@phdthesis{Hartel2013,
  author    = {Hartel, Andreas J. W.},
  title     = {Die laterale Diffusion des variablen Oberfl{\"a}chenglykoproteins in Trypanosomen und in artifiziellen Membranen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-90997},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Die Diffusion von Membranproteinen spielt bei einer Vielzahl von zellbiologischen Prozessen eine zentrale Rolle. So hat die Beweglichkeit von Glykosyl-Phosphatidyl-Inositol-(GPI-) verankerten Proteinen zum Beispiel eine tragende Funktion bei der Alzheimer Krankheit, der Creutzfeldt-Jacob Krankheit und der Afrikanischen Schlafkrankheit. Der Erreger der Afrikanischen Schlafkrankheit, Trypanosoma brucei spec., pr{\"a}sentiert auf seiner Zelloberfl{\"a}che einen dichten Mantel aus identischen GPI-verankerten Proteinen. Diese sogenannten Variant Surface Glycoproteins (VSGs) stellen den zentralen Pathogenit{\"a}tsfaktor der Trypanosomen im Blutstrom des Wirtes dar und erm{\"o}glichen dem Parasiten die Antigene Variation. W{\"a}hrend der Antigenen Variation wird der VSGMantel durch einen immunologisch distinkten Mantel ersetzt. Hierf{\"u}r ist die Diffusion der VSG essentiell. In der vorliegenden Arbeit wird die Diffusion des VSG in lebenden Trypanosomen und in artifiziellen Membranen systematisch untersucht. Auf diese Weise werden der Einfluss der lateralen Proteindichte, der N-Glykosylierung und der Proteingr{\"o}ße auf die Diffusion der GPI-verankerten Proteine charakterisiert. Die Mobilit{\"a}t des VSG auf lebenden Trypanosomen ist an der Grenze zu einem Diffusionsschwellenwert, dieser wird allerdings nicht {\"u}berschritten. Die Mobilit{\"a}t des VSG in der N{\"a}he des Diffusionsschwellenwertes wird durch die N-Glykosylierung der VSG erm{\"o}glicht. Außerdem kann gezeigt werden, dass die Gr{\"o}ße der Proteine einen entscheidenden Einfluss auf den Diffusionskoeffizienten der GPI-verankerten Proteine aus{\"u}bt. Zusammengefasst zeigen die Ergebnisse der vorliegenden Arbeit deutlich, dass der VSG-Mantel der Trypanosomen ein, an seine Anforderungen, hoch-adaptiertes System darstellt. W{\"u}rde entweder die laterale Dichte, die N-Glykosylierung oder die Gr{\"o}ße der Proteine beeintr{\"a}chtigt werden, so w{\"a}re die Funktion der Antigenen Variation gest{\"o}rt und die Pathogenit{\"a}t des Parasiten gef{\"a}hrdet. Da die lokale Verteilung von GPI-verankerten Proteinen in biologischen Membranen ein wichtiges funktionelles Konzept darstellt, ist der Einfluss der untersuchten Faktoren nicht nur f{\"u}r den VSG-Mantel relevant, sondern kann auch f{\"u}r das generelle Verst{\"a}ndnis der Dynamik von Proteinen in zellul{\"a}ren Membranen dienen.},
  subject      = {Trypanosomen},
  language  = {de}
}
@phdthesis{Hofmann2023,
  author    = {Hofmann, Julian},
  title     = {Synthesis of Sterubin, Flavonoid Hybrids, and Curcumin Bioisosteres and Characterization of their Neuroprotective Effects},
  doi       = {10.25972/OPUS-26664},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266641},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Alzheimer´s disease (AD) is a neurodegenerative disease and the most common form of dementia with still no preventive or curative treatment. Besides several risk factors, age is one of the major risks for AD and with an aging society, there is an urgent need for disease modifying agents. The strategy to address only one target within the intertwined network of AD failed so far. Natural products especially the phytochemical flavonoids, which are poly-phenolic natural products, have shown great potential as disease modifying agents against neurodegenerative disorders like Alzheimer´s disease (AD) with activities even in vivo. Flavonoids are produced by many plants and the native Californian plant Eriodictyon californicum is particularly rich in flavonoids. One of the major flavonoids of E. californicum is sterubin, a very potent agent against oxidative stress and inflammation, two hallmarks and drivers of AD and neurodegeneration. Herein, racemic sterubin was synthesized and separated into its pure (R)- and (S)-enantiomer by chiral HPLC. The pure enantiomers showed comparable neuroprotection in vitro with no significant differences. The stereoisomers were configurationally stable in methanol, but fast racemization was observed in culture