Showing papers by "Burkhard König published in 2004"

Tattoo Pigments are Cleaved by Laser Light—The Chemical Analysis In Vitro Provide Evidence for Hazardous Compounds¶

Abstract: In the western world, more than 80 million people decorate their skin with tattoos. Tattoo colorants are injected into the skin, like medical drugs. Most tattoo colorants are industrial pigments, and chemical industries have never produced them for human use but only to stain consumer goods. Up to 10% of tattooed people request removal of their tattoos because of an improved self-image or social stigmatization. In contrast to tattooing, physicians usually perform the tattoo removal. For that purpose laser light at very high intensities irradiates the skin to destroy the tattoo pigments. Based on a recent analysis of tattoo pigments, two widely used azo compounds were irradiated in suspension with laser and subsequently analyzed by using quantitative high-performance liquid chromatography and mass spectrometry. The high laser intensities cleaved the azo compounds, leading to an increase of decomposition products such as 2-methyl-5-nitroaniline, 2-5-dichloraniline and 4-nitro-toluene, which are toxic or even carcinogenic compounds. Moreover, the results of the chemical analysis show that the tattoo colorants already contain such compounds before laser irradiation. Because of a high number of patients undergoing laser treatment of tattoos and based on the results of our findings in vitro, it is an important goal to perform a risk assessment in humans regarding laser-induced decomposition products.

Synthetic creatinine receptor: imprinting of a Lewis acidic zinc(II)cyclen binding site to shape its molecular recognition selectivity.

Abstract: Molecularly imprinted polymers (MIPs) from polymerizable Lewis acidic zinc(II)cyclen complexes and ethylene glycol dimethyl acrylate have been prepared. For the imprinting process the template molecule creatinine is reversibly coordinated to the zinc atom. The high strength of this interaction allows analyte binding to the MIP from aqueous solution with high affinity. Its pH dependence is used for controlled guest release with nearly quantitative analyte recovery rate. The binding capacity and selectivity profile of the MIP remains constant through several pH controlled binding and release cycles. MIPs missing a suitable metal binding site showed no significant affinity for thymine or creatinine. Flavin adsorbs nonspecifically to all polymers. The imprinting process reverses the binding selectivity of zinc(II)cyclen for creatinine and thymine from 1:34 in homogeneous solution to 3.5:1 in the MIP. Scatchard plot analysis of creatinine binding isotherms reveals uniform binding of the imprint, with fits indicating a one-site model; however, similar analysis for thymine indicate high and low affinity sites. This corresponds to unrestricted coordination sites freely accessible for thymine, e.g., at the polymer surface, and misshaped imprinted sites, which still can accommodate thymine. More than 50% of all binding sites exclusively bind creatinine and are not accessible to thymine. The binding properties of a copolymer of polymerizable zinc(II)cyclen and ethylene glycol dimethyl acrylate missing the creatinine template, which match the binding selectivity of the complex in solution, confirm that the origin of altered selectivities is the imprinting process. With binding ability at physiological pH, the MIPs are applicable for tasks in medicinal diagnostics or biotechnology. Imprinted zinc(II)cyclen complexes provide, like a metalloenzyme binding motif, high binding affinity by reversible coordination while the surrounding macromolecule determines binding selectivity.

Chemistry in motion--unidirectional rotating molecular motors.

Abstract: Molecules are in constant motion, if not frozen around 0 K, but their Brownian motion is random. Overcoming this randomizing effect and generating directional motion at the molecular level with artificial systems is still a challenge. Research in this area is inspired by the vision of transferring the concept of an engine or a motor to the molecular level. That this is possible is illustrated by the directional processes found in nature: cell division, translocation of organelles, and membrane transport all rely on directional movement, while processes such as replication, transcription, and translation require encoded information sequences to be read and copied in a directional manner. Macroscopic engines and molecular motors both convert chemical, electrical, or light energy into mechanical work, yet their mode of operation is very different. Because of their dimensions molecular motors must operate at energies only slightly higher than those of the thermal bath surrounding them. They are actuated by Brownian motion and the key to their function is to give a direction to these undirected processes. Chemistry's role is to select one direction from all possible movements by lowering the energy profile of this directional movement compared to all the others. This makes this movement happen preferentially. Chemical or photochemical steps fuel these selection processes. Leigh et al. recently reported a net relative unidirectional circumrotation in a mechanically interlocked molecular rotor. The [2]catenane system (Scheme 1) consists of a larger macro-

Catalytic photooxidation of 4-methoxybenzyl alcohol with a flavin-zinc(II)-cyclen complex.

Abstract: Flavin-zinc(II)-cyclen 10 contains a covalently linked substrate binding site (zinc(II)-cyclen) and a chromophore unit (flavin). Upon irradiation, compound 10 effectively oxidizes 4-methoxybenzyl alcohol (11-OCH3) to the corresponding benzaldehyde both in water and in acetonitrile. In the presence of air, the reduced flavin 10-H2 is reoxidized, and so catalytic amounts of 10 are sufficient for alcohol conversion. The mechanism of oxidation is based on photoinduced electron transfer from the coordinated benzyl alcohol to the flavin chromophore. This intramolecular process provides a much higher photooxidation efficiency, with quantum yields 30 times those of the comparable intermolecular process with a flavin chromophore without a binding site. For the reaction in buffered aqueous solution a quantum yield of Phi = 0.4 is observed. The turnover number in acetonitrile is increased (up to 20) by high benzyl alcohol concentrations. The results show that the covalent combination of a chromophore and a suitable binding site may lead to photomediators more efficient than classical sensitizer molecules.

