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Nowadays, the management of infectious diseases is especially threatened by the rapid emergence of drug resistance. It has been suggested that the medicine quality assurance combined with good medication adherence may help to reduce this impendence. Moreover, the search for new antimicrobial agents from medicinal plants is strongly encouraged for the exploration of alternatives to existing therapies. In this context, the present work focused on both the quality evaluation of commercialized antimalarial medicines from the Democratic Republic of the Congo and on the phytochemical investigations of a Congolese Ancistrocladus species.
The first part of this work focuses on the characterization of systems which complex electronic structures require the application of multi-reference methods. The anti-tumor efficacy of the natural product Neocarzinostatin is based on the formation of diradicals and causes DNA cleavage and finally cytolysis. Computations on model systems performed in the present work show the influence of structural features on the mode of action and the efficacy of this antitumor-antibiotic. The cyclization of systems related to the enyne-cumulene framework like the enyne-allenes was investigated earlier and relations to the more unusual class of enyne-ketenes are analyzed. The class of enyne-ketenes (and also the enyne-allenes) show a broad spectrum of possible intermediates (diradicals, zwitterions, allenes). The electronic structures of these intermediates are also possible for the (heteroatom substituted) 1,2,4-cyclohexatriene and a model for their energetic sequence based on high-level multi-reference computations is proposed. In all three projects the application of multi-reference approaches is necessary to obtain a comprehensive picture of the reactivity and electronic structure but also shows up the limits inherently existing in the currently available programs with respect to the size of the molecules. In the second part, algorithms for a multi-reference Moller-Plesset perturbation theory (MR-MP2) program, designed to perform large-scale computations, were developed and implemented. The MR-MP2 approach represents the most cost-effective multireference ansatz and requires an efficient evaluation of the Hamilton matrix for which an algorithm is designed to instantly recognize only non-vanishing matrix elements and to employ the recurring interaction patterns of the Hamilton matrix. The direct construction of the Hamilton matrix is additionally parallelized to work on cluster environments.
Bei der Biofabrikation werden Zellen mit einem Biomaterial versetzt (vereint werden diese als Biotinte definiert) und durch additive Fertigungsmethoden wie dem 3D-Druck zu hierarchischen Strukturen aufgebaut. Zur Herstellung von künstlichen Gewebe und zukünftig auch von funktionalen Organen ist ein detailliertes Zellverständnis essentiell. Im Rahmen dieser Dissertation wurden Systeme generiert, um die Zellmembranen von mesenchymalen Stromazellen gezielt zu verändern und um die Modifikationen zu charakterisieren. Durch Inkubation mit unnatürlichen Zuckern werden diese von Zellen aufgenommen und in den Zellmetabolismus eingeschleust und auf die Glycoproteine übertragen. Diese Methode ist als metabolic glycoengineering bekannt.
Dazu wurden diverse humane Saccharid-Analoga mit bioorthogonalen Gruppen (Azid oder Alkin) synthetisiert. Alle in dieser Arbeit vorgestellten Moleküle wurden NMR-spektroskopisch als auch massenspektrometrisch charakterisiert.
Die acetylierten Mannosamin-Derivate konnten über zwei Stufen und die Sialinsäure-Derivate über sechs Stufen synthetisiert werden. Sialinsäuren sind die terminalen Zucker an Glycanketten von Proteinen mit wichtigen biologischen Funktionen. Im Rahmen des SFB TRR225 konnte in Kooperation mit der Gruppe von Prof. Dr. R. Ebert der Einbau der Saccharide in mesenchymalen Stromazellen durch Fluoreszenzmikroskopie evaluiert werden. Aufgrund des effizienteren Einbaus der Sialinsäure mit Alkingruppe gegenüber der mit Azidgruppe, wurde dieser in den folgenden massenspektrometrischen Analysen eingesetzt. Die Messungen der markierten Glycoproteine wurden von Dr. Marc Driessen durchgeführt und der metabolische Einbau von SiaNAl und Ac4ManNAl in den Stromazellen gegenübergestellt. 55 Glycoproteine konnten durch SiaNAl und 94 durch Ac4ManNAl charakterisiert werden. Ein Abgleich der Proteindatenbanken eine Anreicherung von Proteine durch Fütterung von SiaNAl die in Signaltransduktion, Zellkontakte und Differenzierung involviert sind, womit metabolic glycoengineering prinzipiell zur Optimierung von Biofabrikationsprozessen genutzt werden kann.
