylic acids products. Based on a mathematical model of consecutive bimolecular reactions, the rate constants for the initial oxidation step k1(diolα-OH ketone) and second oxidation step k2(α-OH ketonedione) must be k1 > 10 k2 in order to obtain a synthetically useful method for α-hydroxy ketone synthesis. The metal-ligand bifunctional hydrogen transfer reactions of Shvo’s catalyst and Noyori’s η6-arene N-tosyl-1,2-diaminoethane ruthenium(II) complexes were investigated with alcohol model systems and it was concluded that hydrogen transfer reactions are insufficient in the oxidation of vicinal diols due to a unfavourable position of the equilibrium. Under oxidizing conditions, the 16-electron ruthenium complexes of the Noyori systems compete with a β-elimination process and thus new degradation resistant ligands were synthesized. The apparent slower oxidation of Noyori’s η6-arene N-tosyl-1,2-diaminoethane ruthenium(II) complexes under oxidizing conditions, i.e. in acetone or cyclohexanone solvent, was investigated through NMR and IR experiments finding no evidence of a kinetic inhibition by the solvent. We propose that the slower reactions depend on a relatively high energy barrier for the reaction of the 16-electron complex with a hydrogen donor and that a kinetic model must account for two effectively different oxidation and reduction catalysts. In an alcohol/ketone equal-concentration experiment with Noyori-type ruthenium(II) complexes a linear relationship was found between the initial rate of alcohol consumption/production and ∆G°. Reactions involving peroxides as the oxidant were investigated in order to avoid equilibrium processes. The oxidation of alcohol model systems with several Mo and W catalysts and peroxide sources indicated a deactivation of the Mo and W catalysts by formation of water or hydroxide complexes. The product distribution of the oxidation of trans-1,2-cyclohexanediol with the MoO2(acac)2/Na2CO3 x 1.5 H2O2 method was in agreement with the theoretical model, yet only had a k1 = 1.5 k2 rate ratio resulting in a maximum α-hydroxy cyclohexanone content of 45 %. The NiBr2 mediated oxidation of alcohols and benzoylperoxide was investigated. The selective oxidation of vicinal diols was unsuccessful with this method. However, the oxidation reaction of mono-alcohol substrates was greatly improved using water in the reaction. The reaction mechanism was investigated and we propose that the actual oxidant in the NiBr2 mediated benzoylperoxide method is [Br+], which is generated by the hydrolysis product of benzoylhypobromite, hypobromic acid (HOBr). Ishii’s stoichiometric NaHSO3/NaBrO3 reagent selectively oxidized vicinal diols to α-OH ketone without overoxidation. This oxidation reaction was investigated with regards to substrate, concentration and pH. The reactivity and selectivity were studied and it was found that the oxidation mechanism is based on a multitude of comproportionation and disproportionation equilibria at low pH. A small but steadily replenished HOBr concentration is the source of the actual oxidant and effectively acts as a redox buffer. While the NaHSO3/NaBrO3 reagent demonstrated excellent selectivities with the alcohol model systems, the oxidation of sugar substrates failed due to side-reactions occurring at the required low pH.