medium. Moreover, the activity of sterubin was investigated in vivo, in an AD mouse model. Sterubin showed a significant positive impact on short- and long-term memory at low dosages. A promising concept for the increase of activity of single flavonoids is hybridization with aromatic acids like cinnamic or ferulic acids. Hybridization of the natural products taxifolin and silibinin with cinnamic acid led to an overadditive effect of these compounds in phenotypic screening assays related to neurodegeneration and AD. Because there are more potent agents as taxifolin or silibinin, the hybrids were further developed, and different flavonoid cinnamic acid hybrids were synthesized. The connection between flavonoids and cinnamic acid was achieved by an amide instead of a labile ester to improve the stability towards hydrolysis to gain better "druggability" of the compounds. To investigate the oxidation state of the C-ring of the flavonoid part, the dehydro analogues of the respective hybrids were also synthesized. The compounds show neuroprotection against oxytosis, ferroptosis and ATP-depletion in the murine hippocampal cell line HT22. While no overall trend within the flavanones compared to the flavones could be assigned, the taxifolin and the quercetin derivative were the most active compounds in course of all assays. The quercetin derivate even shows greater activity than the taxifolin derivate in every assay. As desired no hydrolysis product was found in cellular uptake experiments after 4h, whereas different metabolites were found. The last part of this work focused on synthetic bioisoteres of the natural product curcumin. Due to the drawbacks of curcumin and flavonoids arising from poor pharmacokinetics, rapid metabolism and sometimes instability in aqueous medium, we have examined the biological activity of azobenzene compounds designed as bioisoteres of curcumin, carrying the pharmacophoric catechol group of flavonoids. These bioisosteres exceeded their parent compounds in counteracting intracellular oxidative stress, neuroinflammation and amyloid-beta aggregation. By incorporating an azobenzene moiety and the isosteric behaviour to the natural parent compounds, these compounds may act as molecular tools for further investigation towards the molecular mode of action of natural products.},
  subject      = {Organische Synthese},
  language  = {en}
}
@phdthesis{Schoeppler2012,
  author    = {Sch{\"o}ppler, Friedrich Eugen},
  title     = {Photolumineszenzmikroskopie und-spektroskopie halbleitender Kohlenstoffnanor{\"o}hren},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-73329},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2012},
  abstract  = {Im Rahmen dieser Dissertation wurden optische Eigenschaften von halbleitenden, einwandigen Kohlenstoffnanor{\"o}hren (SWNTs) der (6,5)-Chiralit{\"a}t untersucht. Dies gelang durch Ensemblemessungen aber vor allem durch den Aufbau eines Mikroskops zur Messung an einzelnen SWNTs. Dieses Einzel- SWNT-Mikroskop erm{\"o}glichte nebst „normaler" Bildgebung durch Sammlung und Abbildung der nahinfraroten Photolumineszenz (PL) der (6,5)-SWNTs auch die spektral- und zeitaufgel{\"o}ste Untersuchung der PL. Durch Verwendung von Dichtegradientenultrazentrifugation (DGU) zur chiralen Aufreinigung des SWNT-Rohmaterials konnten alle Messungen unter Minimierung des st{\"o}renden Einflusses von Aggregaten oder SWNTs anderer Chiralit{\"a}t durchgef{\"u}hrt werden. Untersucht und bestimmt wurde der Absorptionsquerschnitt und die Exzitonengr{\"o}ße, die PL-Eigenschaften aggregierter SWNTs und der Einfluß der Permittivit{\"a}t auf die PL einzelner SWNTs.},
  subject      = {Mikroskopie},
  language  = {de}
}
@phdthesis{Buettner2013,
  author    = {B{\"u}ttner, Tobias},
