Publikationen

The behaviour of materials is governed by their microstructures, whether they are naturally occurring or artificially designed. Engineered microstructures lead to materials with new and useful functions, but their real-world application requires scalable microstructuring methods for production. This review discusses several principles of fabrication and their scalability. Replication by imprint and multiplexed probes are obvious candidates for scale-up, but they limit the choice of materials. The assembly of interacting particles is a promising, scalable fabrication method. A wide range of materials can be obtained as particles which assemble into regular superstructures, but large-scale structuring at high precision and yield as yet remains a challenge.

Three synthetic routes to hydrophobic silica nanoparticles are compared in this paper. First, the established synthetic method based on the Stöber process was examined. Monodisperse colloidal silica particles with diameters of 15-25 nm were prepared via the hydrolysis of tetraethyl orthosilicate (TEOS) by aqueous ammonia in ethanol. The surfaces of these particles were rendered hydrophobic with octadecyltrimethoxysilane (ODTMS) after the reaction or, more conveniently, during the growth phase. Secondly, silica particles with diameters of 15-50 nm were prepared using a one-pot synthesis in which TEOS was hydrolyzed by an amino acid and the resulting particles were coated with ODTMS. Lastly a novel, direct approach to the synthesis of hydrophobic organosilica nanoparticles was developed using ODTMS as the single silica source. Hydrolysis of the ODTMS by aqueous ammonia in ethanol yielded monodisperse colloidal organosilica particles with diameters of 15-30 nm.

Gene therapy scientists have developed expression systems for therapeutic transgenes within patients, which must be seamlessly integrated into the patient's physiology by developing sophisticated control mechanisms to titrate expression levels of the transgenes into the therapeutic window. However, despite these efforts, gene-based medicine still faces security concerns related to the administration of the therapeutic transgene vector. Here, molecular tools developed for therapeutic transgene expression can readily be transferred to materials science to design a humanized drug depot that can be implanted into mice and enables the trigger-inducible release of a therapeutic protein in response to a small-molecule inducer. The drug depot is constructed by embedding the vascular endothelial growth factor (VEGF121) as model therapeutic protein into a hydrogel consisting of linear Polyacrylamide crosslinked with a homodimeric variant of the human FKbinding protein 12 (F M), originally developed for gene therapeutic applications, as well as with dimethylsuberimidate. Administrating increasing concentrations of the inducer molecule FK506 triggers the dissociation of FM thereby loosening the hydrogel structure and releasing the VEGF121 payload in a dose-adjustable manner. Subcutaneous implantation of the drug depot into mice and subsequent administration of the inducer by injection or by oral intake triggers the release of VEGF121 as monitored in the mouse serum. This study is the first demonstration of a stimuli-responsive hydrogel that can be used in mammals to release a therapeutic protein on demand by the application of a small-molecule stimulus. This trigger-inducible release is a starting point for the further development of externally controlled drug depots for patient-compliant administration of biopharmaceuticals. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthetic biology as the discipline of reconstructing natural and designing novel biological systems is gaining increasing impact in signaling science. This review article provides insight into synthetic approaches for analyzing and synthesizing signaling processes starting with strategies into how natural and pathological signaling pathways can be reconstructed in an evolutionary distant host to study their topology and function while avoiding interference with the original host background. In the second part we integrate synthetic strategies in the rewiring of signaling systems at the nucleic acid and protein level to reprogram cellular functions for biotechnological applications. The last part focuses on synthetic inter-cell and inter-species signaling devices and their integration into synthetic ecosystems to study fundamental mechanisms governing the co-existence of species. We finally address current bottlenecks in the (re-)design of signaling pathways and discuss future directions in signaling-related synthetic biology. © 2010 The Royal Society of Chemistry.

The design and construction of synthetic gene circuits with complex spatiotemporal dynamics was pioneered in bacteria, but it took almost a decade until synthetic biologists were able to construct genetic circuits with complex spatiotemporal dynamics in mammalian cells. This review highlights the most recent advances in mammalian synthetic biology, and it describes metabolite, hormone, and light-triggered genetic switches as well as the design and construction of synthetic networks that feature tunable oscillations. We conclude by discussing not only the current limitations but also possible ways to transform the construction of synthetic mammalian systems from an art into a predictive engineering discipline. © 2010 Elsevier Ltd.