In dieser Arbeit wurde zum ersten Mal der Einfluss des potentiellen Tumorsuppressors Pdcd4 auf das invasionsassoziierte Urokinase-Rezeptorgen(uPAR), sowie auf den Invasionsvorgang selbst, untersucht. In verschiedenen gastrointestinalen Karzinomzelllinien wurde eine gegenläufige Expression von uPAR und Pdcd4-mRNA und -Protein nachgewiesen. In Reportergen-Assays unter Verwendung von Wildtyp- und mutiertem uPAR-Promotor zeigte sich nach gleichzeitiger Transfektion von Pdcd4 eine dosisabhängige Suppression der uPARPromotoraktivität. Ferner wurden verschiedene cis-Elemente innerhalb des Promotors als potentielle Mediatoren dieser Regulation identifiziert. Bei diesen handelt es sich potentiell um die Region -402/-350bp mit mutmaßlichen Bindestellen für Sp-1, GATA-1, NF-1 und einem PEA3/ets Element an Position -245 bp. Zusätzlich konnte durch eine Mutation der kombinierten Bindungstelle für Sp-1 und Sp-3 an Position -152/-135bp, die über Pdcd4 ermittelte Suppression der Promotoraktivität aufgehoben werden. In Gelshiftanalysen zeigte sich neben einer verminderten Bindung von Transkriptionsfaktoren der GATA- und Sp-Familie innerhalb der Region -402/-350bp insbesondere eine Erhöhung der Bindung von Sp-3 an Promotorregion - 152/-135bp. Dies impliziert neben den oben genannten Mediatoren, dass Pdcd4 durch Induktion der Bindung von Sp-3 an dieses Element den uPAR-Promotor supprimiert. Darüber hinaus konnte durch die Expression von Pdcd4 die Invasionsfähigkeit der Kolonkarzinomzellinie HCT-116 in vivo reduziert werden. Diese Ergebnisse zeigen, dass Pdcd4 die Promotoraktivität von uPAR über verschiedene cis-aktive Elemente des Promotors supprimiert und belegen erstmals die Regulation eines invasionsassoziierten Gens durch den potentiellen Tumorsuppressor Pdcd4. Ferner wird erstmals Sp-3 als Mediator der Pdcd4 vermittelten Genexpression vorgeschlagen. Daneben postulieren die Invasionsdaten auch eine Funktion von Pdcd4 als potentiellen Suppressor von Teilschritten der Metastasierungskaskade. Zusätzlich konnte in dieser Arbeit ein neues quantitatives CAM-Modell etabliert werden, das die Invasion und Intravasation von Tumorzellen in vivo spezifisch im Hühnerei-Modell untersucht. Das Protokoll unterscheidet sich von den bisher publizierten Arbeiten durch die Verwendung einer spezifischen TaqMan-Probe in Zusammenfassung 116 Kombination mit Primern, die spezifisch humane Alu-Sequenzen der YB8-Unterfamilie nachweisen. Durch diese Modifikationen wurde eine höhere Sensitivität der quantitativen Alu-PCR erreicht. Zusätzlich eröffnet die Spezifität der hier entwickelten Primer über den CAM-Assay hinaus die Möglichkeit, humane Zellen und Mikrometastasen auch in murinen in vivo Modellen wie SCID- oder Nacktmäusen nachzuweisen.

This thesis describes crystal structures of complete, 12-subunit yeast RNA polymerase II (Pol II) in complex with a synthetic transcription bubble and product RNA, with an NTP substrate analogue, and in complex with the transcription elongation factor TFIIS. The structure of the Pol II-transcription bubble-RNA complex reveals incoming template and non-template DNA, a seven base-pair DNA-RNA hybrid, and three nucleotides each of separating DNA and RNA. Based on this structure, those parts of Pol II were identified which are involved in separating template DNA from non-template DNA before the active site, and DNA from product RNA at the upstream end of the DNA-RNA hybrid. In both instances, strand separation can be explained by Pol II-induced duplex distortions. Only parts of the complete transcription bubble present in the complexes are ordered in the crystal structure, explaining the way in which high processivity of Pol II is reconciled with rapid translocation along the DNA template. The presence of an NTP substrate analogue in a conserved putative pre-insertion site was unveiled in a Pol II-transcription bubble-RNA complex crystal soaked with the substrate analogue GMPCPP. The structure of the Pol II-TFIIS complex was obtained from Pol II crystals soaked with TFIIS. TFIIS extends from the Pol II surface to the active site and complements the active site with two essential and invariant acidic residues for hydrolytic RNA cleavage. TFIIS also induces extensive structural changes in Pol II that reposition nucleic acids, in particular RNA, near the active centre. These results support the idea that Pol II contains a single tuneable active site for RNA polymerisation and cleavage. The technical obstacles imposed by crystal structure determination of large, transient protein-DNA-RNA complexes were overcome by two novel, fluorescence-based assays to monitor and optimise the composition of the crystals. Both assays are not limited to Pol II complexes, but can serve as a general tool for the crystallographic community.