  title     = {Totalsynthese mono- und dimerer Naphthylisochinolin-Alkaloide sowie Isolierung acetogeniner Sekund{\"a}rmetabolite aus Wurzelkulturen von Triphyophyllum peltatum},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77371},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Die pal{\"a}otropischen Pflanzenfamilien der Ancistrocladaceae und Dioncophyllaceae sind die bisher einzig bekannten Produzenten von Naphthylisochinolin-Alkaloiden. Diese spezielle Klasse acetogeniner Sekund{\"a}rmetabolite weist durch die verschiedenen Kupplungspositionen der beiden namensgebenden Molek{\"u}lbausteine eine breite strukturelle Diversit{\"a}t auf und zeichnet sich durch vielf{\"a}ltige pharmakologische Wirksamkeiten, z.B. antiplasmodiale, antileishmaniale oder antitrypanosomale Aktivit{\"a}ten, aus. Zur Synthese dieser Naturstoffe wurde im Arbeitskreis Bringmann eigens eine Methodik entwickelt, das Lacton -Konzept. Diese Methode erlaubt durch eine Vorfixierung der beiden Molek{\"u}lh{\"a}lften durch eine Esterbr{\"u}cke, anschließender intramolekularer Kupplungsreaktion und der stereoselektiven {\"O}ffnung des erhaltenen Lactons den atropselektiven Aufbau der Naphthylisochinoline. Als Ziele dieser Arbeit ergaben sich somit die Synthese pharmakologisch und strukturell interessanter Naphthylisochinolin-Alkaloide mittels des Lacton-Konzepts sowie die Isolierung und Strukturaufkl{\"a}rung weiterer Sekund{\"a}rmetabolite aus Triphyophyllum peltatum (Dioncophyllaceae), welche anschließend auf ihre Bioaktivit{\"a}t hin untersucht werden sollten, um potenziell neue Leitstrukturen f{\"u}r neue Wirkstoffe zu finden.},
  subject      = {Naphthylisochinolinalkaloide},
  language  = {de}
}
@phdthesis{SanchezNaya2023,
  author    = {S{\´a}nchez Naya, Roberto},
  title     = {Synthesis and Characterization of Dye-Containing Covalent Organic Frameworks},
  doi       = {10.25972/OPUS-28899},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288996},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {The present thesis adress the synthesis and characterization of novel COFs that contain dye molecules as integral components of the organic backbone. These chromophore-containing frameworks open new research lines in the field and call for the exploration of applications such as catalysis, sensing, or in optoelectronic devices. Initially, the fabrication of organic-inorganic composites by the growth of DPP TAPP COF around functionalized iron oxide nanoparticles is reported. By varying the ratio between inorganic nanoparticles and organic COFs, optoelectronic properties of the materials are adjusted. The document also reports the synthesis of a novel boron dipyrromethene-containing (BODIPY) COF. Synthesis, full characterization and the scope of potential applications with a focus on environmental remediation are discussed in detail. Last, a novel diketopyrrolopyrrole-containing (DPP) DPP-Py-COF based on the combination of DDP and pyrene building blocks is presented. The very low bandgap of these materials and initial investigations on the photosensitizing properties are discussed.},
  subject      = {Organische Chemie},
  language  = {en}
}
@phdthesis{Hogenmueller2007,
  author    = {Hogenm{\"u}ller, Boris},
  title     = {Xenophon, Apologie des Sokrates : Ein Kommentar},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29530},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Der Hauptschwerpunkt dieser Untersuchung liegt auf dem Versuch, die noch immer nicht gekl{\"a}rte Frage nach der chronologischen Einordnung von Xenophons Kleinschrift <Apologie des Sokrates> in Xenophons Œuvre zu beantworten. Gerade der eingehende Vergleich mit verschiedenen sokratischen Schriften (u.a. <Memorabilien>, Platons <Apologie>, <Kriton> und <Phaidon>) liefert hierbei aufschlussreiche Ergebnisse. Im zweiten Teil folgt ein ausf{\"u}hrlicher philologisch-literarischer Kommentar der Kleinschrift, woran sich abschließend zwei kleinere Untersuchungen zu Sokrates' sprichw{\"o}rtlicher ‚megalegoria' und der Tradition der sokratischen Apologienschriftstellerei anschließen.},
  subject      = {Xenophon},
  language  = {de}
}
@phdthesis{Hipondoka2005,
  author    = {Hipondoka, Martin H.T.},
  title     = {The development and evolution of Etosha Pan, Namibia},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-14351},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {This study explores and examines the geomorphology of a large endorheic basin, approximately twice the size of Luxemburg, situated in the Etosha National Park, Namibia. The main focus is directed on how and when this depression, known as Etosha Pan, came into being. Geomorphological investigation was complemented and guided primarily by the application and interpretation of satellite-derived information. Etosha Pan has attracted scientific investigations for nearly a century. Unfortunately, their efforts