Refine
Has Fulltext
- yes (16)
Is part of the Bibliography
- yes (16)
Document Type
- Doctoral Thesis (16)
Keywords
- NMR-Spektroskopie (3)
- Bioverfügbarkeit (2)
- Pharmazeutischer Hilfsstoff (2)
- Solubilisation (2)
- Alkaloid (1)
- Alkaloide (1)
- Ancistrocladaceae (1)
- Ancistrocladus (1)
- Anti-infectious activity (1)
- Antiausterity activity (1)
Institute
Sonstige beteiligte Institutionen
Durch stetige Entwicklung der Mikroskopiemethoden in den letzten Jahrzehnten ist es nun möglich Strukturen und Abläufe in biologischen Systemen detaillierter darzustellen als mit der von Abbe entdeckten maximalen Auflösungsgrenze. Oft werden dabei Fluoreszenzmarker benutzt, welche die unsichtbare Welt der Mikrobiologie und deren biochemische Prozesse illuminieren. Diese werden entweder durch Expression, wie z.B. das grün fluoreszierende Protein (GFP), in das zu untersuchende Objekt eingebracht oder durch klassische Markierungsmethoden mithilfe von fluoreszierenden Immunkonjugaten installiert. Jedoch gewinnt eine alternative Strategie, die von der interdisziplinären Zusammenarbeit zwischen Chemikern, Physikern und Biologen profitiert, immer mehr an Bedeutung – die bioorthogonale Click-Chemie. Sie ermöglicht eine effiziente Fluoreszenzmarkierung der biologischen Strukturen unter minimalem Eingriff in die Abläufe der Zelle. Dazu müssen allerdings sowohl Farbstoffe als auch die biologisch aktiven Substanzen chemisch modifiziert werden, da nur dadurch die Bioorthogonalität gewährleistet werden kann.
Mittlerweile existiert eine breite Palette an fluoreszierenden Farbstoffen, die das komplette sichtbare Spektrum abdecken und sich für diverse Mikroskopiemethoden eignen. Allerdings gibt es zwei Farbstoffklassen, die sich aus der gesamten Fülle abheben und sich für hochauflösende bildgebende Experimente auf Einzelmolekülebene eignen. Zum einen ist es die Farbstofffamilie der Cyanine und insbesondere der wasserlöslichen Pentamethincyanine, die reversibel und kontrolliert zum Photoschalten animiert werden können und in der stochastisch optischen Rekonstruktionsmikroskopie Anwendung finden. Zum anderen ist es die Gruppe, der Rhodamine und Fluoresceine, die zu Xanthenfarbstoffen gehören und sich durch gute photophysikalische Eigenschaften auszeichnen.
Trotz der Beliebtheit stellt ihre Darstellung immer noch eine Herausforderung dar und limitiert deren Einsatz. Deshalb war es notwendig im Rahmen der vorliegenden Arbeit Möglichkeiten zur Syntheseoptimierung beider Farbstoffklassen zu finden, damit diese im Folgenden weiterentwickelt und an die biologische Fragestellung angepasst werden können. Die Arbeit unterteilt sich deshalb in Relation an die oben genannten Farbstoffklassen in zwei Bereiche. Im ersten Teil wurden Projekte basierend auf den wasserlöslichen Pentamethincyaninen behandelt. Im zweiten Teil beschäftigte sich die Arbeit mit Projekten, die auf Xanthen-Farbstoffen aufbauen.
For the quality assurance of substances for pharmaceutical use, a variety of analytical techniques are available to address specific analytical problems. In this field of application, liquid chromatography (LC) stands out as the gold standard in the pharmaceutical industry. Various detectors can be employed, which are e.g. based on UV/Vis spectroscopy for the examination of molecules with a chromophore, or mass spectrometry (MS) for structural elucidation of analytes. For the separation of enantiomers, the use of capillary electrophoresis (CE) may be more favorable due to the high separation efficiency and easy-to-use and comparatively inexpensive chiral selectors, in contrast to chiral columns for LC, which are usually very expensive and limited to a restricted number of analytes. For structure elucidation in impurity profiling, one- and multidimensional 1H NMR spectroscopy is a valuable tool as long as the analyte molecule has got nuclei that can be detected, which applies for the magnitude of organic pharmaceutical substances.