Herstellung und Charakterisierung kolloidaler Lösungen diamantbasierter und verwandter Materialien
(2022)
In der vorliegenden Publikation wurden stabile kolloidale Lösungen aus CVD-Diamant, Detonationsdiamant sowie artverwandten Materialien hergestellt und charakterisiert
Besonderes Augenmerk wurde bei der Zerkleinerung von CVD Diamant daraufgelegt, dass die nanoskaligen Partikel ihre materialspezifischen Eigenschaften auch bei Reduktion der Größe beibehalten.
Systematisch wurde die Zerkleinerung in einer Planetenmühle analysiert. Es wurde sowohl die minimal erreichbare Partikelgröße, als auch die Menge an erzeugtem, nanoskaligem Material bewertet.
Um die Vermahlung zu verbessern, wurden die Geschwindigkeit der Mühle, die Größe der Mahlkörper, die Dauer der Vermahlung, sowie die eingesetzten Lösemittel variiert. Des Weiteren konnten durch die Vermahlung unterschiedlich hergestellter CVD Diamantfilme in einer Vibrationsmühle die Einflüsse von Schichtdicke und Korngröße der Diamantkristalle untersucht werden.
Durch Bearbeitung von Detonationsdiamanten und Kohlenstoffnanozwiebeln wurden stabile kolloidale Lösungen hergestellt, mit Partikelgrößen im unteren Nanometerbereich. Diese sind im alkalischen pH-Bereich stabil sein, hierfür wurde durch Luft und Säureoxidation oxidierter Detonationsdiamant und oxidierte Kohlenstoffnanozwiebeln hergestellt. Mithilfe der thermogravimetrischen Analyse und Infrarotspektroskopie wurde die hierfür optimale Temperatur und Dauer bestimmt.
Der Einsatz von computerchemischen Verfahren zur Vorhersage, Bestätigung oder Erklärung von Moleküleigenschaften hat sich zu einem Wissenschaftszweig innerhalb der Chemie entwickelt, der sowohl im universitären Umfeld als auch in der Industrie eine unverzichtbare Rolle einnimmt. So hat die in unserem Arbeitskreis in Zusammenarbeit mit Prof. J. Fleischhauer entwickelte und immer wieder erweiterte Methode zur Berechnung des Circular-Dichroismus (CD) organischer Moleküle schon in vielen Fällen die Arbeit experimentell arbeitender Naturstoffchemiker unseres Arbeitskreises und die vieler Kooperationspartner erleichtert. Im Rahmen der Strukturaufklärung wurde die Methode als effizientes Verfahren zur eindeutigen Zuordnung der absoluten Konfiguration von neuartigen chiralen Natur- und Wirkstoffen eingesetzt. In der vorliegenden Arbeit wurde die zusammen mit Prof. J. Fleischhauer etablierte Molekulardynamik-Methodik (MD-Methodik) – neben der schon vorher angewandten Boltzmann-Methodik (BM-Methodik) – zur Untersuchung des Circular-Dichroismus flexibler Verbindungen eingesetzt. Begonnen wurden die Studien mit der Evaluierung des Verfahrens an besonders flexiblen Molekülen, um im Anschluß den Circular-Dichroismus von Substanzen untersuchen zu können, deren CD-Spektren auf den ersten Blick sehr ungewöhnlich erschienen oder nicht den gängigen Vorstellungen vom chiroptischen Verhalten organischer Moleküle entsprachen. Die Ergebnisse dieser Arbeit zeigen sehr deutlich, daß der Circular-Dichroismus komplexer organischer Verbindungen immer vorsichtig zu interpretieren ist. Zwar ist der einfachste Weg zur Aufklärung der Absolutkonfiguration eines Moleküls derjenige, das CD-Spektrum der unbekannten Verbindung mit dem einer bereits aufgeklärten Substanz sehr ähnlicher Konstitution zu vergleichen. Doch wie an den untersuchten Beispielen deutlich gezeigt wurde, kann trotz vermeintlich guter Übereinstimmung von CD-Spektren leicht eine falsche Zuordnung erfolgen. Einzig bei Enantiomeren oder sehr einfachen Derivaten enantiomerer Grundstruktur kann man durch den Vergleich experimenteller CD-Spektren eine sichere Aussage treffen. Sobald jedoch die CD-Spektren von Diastereomeren oder gar konstitutionell verschiedenen Substanzen verglichen werden sollen, ist immer äußerste Vorsicht geboten.
