At the Ruhr-Universität Bochum (RUB) 2015

Chemistry and Biochemistry at the Ruhr-Universität Bochum (RUB) 2015

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Welcome

It is my pleasure to welcome you to the lytical, Theoretical and Technical Chemistry. Faculty of Chemistry and Biochemistry at Towards the end of the 1980s, two Chairs in the Ruhr-Universität Bochum (RUB). On Biochemistry were founded and in autumn the occasion of the Bunsen-Tagung 2015, 1990, a Biochemistry course was added to this brochure may serve to showcase the the Faculty‘s teaching portfolio. Accordingly, people at our Faculty, as well as our many the Faculty was renamed Faculty of Che- activities. mistry and Biochemistry. In response to the societal need for a strong scientific training Located in the midst of the dynamic met- also of teachers-to-be, a new Professorship ropolitan area of the Ruhr, in the heart of "Didaktik der Chemie" was established in Europe, RUB with its 20 faculties is home 2004, who oversees the education of future to ca. 500 professors, over 5 500 emplo- teachers in Chemistry at RUB, using inter yees and more than 41 000 students from alia the facilities of Germany‘s largest "Schü- 130 countries. Although only 50 years old, lerlabor" (Physical Sciences lab for school- RUB is not just one of the biggest German children of all ages). Today, 1400 students Universities but also unique with its broad are enrolled in a total of seven Bachelor and range of subjects taught. Faculties at RUB Master programs at the Faculty, with ca. 250 include all Physical and Life Sciences, Hu- first-year students starting each autumn. manities, a Law School and Media Sciences, There are 25 full-time professors, and an ad- Engineering, a Medical School and even ditional number of 10 independent groups Sport Sciences. The aerial photograph nice- led by early career researchers – most of Among the many collaborative research ly demonstrates that this unique variety of them funded independently by competitive projects that members of our Faculty have Faculties is all assembled on one coherent grants like the Emmy-Noether program of successfully managed over the last years - campus, which is also beautifully located the German Science Foundation DFG. The EU projects, Collaborative Research Centers in the southern suburbs of Bochum. The Faculty is proud of the fact that the total (SFB) and Research Units (FOR) – the Clus- nearby Lake Kemande (seen at the top right budget it receives from the University has ter of Excellence "RESOLV – Ruhr Explores corner of the photo) is used not only for been more than doubled by such compe- Solvation" (EXC 1069, funded since autumn students relaxing at a barbecue near the titive third-party money in each of the last 2012 in the last round of the so-called lakeside, but also for sports and serious couple of years. Additional funding comes German Excellence Initiative) certainly training. As just one example, four out of from industrial collaborations, of which also stands out. The topic of "Solvation Science" the eight members of the men‘s coxed our students and PhD candidates benefit provides a common roof to many research eight rowing boat which won the gold me- through direct contacts and research place- activities in areas as diverse as Molecular dal for Germany at the 2012 Olympics were ments. As just one example, an endowed and Biomolecular Chemistry, Life Sciences, students of RUB. "Evonik Chair of Organic Chemistry" will be Material Sciences and Nanoscience. The established in 2016 with generous support growing Faculty will have an additional Officially, RUB was founded in Bochum in from Evonik Industries. Our Faculty has also research building ZEMOS (Center for 1965 – by the way the first "new" University recognized the potential for reviving our Molecular Spectroscopy and Simulation of built at all in Germany after World War II – curriculum by switching to the European Ba- Solvent-driven Processes), fully equipped and its 50th anniversary will be celebrated in chelor and Master system, and was among with state-of-the-art laboratories, offices June 2015 with several spectacular events. the first in Germany to make the move away and dedicated rooms for various specialized Teaching in Chemistry started already in from the established Diploma system in applications at its disposal as of spring 1969. Originally, the Faculty started with 2001. Finally, the Faculty‘s Graduate School 2016. Individual articles on both RESOLV two Chairs in Inorganic, Organic and Phy- celebrates between 50 – 60 PhD graduations and ZEMOS are included in this brochure. sical Chemistry, and one chair each in Ana- every year. But, as you will be aware from own experi- ences, it is not numbers, buildings, or euros that matter, but the people and their ideas, their imagination, their visions that really make a difference. In this sense, I invite you to take a virtual tour through our Faculty by browsing through the pages of this brochure, and get to know the researchers of this Faculty!