When the polycyclic alumosiloxane (Ph2SiO)8[AlO(OH)]4, which may be isolated as the diethyl ether adduct (Ph2SiO)8[AlO(OH)]4 · 4OEt2, is allowed to react with the double N-methyl-piperidine (nmp) adduct of monochloroalane, AlH2Cl · 2nmp (1) (crystal structure analysis), the polycycle (Ph2SiO)8[AlO(O)0.5]4 · 2nmp (2) is obtained. Compared to the starting material and apart from the coordinating bases, the compound formally has lost two water molecules. The structure of (Ph2SiO)8[AlO(O)0.5]4 · 2nmp (2) can be derived from (Ph2SiO)8[AlO(OH)]4 by substituting the central Al4(OH)4 motif through an Al4O2 entity which consists of a central Al2O2 ring coordinated to two further aluminum atoms through almost trigonal planar oxygen atoms. Using tris(ethylene)diamine (ted) as base and reacting it with (Ph2SiO)8[Al(OH)]4, we have been able to isolate and completely characterize an intermediate on the way to these formally condensed alumosiloxane polycycles like in (Ph2SiO)8[AlO(O)0.5]4 · 2nmp (2). It has the composition (Ph2SiO)8[AlO(O)0.25]4 ∙ (OH·ted)2 · (OH2·ted) (3) and has, compared to the starting material, the same number of hydrogen, oxygen, aluminum and silicon atoms within the inner molecular framework. Nevertheless, its structure is very different: whereas half of the molecule is structurally similar to (Ph2SiO)8[AlO(OH)]4, with OH groups forming hydrogen bridges to the nitrogen atoms of ted and connecting two aluminum atoms, the other half contains a unique oxygen atom which is in an almost planar trigonal bonding mode to three aluminum atoms. Furthermore, this part of the molecule has an aluminum atom to which a water molecule is coordinated, one of the hydrogen atoms being involved in hydrogen bonding to a further tris(ethylene)diamine (ted). This structure gives some important insights in the possible mechanism of the "condensation reaction" within (Ph2SiO)8[AlO(OH)]4.

When the aluminosiloxane [Ph2SiO]8[AlO(OH)]4·4Et2O (1) is reacted with propane-1,3-diamine, the coordinated ether molecules can be replaced by the nitrogen bases. Depending on the molar ratio of diamine to the aluminosiloxane, several products can be isolated with different ratios of the propanediamine (X-ray structures): [Ph2SiO]8[AlO(OH)]4·2NH2(CH2)3NH2 (2) or [Ph2SiO]8[AlO(OH)]4·3NH2(CH2)3NH2 (3 and 4). Moreover, we noticed that the adduct with three diaminopropane units exists in two different molecular structures, which are related to one another by intramolecular "switching" of hydrogen bonds. The interactions between the inorganic molecule center and the organic amine can be described as a lock-and-key model with hydrogen OH···N and NH···N bridges playing the most important role in this recognition mechanism.

The synthesis, structural characterisation, electrochemistry, and luminescence properties of a series of alkali metal alcoholates and samarium(III) alkoxides with thiophene-based OR substituents are presented. The alkali metal alcoholates 7-15 were obtained by deprotonation of the carbinol with NaH or KH. Their molecular structures consist of tetranuclear alkali metal alcoholates with a distorted cubane-like M4O4 core (X-ray structure analyses). Each alkali metal is surrounded by three carbinolate ligands and (depending on the derivative) by additional tetrahydrofuran molecules. The mononuclear samarium alkoxides {Sm[OC(C4H3S)3]3(thf)3}·thf (16) and {Sm[OC(C16H13S)]3(thf)3}·thf (17) were synthesised by the salt metathesis reactions between {[KOC(C4H3S)3]4(thf)2}·thf (7), [NaOC(C4H3S)3]4(thf)2 (8) or {[KOC(C16H13S)]4(thf)3}·1/2thf (11), respectively, and SmCl3 in thf solution. The molecular structures of these air-sensitive base adducts have been determined by single crystal X-ray crystallography and reveal an approximately octahedral coordination sphere around the samarium metal atoms with three methoxido ligands and three facially arranged tetrahydrofuran molecules. The electrochemical properties are essentially dominated by the oxidation of the thienyl units. The emission spectra of the carbinols and their derived potassium and sodium compounds display broad bands attributed to the π* → π transitions of the aromatic ligands. Luminescence studies performed on complexes 16 and 17 reveal the typical f–f transitions of the SmIII ion. The photophysical data suggest that an energy transfer from the ligand to the metal atom operates.