For the evaluation of the amount of mineral oil aromatic hydrocarbons (MOAH) in various paraffin samples from different suppliers, a straightforward method based on 1H NMR spectroscopy was elaborated. The MOAH/MOSH ratio was used to indicate the amount of MOAH of paraffins and to evaluate the extent of refining. In addition, a representative paraffin sample was measured without sample solvent at high temperatures (about 340 K) to avoid the interfering residual solvent signals in the spectral regions of interest. The results of both methods were in good accordance.
Moreover, the 1H NMR results were complemented with the UV measurements from the purity testing of paraffins according to the DAB 8. Correlations of the NMR and UV spectroscopic data indicated a linear relationship of both methods for the determination of MOAH in paraffins.
Finally, the 1H NMR data was evaluated by principal component analysis (PCA) to explore differences within the paraffin samples and the spectral regions in the 1H NMR spectrum which are responsible for the formation of groups. It could be found that most variation is due to the MOSH of the paraffins. The PCA model was capable of differentiating between soft, liquid and solid paraffins on the one hand and between natural and synthetic liquid paraffins on the other hand.
The impurity profiling of L-ascorbic acid 2-phosphate magnesium (A2PMg) was performed by means of one- and two-dimensional NMR spectroscopy. Several ethylated impurities could be detected, which were likely to be formed during synthesis of A2PMg. The structures of two of the ethylated impurities were identified as ascorbic acid 2-phosphate ethyl ester and ethanol, (residual solvent from synthesis). NMR spectroscopic studies of the fractions obtained from preparative HPLC of A2PMg revealed two additional impurities, which were identified as phosphorylated derivatives of ascorbic acid, ascorbic acid 3,5-phosphate and ascorbic acid 5-phosphate.
Solid state mechanochemistry as an alternative approach for stress testing was applied on the drug substances S-Ibuprofen (Ibu) and Clopidogrel (CLP) using a ball mill, in order to study their degradation profile:
First, the isomerization of S-Ibu was investigated, which was stressed in the solid state applying several milling frequencies and durations under basic, acidic and neutral conditions. For the separation of Ibu enantiomers, a chiral CE method was developed and validated according to ICH Q2(R1). It was found that S-Ibu is overall very stable to isomerization; it shows minor conversion into the R-enantiomer under basic environment applying long milling times and high frequencies.
Last, the degradation profile of clopidogrel hydrogen sulfate (CLP) was investigated, which was stressed in the solid state under various oxidative conditions. An already existing HPLC-UV method was adjusted to sufficiently separate the degradation products, which were characterized by means of UV and MS/(MS) detection. Most of the degradation products identified were already reported to result from conventional CLP stress tests. The degradation profile of CLP was mainly influenced by the material of the milling jar and the type of catalyst used.
Vom Monomer zum Polymer: Iterative Synthese und optische Spektroskopie von Squarain-Oligomeren
(2022)
Mittels einer Schutzgruppenstrategie wurden Squarain-basierte monodisperse Oligomere synthetisiert. Die lösungsmittelabhängigen Konformationen (Random Coil vs. Helix) wie auch der Faltungsprozess der Homooligomere wurden mittels optischer Spektroskopie, verschiedener NMR-Experimenten, Kleinwinkelneutronenstreuungsexperimenten sowie quantenchemischen Berechnungen näher beleuchtet. Die optisch-spektroskopischen Beobachtungen wurden mithilfe der Exzitonenkopplungstheorie und einer Orientierungs- und Winkelabhängigkeit der Übergangsdipolmomente der Oligomere erklärt. Der hohe Windungsabstand der helikalen Konformation führt zu einer Interkalation von Lösungsmittel, wodurch eine Art Klathrat gebildet wird. Zusätzlich wurden mittels eines Frenkel-Exzitonenmodells die Absorptions- und Fluoreszenzspektren modelliert. Es konnten die Exzitonendelokalisationslängen abgeschätzt und die Auswirkung der energetischen und strukturellen Unordnungen auf die Absorptions- und Fluoreszenzspektren bestimmt werden. Die Absorptionsspektren werden vorwiegend durch strukturelle Unordnungen verbreitert, die Fluoreszenzspektren dagegen von energetischen Übergangsenergieabweichungen.
Weiterhin wurden auch alternierende Squarain-Cooligomere synthetisiert und mittels optischer Spektroskopie untersucht. Es wurde, abhängig von dem gewählten Lösungsmittel, eine Verschiebung der Hauptbande beobachtet, was durch einen Random Coil vs. helikale-/schlaufenartige Konformation erklärt wird. Gestützt wurde dies mittels quantenchemischen Berechnungen der jeweiligen Konformationen.