New heterocyclic β-sheet ligands with peptidic recognition elements

Abstract: A detailed and comprehensive overview is presented about the design, modeling, and synthesis, as well as spectroscopic characterization, of a new class of beta-sheet ligands. The characteristic feature of these compounds is a peptidic chimeric structure formed from a specific combination of aminopyrazolecarboxylic acids with naturally occurring alpha-amino acids. These hybrid peptides are designed with the aid of molecular modeling to exist mainly in an extended conformation. All their hydrogen bond donors and acceptors can be aligned at the bottom face in such a way that a perfect complementarity toward beta-sheets is obtained. Thus the aminopyrazoles impart rigidity and a highly efficient DAD sequence for the recognition of whole dipeptide fragments, whereas the natural alpha-amino acids are designed to mimick recognition sites in proteins, ultimately leading to sequence-selective protein recognition. The synthetic protocols either rely upon solution phase peptide coupling with a PMB protecting group strategy or solid-phase peptide coupling based on the Fmoc strategy, using the same protecting group. In solution, a key building block was prepared by catalytic reduction of a nitropyrazolecarboxylic acid precursor. Subsequently, it was (N-1)-protected with a PMB group, and elongated by HCTU- or T3P-assisted peptide coupling with dipeptide fragments, followed by PyClop-assisted coupling with another nitropyrazolecarboxylic acid building block. Final simultaneous deprotection of all PMB groups with hot TFA completed the high-yield protocol, which works racemization-free. After preparing a similar key building block with an Fmoc protection at N-3, we developed a strategy suitable for automated synthesis of larger hybrid ligands on a peptide synthesizer. Attachment of the first amino acid to a polystyrene resin over the Sieber amide linker is followed by an iterative sequence consisting of Fmoc deprotection with piperidine and subsequent coupling with natural alpha-amino acid via HATU/HOAt. High yields of free hybrid peptides are obtained after mild acidic cleavage from the resin, followed by deprotection of the PMB groups with hot TFA. The new aminopyrazole peptide hybrid compounds were characterized by various spectroscopic measurements including CD spectra, VT, and ROESY NMR experiments. All these accumulated data indicate the absence of any intramolecular hydrogen bonds and strongly support an extended conformation in solution, ideal for docking on to solvent-exposed beta-sheets in proteins. Initial results from aggregation tests of pathological proteins with these and related ligands look extremely promising.

Electronic Effects on the Bergman Cyclisation of Enediynes. A Review

Abstract: The thermal cyclisation of enediynes to benzene-1,4-diyl diradicals (Bergman cyclisation) is affected by geometrical and electronic conditions. While the effect of ring strain or conformational constrains on the cyclisation temperature has been investigated in detail, electronic contributions have been less studied. Often geometrical and electronic contributions cannot be clearly distinguished. In most cases metal ion chelation does involve both. In this review we have summarised clear-cut observations of electronic substituents effects on the thermal enediyne reactivity. The effects of substituents in the vinylic and terminal alkyne position, the influence of benzo-fusion and hetarene fusion, as well as the changes induced by heteroatoms in the enediyne skeleton, are within the scope of this review. With the exception of more complex heterocyclic hetarene-fused enediynes the experimental data of electronic substituent effects on the thermal Bergman cyclisation of enediynes follow theoretical predictions. A review with 57 references.

Design, synthesis, and evaluation of a biomimetic artificial photolyase model.

Abstract: Two new artificial photolyase models that recognize pyrimidine dimers in protic and aprotic organic solvents as well as in water through a combination of charge and hydrogen-bonding interactions and use a mimic of the flavine to achieve repair through reductive photoinduced electron transfer are presented. Fluorescence and NMR titration studies show that it forms a 1:1 complex with pyrimidine dimers with binding constants of approximately 10(3) M(-1) in acetonitrile or methanol, while binding constants in water at pH 7.2 are slightly lower. Excitation of the complex with visible light leads to clean and rapid cycloreversion of the pyrimidine dimer through photoinduced electron transfer catalysis. The reaction in water is significantly faster than in organic solvents. The reaction slows down at higher conversions due to product inhibition.

PEG-supported synthesis of pyrazole oligoamides with peptide β-sheet affinity

Abstract: Pyrazole amino acid oligoamides were prepared on polyethylene glycol starting from nitro pyrazole carboxylic acids or protected pyrazole amino acids. The polymer support facilitates product isolation during synthesis and makes the target oligoamides soluble in chloroform and water. This allows the determination of their binding properties towards peptides. Moderate affinity, which increases with the number of pyrazole units, is observed in chloroform and water.

NOP – Ein neues organischchemisches Grundpraktikum: Nachhaltigkeit per Internet

Abstract: Das Neue und nachhaltigere Organisch-chemische Praktikum NOP nutzt die zusatzlichen Moglichkeiten, die eine Website im Vergleich zu einem konventionellen Laborpraktikum in Buchform hat, um angehenden Synthesechemikern ein breiteres Verstandnis der durchgefuhrten Versuche zu vermitteln. Hierzu gehoren Informationen zu analytischen Methoden, Hintergrundinformationen zu den eingesetzten und entstehenden Stoffen sowie Kennzahlen zur Bewertung von Stoff- und Energieeffizienz der Versuche. Nicht zuletzt wird dabei Hintergrundwissen zum Konzept der nachhaltigen Entwicklung fur den Themenbereich Synthesechemie aufbereitet. The sustainable organic chemistry lab course for the new milennium (NOP) makes use of the possibilities that an interactive website provides compared to a conventional lab course published as a textbook or manual. The prospective synthetic chemist can thus gain a more in-depth understanding of his/her experiments. Detailed information about analytical methods, background information about the sub- stances being used and being formed during the experiment and “management ratios” like substance efficiency and energy efficiency are provided. Last but not least, knowledge about the concept “sustainable development” is being adapted to the domain of synthetic chemistry.