Synkinesis of rigid mixed lipid-porphyrin monolayers on gold with 2 nm pores

Titelblatt Inhaltsverzeichnis 1\. Einleitung 1 2\. Synthesen und Charakterisierung 7 2.1 Synthese des Octacarbonsäureporphyrins 1 7 2.1.1 Synthese des Formylisophtalsäurediesters 4 7 2.1.2 Synthese des Porphyrinoctaethylesters 5 und des Octacarbonsäureporphyrins 1 10 2.2 Synthese des Tetrapyridylphenylporphyrins 13 2.2.1 Synthese des Pyridybenzaldehyds 6 13 2.2.2 Synthese des Pyridylphenylporphyrins 7 15 2.2.3 Metallinsertion 17 2.2.4 Quaternisierung der Pyridinsubstituenten 17 2.3 Synthese der Mercaptoporphyrine 18 2.3.1 Synthese der Benzaldehyde 19 2.3.2 Porphyrinsynthesen 23 2.3.3 Einführung der Disulfidgruppe 27 2.3.4 Spaltung der Xanthatgruppen der Porphyrine 29 2.3.5 Verseifung des Methylesters 31 2.4 Synthese der Bolaamphiphile 31 3\. Charakterisierungsmethoden 38 3.1 UV/Vis-Spektroskopie 38 3.2 Fluoreszenzspektroskopie 40 3.2.1 Fluoreszenz an Metalloberflächen 40 3.3 Infrarot-Spektroskopie 42 3.4 Zyklische Voltammetrie 44 4\. Self-Assembly zweidimensionaler gemischter Monoschichten 47 4.1. Charakterisierung von Porphyrinmonoschichten auf Gold 47 4.1.1 UV/Vis-Spektroskopie 47 4.1.2. Fluoreszenzspektroskopie 49 4.2 Fluoreszenzlöschung durch Heterodimerisation 50 4.3. Charakterisierung von gemischten Monoschichten aus Porphyrinen und Alkanthiolen 54 4.3.1 Fluoreszenz- und UV/Vis-Spektroskopie 54 4.3.2 Zyklische Voltammetrie 56 4.3.3 RAIR-Spektroskopie 62 4.3.3.1 Octadecylthiol und Porphyrin 1 62 4.3.3.2 Alkandiamide und Porphyrin 1 64 4.3.4. Strukturvorschlag 68 4.3.5 Fluoreszenzlöschung in den Membranporen 70 4.3.6 Löschversuche mit Porphyrin Mn-8 72 4.3.7 Fluoreszenzlöschung in gemischten Monoschichten von 1 und ODT 74 4.4 Untersuchung der Adsorptionseigenschaften in den Membranporen 76 4.4.1 Zyklische Voltammetrie 77 4.4.2 Fluoreszenzspektroskopie 80 4.6 Diskussion 81 4.7 Monoschichten von Mercaptoporphyrinen 83 5\. Strukturierung auf kolloidalen Goldoberflächen 86 5.1 Alkanthiole auf kolloidalem Gold 90 5.2 Fixierung von Porphyrinen durch elektrostatische Bindung 94 5.2.1 Elektrostatische Bindung an modifizierte Citrat-Goldkolloide 94 5.2.2 Elektrostatische Bindung an 2nm Goldcluster 98 5.3 Kovalente Bindung von Porphyrinen auf Citrat-Goldkolloiden 102 5.3.1 UV/Vis-Spektren 103 5.3.2 Fluoreszenzspektroskopie 106 5.3.3 Gemischte Monoschichten auf Citrat-Kolloiden 108 5.4 Kovalente Bindung an Goldcluster 110 5.5 Diskussion 113 6\. Zusammenfassung 115 6.1 Deutsche Zusammenfassung 115 6.2 English Conclusion 119 7\. Experimenteller Teil 122 7.1 Messgeräte und Hilfsmittel 122 7.2 Präparationen 124 7.3 Präparation der Goldkolloide 126 7.4 Synthesen 129 8\. LiteraturverzeichnisZusammenfassung Das synthetisierte octaanionische meso-Tetra(3,5-dicarboxylatophenyl)porphyrin wurde auf Goldoberflächen adsorbiert. Die Zugabe eines tetrakationischen Manganporphyrins führte zu einer quantitativen Löschung der Fluoreszenz. Beide Porphyrine konnten danach auf der Oberfläche nachgewiesen werden. Das octaanionische Porphyrin wurde in einem folgenden Self-Assembly-Prozess in eine Monoschicht synthetisierter Mer-captodiamide eingebettet. Die Zugabe des kationischen Manganporphyrins führte wiederum zu einer quantitativen, aber zeitlich verzögerten Fluoreszenzlöschung. Ein 10 Å größeres kationisches Manganporphyrin wurde als Löscher synthetisiert. Die Fluoreszenz des am Boden liegenden Porphyrins in der gemischten Porphyrin/Mercaptodiamid-Monoschicht konnte jetzt nicht mehr gelöscht werden. Während das kleinere Manganporphyrin durch die Membranpore dringen kann, passt das größere Porphyrin nicht mehr hinein. In einer gemischten Porphy-rin/Octadecanthiol-Monoschicht führte dagegen auch die Zugabe des größeren Mangan-porphyrins zu einer vollständigen Löschung. Nur die Pore der rigiden Monoschicht aus Mer-captodiamiden ist demnach größenselektiv. Die Poren konnten durch die Adsorption von trans-1,2-Cyclohexandiol für Hexacyanoferrationen unzugänglich gemacht werden. Das cis-Diastereomer löste hingegen keine Blockade aus. Die Selektivität wurde durch ein Modell erklärt, in dem cyclische Moleküle mit äquatorialen Hydroxygruppen mit Wassermolekülen einen Ko-Kristall bilden. Zusätzlich konnte auch durch die Anwendung der RAIR-Spektroskopie (IRAS) gezeigt werden, dass Self-Assembly-Monoschichten von Diamiden aufgrund intermolekularer Wasserstoffbrückenbindungen stabilisiert werden und ihre Formstabilität auch bei der Perforation durch die Porphyrine nicht verlieren. Synthetisierte meso-Tetra(3-carboxymethyl-4-mercaptoalkoxyphenyl)porphyrine und meso-Tetra(pyridinium)porphyrine wurden auf Goldkolloide und Goldcluster gebunden. Die Anwendung der zeitaufgelösten Fluoreszenz- und Fluoreszenzanisotropie-Spektroskopie konnte die Fixierung der Porphyrine bestätigen. Hier erfolgte eine starke Fluoreszenzlöschung durch die Goldoberfläche und eine vollständige Löschung wurde wiederum durch Zugabe von Manganporphyrinen erreicht. Erste Schritte wurden unternommen, die Porphyrine in eine Self-Assembly-Monoschicht aus Mercaptodiamiden und Mercaptocarbonsäuren einzubetten. Diese Versuche stellen eine neue Methode dar, die Struktur perforierter Monoschichten indirekt über die Fluoreszenzspektroskopie und die zyklische Voltammetrie zu bestimmen.Abstract The octaanionic meso-tetra(3,5-dicarboxylatophenyl)porphyrin was synthesized and adsorbed to gold electrodes. Addition of a cationic manganese porphyrin quenched the fluorescence quantitatively. Visible spectroscopy proved that both porphyrins remained on the surface. The octaanionic porphyrin was then embedded in a membrane by self-assembly of a bolaamphi-phile containing two secondary amide groups. The fluorescence of the porphyrin remained after the self-assembly process. It is now localized on the bottom of rigid membrane gap. Af-ter the addition of the manganese porphyrin the fluorescence was again quantitatively quenched. A 10 Å larger cationic manganese porphyrin with a phenyl spacer was synthesized. The large porphyrin could not enter the gap and no quenching was observed. While the small manganese porphyrin fitted into the gap the large porphyrin was rejected. In a mixed monolayer of the octaanionic porphyrin and octadecanethiol even the addition of large man-ganese porphyrin quenched the fluorescence. The hydrogen bonds of the amide groups rigid-ify the structure of the mixed monolayer and provide for size-discrimination. Infrared reflec-tion-absorption spectroscopy (IRAS) confirmed the effect of hydrogen-bond stabilization. The pores were sealed after the adsorption of trans-1,2-cyclohexanediol. No current was observed in cyclic voltammogramms of ferrocyanate. The cis-diastereomer did not show a blocking effect. A model of an immobile water/solute co-crystal explains the effect of stereo selectiv- ity. Meso-tetra(3-carboxymethyl-4-mercaptoalkoxyphenyl)porphyrins and meso- tetra(pyridinium)porphyrins were synthesized and attached to gold colloids and gold clusters. Time resolved fluorescence and fluorescence anisotropy was applied to investigate the por-phyrins on the particles. The live-time of the porphyrins was shortened due to the interaction with the gold surface. Complete fluorescence quenching was observed again after addition of a manganese porphyrin. These experiments represent new methods to examine the structure of mixed monolayers indi-rectly with cyclic voltammetry, fluorescence and infrared spectroscopy

