The University of Göttingen , known informally as Georgia Augusta, is a Public comprehensive research university in the city of Göttingen, Germany. Founded in 1734 by George II, King of Great Britain and Elector of Hanover and starting classes in 1737, the university is the oldest in the state of Lower Saxony, and also the biggest in student enrollment, which stands at around 26,000. The university is highly renowned and respected both in Germany and in the world and has shaped Göttingen into a university city with a high student and faculty population. Wikipedia.
Dobbelstein M.,University of Gottingen |
Sorensen C.S.,Copenhagen University
Nature Reviews Drug Discovery | Year: 2015
DNA replication in cancer cells is accompanied by stalling and collapse of the replication fork and signalling in response to DNA damage and/or premature mitosis; these processes are collectively known as 'replicative stress'. Progress is being made to increase our understanding of the mechanisms that govern replicative stress, thus providing ample opportunities to enhance replicative stress for therapeutic purposes. Rather than trying to halt cell cycle progression, cancer therapeutics could aim to increase replicative stress by further loosening the checkpoints that remain available to cancer cells and ultimately inducing the catastrophic failure of proliferative machineries. In this Review, we outline current and future approaches to achieve this, emphasizing the combination of conventional chemotherapy with targeted approaches. © 2015 Macmillan Publishers Limited.
Hanisch U.-K.,University of Gottingen
Frontiers in Cellular Neuroscience | Year: 2013
Microglia serve in the surveillance and maintenance, protection and restoration of the central nervous system (CNS) homeostasis. By their parenchymal location they differ from other CNS-associated myeloid cells, and by origin as well as functional characteristics they are also-at least in part-distinct from extraneural tissue macrophages. Nevertheless, microglia themselves may not comprise a uniform cell type. CNS regions vary by cellular and chemical composition, including white matter (myelin) content, blood-brain barrier properties or prevailing neurotransmitters. Such a micromilieu could instruct as well as require local adaptions of microglial features. Yet even cells within circumscribed populations may reveal some specialization by subtypes, regarding house-keeping duties and functional capacities upon challenges. While diversity of reactive phenotypes has been established still little is known as to whether all activated cells would respond with the same program of induced genes and functions or whether responder subsets have individual contributions. Preferential synthesis of a key cytokine could asign a master control to certain cells among a pool of activated microglia. Critical functions could be sequestered to discrete microglial subtypes in order to avoid interference, such as clearance of endogenous material and presentation of antigens. Indeed, several and especially a number of recent studies provide evidence for the constitutive and reactive heterogeneity of microglia by and within CNS regions. While such a principle of "division of labor" would influence the basic notion of "the" microglia, it could come with the practival value of addressing separate microglia types in experimental and therapeutic manipulations. © 2013 Hanisch.
Rizzoli S.O.,University of Gottingen
EMBO Journal | Year: 2014
Synaptic vesicle recycling is one of the best-studied cellular pathways. Many of the proteins involved are known, and their interactions are becoming increasingly clear. However, as for many other pathways, it is still difficult to understand synaptic vesicle recycling as a whole. While it is generally possible to point out how synaptic reactions take place, it is not always easy to understand what triggers or controls them. Also, it is often difficult to understand how the availability of the reaction partners is controlled: how the reaction partners manage to find each other in the right place, at the right time. I present here an overview of synaptic vesicle recycling, discussing the mechanisms that trigger different reactions, and those that ensure the availability of reaction partners. A central argument is that synaptic vesicles bind soluble cofactor proteins, with low affinity, and thus control their availability in the synapse, forming a buffer for cofactor proteins. The availability of cofactor proteins, in turn, regulates the different synaptic reactions. Similar mechanisms, in which one of the reaction partners buffers another, may apply to many other processes, from the biogenesis to the degradation of the synaptic vesicle. Silvio Rizzoli reviews the different steps and mechanisms involved in synaptic vesicle biogenesis and recycling. © 2014 The Authors.