Nils Metzler-Nolte Dean of the Faculty of Chemistry and Biochemistry at the Ruhr-Universität Bochum 2 Content

1 Welcome 26 Electrobiochemistry: 46 Physical Chemistry: Prof. Dr. Nils Metzler-Nolte, Dean of the Molecular Regulation of Voltage- From Microsolvation to Faculty of Chemistry and Biochemistry Gated Transmembrane Ion Currents Bulk Water Dynamics at the Ruhr-Universität Bochum Underlying Fast Signaling in Living Cells Prof. Dr. Martina Havenith, Prof. Dr. Irmgard Dietzel-Meyer, Physical Chemistry II 3 RESOLV – Ruhr Explores Solvation Biochemistry II Cluster of Excellence 48 Biopolymers In Vivo – Prof. Dr. Martina Havenith-Newen, 28 Biomolecular Spectroscopy: from the Test Tube into the Cell Speaker of the Executive Board NMR to Study the Structure and Jun.-Prof. Dr. Simon Ebbinghaus, Function of Medically Relevant Proteins Physical Chemistry II 6 Novel Research Infrastructure Prof. Dr. Raphael Stoll, for Solvation Science Biochemistry II 50 Ultrafast Photochemistry: Prof. Dr. Martina Havenith-Newen, In Hot Pursuit of Chemical Reactions ZEMOS – Center of Molecular Spectro- 30 Chemistry Education: Prof. Dr. Patrick Nürnberger, scopy and Simulation of Solvent-driven Scientific Ways of Thinking and Working Physical Chemistry II Processes Prof. Dr. Katrin Sommer, Didactics 52 Heterogeneous Redox Catalysis: 7 Electrochemistry: From Bioelectro- From Fundamental Insight to chemistry to Electrocatalysis 32 Systems Chemistry: Industrial Application Prof. Dr. Wolfgang Schuhmann, Self-Replication and Self-Assembly Prof. Dr. Martin Muhler and Dr. Wei Xia, Analytical Chemistry Prof. Dr. Günter von Kiedrowski, Industrial Chemistry Organic Chemistry I 9 Analytical Chemistry – Biointerfaces: 55 Heterogeneous Catalysis: Understanding Biological Adhesion 34 Multidentate Halogen Bonding Relations between Structure and Processes in Solution: Organocatalysis and Performance of Catalysts Prof. Dr. Axel Rosenhahn, Supramolecular Chemistry Prof. Dr. Wolfgang Grünert, Analytical Chemistry Prof. Dr. Stefan M. Huber, Industrial Chemistry Organic Chemistry I 11 Center for Electrochemical Sciences (CES) 58 Ab Initio Simulations: Dr. Nicola Plumeré, Dr. Fabio La Mantia, 36 Natural Product Research: Chemical Reactions in the Dr. Sabine Seisel, Prof. Dr. Wolfgang Chemical, Enzymatic and Fermentative "Virtual Laboratory" Schuhmann Synthesis of Medicinally Important Prof. Dr. Dominik Marx, Compounds Theoretical Chemistry 13 Bioinorganic and Prof. Dr. Frank Schulz, Medicinal Inorganic Chemistry Organic Chemistry I 61 Quantum Chemistry Prof. Dr. Nils Metzler-Nolte Prof. Dr. Christof Hättig, and Dr. Ulf-Peter Apfel, 38 Physical Organic Chemistry: Theoretical Chemistry Inorganic Chemistry I Understanding Reactions Prof. Dr. Wolfram Sander, 63 Theoretical Chemistry: 16 Synergy between Synthesis, Organic Chemistry II Molecular Simulation Computational Chemistry and Prof. Dr. Lars Schäfer, Materials Development 40 Metals in Catalysis and Theoretical Chemistry Prof. Dr. Roland A. Fischer, Self-Organization Jun. Prof. Dr. Radim Beranek, Prof. Dr. Prof. Dr. Gerald Dyker, 65 Large-Scale Molecular Dynamics Anjana Devi, PD Dr. Rochus Schmid, Organic Chemistry II Simulations of Complex Systems Inorganic Chemistry II Employing Neural Network Potentials 42 Reactions of Molecules on PD Dr. Jörg Behler, 22 Ionotropic Glutamate Receptors: Hybrid Surfaces Theoretical Chemistry Structure, Function, Regulation Prof. Dr. Karina Morgenstern, and Modulation Physical Chemistry I 67 Quantum Chemistry: Wavefunction- Prof. Dr. Michael Hollmann, Based Electronic Structure Theory Biochemistry I 44 Biophysical Chemistry: Prof. em. Dr. Volker Staemmler, Protein Interactions Theoretical Chemistry 24 Molecular Neurobiochemistry: Prof. Dr. Christian Herrmann, Towards Protection and Physical Chemistry I 68 Physical Chemistry at High Presssures Regeneration of Brain Neurons Prof. em. Dr. rer. nat. Dr. hc(UA) Prof. Dr. Rolf Heumann, Gerhard M. Schneider, Biochemistry II Physical Chemistry II

