Robert Kretschmer

Dicarbonyl-bis(cysteamine)iron(II): a light induced carbon monoxide releasing molecule based on iron (CORM-S1).

Carbon monoxide releasing molecules (CORMs) deliver controlled amounts of CO to biological targets and organs. The reaction of cysteamine with triirondodecacarbonyl yields dicarbonyl bis(aminoethylthiolato)iron(II) that represents an iron-based CORM with biogenic ligands. X-ray diffraction studies at a single crystal show a cis-arrangement of the carbonyl ligands in trans-position to the amino groups with average Fe-C and C-O distances of 176.8 and 114.8 pm. The CO release is mediated by irradiation with visible light (λ>400 nm). Physiological tests using ion channels sensitive to CO revealed the light- and time-dependent decomposition of CORM-S1 without obvious adverse effects on the cellular level. CORM-S1 is thus suitable for selective CO release and possesses a high potential for therapeutic application.

Structure of the oxygen-rich cluster cation Al2O7+ and its reactivity toward methane and water.

The oxygen-rich cluster Al(2)O(7)(+) is generated in the gas phase and investigated with respect to both its structure and its reactivity toward small, inert molecules using Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry and DFT-based calculations. Al(2)O(7)(+) reacts with CH(4) under ambient conditions via hydrogen atom transfer (HAT), and with H(2)O a ligand exchange occurs which gives rise to the evaporation of two O(2) molecules. The resulting product ion Al(2)O(4)H(2)(+) is also capable of abstracting a hydrogen atom from both H(2)O and CH(4). As indicated in the H(2)O/2O(2) ligand exchange and supported by collision-induced dissociation (CID) experiments, two O(2) units constitute structural elements of Al(2)O(7)(+). Further insight is provided by DFT calculations, performed at the unrestricted B3LYP/TZVP level, and reaction mechanisms are suggested on the basis of both the experimental and theoretical results.

SERS as tool for the analysis of DNA-chips in a microfluidic platform

A sequence-specific detection method of DNA is presented combining a solid chip surface for immobilisation of capture DNAs with a microfluidic platform and a readout of the chip based on SERS. The solid chip surface is used for immobilisation of different capture DNAs, where target strands can be hybridised and unbound surfactants can be washed away. For the detection via SERS, short-labelled oligonucleotides are hybridised to the target strands. This technique is combined with a microfluidic platform that enables a fast and automated preparation process. By applying a chip format, the problems of sequence-specific DNA detection in solution phase by means of SERS can be overcome. With this setup, we are able to distinguish between different complementary and non-complementary target sequences in one sample solution.

Development of a lab-on-a-chip device for diagnosis of plant pathogens

A lab-on-a-chip system for rapid nucleic acid-based analysis was developed that can be applied for diagnosis of selected Phytophthora species as a first example for use in plant pathology. All necessary polymerase chain reaction process (PCR) and hybridization steps can be performed consecutively within a single chip consisting of two components, an inflexible and a flexible one, with integrated microchannels and microchambers. Data from the microarray is collected from a simple electrical measurement that is based on elementary silver deposition by enzymatical catalyzation. Temperatures in the PCR and in the hybridization zone are managed by two independent Peltier elements. The chip will be integrated in a compact portable system with a pump and power supply for use on site. The specificity of the lab-on-a-chip system could be demonstrated for the tested five Phytophthora species. The two Pythium species gave signals below the threshold. The results of the electrical detection of the microarray correspond to the values obtained with the control method (optical grey scale analysis).

A disposable and cost efficient microfluidic device for the rapid chip-based electrical detection of DNA

Requirements for a point-of-care device are an easy and robust read-out and--above all--a simple handling. We integrated an established robust electrical read-out for DNA-chips into a microfluidic device, thereby creating an automated analysis system that combines the necessary steps for a chip-based analysis. It is based on the electrical detection of biotin-labeled DNA in a gap between two microstructured electrodes on the surface of a DNA-chip. The biotin serves as binding molecule for streptavidin-conjugated horseradish peroxidase. A following enzyme-induced silver deposition bridges the gap by a conductive layer. The miniaturized chip gives the possibility to realize a durable system suitable for point-of-care applications. To enable an initial automation, all corresponding process steps were executed in a miniaturized silicone flow cell. The required defined temperatures for the hybridization and the washing steps can be adjusted by a heating foil. This paper characterizes the performance of the flow cell based system in terms of reaction speed and analysis time, sensitivity as well as specificity, and the comparison to a conventional system, without flow cell. These first steps of automation and integration will help to realize a laboratory-independent bioanalytical tool, for the use outside of specialized laboratories for fast analysis of different chemical and biological applications.

