International Max Planck Research Schools: Neue Wege der Graduiertenausbildung

"Die IMPRS [International Max Planck Research Schools] bilden Zentren wissenschaftlicher Exzellenz auf innovativen und interdisziplinären Forschungsgebieten, wie z.B. Neurowissenschaften oder Polymerforschung, aber auch Demografie und Bildungsforschung." Die Nachwuchsförderung findet in enger Kooperation von Universitäten und Max-Planck-Instituten statt. Es werden Promotionsstudiengänge angeboten, "die gezielt besonders qualifizierte junge Wissenschaftlerinnen und Wissenschaftler aus dem In- und Ausland in der Phase zwischen dem ersten berufsqualifizierenden Abschluss und der Promotion anziehen sollen." Die Autorinnen geben allgemeine Informationen über die IMPRS und gehen speziell auf die International Max Planck Research School "The Life Course: Evolutionary and Ontogenetic Dynamics" (LIFE) ein. Abschließend findet eine Bewertung dieser Research School statt. (DIPF/Orig./av

Synthetic molecular walkers

The work presented in this thesis was inspired by one of the most fascinating classes of naturally occurring molecules: bipedal motor proteins from the kinesin, dynein and myosin superfamilies walk along cellular tracks, carrying out essential tasks, such as vesicle transport, muscle contraction or force generation. Although a few synthetic mimicks based on DNA have been described, small-molecule analogues that exhibit the most important characteristics of the biological walkers were still missing until recently. In this thesis, the design, synthesis and operation of several small-molecule walker-track systems is described. All presented systems share a similar molecular architecture, featuring disulfide and hydrazone walker-track linkages, yet deviate fundamentally in the mechanism and energy input that is required for directional walker transport. Chapter I includes an overview of the biological walker proteins, as well as a comprehensive review of the DNA-based mimicks published to date. A set of fundamental walker characteristics is identified and special emphasis is given to the underlying physical mechanisms. Chapter II describes a series of experiments, which lay the groundwork for all smallmolecule walker systems presented in the following Chapters of this thesis. The mutually exclusive nature of disulfide and hydrazone exchange under basic and acidic reaction conditions, was demonstrated using an unprecedented type of macrocycle. The first small-molecule walker-track system is described in Chapter III. Due to the passive nature of both the track and the walker unit, an oscillation of acidic and basic reaction conditions led to a directionally un-biased, intramolecular ‘diffusion’ of the walker unit along the track. Using an irreversible redox-reaction for one of the foot-track exchange reactions conferred a certain degree of directionality to the walking sequence, with the oxidant iodine providing the chemical fuel for the underlying Brownian information ratchet mechanism. Chapter IV contains a comprehensive investigation of the dynamic properties of a series of walker-track conjugates derived from the walker-track conjugate presented in Chapter III. The most significant observation was that ring strain appears to be a requirement for the emergence of directional bias, a phenomenon that has also been found in biological walkers. In Chapter V a different type of walker-track conjugate is described, in which the track plays an active role and light is used as the fuel required for directional walker transport. The key for achieving directionality was the presence of a stilbene unit as part of the molecular track, through which ring strain could be induced in the isomer where the walker unit bridges the E-stilbene linkage. Significantly, the underlying Brownian energy ratchet mechanism allowed walker transport in either direction of the molecular track. Chapters II to V are presented in the form of articles that have recently been published or will be published in due course in peer-reviewed journals. No attempt has been made to re-write this work out of context, other than to avoid repetition, insert crossreferences to other Chapters (where appropriate) and to ensure consistency of presentation throughout this thesis. Chapters II, III, IV and V are reproduced in the Appendix, in their published formats. The Outlook contains closing remarks about the scope and significance of the presented work as well as ideas for the design and operation of a next generation of small-molecule walkers, some of which are well under way in the laboratory

'Science first': An exploration of the assessment and role of language in the editorial practices of 'hard science' academic journals