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RESOLV – Ruhr Explores Solvation Cluster of Excellence

Prof. Dr. Martina Havenith-Newen

Solvation Science @ RUB – Who we are and what we do

A liquid environment is natural to almost all chemical reactions in nature and technology. It is known for many decades that the solvent, forming the surrounding of a reaction, has a certain influence. Therefore solvation, as one of the core topics in chemistry, has been the subject of extensive research for many years. Furthermore solvation processes recently have attracted considerable attention from physicists, engineers, and biologists. However, in most cases expensive and time consuming trial and error experiments are still necessary to find the optimum solvent for one specific reaction. Besides this, the influence of the solvent e.g. on protein functions in biological systems is poorly understood, so far.

Over 50 scientific working groups have joined their forces in RESOLV to work together on developing a bottom up approach to understand solvation. Distributed over seven institutions in the Metropolis Ruhr they intensively expand the frontiers of science. Over 80 Ph.D. students have joint the inte- within the field of Solvation Science. Next ve as possible. The aim is the development grated Graduate School Solvation Science year an endowed chair by Evonik Industries of predictive Solvation Science based on (GSS) and spend a three-month research will be appointed. a molecular rational-design perspective. stay abroad at one of over 20 international Within this framework, solvent molecules partner institutions within the RESOLV The scientific strategy of RESOLV is vastly are regarded to be functional themselves International Faculty. A main effort, named different from the traditional, empirical, and employed as active species or reactive TranSOLV, is undertaken to transfer the macroscopic, and descriptive approach agents in solvent-mediated and solvent- research results to industry and to establish which is often followed. RESOLV is instead controlled processes, respectively, rather joint scientific-industrial projects. We have working on a unifying, bottom-up frame- than only being considered as inert and recently hired three new faculty members work, being as universal and comprehensi- passive bystanders.

RESOLV is intimately coupling the most so- phisticated state-of-the-art experimental, spectroscopic, and synthetic approaches with the most recent advances in computer simulation to tackle the important scientific challenges. Understanding solvation phenomena on this molecular level will most directly impact a wide range of applications, such as pitting corrosion of steel, biosensor development, biomass conversion for platform chemicals, micro- capsules for drug release, fluid extraction/ purification processes, high-tech batteries, "green" asymmetric organocatalysis, and low-energy brine electrolysis. 4