No abstract available
Various structural possibilities for Si\(_3\)C\(_3\) clusters are investigated by ab initio calculations employing basis sets of double- and triple-zeta quality augmented by d polarization functions. Correlation effects are included by a second-order Moeller Piesset perturbation treatment. For the two lowest-lying structures higher-order correlation corrections and multi-reference effects are also included. Bonding features are investigated by two different types of population analyses to obtain insight into the nature of chemical bonding. A total of 17 stationary points were investigated, 14 of which correspond to local minima and three being transition states. The energetically lowest-lying structures are: A "pyramidlike" structure with various multicenter bonds, followed by a es symmetric isomer closely related to the ground state Si6 structure. Planar structures, favoured in small carbon clusters, lie higher in energy and are transition states. The lowest-lying triplet system is found to be the linear nonsymmetric Si - C-C-C-Si -Si structure, which is calculated to lie about 38 kcalfmole above the singlet ground state. A building-up principle based on bonding criteria is suggested for the occurence of the various structural possibilities.
n this work the synthesis and analysis of chromophore functionalized spherical gold nanoparticles is presented. The optical, electrochemical and spectroelectrochemical properties of these hybrid materials are furthermore studied. The work therefore is divided into two parts. The first part deals with triarylamine and PCTM-radical functionalized gold nanoparticles. The focus thereby was on the synthesis and on the investigations of chromophore-chromophore interactions and gold core-chromophore interactions. The chromopores, especially triarylamines, were attached to the gold core via different bridging units and were studied with optical and electrochemical methods. The purity and dimensions of the nanoparticles was determined by 1H-NMR spectroscopy, diffusion ordered NMR spectroscopy (DOSY), TGA, XPS and STEM. Furthermore a cyclic voltammetry technique was used to determine the composition of the particles via the Randles-Sevcik equation. An analysis of these parameters led to a model of a sea urchin-shaped nanoparticle. Optical measurements of the particles revealed an anisotropic absorption behavior of the triarylamine units due to gold core-chromophore interaction. However this behavior depends strongly on the relative orientation of the transition dipole moment of the chromophore to the gold surface and the distance of the chromophore to the surface. Hence, the anisotropic behavior was exclusively detected in the spectra of the Au-Tara1 particles. The short and rigid pi-conjugated bridging unit thereby facilitates this gold core-chromophore interaction. It was shown from electrochemical investigations that the triarylamine units can be chemically reversibly oxidized to the triarylamine monoradical cation. Furthermore, the measurements revealed a strong interligand triarylamine-triarylamine interaction which was only seen for the Au-Tara1 particles. The long pi-conjugated bridging units of the Au-Tara2 and Au-Tara3 particles as well as the aliphatic bridging unit of Au-Tara4 prevent any detectable interligand interactions. One may conclude that both the gold core-chromophore and the interligand triarylamine-triarylamine interaction depend on the length and the rigidity of the bridging unit. The electron transfer behavior of the triarylamine units adsorbed onto the gold core was additionally studied via spectroelectrochemical (SEC) measurements which are able to reveal weaker interactions. The investigations of Au-Tara1 and Au-Tara2 revealed a significant strong coupling between neighboring triarylamine units which is due to through-space intervalence interactions. This behavior was not detected for Au-Tara3 or for Au-Tara4. The SEC analysis also revealed that these observed interligand interactions depend on the length and the rigidity of the bridging unit. Thus, the systematic variation of the bridging unit gave a basic insight in the optical and electrochemical properties of triarylamines, located in the vicinity of a gold nanoparticle. The second part of this work aimed at the synthesis of new molecules, denoted as SERS-markers, for immuno SERS applications. For this purpose, the SERS-markers were designed to have a Raman-active unit and a thiol group for chemisorptions to Au/Ag nanoshells. In cooperation with the group of Schlücker (University of Osnabrück) the SERS-markers were absorbed onto Au/Ag nanoshells, denoted as SERS-labels, and characterized. The SERS spectra of the SERS-labels exhibited intense and characteristic SERS-signals for each marker. For immuno SERS investigations SEMA3 was functionalized with a hydrophilic end unit. This marker was adsorbed onto an Au/Ag nanoshell and encapsulated with silica. An anti-p63 antibody was bound to the silica surface in order to generate a SERS-labeled antibody for the detection of the tumor suppressor p63 in benign prostate. Immuno-SERS imaging of prostate tissue incubated with SERS-labeled anti-p63 antibodies demonstrated the selective detection of p63 in the basal epithelium. The results show the potential of the method for the detection of several biomolecules in a multiplexing SERS experiment.
