Proceedings of

the Beilstein Bozen Symposium

Molecular Engineering and Control

14 – 18 May 2012, Prien (Chiemsee), Germany

The articles of the conference proceedings are available in PDF format.

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The Beilstein Bozen Symposia address contemporary issues in the chemical and related sciences by employing an interdisciplinary approach. Scientists from a wide range of areas – often outside chemistry – are invited to present aspects of their work for discussion with the aim of not only to advance science, but also, to enhance interdisciplinary communication.

With the increasing understanding of molecular systems it is now possible to build materials and new systems with nano-scale precision through the control of the structure of matter at the atomic and molecular level. Since the forces that dominate the macroscopic world have either less relevance or different consequences at the nano-level, we must employ different paradigms when conceiving molecular-scale machines that will build, in turn, new types of materials and machines, etc. In this respect biological systems are the best proof of concept that this kind of technology already exists. Multicomponent systems such as ribosomes can be considered as molecular-scale machines that read RNA, decode the information, generate proteins and finally assist in the folding process to ensure the generation of a correct three-dimensional configuration. This newly created entity can carry out structural functions, catalytic activities in chemical processes, and even form a constituent part of further ribosomes for the construction of new molecular machines. Inspired by biological systems, researchers are beginning to mimic nature in the design of molecules and supramolecular systems but also in the modification of nature's own factories.

A key aim is to be able to routinely design molecules or systems with desired physicochemical or physiological properties.

For example, the manipulation and control of molecules on surfaces to bring about the functionalization of the surface or of the molecules themselves is important for a wide variety of applications. Accomplishing this requires not only expertise in synthesis but also in many other techniques such as imaging, lithography and computation. Many difficulties associated with being able to simultaneously understand and control assembly, recognition, transport and motion at the molecular and systems levels remain and need to be addressed by future research.

This symposium brought together experts from different disciplines to discuss, from their own points of view, the contemporary state and future perspectives including the following aspects of molecular engineering and control, i.e. molecular control of surfaces, manipulation of metabolic pathways and engineering of proteins and nucleotides, self-organization and molecular selfassembly, imaging, diagnostics and sensors, and artificial (biological) systems.

We would like to thank particularly the authors who provided us with written versions of the papers that they presented. Special thanks go to all those involved with the preparation and organization of the symposium, to the chairmen who piloted us successfully through the sessions and to the speakers and participants for their contribution in making this symposium a success.

Frankfurt/Main, December 2013

Martin G. Hicks
Carsten Kettner

Molecular Control of (Stem) Cell Fate

David A. Winkler

CSIRO Materials Science & Engineering, Clayton 3168, Australia and Monash Institute of Pharmaceutical Sciences, Parkville 3052, Australia

The notion of cell identity or phenotype has undergone a seismic shift over the past decade. Until then, cell biologists largely regarded terminally differentiated somatic (i.e. non-germ line) cells as deriving from more plastic progenitors via an essentially one-way route. Only recently was the question of reversibility of cell differentiation, a by-product of the inherent stochasticity and plasticity of cells, raised by researchers such as Roeder and Loeffler [1]. The explosion of research into stem cells over the past decade in particular has vindicated these early suggestions of mutability and plasticity of cell phenotypes. A recently as 2006, Yamanaka announced the startling discovery that somatic cells can be reprogrammed to pluripotency by a cocktail of transcription factors [2]. Subsequent research has shown that it may be possible to reprogram somatic cells of one type into those of a different type, such as reprogramming skin epithelial cells to neural cells. The idea that a cell’s identity is better described as a probabilistic property than a fixed one is now becoming more widely accepted...

PLP-dependent Enzymes: a Powerful Tool for Metabolic Synthesis of Non-canonical Amino Acids

Martino L. di Salvo1, Nediljko Budisa2, and Roberto Contestabile1

1Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Sapienza Università di Roma.

2Institut für Biologische Chemie, Biocatalysis Group, Technische Universität Berlin.