Abschließend wurden alternierende Squarain-Copolymere synthetisiert, in verschiedenen Größen aufgetrennt und mittels optischer Spektroskopie untersucht. Mittels EEI2D-Experimenten wurde die Exzitonendynamik in Abhängigkeit von der Kettenlänge eingehender untersucht. Hierbei wird eine steigende, aber relativ abnehmende Kohärenzlänge bestimmt, die Auswirkungen auf die Exzitonendynamik hat. Der Exzitonentransport weist erst wellenförmiges und dann subdiffuses Verhalten auf.
Nucleic acids are one of the important classes of biomolecules together with carbohydrates, proteins and lipids. Both deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are most well known for their respective roles in the storage and expression of genetic information.
Over the course of the last decades, nucleic acids with a variety of other functions have been discovered in biological organisms or created artificially. Examples of these functional nucleic acids are riboswitches, aptamers and ribozymes. In order to gain information regarding their function, several analytical methods can be used.
Electron paramagnetic resonance (EPR) spectroscopy is one of several techniques which can be used to study nucleic acid structure and dynamics. However, EPR spectroscopy requires unpaired electrons and because nucleic acids themselves are not paramagnetic, the incorporation of spin labels which carry a radical is necessary.
Here, three new spin labels for the analysis of nucleic acids by EPR spectroscopy are presented. All of them share two important design features. First, the paramagnetic center is located at a nitroxide, flanked by ethyl groups to prevent nitroxide degradation, for example during solid phase synthesis. Furthermore, they were designed with rigidity as an important quality, in order to be useful for applications like pulsed electron double resonance (PELDOR) spectroscopy, where independent motion of the spin labels relative to the macromolecule has a noticeable negative effect on the precision of the measurements.
Benzi-spin is a spin label which differs from most previous examples of rigid spin labels in that rather than being based on a canonical nucleoside, with a specific base pairing partner, it is supposed to be a universal nucleoside which is sufficiently rigid for EPR measurements when placed opposite to a number of different nucleosides. Benzi-spin was successfully incorporated into a 20 nt oligonucleotide and its base pairing behavior with seven different nucleosides was examined by UV/VIS thermal denaturation and continuous wave (CW) EPR experiments. The results show only minor differences between the different nucleosides, thus confirming the ability of benzi-spin to act as a universally applicable spin label.
Lumi-spin is derived from lumichrome. It features a rigid scaffold, as well as a free 2'-hydroxy group, which should make it well suited for PELDOR experiments once it is incorporated into RNA oligonucleotides.
EÇr is based on the Ç family of spin labels, which contains the most well known rigid spin labels for nucleic acids to this day. It is essentially a version of EÇm with a free 2'-hydroxy group. It was converted to triphosphate EÇrTP and used for primer extension experiments to test the viability of enzymatic incorporation of rigid spin labels into oligonucleotides as an alternative to solid-phase synthesis. Incorporation into DNA by Therminator III DNA polymerase in both single-nucleotide and full-length primer extensions was achieved.
All three of these spin labels represent further additions to the expanding toolbox of EPR spectroscopy on nucleic acids and might prove valuable for future research.
The bile system in vertebrates is an evolutionary conserved endogenous solubilization system for hydrophobic fats and poorly water-soluble vitamins. Bile pours out from the gallbladder through the common bile duct into the duodenum triggered by cholecystokinin. Cholecystokinin is released from enteroendocrine cells after food intake. The small intestine is also the absorption site of many orally administered drugs. Most emerging drug candidates belong to the class of poorly water-soluble drugs (PWSDs). Like hydrophobic vitamins, these PWSDs might as well be solubilized by bile. Therefore, this natural system is of high interest for drug formulation strategies. Simulated intestinal fluids containing bile salts (e.g., taurocholate TC) and phospholipids (e.g., lecithin L) have been widely applied over the last decade to approximate the behavior of PWSDs in the intestine. Solubilization by bile can enhance the oral absorption of PWSDs being at least in part responsible for the positive “food effect”. The dissolution rate of PWSDs can be also enhanced by the presence of bile. Furthermore, some PWSDs profit from supersaturation stabilization by bile salts. Some excipients solubilizing PWSDs seemed to be promising candidates for drug formulation when investigated in vitro without bile. When tested in vivo, these excipients reduced the bioavailability of drugs. However, these observations have been hardly examined on a molecular level and general links between bile interaction in vitro and bioavailability are still missing.