We investigated the folding kinetics of G‐quadruplex (G4) structures by comparing the K\(^{+}\)‐induced folding of an RNA G4 derived from the human telomeric repeat‐containing RNA (TERRA25) with a sequence homologous DNA G4 (wtTel25) using CD spectroscopy and real‐time NMR spectroscopy. While DNA G4 folding is biphasic, reveals kinetic partitioning and involves kinetically favoured off‐pathway intermediates, RNA G4 folding is faster and monophasic. The differences in kinetics are correlated to the differences in the folded conformations of RNA vs. DNA G4s, in particular with regard to the conformation around the glycosidic torsion angle χ that uniformly adopts anti conformations for RNA G4s and both, syn and anti conformation for DNA G4s. Modified DNA G4s with \(^{19}\)F bound to C2′ in arabino configuration adopt exclusively anti conformations for χ. These fluoro‐modified DNA (antiTel25) reveal faster folding kinetics and monomorphic conformations similar to RNA G4s, suggesting the correlation between folding kinetics and pathways with differences in χ angle preferences in DNA and RNA, respectively.
Die kausalen Ursachen, die zur Auslösung der neurodegenerativen Erkrankung Morbus Parkinson führen, sind noch immer unklar. Man nimmt heute an, daß das Absterben dopaminerger Neurone im Mittelhirn von Parkinsonpatienten multifaktoriell ausgelöst wird. Genetische Prädisposition sowie endogene und exogene Umweltgifte wie etwa Substanzen, die strukturelle Ähnlichkeit mit dem bekanntesten dopaminergen Neurotoxin MPTP (1-Methyl-4-phenyl-1,2,3,5-tetrahydropyridin) besitzen, werden als Hauptursachen für die Entstehung des Parkinsonsyndroms diskutiert. Diese Arbeit beschäftigt sich mit einer neuen Klasse von neurotoxisch wirksamen Tetrahydro-b-carbolinen, die sich von Trichloracetaldehyd (Chloral) ableiten. Die wohl prominenteste Verbindung in dieser Reihe ist TaClo (1-Trichlormethyl-1,2,3,4-tetrahydro-b-carbolin), das im menschlichen Körper nach Aufnahme des Schlafmittels Chloralhydrat durch Pictet-Spengler-Kondensation mit dem endogen vorhandenen Tryptamin gebildet wird. Zusätzlich scheint die Bildung von TaClo aus dem Industrielösungsmittel TRI (Trichlorethylen), das im Organismus zu Chloral metabolisiert wird, möglich. Die über Chloral eingeführte große CCl3-Gruppe erhöht die Lipophilie von TaClo, die Passage der Blut-Hirn-Schranke ist erleichtert. In der Tat haben zahlreiche Untersuchungen in vitro und in vivo gezeigt, daß TaClo toxische Prozesse in dopaminergen und serotonergen Systemen zu induzieren vermag. Ein wesentliches Ziel dieser Arbeit bestand darin, die in-vivo-Entstehung und Metabolisierung von TaClo im Menschen sowie den Einfluß dieses Neurotoxins auf die DNA herauszuarbeiten und näher zu untersuchen. Im einzelnen wurden folgende Ergebnisse erzielt: TaClo schädigt die DNA, wie Versuche an zellfreier DNA und in-vitro-Experimente an PC12-Zellen belegen. Die endogene Bildung von TaClo in Chloralhydrat-behandelten Patienten und die in-vitro-Entstehung von TaClo aus Trichlorethylen wurde mittels HPLC-ESI-MS-MS-Analytik eindeutig bewiesen. Außerdem wurden erste Hinweise auf eine Anreicherung des Neurotoxins im menschlichen Körper erhalten. Stereostrukturelle Aspekte der Bildung und Verstoffwechslung von TaClo wurden aufgeklärt und TaClo-Metabolite in in-vitro- und in-vivo-Proben identifiziert. Das Tetrahydro-b-carbolin entsteht in racemischer Form, wird also nicht enzymatisch sondern spontan durch Pictet-Spengler-Reaktion gebildet. Zusätzlich wurden Hinweise auf eine enzymatische Metabolisierung von TaClo gefunden. Außerdem gelang es, eine etablierte Methode des oxidativen Abbaus zur Aufklärung der absoluten Konfiguration von Tetrahydropyridin-Heterocyclen [z.B. Eleagnin] auf Substanzen mit benzylischer Hydroxy- oder Metylether-Gruppe zu erweitern. Geringe Mengen (1-2 mg) an Substanzen, die in benzylischer Position eine chirale Sauerstoffunktion besitzen, wurden durch Ruthenium-katalysierte Oxidation zu GC-gängigen Säuren abgebaut, deren absolute Konfiguration nach Trennung an chiraler Phase durch Vergleich mit enantiomerenreinem Referenzmaterial bestimmt wurde. Diese Zuordnung erlaubte den Rückschluß auf die absolute Konfiguration einer Reihe Ausgangsverbindungen.
