Showing papers by "Burkhard König published in 2014"

Reduction of aryl halides by consecutive visible light-induced electron transfer processes

Abstract: Biological photosynthesis uses the energy of several visible light photons for the challenging oxidation of water, whereas chemical photocatalysis typically involves only single-photon excitation. Perylene bisimide is reduced by visible light photoinduced electron transfer (PET) to its stable and colored radical anion. We report here that subsequent excitation of the radical anion accumulates sufficient energy for the reduction of stable aryl chlorides giving aryl radicals, which were trapped by hydrogen atom donors or used in carbon-carbon bond formation. This consecutive PET (conPET) overcomes the current energetic limitation of visible light photoredox catalysis and allows the photocatalytic conversion of less reactive chemical bonds in organic synthesis.

The Photoredox‐Catalyzed Meerwein Addition Reaction: Intermolecular Amino‐Arylation of Alkenes

Abstract: A variety of amides are efficiently accessible under mild conditions by intermolecular amino-arylation using a photo Meerwein addition with visible light. The reaction has a broad substrate scope, tolerates a large range of functional groups, and was applied to the synthesis of a 3-aryl-3,4-dihydroisoquinoline.

Fast and Effective Photodynamic Inactivation of Multiresistant Bacteria by Cationic Riboflavin Derivatives

Abstract: Photodynamic inactivation of bacteria (PIB) proves to be an additional method to kill pathogenic bacteria. PIB requires photosensitizer molecules that effectively generate reactive oxygen species like singlet oxygen when exposed to visible light. To allow a broad application in medicine, photosensitizers should be safe when applied in humans. Substances like vitamin B2, which are most likely safe, are known to produce singlet oxygen upon irradiation. In the present study, we added positive charges to flavin derivatives to enable attachment of these molecules to the negatively charged surface of bacteria. Two of the synthesized flavin derivatives showed a high quantum yield of singlet oxygen of approximately 75%. Multidrug resistant bacteria like MRSA (Methicillin resistant Staphylococcus aureus), EHEC (enterohemorrhagic Escherichia coli), Pseudomonas aeruginosa, and Acinetobacter baumannii were incubated with these flavin derivatives in vitro and were subsequently irradiated with visible light for seconds only. Singlet oxygen production in bacteria was proved by detecting its luminescence at 1270 nm. After irradiation, the number of viable bacteria decreased up to 6 log10 steps depending on the concentration of the flavin derivatives and the light dosimetry. The bactericidal effect of PIB was independent of the bacterial type and the corresponding antibiotic resistance pattern. In contrast, the photosensitizer concentration and light parameters used for bacteria killing did not affect cell viability of human keratinocytes (therapeutic window). Multiresistant bacteria can be safely and effectively killed by a combination of modified vitamin B2 molecules, oxygen and visible light, whereas normal skin cells survive. Further work will include these new photosensitizers for topical application to decolonize bacteria from skin and mucosa.

Acetylcholinesterase inhibitors with photoswitchable inhibition of β-amyloid aggregation.

Abstract: Photochromic cholinesterase inhibitors were obtained from cis-1,2-α-dithienylethene-based compounds by incorporating one or two aminopolymethylene tacrine groups. All target compounds are potent acetyl- (AChE) and butyrylcholinesterase (BChE) inhibitors in the nanomolar concentration range. Compound 11b bearing an octylene linker exhibited interactions with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Yet upon irradiation with light, the mechanism of interaction varied from one photochromic form to another, which was investigated by kinetic studies and proved "photoswitchable". The AChE-induced β-amyloid (Aβ) aggregation assay gave further experimental support to this finding: Aβ1-40 aggregation catalyzed by the PAS of AChE might be inhibited by compound 11b in a concentration-dependent manner and seems to occur only with one photochromic form. Computational docking studies provided potential binding modes of the compound. Docking studies and molecular dynamics (MD) simulations for the ring-open and -closed form indicate a difference in binding. Although both forms can interact with the PAS, more stable interactions are observed for the ring-open form based upon stabilization of a water molecule network within the enzyme, whereas the ring-closed form lacks the required conformational flexibility for an analogous binding mode. The photoswitchable inhibitor identified might serve as valuable molecular tool to investigate the different biological properties of AChE as well as its role in pathogenesis of AD in in vitro assays.

Exploiting Protein Symmetry To Design Light-Controllable Enzyme Inhibitors†

Abstract: The activity of the metabolic branch-point enzyme PriA from Mycobacterium tuberculosis (mtPriA) can be controlled reversibly by light. Two-pronged inhibitors based on the dithienylethene scaffold were designed utilizing mtPriA's natural rotational symmetry. Switching from the flexible, ring-open to the rigid, ring-closed isomer reduces inhibition activity by one order of magnitude.