This thesis investigated the interplay of bile, PWSDs, and excipients on a molecular level, providing formulation scientists a blueprint for rational formulation design taking bile/PWSD/excipient/ interaction into account. The first chapter focus on an in silico 1H nuclear magnetic resonance (NMR) spectroscopy-based algorithm for bile/drug interaction prediction. Chapter II to IV report the impact of excipients on bioavailability of PWSDs interacting with bile. At last, we summarized helpful in vitro methods for drug formulation excipient choice harnessing biopharmaceutic solubilization in chapter V.
Chapter I applies 1H NMR studies with bile and drugs on a large scale for quantitative structure-property relationship analysis. 141 drugs were tested in simulated intestinal media by 1H NMR. Drug aryl-proton signal shifts were correlated to in silico calculated molecular 2D descriptors. The probability of a drug interacting with bile was dependent on its polarizability and lipophilicity, whereas interaction with lipids in simulated intestinal media components was dependent on molecular symmetry, lipophilicity, hydrogen bond acceptor capability, and aromaticity. The probability of a drug to interact with bile was predictive for a positive food effect. This algorithm might help in the future to identify a bile and lipid interacting drug a priori.
Chapter II investigates the impact of excipients on bile and free drug fraction. Three different interaction patterns for excipients were observed. The first pattern defined excipients that interacted with bile and irreversibly bound bile. Therefore, the free drug fraction of bile interacting drugs increased. The second pattern categorized excipients that formed new colloidal entities with bile which had a high affinity to bile interacting drugs. These colloids trapped the drug and decreased the free drug fraction. The last excipient pattern described excipients that formed supramolecular structures in coexistence with bile and had no impact on the free drug fraction. These effects were only observed for drugs interacting with bile (Perphenazine and Imatinib). Metoprolol’s free drug fraction, a compound not interacting with bile, was unaffected by bile or bile/excipient interaction. We hypothesized that bile/excipient interactions may reduce the bioavailability of bile interacting drugs.
Chapter III addresses the hypothesis from chapter II. A pharmacokinetic study in rats revealed that the absorption of Perphenazine was reduced by bile interacting excipients due to bile/excipient interaction. The simultaneous administration of excipient patterns I and II did not further reduce or enhance Perphenazine absorption. Conversely, the absorption of Metoprolol was not impacted by excipients. This reinforced the hypothesis, that drugs interacting with bile should not be formulated with excipients also interacting with bile.
Chapter IV further elaborates which in vitro methods using simulated intestinal fluids are predictive for a drug’s pharmacokinetic profile. The PWSD Naporafenib was analyzed in vitro with simulated intestinal fluids and in presence of excipients regarding solubility, supersaturation, and free drug fraction. Naporafenib showed a strong interaction with TC/L from simulated bile. Assays with TC/L, but not without identified one excipient as possibly bioavailability reducing, one as supersaturation destabilizing, and the last as bile not interacting and supersaturation stabilizing excipient. A pharmacokinetic study in beagle dogs outlined and confirmed the in vitro predictions.
The Appendix summarizes in vivo predictive methods as presented in chapter I to IV and rationalizes experimental design paving the way towards a biopharmaceutic excipient screening. The first presented preliminary decision tree is transformed into a step-by-step instruction. The presented decision matrix might serve as a blueprint for processes in early phase drug formulation development.
In summary, this thesis describes how a drug can be defined as bile interacting or non-interacting and gives a guide as well how to rate the impact of excipients on bile. We showed in two in vivo studies that bile/excipient interaction reduced the bioavailability of bile interacting drugs, while bile non-interacting drugs were not affected. We pointed out that the bile solubilization system must be incorporated during drug formulation design. Simulated gastrointestinal fluids offer a well-established platform studying the fate of drugs and excipients in vivo. Therefore, rational implementation of biopharmaceutic drug and excipient screening steers towards efficacy of oral PWSD formulation design.
Nanodiamond (ND) is a versatile and promising material for bio-applications. Despite many efforts, agglomeration of nanodiamond and the non-specific adsorption of proteins on the ND surface when exposed to bio-fluids remains a major obstacle for biomedical applications. An assortment of branched and linear molecules with superior ability to colloidally stabilize nanoparticles in salt and cell media environment, for up to 30 days, was attached to the ND’s surface.