Chip‐based detection system for the on‐site analysis of animal diseases

A portable and robust system which is suitable for the automated analysis of DNA or RNA of selected pathogens such as foot‐and‐mouth disease virus (FMDV) is developed. The system incorporates a stationary PCR chip and is coupled with a DNA chip and an electrical detection for the sequence‐specific identification of the PCR products. The PCR chip represents a miniaturized form of the classical thermocyclers and enables a fast and sensitive amplification as well as labeling of specific DNA sequences with minimal space and energy requirements. The detection and identification of the PCR products is performed on a DNA chip with an electrical detection scheme. The combination of the two technologies allows a very fast and highly specific sequence‐based detection and differentiation of pathogens. Further, it combines the accuracy of sequence analysis with the speed of chip technologies. For the total analysis including DNA amplification and DNA detection, less than 2 h are required.

Rubidium-Mediated Birch-Type Reduction of 1,2-Diphenylbenzene in Tetrahydrofuran

The reaction of 1,2-diphenylbenzene with rubidium metal in THF yields extremely sensitive and pyrophoric [η(5)-{1,2-diphenyl-2,5-cyclohexadienyl}rubidium](∞) (1). Compound 1 characterizes a possible intermediate in a Birch-type reaction and represents a very rare example of a fully characterized organorubidium complex as well as an open main-group metal pentadienide as part of a six-membered ring. In the solid state the rubidium atoms interact with the cyclohexadienyl moiety, whereas the coordination sphere of the soft cation is additionally stabilized exclusively by several metal π-arene interactions despite the presence of strongly coordinating donors. The bonding situation was elucidated by MP2/def2-TZVPP calculations including population analysis.

Residues at the Indole‐NH of LE300 Modulate Affinities and Selectivities for Dopamine Receptors

To further investigate SAR in the class of azecine‐type dopamine receptor antagonists, we synthesized a series of derivatives, substituted at the indole‐NH of the lead compound LE300 by different alkyl chains in addition to phenylpropyl, allyl, propargyl, and acetyl residues. The affinities of the target compounds for all human dopamine receptors (D1–D5) were investigated by radioligand binding assay and their functionality by a calcium assay. Both the affinities and selectivities for the dopamine receptors were found to be affected by the nature of the substituent. The N14‐methylated derivative displayed the highest affinities for all D‐receptors. In general, the affinities decreased with increasing chain length of the N‐alkyl. Different substituents, partly led to altered affinity, and selectivity profile when compared with our lead LE300.

Manipulation of metal nanoparticles in micrometer electrode gaps by dielectrophoresis

The integration of molecular structures into microscopic electrode arrays can be achieved by dielectrophoresis of gold nanoparticles in electrode gaps. Using microelectrodes realized by photolithography, we demonstrate here the generation of pearl chain arrangements of nanoparticles in structures accessible for standard technologies. In order to preserve the individual particle structures in the final nanowire arrangement, various strategies were employed. This method for defined positioning of nanoparticle chains offers the potential to wire DNA or DNA superstructures after conjugation to the particles and dielectrophoresis. It allows a parallel processing of molecular structures and their integration into microsystem technology.

[1-Meth­oxy-3-(pyridin-2-yl)indolizin-2-yl](pyridin-2-yl)methanone

Methylation of [1-hydroxy-3-(pyridin-2-yl)indolizin-2-yl](pyridin-2-yl)methanone was performed via metalation with potassium tert-butanolate in toluene and a subsequent metathesis reaction with methyl iodide yielded the yellow title compound, C20H15N3O2. The substituents at the indolizine unit are twisted [the indolizine ring system makes dihedral angles of 34.67 (7) and 77.49 (5)°, respectively, with the pyridyl and pyridinoyl rings] with single bonds between the central unit and the attached pyridine ring [1.459 (3) Å] and the pyridinoyl group [1.483 (3) Å]. There are no classical hydrogen bonds in the crystal structure.