Herein we devise and execute a new synthesis of a pristine boron-doped nanographene. Our target boron-doped nanographene was designed based on DFT calculations to possess a low LUMO energy level and a narrow band gap derived from its precise geometry and B-doping arrangement. Our synthesis of this target, a doubly B-doped hexabenzopentacene (B\(_{2}\)-HBP), employs six net C−H borylations of an alkene, comprising consecutive hydroboration/electrophilic borylation/dehydrogenation and BBr\(_{3}\)/AlCl\(_{3}\)/2,6-dichloropyridine-mediated C−H borylation steps. As predicted by our calculations, B\(_{2}\)-HBP absorbs strongly in the visible region and emits in the NIR up to 1150 nm in o-dichlorobenzene solutions. Furthermore, B\(_{2}\)-HBP possesses a very low LUMO level, showing two reversible reductions at −1.00 V and −1.17 V vs. Fc\(^{+}\)/Fc. Our methodology is surprisingly selective despite its implementation of unfunctionalized precursors and offers a new approach to the synthesis of pristine B-doped polycyclic aromatic hydrocarbons.
In aqueous environment, hydrophobic interactions play an important role for DNA. The introduction of modifications based on hydrophobic aromatic moieties offers additional ways for controlling recognition and reactivity of functional groups in DNA. Modifications are introduced through an artificial backbone or in the form of an extension of the nucleobases, resulting in additional properties of the DNA.
This dissertation focuses on the use of hydrophobic units for the functionalization of DNA.
In the first part of the work, the tolane (i. e. diphenylacetylene) motif was used in combination with the acyclic backbone of GNA and BuNA to generate recognition units in the DNA context. Fluorination of the aromatic rings in the tolane moiety provided the basis for a supramolecular language based on arene-fluoroarene interactions. The specific recognition was investigated by thermodynamic, kinetic and NMR spectroscopic methods.
In the second part of the work, deoxyuridine derivatives with a hydrophobic aromatic modification were prepared and incorporated into DNA duplexes. The irradiation with UV light led to a [2+2] cycloaddition reaction between two modified nucleosides in the DNA. This reaction product was structurally characterized and the reaction was used in various biochemical and nanotechnological DNA applications.
Arene‐fluoroarene interactions offer outstanding possibilities for engineering of supramolecular systems, including nucleic acids. Here, we implement the tolane‐perfluorotolane interaction as base pair replacement in DNA. Tolane (THH) and perfluorotolane (TFF) moieties were connected to acyclic backbone units, comprising glycol nucleic acid (GNA) or butyl nucleic acid (BuNA) building blocks, that were incorporated via phosphoramidite chemistry at opposite positions in a DNA duplex. Thermodynamic analyses by UV thermal melting revealed a compelling stabilization by THH/TFF heteropairs only when connected to the BuNA backbone, but not with the shorter GNA linker. Detailed NMR studies confirmed the preference of the BuNA backbone for enhanced polar π‐stacking. This work defines how orthogonal supramolecular interactions can be tailored by small constitutional changes in the DNA backbone, and it inspires future studies of arene‐fluoroarene‐programmed assembly of DNA.