The building box system with azide as external groups offers a huge variety of binding with many molecules, such as drugs, dyes or targeting molecules, is possible. Clicking, for instance, zwitterions moieties to the chain protects ND surface from protein corona forming when the particles get in contact with biofluids containing proteins.
Thermogravimetric analysis results of the ND surface loading show a significant prevention of up to 98 % of the protein adsorption compared with NDs without zwitterionic headgroups and long colloidal stability when tetraethylene glycol (TEG) are attached to the surface.
The versatility of the modular system to bind not only zwitterionic chains but also clickable functional molecules to fluorescent nanodiamonds (fNDs) demonstrates the potential of the system at the nanodiamond. Using defect structures, such as nitrogen-vacancy (NV) centers, diamond particles, due to their widely non-toxic behavior, can be used as fNDs for photostable labeling, bioimaging and nanoscale sensing in living cells and organisms. To functionalize the fND surface a novel milling technique with diazonium salts was established to perform grafting on poorly reactive HPHT fNDs yielding in high surface loading and high negative zeta potential.
Combining the benefits of TEG and zwitterion containing groups with antibody enabled nucleus targeting ability on fND confirms the enhanced colloidal stability in living cells experiments for the first time. Furthermore, the results indicate an improved corona repulsion compared with fND without zwitterion containing headgroups. As a result, the circulation times were enlarged from 4 (fND without zwitterion chain but with antibody) to 17 (with antibody and zwitterion chains) hours.
In non-biomedical applications, the modular system can be used as a probe for heavy metals by binding it to dyes. Detection of metals in different environments with high selectivity and specificity is one of the prerequisites of the fight against environmental pollution with these elements. Pyrenes are well suited and known for fluorescence sensing in different media.
The applied sensing principle typically relies on the formation of intra- and intermolecular excimers, which is however limiting the sensitivity range due to masking of e.g. quenching effects by the excimer emission. This study shows a highly selective, structurally rigid chemical sensor based on the monomer fluorescence of pyrene moieties bearing triazole groups.
This probe can quantitatively detect Cu2+, Pb2+ and Hg2+ in organic solvents over a broad concentration range, even in the presence of ubiquitous ions such as Na+, K+, Ca2+ and Mg2+. The strongly emissive sensor’s fluorescence with a long lifetime of 165 ns is quenched by a 1:1 complex formation upon addition of metal ions in acetonitrile. Upon addition of a tenfold excess of the metal ion to the sensor, agglomerates with a diameter of about 3 nm are formed. Due to complex interactions in the system, conventional linear correlations are not observed for all concentrations. Therefore, a critical comparison between the conventional Job plot interpretation, the method of Benesi-Hildebrand, and a non-linear fit is presented. The reported system enables the specific and robust sensing of medically and environmentally relevant ions in the health-relevant nM range and could be used e.g. for the monitoring of the respective ions in waste streams.
Nonetheless, often these waste streams end up in sensitive aquacultures, where such sensor technology only works if the probe is water-soluble to monitor the spread and formation of environmental damage from heavy metals. Many chemosensors only work quantitatively in specific solvents and under highly pure conditions. In this thesis a method to stabilize water-insoluble chemosensors on nanodiamonds in saline water while maintaining the sensor efficacy and specificityas as well as colloidal stability is presented. Additionally, the sensor capability is retained in organic solvents. This study provides insight into the absorptivity of pyrene derivatives to the nanodiamond surface and a way to reversibly desorb them.
Moreover, the system proves that in presence of 95 % oxygen atmosphere while the fluoresce measurement the results of the do not vary from the one in argon atmosphere. Furthermore, the presence of common ions in water do not disturb the colloidal stability of the NDs and also no influence the sensor functionality and thus is highly promising candidate for measurement without cumbersome preparation steps.
In Deutschland starben im Jahr 2016 knapp 6 000 Menschen an den Folgen des Multiplen Myeloms. Die Zahl der Todesopfer dieser Krebsart ist in den letzten 16 Jahren um ca. 20% gestiegen. Da das Multiple Myelom mit einem Durchschnittsalter von 73 Jahren bei Erstdiagnose zu den Erkrankungen des höheren Lebensalters zählt, ist der Anstieg der Inzidenz und Todesfälle am ehesten auf eine höhere Lebenserwartung der Menschen durch umfassende medizinische Versorgung zurückzuführen. Auch die Behandlungsmöglichkeiten des Multiplen Myeloms wurden in den letzten zwei Jahrzehnten kontinuierlich verbessert und bieten in Form von medikamentösen Therapien für alle Erkrankten und Knochenmarktransplantationen speziell für Patienten unter 70 Jahren die Chance auf eine Verlängerung der beschwerdefreien Krankheitsphase. Nach wie vor verläuft das Multiple Myelom jedoch tödlich, sodass die Erforschung und Entwicklung neuer potenter Wirkstoffe zur Verbesserung der Prognose oder zur vollständigen Heilung essentiell ist.