This thesis focuses on the experimental and theoretical investigation of tellurium pseudohalides, especially azides. Tellurium tetraazide, Te(N3)4, was prepared directly from TeF4 with Me3SiN3 as an extremely sensitive solid; and azidation of pentafluorotellurate(iv) TeF5- gave the pentaazidotellurate(iv) anion. The crystal structure of the pyridinium salt [pyH][Te(N3)5] consists of [Te(N3)5]- units, considerably distorted from ideal square pyramidal symmetry and linked by Te-N interactions between two anions. The labile tellurium cyanide species Te(CN)2 and Te(CN)4 have been prepared by treatment of tellurium(iv) tetrahalides with cyanide. Both are thermosensitive solids and in addition, the tetracyanide was found to be pyrophoric. Fluorination of R2Te (R = 2,4,6-Me3C6H2 (= Mes), 2,4,6-iPr3C6H2 (= Trip)) with xenon difluoride afforded the sterically demanding diorganotellurium(iv) difluorides R2TeF2. The reaction of R2TeF2 (R = Me, Ph, Mes, Trip) with trimethylsilyl cyanide resulted in the formation of either R2Te(CN)2 (R = Ph, Mes) or the tellanes R2Te (R = Me, Trip). The crystal structure of Te(CN)2, a binary tellurium cyanide and (Mes2TeCN)2O have been determined. All structures of Te(CN)2, Te(CN)4, and Te(CN)6 have been calculated at various levels of theory. The perfluoroaryl tellurolates C6F5TeLi and 4-CF3C6F4TeLi were prepared. These intermediates were identified by NMR spectroscopy and may form, depending on the reaction conditions, either the corresponding ditellanes (C6F5Te)2 and (4-CF3C6F4Te)2 by subsequent oxidation, or a telluranthrene (C6F4Te)2 depending on the reaction conditions. The halogenation products of (C6F4Te)2, (C6F4Te)2F4, (C6F4Te)2Cl4, (C6F4Te)2Br4, as well as the azidation product (C6F4Te)2(N3)4 were synthesized. Furthermore, in pursuit of our recent work on tellurium azides, the syntheses and properties of R2Te(N3)2 (R = CF3, C6F2H3) and RTe(N3)3 (R = CF3 and C6F5) are reported. The crystal structures of (CF3C6F4Te)2, (C6F4Te)2Br4, and (C6F2H3)2Te(N3)2 were determined. The reaction of azide with organotellurium(vi) halides Ph5TeBr and (biphen)2TeF2 (biphen = 2,2'-biphenyldiyl) resulted in the formation and isolation of Ph5TeN3 and (biphen)2Te(N3)2, which are the first tellurium(vi)-pseudohalide species. In addition to spectroscopic data, both crystal structures have been determined. Furthermore, the stability of possible Te(vi) species with higher azide contents PhxTe(N3)6-x and MexTe(N3)6-x as well as the syntheses and properties of their Ph/MexTeFy precursors were investigated, including the crystal structure determination of trans-Ph2TeF4. Ab initio and density functional studies of all molecules regarding the structures and electronic populations were performed. The first tellurium compounds containing the extremely bulky tris(phenyldimethylsilyl)methyl (Tpsi) and 2,6-bis(2,4,6-tri{isopropylphenyl)phenyl (2,6-Trip2C6H3) moieties have been synthesized and isolated. Careful oxidation of the tellurolate TpsiTeLi resulted in the formation of the crowded ditellane (TpsiTe)2; subsequent iodination gave the alkanetellurenyl iodide TpsiTeI. In a similar fashion, the terphenyl substituted ditellane (2,6-Trip2C6H3Te)2 and the arenetellurenyl iodide 2,6-Trip2C6H3TeI were prepared. Reaction of the tellurenyl iodides TpsiTeI, 2,6-Trip2C6H3TeI, as well as TripTeI, Mes*TeI and the donor-stabilized 2-Me2NCH2C6H4TeI with AgN3 resulted in the formation and isolation of the corresponding tellurenyl azides TpsiTeN3, TripTeN3, Mes*TeN3, 2,6-Trip2C6H3TeN3, and 2-Me2NCH2C6H4TeN3. Furthermore, the tris(ethyldimethylsilyl)methyl (Tesi) tellurium compounds (TesiTe)2, TesiTeI, and TesiTeN3 have been prepared, but could not be isolated in pure form. The crystal structures of TpsiTeLi, (TpsiTe)2, TpsiTeN3, 2,6-Trip2C6H3TeI, 2,6-Trip2C6H3TeN3, and 2-Me2NCH2C6H4TeN3 have been determined by X-ray diffraction. Additionally, computational studies of the molecules for which experimental structural data were available, were performed.