Sheldrick G.M.,University of Gottingen
Acta Crystallographica Section A: Foundations of Crystallography | Year: 2015
The new computer program SHELXT employs a novel dual-space algorithm to solve the phase problem for single-crystal reflection data expanded to the space group P1. Missing data are taken into account and the resolution extended if necessary. All space groups in the specified Laue group are tested to find which are consistent with the P1 phases. After applying the resulting origin shifts and space-group symmetry, the solutions are subject to further dual-space recycling followed by a peak search and summation of the electron density around each peak. Elements are assigned to give the best fit to the integrated peak densities and if necessary additional elements are considered. An isotropic refinement is followed for non-centrosymmetric space groups by the calculation of a Flack parameter and, if appropriate, inversion of the structure. The structure is assembled to maximize its connectivity and centred optimally in the unit cell. SHELXT has already solved many thousand structures with a high success rate, and is optimized for multiprocessor computers. It is, however, unsuitable for severely disordered and twinned structures because it is based on the assumption that the structure consists of atoms. © 2015 International Union of Crystallography.
Wenger O.S.,University of Gottingen
Chemical Society Reviews | Year: 2011
Phenylene oligomers represent a borderline case between very strongly π-conjugated molecular wires such as oligo-p-phenylene vinylenes and saturated molecular bridges. Even subtle chemical modifications of phenylene oligomers can therefore have a strong impact on charge transfer rates and mechanisms. On the basis of recently published selected case studies, this tutorial review discusses the key factors that affect charge transfer kinetics in phenylene oligomers with particular focus on the role of donor-bridge energy matching. Selected examples of triplet-triplet energy transfer reactions across phenylene oligomers are also discussed. © 2011 The Royal Society of Chemistry.
Ackermann L.,University of Gottingen
Chemical Reviews | Year: 2011
The development and scope of carboxylates as cocatalysts in transition-metal-catalyzed C-H functionalizations is reviewed. Ryabov and co-workers probed the mechanism of ortho-palladation reactions with N,N-dimethylbenzylamines (DMBA-H, 5) as substrate. Jones and coworkers performed detailed mechanistic studies on the formation of irida- and rhodacycles derived from electron-rich and electron-poor imines, which indicated [Cp*M(OAc)]+ (M = Rh, Ir) to be the key intermediates for acetate-assisted electrophilic activations via transition state. Intermolecular palladium-catalyzed direct benzylations of various five-membered heteroarenes through carboxylate assistance were reported by Fagnou and Lapointe. Dixneuf and Pozgan also reported a ruthenium-catalyzed direct arylation of one 2-phenylpyridine with KOAc as additive.
Ackermann L.,University of Gottingen
Angewandte Chemie - International Edition | Year: 2011
CO 2 in a fix: Gold and copper complexes of N-heterocyclic carbenes recently enabled efficient direct carboxylation of (hetero)arenes having moderately acidic C-H bonds under remarkably mild reaction conditions (IPr=1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene). © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Ackermann L.,University of Gottingen
Accounts of Chemical Research | Year: 2014
To improve the atom- and step-economy of organic syntheses, researchers would like to capitalize upon the chemistry of otherwise inert carbon-hydrogen (C-H) bonds. During the past decade, remarkable progress in organometallic chemistry has set the stage for the development of increasingly viable metal catalysts for C-H bond activation reactions. Among these methods, oxidative C-H bond functionalizations are particularly attractive because they avoid the use of prefunctionalized starting materials. For example, oxidative annulations that involve sequential C-H and heteroatom-H bond cleavages allow for the modular assembly of regioselectively decorated heterocycles. These structures serve as key scaffolds for natural products, functional materials, crop protecting agents, and drugs. While other researchers have devised rhodium or palladium complexes for oxidative alkyne annulations, my laboratory has focused on the application of significantly less expensive, yet highly selective ruthenium complexes.This Account summarizes the evolution of versatile ruthenium(II) complexes for annulations of alkynes via C-H/N-H, C-H/O-H, or C-H/N-O bond cleavages. To achieve selective C-H bond functionalizations, we needed to understand the detailed mechanism of the crucial C-H bond metalation with ruthenium(II) complexes and particularly the importance of carboxylate assistance in this process. As a consequence, our recent efforts have resulted in widely applicable methods for the versatile preparation of differently decorated arenes and heteroarenes, providing access to among others isoquinolones, 2-pyridones, isoquinolines, indoles, pyrroles, or α-pyrones. Most of these reactions used Cu(OAc)2·H 2O, which not only acted as the oxidant but also served as the essential source of acetate for the carboxylate-assisted ruthenation manifold. Notably, the ruthenium(II)-catalyzed oxidative annulations also occurred under an ambient atmosphere of air with cocatalytic amounts of Cu(OAc) 2·H2O. Moreover, substrates displaying N-O bonds served as "internal oxidants" for the syntheses of isoquinolones and isoquinolines. Detailed experimental mechanistic studies have provided strong support for a catalytic cycle that relies on initial carboxylate-assisted C-H bond ruthenation, followed by coordinative insertion of the alkyne, reductive elimination, and reoxidation of the thus formed ruthenium(0) complex. © 2013 American Chemical Society.