Ziel der vorliegenden Arbeit war daher die Biotinylierung von Dioncochinon B, einem natürlich vorkommenden Naphthochinon, erstmals isoliert aus Kallus-Kulturen von T. peltatum, das eine gute Aktivität (IC50 = 11 µM) gegen Zellen des Multiplen Myeloms aufweist. Der Affinitätsmarker Biotin sollte dabei über einen kurzen Linker an die 7- oder 8-Position des Naturstoffs angebracht werden. Nach der Etablierung einer geeigneten Syntheseroute sollten nanoLC-MS/MS-Analysen Aufschluss über mögliche Wirkstoff-Target-Interaktionen liefern.
Des Weiteren wurde in dieser Arbeit die Synthese von 7,8'-gekuppelten Naphthylisochinolin-Alkaloiden im Allgemeinen und von Yaoundamin A und dessen M-Atropisomer im Speziellen untersucht.
Die Naturstoffklasse der Naphthylisochinolin-Alkaloide ist neben ihrer strukturellen Vielfalt vor allem wegen ihrer Aktivitäten gegen eine Vielzahl an Erregern von Infektionskrankheiten, wie z. B. der Malaria, der Afrikanischen Schlafkrankheit oder der Leishmaniose interessant. Strukturell sind Naphthylisochinolin-Alkaloide unter anderem durch eine meist rotationsgehinderte Biaryl-Achse gekennzeichnet. Der synthetische Aufbau dieser Verbindungsachse zwischen Naphthalin- und Isochinolin-Baustein war in der Literatur bereits ausführlich behandelt worden. Da die Darstellung eines 7,8'-verknüpften Naphthyldihydroisochinolin-Alkaloids allerdings noch nie beschrieben worden war, war das Ziel dieser Arbeit die erste Totalsynthese eines Naturstoffs dieses Typs.
The thesis is mainly about the reactivities of borylene complexes. Including the investigation of the reaction of base stabilized terminal borylene with elemental chalcogens. On the other hand the are also the reactivity of borylene with bipyridine species is also studies. A C-H activation of the Cp2WH2 using borylene is also discovered. Finally the reaction of a borylene with Lewis acids such as GaCl3 and InBr3 is also studied.
Herein described is the discovery of three novel types of dimeric naphthylisoquinoline alkaloids, named mbandakamines, cyclombandakamines, and spirombandakamines. They were found in the leaves of a botanically as yet unidentified, potentially new Ancistrocladus species, collected in the rainforest of the Democratic Republic of the Congo (DRC). Mbandakamines showed an exceptional 6′,1′′-coupling, in the peri-position neighboring one of the outer axes, leading to an extremely high steric hindrance at the central axis, and to U-turn-like molecular shape, which – different from all other dimeric NIQs, whose basic structures are all quite linear – brings three of the four bicyclic ring systems in close proximity to each other. This created an unprecedented follow-up chemistry, involving ring closure reactions, leading to two further, structurally even more intriguing subclasses, the cyclo- and the spirombandakamines, displaying eight stereogenic elements (the highest total number ever found in naphthylisoquinoline alkaloids). The metabolites exhibited pronounced antiplasmodial and antitrypanosomal activities. Likewise reported in this doctoral thesis are the isolation and structural elucidation of naphthylisoquinoline alkaloids from two further potentially new Ancistrocladus species from DRC. Some of these metabolites have shown pronounced antiausterity activities against human pancreatic cancer PANC-1 cells.
In this work the catalytic activity of nanodiamond particles with different dopants and surface terminations and of diamond nanomaterials funtionalized with ruthenium-based photocatalysts was investigated, illustrating materials application in photoredox chemistry and the photo(electro)catalytic reduction of CO2. Regarding the application of diamond nanomaterials in photocatalysis, methods to fabricate and characterize several (un)doped nanoparticles with different surface termination were successfully developed. Various photocatalysts, attached to nanodiamond particles via linker systems, were tested in photoredox catalysis and the photo(electro)catalytic reduction of CO2.