Photocatalytic water oxidation at soft interfaces

Abstract: Molecular water oxidation catalysts have been, for the first time, co-embedded with a photosensitizer into phospholipid membranes. The functionalized small unilamellar vesicles produce molecular oxygen by photocatalysis when irradiated with visible light in aqueous buffer. The two dimensional assembly of the catalysts at the lipid–water interface mimics photoactive membranes in biology and allows photocatalytic water oxidation at very low catalyst concentrations of 500 nM, which cannot be reached in homogeneous systems. Highest TONs are obtained below the membrane's main transition temperature indicating that phase separation, clustering and a limited dynamic enhance the photocatalytic activity of the assembly. The concept of membrane co-embedding can be applied to various combinations, ratios and concentrations of photosensitizers and water oxidizing catalysts, providing a new approach for artificial photosynthesis.

Die photoredoxkatalysierte Meerwein-Addition: intermolekulare Aminoarylierung von Alkenen

Abstract: Eine Vielzahl von Amiden ist unter milden Bedingungen durch intermolekulare Aminoarylierung unter Verwendung einer photokatalytischen Meerwein-Addition mit sichtbarem Licht erhaltlich. Das Syntheseprotokoll erlaubt einen breiten Substratbereich, toleriert eine Bandbreite von funktionellen Gruppen und wurde auf die Synthese eines Isochinolidalkaloids angewendet.

Chromo-pharmacophores: photochromic diarylmaleimide inhibitors for sirtuins

Abstract: Controlling the activity of sirtuins is of high biomedical relevance as the enzymes are involved in cancer, neurodegeneration and other diseases. Therefore structural elements of 3,4-bisindoylmaleimides (BIMs), which are known NAD+-dependent histone deacetylase (sirtuin) inhibitors, were merged with photochromic diarylmaleimides to yield photoswitchable enzyme inhibitors. The new inhibitors show excellent photophysical properties, are switchable even in polar solvents, and subtype selective against hSirt2. The inhibitory activity changes up to a factor of 22 for the two photoisomers and physiological properties can therefore be effectively toggled by irradiation with light of different wavelengths. Docking experiments using the enzyme crystal structure explain the observed activity changes based on the steric demand of the thiophene substitution and the rigidity of the molecular structure.

Functionalized Membranes for Photocatalytic Hydrogen Production

Abstract: Functionalized vesicles for photocatalytic hydrogen production in water have been prepared by co-embedding of amphiphilic photosensitizers and a hydrogen-evolving catalyst in phospholipid membranes. The self-assembly allows a simple two-dimensional arrangement of the multicomponent system with close spatial proximity, which gave turnover numbers up to 165 for the incorporated amphiphilic cobaloxime water reduction catalyst 3 b under optimized conditions in purely aqueous solution. Superior photocatalytic activity in fluid membranes indicates that mobility and dynamic reorganization of catalytic subunits in the membrane promote the visible-light-driven hydrogen production. The functionalized membranes represent nanostructured assemblies for hydrogen production in aqueous solution mimicking natural photosynthesis.

Heterogeneous photocatalysts in organic synthesis

Abstract: The review deals with the application of inorganic semiconductors in organic synthesis. Although the majority of reported reactions still aim at the photocatalytic decomposition of organic compounds, the number of examples in synthetic applications is growing. The principal mechanisms of heterogeneous semiconductor photocatalysis are considered and examples illustrating the use of inorganic semiconductors in organic synthesis are given. The discussion is arranged according to the required excitation wavelength (UV or visible light) and to the new bond that is formed (carbon–carbon or carbon–heteroatom bond). The bibliography includes 47 references.

Black tattoos entail substantial uptake of genotoxicpolycyclic aromatic hydrocarbons (PAH) in human skin and regional lymph nodes.

Abstract: Hundreds of millions of people worldwide have tattoos, which predominantly contain black inks consisting of soot products like Carbon Black or polycyclic aromatic hydrocarbons (PAH). We recently found up to 200 μg/g of PAH in commercial black inks. After skin tattooing, a substantial part of the ink and PAH should be transported to other anatomical sites like the regional lymph nodes. To allow a first estimation of health risk, we aimed to extract and quantify the amount of PAH in black tattooed skin and the regional lymph nodes of pre-existing tattoos. Firstly, we established an extraction method by using HPLC – DAD technology that enables the quantification of PAH concentrations in human tissue. After that, 16 specimens of human tattooed skin and corresponding regional lymph nodes were included in the study. All skin specimen and lymph nodes appeared deep black. The specimens were digested and tested for 20 different PAH at the same time.PAH were found in twelve of the 16 tattooed skin specimens and in eleven regional lymph nodes. The PAH concentration ranged from 0.1–0.6 μg/cm2 in the tattooed skin and 0.1–11.8 μg/g in the lymph nodes. Two major conclusions can be drawn from the present results. Firstly, PAH in black inks stay partially in skin or can be found in the regional lymph nodes. Secondly, the major part of tattooed PAH had disappeared from skin or might be found in other organs than skin and lymph nodes. Thus, beside inhalation and ingestion, tattooing has proven to be an additional, direct and effective route of PAH uptake into the human body.