Covalent crosslinking of DNA strands provides a useful tool for medical, biochemical and DNA nanotechnology applications. Here we present a light-induced interstrand DNA crosslinking reaction using the modified nucleoside 5-phenylethynyl-2’-deoxyuridine (\(^{Phe}\)dU). The crosslinking ability of \(^{Phe}\)dU was programmed by base pairing and by metal ion interaction at the Watson-Crick base pairing site. Rotation to intrahelical positions was favored by hydrophobic stacking and enabled an unexpected photochemical alkene-alkyne [2+2] cycloaddition within the DNA duplex, resulting in efficient formation of a \(^{Phe}\)dU-dimer after short irradiation times of a few seconds. A \(^{Phe}\)dU dimer-containing DNA was shown to efficiently bind a helicase complex, but the covalent crosslink completely prevented DNA unwinding, suggesting possible applications in biochemistry or structural biology.
A tolane-modified 5-ethynyluridine as a universal and fluorogenic photochemical DNA crosslinker
(2023)
We report the fluorescent nucleoside ToldU and its application as a photoresponsive crosslinker in three different DNA architectures with enhanced fluorescence emission of the crosslinked products. The fluorogenic ToldU crosslinking reaction enables the assembly of DNA polymers in a hybridization chain reaction for the concentration-dependent detectio of a specific DNA sequence.
About 2.4 billion years ago, nature has fundamentally revolutionized life on earth by inventing the multi-subunit protein complex photosystem II, the only molecular machine in nature that catalyzes the thermodynamically demanding photosynthetic splitting of water into oxygen and reducing equivalents. Nature chose a distorted Mn4CaO5 cluster as catalyst, better known as oxygen-evolving complex (OEC), thus recognizing the need for transition metals to achieve high-performance catalysts. The curiosity has always driven mankind to mimic nature’s achievements, but the performance of natural enzymes such as the oxygen-evolving complex in photosystem II remain commonly unmatched. An important role in fine-tuning and regulating the activity of natural enzymes is attributed to the surrounding protein domain, which facilitates substrate preorganization within well-defined nanoenvironments.
In light of growing energy demands and the depletion of fossil fuels, the unparalleled efficiency of natural photosynthesis inspires chemists to artificially mimic its natural counterpart to generate hydrogen as a ‘solar fuel’ through the light-driven splitting of water. As a result, significant efforts have been devoted in recent decades to develop molecular water oxidation catalysts based on earth-abundant transition metals and the discovery of the Ru(bda) (bda: 2,2’ bipyridine-6,6’-dicarboxylate) catalyst family enabled activities comparable to the natural OEC. Similar to the natural archetypes, the design of homogeneous catalysts that interplay judiciously with the second coordination sphere of the outer ligand framework proved to be a promising concept for catalyst design. In this present thesis, novel supramolecular design approaches for enzyme like activation of substrate water molecules for the challenging oxidative water splitting reaction were established via tailor-made engineering of the secondary ligand environment of macrocyclic Ru(bda) catalysts.
Proton‐coupled electron‐transfer (PCET) processes play a key role in biocatalytic energy conversion and storage, for example, photosynthesis or nitrogen fixation. Here, we report a series of bipyridine‐containing di‐ to tetranuclear Ru(bda) macrocycles 2 C–4 C (bda: 2,2′‐bipyridine‐6,6′‐dicarboxylate) to promote O−O bond formation. In photocatalytic water oxidation under neutral conditions, all complexes 2 C–4 C prevail in a folded conformation that support the water nucleophilic attack (WNA) pathway with remarkable turnover frequencies of up to 15.5 s\(^{−1}\) per Ru unit respectively. Single‐crystal X‐ray analysis revealed an increased tendency for intramolecular π‐π stacking and preorganization of the proximal bases close to the active centers for the larger macrocycles. H/D kinetic isotope effect studies and electrochemical data demonstrate the key role of the proximal bipyridines as proton acceptors in lowering the activation barrier for the crucial nucleophilic attack of H\(_{2}\)O in the WNA mechanism.
Inspired by the proficiency of natural enzymes, mimicking of nanoenvironments for precise substrate preorganisation is a promising strategy in catalyst design. However, artificial examples of enzyme-like activation of H\(_2\)O molecules for the challenging oxidative water splitting reaction are hardly explored. Here, we introduce a mononuclear Ru(bda) complex (M1, bda: 2,2’-bipyridine-6,6’-dicarboxylate) equipped with a bipyridine-functionalized ligand to preorganize H\(_2\)O molecules in front of the metal center as in enzymatic clefts. The confined pocket of M1 accelerates chemically driven water oxidation at pH 1 by facilitating a water nucleophilic attack pathway with a remarkable turnover frequency of 140 s\(^{−1}\) that is comparable to the oxygen-evolving complex of photosystem II. Single crystal X-ray analysis of M1 under catalytic conditions allowed the observation of a 7th H\(_2\)O ligand directly coordinated to a RuIII center. Via a well-defined hydrogen-bonding network, another H\(_2\)O substrate is preorganized for the crucial O–O bond formation via nucleophilic attack.