Abstract Publication in international, peer-reviewed, academic journals is increasingly characterized by the dominance of English as the language of research dissemination. Multiple studies attest to the disadvantages perceived and encountered by NNES (non-native English speaking) scholars as a result; yet, only a limited number have addressed the ‘gatekeeper’ side of the editorial process, with an exclusive focus on publication within social science journals (Belcher, 2007; Flowerdew, 2001). Recent evidence, highlighting significant disciplinary differences in publication practices (Gnutzmann and Rabe, 2014), points towards a lack of knowledge of editorial practices and perceptions of NNES scholars’ submissions in the ‘hard sciences’. This dissertation presents the results of an interview case study with the editors of a top-ranked, international chemistry journal. The purpose was to find out how these editors assess and perceive the role of language in the scientific editorial process and to gain insight into how to enhance the chances of successful publication by NNES authors. Analysis of the data suggests that language assessment is based on overall comprehension instead of quality, with a clear precedence given to the value of the scientific content over the way in which it is linguistically presented. Moreover, the results highlight the incidence of problematic linguistic errors and unfamiliarity with academic discourse from both NES (native English speaking) and NNES scholars. Recommendations include the need for NNES authors working in the ‘hard science’ disciplines to pay more specific attention to clear and comprehensible language in order to achieve success in publishing

Trithioorthoester Exchange and Metathesis: New Tools for Dynamic Covalent Chemistry

To expand the toolbox of dynamic covalent and systems chemistry, we investigated the acid-catalyzed exchange reaction of trithioorthoesters with thiols. We found that trithioorthoester exchange occurs readily in various solvents in the presence of stoichiometric amounts of strong Bronsted acids or catalytic amounts of certain Lewis acids. The scope of the exchange reaction was explored with various substrates, and conditions were identified that permit clean metathesis reactions between two different trithioorthoesters. One distinct advantage of S, S, S-orthoester exchange over O, O, O-orthoester exchange is that the exchange reaction can kinetically outcompete hydrolysis, thereby making the process less sensitive to residual moisture. We expect that the relatively high stability of the products might be beneficial in future supramolecular receptors or porous materials.Fil: Bothe, Michael. Universitat Ulm; AlemaniaFil: Orrillo, Alfredo Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Furlan, Ricardo Luis Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: von Delius, Max. Universitat Ulm; Alemani

Ammonium Complexes of Orthoester Cryptands Are Inherently Dynamic and Adaptive

© 2019 American Chemical Society. Fluxional chemical species such as bullvalene have been a valuable source of inspiration and fundamental insight into the nature of chemical bonds. A supramolecular analogue of bullvalene, i.e., a "fluxional host-guest system", in which the ensemble of a well-defined host and guest is engaged in continuous, degenerate constitutional rearrangements, is still elusive, however. Here, we report experimental and computational evidence for guest-induced dynamic covalent rearrangements in the ammonium complexes of self-assembled orthoester cryptands. This unique behavior is made possible by the ammonium guest playing a dual role: it is sufficiently acidic to initiate dynamic covalent exchange reactions at the orthoester bridgeheads, and as a hydrogen bond donor it acts as a supramolecular template, governing the outcome of a multitude of possible intra- and intermolecular rearrangement reactions. One particularly striking example of inherent dynamic behavior was observed in host-guest complex [NH4+o-Me2-2.1.1], which spontaneously rearranged into the larger and thermodynamically more stable complex [NH4+o-Me2-2.2.1], even though this process led to the formation of poor host o-Me2-1.1.1 as a consequence of the excess of one subcomponent (diethylene glycol; "1" in our nomenclature). These inherently adaptive host-guest networks represent a unique platform for exploring the interrelationship between kinetic and thermodynamic stability. For instance, as a result of optimal NH4+ binding, complex [NH4+o-Me2-2.2.1] was found to be thermodynamically stable (negligible intermolecular rearrangements over weeks), whereas computational studies indicate that the compound is far from kinetically stable (intramolecular rearrangements)

