Scientific publications

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.

Indium tin oxide (ITO) thin film is one of the most widely used as transparent conductive electrodes in all forms of flat panel display (FPD) and microelectronic devices. Suspension of already crystalline conductive ITO nanoparticles fully dispersed in alcohol was spun, after modifying with coupling agent, on glass substrates. The low cost, simple and versatile traditional photolithography process without complication of the photoresist layer was used for patterning ITO films. Using of UV light irradiation through mask and direct UV laser beam writing resulted in an accurate linear, sharp edge and very smooth patterns. Irradiated ITO film showed a high transparency (similar to 85%) in the visible region. The electrical sheet resistance decrease with increasing time of exposure to UV light and UV laser. Only 5 min UV light irradiation is enough to decrease the electrical sheet resistance down to 5 k Omega square.

The corundum structures of In2O3:Sn (ITO) nanoparticles were synthesized by hydrothermal processing of InCl3 and SnCl4·5H2O precursor at low temperature of 250 °C and 40 bar pressure for 3 h. The precursor was precipitated in a white gel of InOOH. After drying at 150 °C in air, it was crystallized in orthorhombic structure. InOOH powder was transformed into dark-gray rhombohedral In2O3 by sintering at 420 °C in forming gas for 1 h. The samples were characterized by means of XRD, SEM, and TEM. The particle size of the resulted ITO powder was about 32 nm.

Low temperature processable materials with high dielectric constants are required for application on flexible organic substrates, for example, in printed electronics. To date, mainly organic polymers with embedded functional particles have been investigated for this purpose. For the first time, we present a printable dielectric composite material composed of ferroelectric high permittivity particles (BaTiO3) bonded by a mainly inorganic sol-gel derived network. The exemplary optimization of the properties by varying the sol-gel precursor illustrates the potential of sol-gel chemistry for printable functional materials. An operational gravure printed capacitor including printed silver electrodes is presented. The measured dielectric constants are among the highest reported in literature for low temperature cured films with moderate dissipation factors. Besides these promising dielectric properties, this composite film shows a ferroelectric response.

Proton-conducting gel polymer electrolytes based on gelatin plasticized with glycerol and containing acetic acid were investigated, characterized, and applied to electrochromic window. For glycerol contents varying from 7% to 48%, the conductivity of the uniform and predominantly amorphous gel electrolyte was found to follow a Vogel-Tamman-Fulcher behavior with the temperature. Typically, for the electrolyte chosen to make 7×2 cm2 electrochromic smart window with the configuration: glass/fluor-doped tin oxide (FTO)/WO3/gelatin electrolyte/CeO2-TiO2/FTO/glass and containing 28% of glycerol, the conductivities were found to be of the order of 5×10−5 S/cm at room temperature and 3.6×10−4 S/cm at 80°C. The device was characterized by spectroelectrochemical techniques and was tested up to 10,000 cycles showing a fast coloring/bleaching behavior, where the coloring process was achieved in 10 s and the bleaching in 2 s. The transmission variation at the wavelength of 550 nm was about 15%. The cyclic voltammograms showed a very good reversibility of the cathodic/anodic processes, and the charge density was about 3.5 mC/cm2. The memory tests showed that the transmittance in the colored state increased by 8% in 90 min after removing the potential.