Nutzung natürlicher Proteinsymmetrie zum Design lichtschaltbarer Enzyminhibitoren

Abstract: Die Aktivitat des metabolischen Schlusselenzyms PriA aus Mycobacterium tuberculosis (mtPriA) kann reversibel durch Licht kontrolliert werden. Auf der Grundlage des Dithienylethen-Gerusts wurden entsprechend der zweifachen Rotationssymmetrie des Proteins symmetrische Inhibitoren mit terminalen Ankern entworfen. Durch Schalten vom flexiblen, offenen Isomer zur starren, geschlossenen Form wurde die Inhibitionsaktivitat um eine Grosenordnung reduziert.

First synthesis of naphthalene annulated oxepins

Abstract: Highly condensed oxepins have been prepared in good yields from their corresponding diols by etherification using p-toluenesulfonic acid. Their intriguing twisted structures were unambiguously determined by X-ray crystallography. Substitution effects of a novel highly aromatic naphthalene annulated oxepin indicate that structural and conjugative effects have an influence on the optoelectronic properties.

Cooperative hydrolysis of aryl esters on functionalized membrane surfaces and in micellar solutions.

Abstract: Catalytic hydrolysis of peptides, proteins, phosphates or carboxylate esters in nature is catalysed by enzymes, which are efficient, fast and selective. Most of the hydrolytic chemical catalysts published so far mimic the active site of enzymes and contain metal complexes and amino acid residues. Their synthesis can be laborious, while the hydrolytic activity is still limited compared to enzymes. We present an approach that uses fluid membranes of vesicles and micelles as a support for amphiphilic additives, which cooperatively cleave aryl ester bonds. The membrane anchored bis-Zn(II)-complex 1 is hydrolytically active and hydrolyses fluorescein diacetate (FDA) with a second order rate constant (k2) of 0.9 M−1 s−1. The hydrolytic activity is modulated by co-embedded membrane additives, bearing common amino acid side chain functional groups. With this approach, the hydrolytic activity of the system is enhanced up to 16 fold in comparison with cyclen 1 (k2 = 14.7 M−1 s−1). DOPC and DSPC lipids form at room temperature fluid or gel phase membranes, respectively. Omitting the lipid, micellar solutions were obtained with hydrolytic activity reaching k2 = 13.4 M−1 s−1. It is shown that cooperative hydrolysis is favoured in fluid membranes and micelles, allowing the active moieties to arrange freely. The embedding and dynamic self-assembly of membrane active components in fluid membranes and micelles provide facile access to hydrolytically active soft interfaces.

Photocatalytic disassembly of tertiary amine-based dendrimers to monomers and their application to the ‘catch and release’ of a dye in aqueous solution

Abstract: Photocatalytic disassembly of tertiary amine-based poly(propyl ether imine) dendrimers, in the presence of either 9,10-anthraquinone or riboflavin tetraacetate and O2(g), leads to di- and tripropanolamine monomers. An application is shown by solubilisation of a water-insoluble dye, Sudan I, in aq. dendrimer solution (‘catch’), followed by its ‘release’ upon disassembly of the dendrimer.

A binary catalytic system based on mixed monolayers of a phospholipid and amphiphilic bis(Zn2+-cyclen)

Abstract: Herein, we report on the study of the properties of mixed Langmuir monolayers composed of a synthetic amphiphilic receptor, alkylated bis-cyclic zinc complex of 1,4,7,10-tetraazacyclododecane, and a lipid, distearoyl phosphatidylcholine. The kinetics of a hydrolysis of a model substrate, bis(p-nitrophenyl) phosphate in individual and mixed monolayers of the amphiphilic receptor was studied by using fiber-optical absorption/reflection spectroscopy. The hydrolysis of the organic phosphate in these planar systems proceeded by a two-stage mechanism. This mechanism comprises substrate adsorption on the monolayer via a reaction of the zero order with respect to the adsorbate followed by the pseudo-second-order reaction of the hydrolytic decomposition of the substrate. Unlike the reaction in molecular and colloidal solutions, the process in the monolayer results in the complete decomposition of the model substrate into nitrophenol and phosphate anion. The amphiphilic receptor is directly involved in this reaction to yield a stable complex with the phosphate anion as a resulting product of hydrolysis. An increase in the receptor affinity for the phosphate anion is, most likely, due to the effect of the interface on the strength of the coordination bonds in an intermediate product and the receptor-phosphate complex. Immobilization of the receptor within the lipid matrix increases the rate of substrate decomposition in the monolayer by almost an order of magnitude. We suggested an explanation for the observed effect of the lipid matrix on the catalytic properties of the amphiphilic metallocomplex.

Dye‐Labeled Cα‐Tetrasubstituted α‐Amino Acids

Abstract: We report the synthesis of pyrene- and carboxyfluorescein labeled Cα-tetrasubstituted amino acids (TAAs). The fluorescent dye can be coupled to the TAA before or after its incorporation into a peptide sequence using a Suzuki-type CC bond formation.