resulted into two diverging and mutually exclusive views with respect to its development. The first and oldest view dates back to the 1920s. It hypothesized Etosha Pan as a desiccated palaeolake which was abandoned following the river capture of its major fluvial system, the Kunene River. The river capture was assumed to have taken place in the Pliocene/Early Pleistocene. In spite of the absence of fluvial input that the Kunene contributed, the original lake was thought to have persisted until some 35 ka ago, long after the Kunene severed its ties with the basin. The current size of the basin and its playa status was interpreted to have resulted from deteriorating climatic conditions. The opposing view emerged in the 1980s and gained prominence in the 1990s. This view assumed that there were an innumerable number of small pans on the then surface of what later to become Etosha Pan. Since the turn of the Pliocene to Early Pleistocene, these individual pans started to experience a combined effect of fluvial erosion during the rainy season and wind deflation during the dry period. The climatic regime during that entire period was postulated to be semi-arid as today. This climatic status was used to rule out any existence of a perennial lake within the boundary of Etosha since the Quaternary. Ultimately, these denudational processes, taking place in a seasonal rhythm, caused the individual pans to deepen and widen laterally into each other and formed a super-pan that we call Etosha today. Thus the Kunene River had no role to play in the development of the Etosha Pan according to this model. However, proponents of this model acknowledged that the Kunene once fed into the Owambo Basin and assigned the end of the Tertiary to the terminal phase of that inflow. Findings of this study included field evidence endorsing the postulation that the Kunene River had once flowed into the Owambo Basin. Its infilled valley, bounding with the contemporary valley of the Kunene near Calueque, was identified and points towards the Etosha Pan. It is deliberated that a large lake, called Lake Kunene, existed in the basin during the time. Following the deflection of the Kunene River to the coast under the influence of river incision and neo-tectonic during the Late Pliocene, new dynamics were introduced over the Owambo Basin surface. After the basin was deprived of its major water and sediment budget that the Kunene River contributed, it was left with only smaller rivers, most notably the Cuvelai System, as the only remaining supplier. This resulted in the Cuvelai System concentrating and limiting its collective load deposition to a lobe of Lake Kunene basin floor. The accident of that lobe is unclear, but it is likely that it constituted the deepest part of the basin at the time or it was influenced by neo-tectonic that helped divert the Kunene River or both. Against the backdrop of fluvial action that was initiating the new lake, most parts of the rest of the basin, then denied of lacustrine activity, were intermittently riddled with a veneer of sediment, especially during phases of intensified aeolian activity. In the mean time, the area that was regularly receiving fluvial input started to shape up as a distinct lake with the depositions of sediments around the water-body, primarily via littoral action, serving as embankment. Gradually, a shoreline is formed and assisted in fixing and delineating the spatial extent of the new and much smaller lake, called Lake Etosha. That Lake Etosha is the predecessor of the modern day Etosha Pan. Indicators for a perennial lake found in this study at Etosha include fossil fragments of Clariidae species comparable to modern species measuring some 90 cm, and those of sitatunga dated to approximately 5 ka. None of these creatures exist today at Etosha because of their ecological requirements, which among others, include permanent water. The sitatunga, in addition, is known as the only truly amphibious antelope in the world. Since its inception, the new lake underwent a number of geomorphological modifications. A prominent character amongst these modifications is the orientation of the lake, which has its long-axis oriented in the ENE-WSW direction. It resulted from wave action affected by the prevailing dominant northeasterly wind, which is believed to have been in force since the Middle Pleistocene. Lake Etosha has also witnessed phases of waning and waxing under the influence of the prevailing climatic regime. Over the last 150 ka, the available data intercepted about seven phases of high lake levels. These data are generally in agreement with regional palaeoclimatic data, particularly when compared with those obtained from neighbouring Makgadikgadi Pans in Botswana. The last recorded episode of the wet phase at Etosha was some 2,400 years before the present.},