Pyridoxal 5'-phosphate (PLP), the biologically active of vitamin B6, was first identified in the mid-forties as the cofactor for the transamination reaction. Since then, PLP-dependent enzymes have been the focus of extensive biochemical research. The interest aroused by these enzymes is due to their unrivalled catalytic versatility and their widespread involvement in cellular metabolism. As a matter of fact, PLP acts as cofactor in more than 160 different enzymes classified by the Enzyme Commission, representing 4% of all known cellular catalytic activities [1]. PLP-dependent enzymes serve vital roles in all living organisms and catalyze a number of diverse chemical reactions, such as transamination, decarboxylation, racemization, carbon-carbon bond cleavage and formation...

Messages from Nature – How CHEMICAL Synthetic Biology Could Look Like

Andreas Kirschning, Olena Mancuso, Jekaterina Hermane, and Gerrit Jrjens

Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz University Hannover

The term synthetic biology is a relative new expression for an emerging topic at the interface between chemistry and biology. Other, related fields may include medicinal chemistry, bioorganic chemistry and chemical biology; all these subfields are still based on chemical synthesis. Likewise one can see this trend of diversification in the field of biotechnology which has been complemented with terms like metabolic engineering or combinatorial biosynthesis. Many of these terms are not that strictly defined and substantially overlap and redundancy has to be acknowledged. There is still some debate of what synthetic biology covers. In short, one may describe it to assemble and merge genes in vitro to create a new useful biological system...

Nanoparticle Superlattice Engineering with DNA

Robert J. Macfarlane and Chad A. Mirkin

Department of Chemistry, Northwestern University, Evanston

A major challenge in materials synthesis is developing methodologies to synthesize materials by design, the concept that one can know what building blocks are necessary to create a material a priori to synthesis. Typically, the building blocks used to synthesize these materials are atoms or molecules, and the identity of the structure being assembled is a function of which atoms are used and how those atoms are bonded to one another. However, developing materials by design using atoms as building blocks is a significant challenge, as the complex factors that dictate how atoms interact with one another makes predicting what structure will be created from a given set of building blocks a difficult task. Moreover, programmability of these interactions is impossible due to the fact that certain factors (such as electronegativity or atomic number) are immutable for atoms. Therefore, once a given set of atoms is chosen, the resulting structures that can be created are inherently linked to the set of building blocks being used. Linus Pauling famously developed a set of rules that explain (in the context of ionic solids) why certain lattices are preferred over others. However, these rules are really a look backwards, as they lack true predictive power and do not always apply to all ionic solids. Given the challenges associated with using atomic or molecular species as building blocks to create materials by design, a more amenable strategy would be to choose building
blocks that are more controllable...

Designing, Measuring, and Controlling Functional Molecules and Precise Assemblies

Yue Bing Zheng and Paul S. Weiss

California NanoSystems Institute and Departments of Chemistry & Biochemistry and Materials Science & Engineering, University of California, Los Angeles.

Bottom-up assembly of functional molecules on solid surfaces provides a promising approach toward ever smaller and more functional devices. Molecule-substrate and intermolecular interactions can be exploited so that when molecules are transferred from solutions to substrates targeted structures can be obtained. Understanding correlations between the interactions and function of molecules is essential to elucidating the
rules of working towards the ultimate limits of miniaturization. This paper covers our recent progress towards this goal by measuring single molecules and precise assemblies confined in self-assembled monolayers (SAMs). By isolating molecules in SAMs, we are able to obtain both accurate measurements and precise control of function. The measurements, in combination with theoretical calculations, allow us to
apply molecular design to optimize function and to direct the assembly of molecules. We are now applying the assembly strategies that we have developed for flat surfaces to curved and faceted substrates, while
developing new tools to measure the environment, interactions, and dynamics of single molecules and precise assemblies.

Organic Charge Transfer Systems:
the Next Step in Molecular Electronics?

Michael Huth

Physikalisches Institut, Goethe-Universität, Frankfurt am Main.