Stereoselective [4+2] Cycloaddition of Singlet Oxygen to Naphthalenes Controlled by Carbohydrates

Stereoselective reactions of singlet oxygen are of current interest. Since enantioselective photooxygenations have not been realized efficiently, auxiliary control is an attractive alternative. However, the obtained peroxides are often too labile for isolation or further transformations into enantiomerically pure products. Herein, we describe the oxidation of naphthalenes by singlet oxygen, where the face selectivity is controlled by carbohydrates for the first time. The synthesis of the precursors is easily achieved starting from naphthoquinone and a protected glucose derivative in only two steps. Photooxygenations proceed smoothly at low temperature, and we detected the corresponding endoperoxides as sole products by NMR. They are labile and can thermally react back to the parent naphthalenes and singlet oxygen. However, we could isolate and characterize two enantiomerically pure peroxides, which are sufficiently stable at room temperature. An interesting influence of substituents on the stereoselectivities of the photooxygenations has been found, ranging from 51:49 to up to 91:9 dr (diastereomeric ratio). We explain this by a hindered rotation of the carbohydrate substituents, substantiated by a combination of NOESY measurements and theoretical calculations. Finally, we could transfer the chiral information from a pure endoperoxide to an epoxide, which was isolated after cleavage of the sugar chiral auxiliary in enantiomerically pure form