  subject      = {Etoschapfanne},
  language  = {en}
}
@phdthesis{Kaufmann2011,
  author    = {Kaufmann, Franziska},
  title     = {Chirurgische Hernienbehandlung im Juliusspital zu W{\"u}rzburg im ausgehenden 19. Jahrhundert},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-57572},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Ausgangspunkt dieser Dissertation waren 23 aus den Jahren 1883 und 1893 {\"u}berlieferte handschriftliche Krankenbl{\"a}tter der chirurgischen Abteilung des Juliusspitals zu W{\"u}rzburg. Ziel war es, anhand dieser Krankenbl{\"a}tter eine retrospektive Sicht in den Operationssaal des Juliusspitals zu erm{\"o}glichen und insbesondere die chirurgische Hernienbehandlung im ausgehenden 19. Jahrhundert zu rekonstruieren. Das Augenmerk galt dem chirurgischen Tagesgesch{\"a}ft: Es sollte aufgezeigt werden, wie sich dieses innerhalb von 10 Jahren ver{\"a}ndert hat und wie diese Ver{\"a}nderung im Kontext interpretiert werden k{\"o}nnen. Es wurden quantitative und qualitative Aspekte untersucht (quantitative Aspekte: 1. Geschlechterrelation, 2. Relation {\"U}berlebende/Verstorbene, 3. Relation operative/konservative Behandlung; qualitative Aspekte: 1. formaler Vergleich, 2. stilistische Vergleich, 3. Arzt-Patienten-Verh{\"a}ltnis, 4. Anti-/Asepsis 5. Arzneimittel 6. Heilungsbegriff 7. Vergleich Operationstechniken). Eine besondere Bedeutung kommt dem gl{\"u}cklichen Zufall zu, dass zeitgen{\"o}ssische Publikationen existieren, welche zum Teil die im Original {\"u}berlieferten Krankengeschichten enthalten. Somit konnte eine Querverbindung zwischen gelehrter Theorie und Praxis gezogen werden und untersucht werden, ob Erstere auch im Alltag umgesetzt wurde. Trotz der nur l{\"u}ckenhaften {\"U}berlieferung und der Tatsache, dass die Krankenbl{\"a}tter urspr{\"u}nglich nicht zu dem Zweck geschrieben wurden, zu welchem sie im Rahmen dieser Dissertation verwendet wurden, war durch sie eine retrospektive Sicht in den Operationssaal des Juliusspitals des ausgehenden 19. Jahrhunderts m{\"o}glich, welche ohne ihre {\"U}berlieferung vom heutigen Standpunkt aus nicht mehr zu rekonstruieren w{\"a}re.},
  subject      = {Hernie},
  language  = {de}
}
@phdthesis{Hofmann2021,
  author    = {Hofmann, Markus},
  title     = {Die palliative und kurative Behandlung von Hernien am St. Johanns Spital in Salzburg im fr{\"u}hen 19. Jahrhundert},
  doi       = {10.25972/OPUS-23517},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235175},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Die Palliativmedizin gilt oft als ein vergleichsweise junges Themengebiet, welches in den zur{\"u}ckliegenden Jahrzehnten kontinuierlich an Bedeutung gewinnen konnte. Palliativmedizin ist jedoch keine reine Erfindung des 20. Jahrhunderts. So galt die Versorgung Schwerkranker oder Sterbender bereits viel fr{\"u}her als {\"a}rztliche Pflicht. Grundgedanke der Arbeit war es, palliativmedizinische Facetten im {\"a}rztlichen Handeln zu Beginn des 19. Jahrhunderts nachzuweisen. Hierzu erfolgte eine beispielhafte Betrachtung der chirurgische Hernien-Therapie des St. Johanns Spitals in Salzburg. Als Grundlage dienten handschriftlich verfasste Krankengeschichten des St. Johanns Spitals aus der ersten H{\"a}lfte des 19. Jahrhunderts. Neben der Detektion und einer vergleichenden Darstellung palliativmedizinischer Handlungsweisen gelang mit Hilfe der in ihrer Ausf{\"u}hrlichkeit bemerkenswerten Prim{\"a}rquelle eine Darstellung der damaligen chirurgischen Hernientherapie am Salzburger St. Johanns Spital. Erg{\"a}nzend erfolgt ein Vergleich mit zeitgen{\"o}ssischen Ver{\"o}ffentlichungen zur Thematik der Hernienchirurgie, welche sich zum damaligen Zeitpunkt am Vorabend zur Asepsis bereits in einem Prozess des Umbruchs befand.},
  subject      = {Hernie},
  language  = {de}
}