Since the 1950s a lot of effort has been devoted into the development of organic conductors. By a substantial degree this has been inspired by W. A. Little’s theoretical analysis of London’s idea that superconductivity might occur in organic macromolecules or polymers. Over time this has resulted in the discovery of several organic metals and superconductors, albeit not with spectacularly high critical temperatures. The dominating material class in this respect are the organic charge transfer (CT) compounds which have provided an extended playground for studying the physics of low-dimensional, strongly correlated electron systems. On the other hand, the practical application of organic materials relies on organic semiconductors rather than organic metals. Presently, polymers have found access to the semiconductor industry in capacitors and rechargeable batteries. Current research interests, which have been initiated already in the 1980s, are devoted to an application-oriented development for the growing market of organic electroluminescence devices, field effect transistors and solar cells. These devices are largely based on one-component organic materials or blends. Quite recently the research field of single-molecule electronics becomes increasingly popular.


This presentation gives a very brief introduction into some aspects of organic CT systems and will provide a short overview of the different electronic structures which can be observed in this material class. The major part will be devoted to introducing the so called neutral-ionic phase transition CT systems which are of the mixed-stack type and show a pressure- or temperature-driven transition between two different charge transfer states. This gives rise to a wealth of unconventional charge transport phenomena which might have a role to play in future organic electronics.

Simulating "Soft" Electronic Devices

Timothy Clark1,2, Marcus Halik2,3, Matthias Hennemann1, and Christof M. Jäger1,2

1Computer-Chemie-Centrum and Interdisciplinary Center for Molecular Materials, Department Chemie und Pharmazie.

2Excellence Cluster "Engineering of Advanced Materials".

3Organic Materials & Devices, Institute of Polymer Materials, Department of Materials Science

Friedrich-Alexander-Universität Erlangen-Nürnberg..

A combination of classical molecular dynamics simulations and very large scale semiempirical molecular orbital calculations has been used to simulate field-effect transistors in which both the dielectric layer and the semiconductor are incorporated in a self-assembled monolayer of suitable functionalized alkylphosphonic acids. In such simulations, both the dynamics of the flexible organic molecules and the electronic properties of the molecular aggregates must be taken into account. First steps towards realistic simulations of such devices are described.

Non Equilibrium Structured Polynuclear-metal-oxide Assemblies

Leroy Cronin

School of Chemistry, University of Glasgow, WestCHEM, Glasgow

One pot reactions are deceptively simple systems often yielding complex mixtures of compounds, nanomolecular self-assembled architectures and intricate reaction networks of interconnected mutually dependent processes. As such, the elucidation of mechanism and various reaction pathways can be hard if not impossible to deduce. Herein, I show how by moving a ‘one-pot’ reaction from the time domain into a flow-system, the time domain translates into distance and flow rate thereby allowing monitoring and control of one-pot reactions in new ways; for example by changing the tube length/diameter. Three types of flow system are presented: (i) a system for the trapping of an intermediate host guest complex responsible for the  formation of the giant wheel cluster which is the major component of molybdenum blue; (ii) a linear flow system array for the scale up of inorganic clusters; (iii) a networked reactor system which allowed the combination of multiple one-pot conditions in a single system allowing the discovery of a fundamental new class of inorganic cluster not accessible by any other means. I also briefly describe our recent work on the growth of inorganic tubules and our 3D printed ‘reactionware’ for the fabrication of bespoke flow-systems at a fraction of the cost of commercial systems and also show how the ability to configure the systems in new ways leads to new science.

1 nm Thick Functional Carbon Nanomembrane (CNM): New Opportunities for Nanotechnology

Min Ai and Armin Gölzhäuser

Physics of Supramolecular Systems and Surfaces, University of Bielefeld

One nanometer thick, mechanically stable carbon nanomembranes (CNMs) are made by electron induced cross-linking of surface bound self-assembled monolayers (SAMs). The cross-linked SAMs are then released from the surface and can be placed onto solid materials or spanned over holes as free-standing membranes. Annealing at ~1000K transforms CNMs into graphene or graphenoids accompanied by a continuous change of mechanical stiffness and electrical resistance from insulating to conducting, which allows the tailoring of the CNM’s electrical and mechanical properties. Recently, Janus membranes, i. e. CNMs functionalized by coupling different molecules to their top and bottom surfaces were built. Janus membranes have been built with functional polymers, proteins, and dyes, which demonstrates that Janus CNMs can act as platforms for two-dimensional chemistry. By combining different types of CNMs, hybrid nanolayers and biomimetic membranes can be built.