Conspectus
Nature has established a sustainable way to maintain aerobic life on earth by inventing one of the most sophisticated biological processes, namely, natural photosynthesis, which delivers us with organic matter and molecular oxygen derived from the two abundant resources sunlight and water. The thermodynamically demanding photosynthetic water splitting is catalyzed by the oxygen-evolving complex in photosystem II (OEC-PSII), which comprises a distorted tetramanganese–calcium cluster (CaMn\(_4\)O\(_5\)) as catalytic core. As an ubiquitous concept for fine-tuning and regulating the reactivity of the active site of metalloenzymes, the surrounding protein domain creates a sophisticated environment that promotes substrate preorganization through secondary, noncovalent interactions such as hydrogen bonding or electrostatic interactions. Based on the high-resolution X-ray structure of PSII, several water channels were identified near the active site, which are filled with extensive hydrogen-bonding networks of preorganized water molecules, connecting the OEC with the protein surface. As an integral part of the outer coordination sphere of natural metalloenzymes, these channels control the substrate and product delivery, carefully regulate the proton flow by promoting pivotal proton-coupled electron transfer processes, and simultaneously stabilize short-lived oxidized intermediates, thus highlighting the importance of an ordered water network for the remarkable efficiency of the natural OEC.
Transferring this concept from nature to the engineering of artificial metal catalysts for fuel production has fostered the fascinating field of metallosupramolecular chemistry by generating defined cavities that conceptually mimic enzymatic pockets. However, the application of supramolecular approaches to generate artificial water oxidation catalysts remained scarce prior to our initial reports, since such molecular design strategies for efficient activation of substrate water molecules in confined nanoenvironments were lacking. In this Account, we describe our research efforts on combining the state-of-the art Ru(bda) catalytic framework with structurally programmed ditopic ligands to guide the water oxidation process in defined metallosupramolecular assemblies in spatial proximity. We will elucidate the governing factors that control the quality of hydrogen-bonding water networks in multinuclear cavities of varying sizes and geometries to obtain high-performance, state-of-the-art water oxidation catalysts. Pushing the boundaries of artificial catalyst design, embedding a single catalytic Ru center into a well-defined molecular pocket enabled sophisticated water preorganization in front of the active site through an encoded basic recognition site, resulting in high catalytic rates comparable to those of the natural counterpart OEC-PSII.
To fully explore their potential for solar fuel devices, the suitability of our metallosupramolecular assemblies was demonstrated under (electro)chemical and photocatalytic water oxidation conditions. In addition, testing the limits of structural diversity allowed the fabrication of self-assembled linear coordination oligomers as novel photocatalytic materials and long-range ordered covalent organic framework (COF) materials as recyclable and long-term stable solid-state materials for future applications.
Polyketide stellen aufgrund ihrer großen strukturellen Vielfalt nach wie vor Leit- und Wirkstoffe für die Pharma- und Pflanzenschutzforschung in den Industrieländern dar und bilden außerdem eine der wichtigsten Klassen von Naturstoffen (Sekundärmetaboliten) überhaupt. Besonders die Biosynthese aromatischer Polyketide und die hierbei involvierten Enzyme, die Polyketidsynthasen (PKS), wurden von Biosyntheseforschern als hervorragendes Modellsystem zur Untersuchung von Struktur-Funktions-Beziehungen von Multienzymkomplexen erkannt. Für annelierte aromatische Polyketide existiert seit dem Jahr 2001 eine biosynthetische Klassifizierung auf Metabolitebene, das sogenannte Modus-F/S-System, mit dessen Hilfe man zwischen pro- und eukaryotischen Produzenten unterscheiden kann. Die Erforschung der detaillierten Biosynthese von aromatischen Polyketiden ist somit in mehrfacher Hinsicht ein lohnendes Ziel. In der vorliegenden Dissertation sollten die Biosynthese und die Faltungsmodi ausgewählter aromatischer Polyketide einschließlich der Charakterisierung potentieller Vorstufen in verschiedensten biologischen Systemen untersucht werden. Die dabei gewonnenen Resultate sind das Ergebnis interdisziplinärer Zusammenarbeit.