Wenger O.S.,University of Gottingen
Chemical Society Reviews | Year: 2012
For a molecular electronics technology to be fully serviceable, switching functions will be indispensable. Specifically, it will be desirable to control the conductivity of a given molecule using an external stimulus. This tutorial review discusses photoswitchable mixed valence systems that are comprised of a reversibly photoisomerizable bridging unit connecting two redox-active moieties, and as such represent some of the most simple chemical systems in which switching of charge delocalization can be explored. As photoisomerizable units, dithienylethenes have received much attention in the context of photoswitchable mixed valence, but there are also more exotic examples such as norbornadiene- and dimethyldihydropyrene-based switchable systems. As redox-active units responsible for the mixed valence phenomenon, both metal-containing as well as purely organic moieties have been employed. Typical investigations in this area involve the comparison of cyclic voltammograms and (near-infrared) optical absorption spectra of the two isomeric forms of a given system. The magnitude of the comproportionation constant and evaluation of intervalence absorption bands using appropriate theoretical models yield information regarding the extent of charge delocalization in the two isomeric forms. In several of the compounds investigated so far, the light stimulus induces a substantial increase of charge delocalization, or in the terminology commonly used in mixed valence chemistry, a changeover from class I to class II or even class III behavior. © 2012 The Royal Society of Chemistry.
Wenger O.S.,University of Gottingen
Accounts of Chemical Research | Year: 2011
Long-range electron transfer may occur via two fundamentally different mechanisms depending on the combination of electron donor, acceptor, and the bridging medium between the two redox partners. Activating the so-called hopping mechanism requires matching the energy levels of the donor and the bridge. If electrons from the donor can thermodynamically access bridge-localized redox states, the bridge may be temporarily reduced before the electron is forwarded to the acceptor. As a result, electron transfer rates may demonstrate an extremely shallow dependence on distance. When transient reduction of the bridging medium is thermodynamically impossible, a tunneling mechanism that exponentially depends on distance becomes important for electron transport. Fifty years ago, superexchange theory had already predicted that electron transfer rates should be affected by donor - bridge - acceptor energetics even in the tunneling regime, in which the energy gap (Δε) is too large for electrons to hop from the donor onto the bridge. However, because electron tunneling rates depend on many parameters and the influence of donor - bridge energy gaps is difficult to distinguish from other influences, direct experimental support for the theoretical prediction has been difficult to find. Because of remarkable progress, particularly in the past couple of years, researchers have finally found direct evidence for the long-sought but elusive tunneling-energy gap effect. After a brief introduction to the theory of the tunneling mechanism, this Account discusses recent experimental results describing the importance of the tunneling-energy gap. Experimental studies in this area usually combine synthetic chemistry with electrochemical investigations and time-resolved (optical) spectroscopy. For example, we present a case study of hole tunneling through synthetic DNA hairpins, in which different donor - acceptor couples attached to the same hairpins resulted in tunneling rates with significantly different dependences on distance. Recent systematic studies of conjugated molecular bridges have demonstrated the same result: The distance decay constant (β), which describes the steepness of the exponential decrease of charge tunneling rates with increasing donor-acceptor distance, is not a property of the bridge alone; rather it is a sensitive function of the entire donor - bridge - acceptor (D-b-A) combination. In selected cases, researchers have found a quantitative relationship between the experimentally determined distance decay constant (β) and the magnitude of the tunneling-energy gap (Δε). The rates and efficiencies of charge transfer reactions occurring over long distances are of pivotal importance in light-to-chemical energy conversion and molecular electronics. Tunneling-energy gap effects play an intriguing role in the formation of long-lived charge-separated states after photoexcitation: The kinetic stabilization of these charge-separated states frequently exploits the inverted driving-force effect. Recent studies indicate that tunneling-energy gap effects can differentiate the distance dependences of energy-storing charge-separation reactions from those of energy-wasting charge-recombination processes. Thus, the exploitation of tunneling-energy gap effects may provide an additional way to obtain long-lived charge-separated states. © 2010 American Chemical Society.