Into the dynamics of rotaxanes at atomistic resolution

Mechanically-interlocked molecules (MIMs) are at the basis of artificial molecular machines and are attracting increasing interest for various applications, from catalysis to drug delivery and nanoelectronics. MIMs are composed of mechanically-interconnected molecular sub-parts that can move with respect to each other, imparting these systems innately dynamical behaviors and interesting stimuli-responsive properties. The rational design of MIMs with desired functionalities requires studying their dynamics at sub-molecular resolution and on relevant timescales, which is challenging experimentally and computationally. Here, we combine molecular dynamics and metadynamics simulations to reconstruct the thermodynamics and kinetics of different types of MIMs at atomistic resolution under different conditions. As representative case studies, we use rotaxanes and molecular shuttles substantially differing in structure, architecture, and dynamical behavior. Our computational approach provides results in agreement with the available experimental evidence and a direct demonstration of the critical effect of the solvent on the dynamics of the MIMs. At the same time, our simulations unveil key factors controlling the dynamics of these systems, providing submolecular-level insights into the mechanisms and kinetics of shuttling. Reconstruction of the free-energy profiles from the simulations reveals details of the conformations of macrocycles on the binding site that are difficult to access via routine experiments and precious for understanding the MIMs' behavior, while their decomposition in enthalpic and entropic contributions unveils the mechanisms and key transitions ruling the intermolecular movements between metastable states within them. The computational framework presented herein is flexible and can be used, in principle, to study a variety of mechanically-interlocked systems

Into the dynamics of rotaxanes at atomistic resolution

Mechanically-interlocked molecules (MIMs) are at the basis of artificial molecular machines and are attracting increasing interest for various applications, from catalysis to drug delivery and nanoelectronics. MIMs are composed of mechanically-interconnected molecular sub-parts that can move with respect to each other, imparting these systems innately dynamical behaviors and interesting stimuli-responsive properties. The rational design of MIMs with desired functionalities requires studying their dynamics at sub-molecular resolution and on relevant timescales, which is challenging experimentally and computationally. Here, we combine molecular dynamics and metadynamics simulations to reconstruct the thermodynamics and kinetics of different types of MIMs at atomistic resolution under different conditions. As representative case studies, we use rotaxanes and molecular shuttles substantially differing in structure, architecture, and dynamical behavior. Our computational approach provides results in agreement with the available experimental evidence and a direct demonstration of the critical effect of the solvent on the dynamics of the MIMs. At the same time, our simulations unveil key factors controlling the dynamics of these systems, providing submolecular-level insights into the mechanisms and kinetics of shuttling. Reconstruction of the free-energy profiles from the simulations reveals details of the conformations of macrocycles on the binding site that are difficult to access via routine experiments and precious for understanding the MIMs' behavior, while their decomposition in enthalpic and entropic contributions unveils the mechanisms and key transitions ruling the intermolecular movements between metastable states within them. The computational framework presented herein is flexible and can be used, in principle, to study a variety of mechanically-interlocked systems

Submucosal Endoscopy, a New Era of Pure Natural Orifice Translumenal Endoscopic Surgery (NOTES)

Natural orifice translumenal endoscopic surgery (NOTES) involves the intentional perforation of the viscera with an endoscope to access the abdominal cavity and perform an intraabdominal operation. In a brief time period, NOTES has been shown to be feasible in laboratory animal and human studies. Easy access to the peritoneal cavity and complete gastric closure should be secured before NOTES can be recommended as an acceptable alternative in clinical practice. The concept of submucosal endoscopy has been introduced as a solution to overcome these two primary barriers to human NOTES application. Its offset entry/exit access method effectively prevents contamination and allows the rapid closure of the entry site with a simple mucosal apposition. In addition, it could be used as an endoscopic working space for various submucosal conditions. Herein, the detailed procedures, laboratory results and human application of the submucosal endoscopy will be reviewed