Two novel mononuclear neodymium alkoxides [Nd{OC(C14H11S2)}3(thf)3]·thf (9) and [Nd{OC(C16H13S)}3(thf)3]·thf (10) have been prepared by the reaction between Nd[N(SiMe3)2]3 and the tertiary alcohols HO-C(C14H11S2) (3) and HO-C(C16H13S) (4). The geometry around the neodymium metal is almost octahedral with a facial ligand arrangement similar to [Nd{OC(C8H5S2)3}3(thf)3]·4thf (5), [Nd{OC(C4H3S)3}3(thf)3]·thf (7) and Er[OC(C4H3S)3]3(thf)3 (8) (X-ray diffraction on single crystals). The cyclic voltammograms of a series of neodymium and erbium alkoxides indicate that the electrochemical properties are essentially dominated by the organic ligands. In comparison to the carbinols HO-C(C8H5S2)3 (1), HO-C(C4H3S)3 (2), HO-C(C14H11S2) (3) or HO-C(C16H13S) (4), the oxidation peak potentials of the thienyl units for the neodymium alkoxides [Nd{OC(C8H5S2)3}3(thf)3]·4thf (5), [Nd{OC(C4H3S)3}3(thf)3]·thf (7), [Nd{OC(C14H11S2)}3(thf)3]·thf (9) and [Nd{OC(C16H13S)}3(thf)3]·thf (10) are marginally shifted towards higher values by 0.03-0.10 V, whereas for Er[OC(C8H5S2)3]3(thf) (6) and Er[OC(C4H3S)3]3(thf)3 (8) a decrease of these potentials is noticed. Repetitive cyclic voltammetry does not generate polymeric films for 7-10, as found for the free organic ligands 2-4. Contrarily, the mononuclear precursors [Nd{OC(C8H5S2)3}3(thf)3]·4thf (5) and Er[OC(C8H5S2)3]3(thf) (6) are electro-oxidized and electro-active polymer films are obtained and characterized. To investigate the positions of the excited states of the ligands, emission spectra of the carbinols 1-4 have been recorded. The luminescence studies of the neodymium alkoxides reveal an energy transfer from the ligand to the metal centre with a remarkable Nd emission efficiency upon ligand excitation in the case of 5.

The development of micro- and nanostructured surfaces which improve the cell-substrate interaction is of great interest in today's implant applications. In this regard, Al/Al2O3 bi-phasic nanowires were synthesized by chemical vapor deposition of the molecular precursor (tBuOAlH2)2. Heat treatment of such bi-phasic nanowires with short laser pulses leads to micro- and nanostructured Al2O3 surfaces. Such surfaces were characterized by scanning electron microscopy (SEM), electron dispersive spectroscopy and x-ray photoelectron spectroscopy. Following the detailed material characterization, the prepared surfaces were tested for their cell compatibility using normal human dermal fibroblasts. While the cells cultivated on Al/Al2O3 bi-phasic nanowires showed an unusual morphology, cells cultivated on nanowires treated with one and two laser pulses exhibited morphologies similar to those observed on the control substrate. The highest cell density was observed on surfaces treated with one laser pulse. The interaction of the cells with the nano- and microstructures was investigated by SEM analysis in detail. Laser treatment of Al/Al2O3 bi-phasic nanowires is a fast and easy method to fabricate nano- and microstructured Al2O3-surfaces for studying cell-surface interactions. It is our goal to develop a biocompatible Al2O3-surface which could be used as a coating material for medical implants exhibiting a cell selective response because of its specific physical landscape and especially because it promotes the adhesion of osteoblasts while minimizing the adhesion of fibroblasts.