Stereoselective [4+2] Cycloaddition of Singlet Oxygen to Naphthalenes Controlled by Carbohydrates

Stereoselective reactions of singlet oxygen are of current interest. Since enantioselective photooxygenations have not been realized efficiently, auxiliary control is an attractive alternative. However, the obtained peroxides are often too labile for isolation or further transformations into enantiomerically pure products. Herein, we describe the oxidation of naphthalenes by singlet oxygen, where the face selectivity is controlled by carbohydrates for the first time. The synthesis of the precursors is easily achieved starting from naphthoquinone and a protected glucose derivative in only two steps. Photooxygenations proceed smoothly at low temperature, and we detected the corresponding endoperoxides as sole products by NMR. They are labile and can thermally react back to the parent naphthalenes and singlet oxygen. However, we could isolate and characterize two enantiomerically pure peroxides, which are sufficiently stable at room temperature. An interesting influence of substituents on the stereoselectivities of the photooxygenations has been found, ranging from 51:49 to up to 91:9 dr (diastereomeric ratio). We explain this by a hindered rotation of the carbohydrate substituents, substantiated by a combination of NOESY measurements and theoretical calculations. Finally, we could transfer the chiral information from a pure endoperoxide to an epoxide, which was isolated after cleavage of the sugar chiral auxiliary in enantiomerically pure form

Why Triple Bonds Protect Acenes from Oxidation and Decomposition

An experimental and computational study on the impact of functional groups on the oxidation stability of higher acenes is presented. We synthesized anthracenes, tetracenes, and pentacenes with various substituents at the periphery, identified their photooxygenation products, and measured the kinetics. Furthermore, the products obtained from thermolysis and the kinetics of the thermolysis are investigated. Density functional theory is applied in order to predict reaction energies, frontier molecular orbital interactions, and radical stabilization energies. The combined results allow us to describe the mechanisms of the oxidations and the subsequent thermolysis. We found that the alkynyl group not only enhances the oxidation stability of acenes but also protects the resulting endoperoxides from thermal decomposition. Additionally, such substituents increase the regioselectivity of the photooxygenation of tetracenes and pentacenes. For the first time, we oxidized alkynylpentacenes by using chemically generated singlet oxygen (¹O₂) without irradiation and identified a 6,13-endoperoxide as the sole regioisomer. The bimolecular rate constant of this oxidation amounts to only 1 × 10⁵ s^–1 M^–1. This unexpectedly slow reaction is a result of a physical deactivation of ¹O₂. In contrast to unsubstituted or aryl-substituted acenes, photooxygenation of alkynyl-substituted acenes proceeds most likely by a concerted mechanism, while the thermolysis is well explained by the formation of radical intermediates. Our results should be important for the future design of oxidation stable acene-based semiconductors

Role of Distance in Singlet Oxygen Applications: A Model System

Herein, we present a model system that allows the investigation of a directed intramolecular singlet oxygen (¹O₂) transfer. Furthermore, we show the influence of singlet oxygen lifetime and diffusion coefficient (<i>D</i>) on the preference of the intramolecular reaction over the intermolecular one in competition experiments. Finally, we demonstrate the distance dependence in quenching experiments, which enables us to draw conclusions about the role of singlet oxygen and ¹O₂ carriers in photodynamic therapy

Antileishmanial Anthracene Endoperoxides: Efficacy In Vitro, Mechanisms and Structure-Activity Relationships

Leishmaniasis is a vector-borne disease caused by protozoal Leishmania parasites. Previous studies have shown that endoperoxides (EP) can selectively kill Leishmania in host cells. Therefore, we studied in this work a set of new anthracene-derived EP (AcEP) together with their non-endoperoxidic analogs in model systems of Leishmania tarentolae promastigotes (LtP) and J774 macrophages for their antileishmanial activity and selectivity. The mechanism of effective compounds was explored by studying their reaction with iron (II) in chemical systems and in Leishmania. The correlation of structural parameters with activity demonstrated that in this compound set, active compounds had a LogPOW larger than 3.5 and a polar surface area smaller than 100 &Aring;2. The most effective compounds (IC50 in LtP &lt; 2 &micro;M) with the highest selectivity (SI &gt; 30) were pyridyl-/tert-butyl-substituted AcEP. Interestingly, also their analogs demonstrated activity and selectivity. In mechanistic studies, it was shown that EP were activated by iron in chemical systems and in LtP due to their EP group. However, the molecular structure beyond the EP group significantly contributed to their differential mitochondrial inhibition in Leishmania. The identified compound pairs are a good starting point for subsequent experiments in pathogenic Leishmania in vitro and in animal models