@phdthesis{Faber2007,
  author    = {Faber, Johan Henrik},
  title     = {Naphthylisoquinoline Alkaloids : Structural Elucidation, Metabolism and Functional Analysis of their Bioactivities},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-22789},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {This thesis deals with the isolation and structural elucidation of bioactive naphthylisoquinoline alkaloids and related analogs. The mode of action of the antiplasmodial activity exhibited by the naphthylisoquinoline alkaloids was explored and compared to that of the antimalarial drug chloroquine. Furthermore, the phase 1 and 2 metabolism of dioncophyllines A and C and dioncopeltine A were investigated. In detail the following results have been obtained: • From the leaves of the recently discovered East African liana A. tanzaniensis six naphthylisoquinoline alkaloids were isolated. • The leaves of a botanical yet undescribed Ancistrocladus species, collected by Prof. Dr. V. Mudogo in the Democratic Republic of Congo in the habitat Yeteto near the town Ikela, were analyzed for naphthylisoquinoline alkaloids for the first time. The isolation work led to the first identification of an N,C-coupled naphthyldihydroisoquinoline alkaloid; ancistrocladinium B. Phytochemical investigation of the roots of the Congolese Ancistrocladus species (habitat Yeteto), , afforded five new derivatives of known naphthylisoquinoline alkaloids, namely 5'-O-demethylhamatine, 5'-O-demethylhamatinine, 6-O-demethylancistroealaine A, 6,5'-O,O-didemethylancistroealaine A, and 5-epi-6-O-methylancistrobertsonine A, along with six known naphthylisoquinoline alkaloids. • The antiplasmodial activity guided purification of 60Co irradiated samples containing commercially available naphthylisoquinoline related substances, afforded the isolation of the irradiation products 3,4-dihydro-1-isoquinolinone, 3,4-dihydro-1-isoquinolineamine, and 1,2,3,4-tetrahydro-1,2-diazirino-isoquinoline. The compounds were found to be more active than the starting material, although only exhibiting weak antiplasmodial activity against P. falciparum. • The effect on the absorption spectrum of FPIX due to complex formation with the naphthylisoquinoline alkaloids dioncophyllines A and C, dioncopeltine A korupensamine A, and ancistrocladine was examined by a titration study. Job's plot analyses by UV-spectroscopy determined the stoichiometry for the complex formation of FPIX and naphthylisoquinoline alkaloids to be 2:1. Furthermore, the dissociation constants for the complexation with FPIX were determined for each of the naphthylisoquinoline alkaloids investigated. Dioncophylline C and dioncopeltine A were found to possess dissociation constants, which are comparable to the one reported for the antimalarial drug chloroquine. The ability of ESI to transfer noncovalent solution-phase assemblies intact into the gas phase, was conducted on solution mixtures of naphthylisoquinoline alkaloid and FPIX, as well as on mixtures of chloroquine and FPIX. The mass spectrometry analyses revealed several peaks, which corresponded to the complex formation of FPIX to the respective ligands investigated. The most interesting results obtained were the detection of peaks corresponding to the complex formation between a chelated dimer of FPIX and dioncophylline Cand of peaks corresponding to a double protonated tetramer of FPIX - consisting of two chelated \&\#61549;-oxo dimers of FPIX - in complex formation with two molecules of chloroquine. • Two phase 1 metabolism products of dioncophylline A were identified. Coelution in combination with HPLC-MS/MS, NMR, and CD investigations assigned the major metabolic product as 5'-O-demethyldioncophylline A. The minor metabolic product was only present in small amounts, which disabled an unambiguous structural characterization of the compound. However, as deduced from the mass spectrometry analyses and exclusion of a possible metabolic oxidation product by coelution with authentic reference material, the metabolite should possess a 4-hydroxylated isoquinoline portion and is assumed to be represented by structure. Dioncophylline C and dioncopeltine A were found to be stable to phase 1 metabolism reactions caused by rat liver microsomes.},
  subject      = {Naphthylisochinolinalkaloide},
  language  = {en}
}