Tackle the Problem – and four non-university institutions within partnerships at the institutional level and The Canon of Methods in RESOLV a 30 kilometers radius from the RUB by provides flexible funds for ensuring their mutually granting free access to their core long lasting implantation. The experimental techniques in physical facilities. Moreover, all institutions are chemistry which are available in RESOLV co- linked by joint research projects and an Splitting the Problem – ver the time scales of femto-seconds (fsec- overarching education platform, which in- The Research Areas of RESOLV spectroscopy group of Patrick Nürnberger), cludes a Graduate School Solvation Science sub-pico-seconds (THz spectroscopy by (GSS). Within RESOLV, we have established Research Area A – Understanding and Martina Havenith), nano-seconds (dielectric joint Early Career Researchers Groups Exploiting Solvation in Chemical Processes relaxation by Hermann Weingärtner and (ECRGs), which are simultaneous mem- EPR by Wolfgang Lubitz), micro-seconds bers of a Max-Planck-Institut (Düsseldorf, The understanding of chemical reactivity is (Overhauser dynamic nuclear polarization Mülheim) or Fraunhofer Institute as well as of key importance for the development and by Songi Han) to milli-seconds (FRel by Ruhr-Universität Bochum, thereby granting optimization of chemical processes in both Simon Ebbinghaus). Furthermore there are full-right privileges to the ECRG leaders in the laboratory and in industry. Solvation equilibrium measurements available by dif- both groups of institutions. not only changes the properties of the fraction methods (Roland Winter) as well as reactants and the products, but also affects calorimetry (Christian Herrmann) and the RESOLV successfully established an Inter- transition states and intermediates. Sol- scanning microscopy (Karina Morgenstern). national Faculty of Solvation Science (IF) as vents thus influence the thermodynamics, an international network of top institutions the kinetics, and the product selectivity in This is complimented by state-of-the-art in the US, Europe, Asia, and Israel to foster liquid phase reactions. The selection of a theory techniques: ab initio MD (Dominik long-term mutually beneficial scientific suitable solvent frequently determines the Marx), MD simulations (Lars Schäfer), and collaborations. The IF is a strategical key success or failure of a chemical reaction. QM/MM (Walter Thiel, Elsa Sacnchez-Gar- element to promote the exchange of know- One example with possibly broad implica- cia, and Eckhard Spohr). ledge, people, and ideas between leading tions is the synthesis of enantiomerically scientists at all levels of their scientific pure products that is mandatory for any Partners in RESOLV – careers. The IF groups include more than new drug development. This poses the Reaching higher Levels of national 30 leading scientists in Solvation Science scientific challenge to develop highly ste- and international Cooperation and are linked to RESOLV by joint-funded reoselective synthetic strategies, for which proposals, and individual exchange visits of the choice of a suitable solvent system is RESOLV achieved a new stage in the students and postdocs, as reflected by joint crucial. cooperation between three universities publications. The IF has embedded these 5

RESOLV addresses key questions on this topic. To achieve these ambitious goals, RESOLV draws on the state-of-the-art experimental and theoretical methods and thus contributes to the development of Solvation Science in the biomolecular realm.

Research Area C – Ion Solvation and Charge Transfer at Interfaces

Interfaces play a dominant role in molecular science. Heterogeneous catalysis is the prime example where reactions are accelerated due to the presence of surfaces including catalytically active liquid solid interfaces. Within the last decades, surface science has triggered an impressive boost in the molecular understanding of catalytic processes at solid-gas interfaces. In stark contrast, close to nothing is yet known about how reactants de-solvate, intermediates stabilize, and products re-solvate at liquid-solid interfaces. It is unclear which of the concepts developed for reactions at gas-solid interfaces – if any – can be transferred to those at liquid-solid interfaces. Even less understood are the mechanisms of electrocatalytic reactions. The scientific challenge arises from the strong influence of the solvent on the properties of electrified interfaces, adsorbed species, and transition states. Improvements in chemical energy conversion depend to a large extent on the control of reactions at aqueous interfaces. One focus of RESOLV will be the investigation of the molecular The core thrust of Research Area A is to packing density of up to 400 mg/ml of basis of oxygen reduction reactions at understand and to predict specific solvent proteins, nucleic acids, lipids, carbohydrates, liquid-solid interfaces. Achieving a detailed effects in molecular detail using a broad small molecules, and ions, the distance molecular understanding of these fun- variety of chemical reaction systems fea- between the solutes is less than 20-30 Å. damental processes would be a vital step turing neutral, ionic, or open-shell (radi- The few water layers that can fit between towards enabling major breakthroughs in cal) intermediates and covering classical are highly perturbed and exhibit largely key technologies, since these processes not solvents and solvent mixtures, as well as different properties from the bulk, when only determine the performance of fuel non-conventional solvents. issues like crowding, confinement, and cells, but also have an impact on corrosion, interfaces gain importance. But even small the efficiency of metal-air batteries, and Research Area B – Connecting Solvation biomolecules, in particular if they are char- the performance of photo-electrochemical Dynamics with Biomolecular Function ged, are strongly influenced by the solvent cells. and conversely change the structure of the Water is the lubricant of life. Despite the surrounding solvent layers. It is now widely All these strategies will serve to RESOLVe fact that all life takes place in water, the recognized that hydration water in the pro- urgent questions related to Solvation Sci- treatment of water on the molecular level ximity of protein surfaces plays an essential ence while crossing traditional boundaries was initially not thought to be essential. role for the structure, stability, and dyna- of academic subjects, disciplines, depart- However, water has a vital function in most mics of proteins. Yet, it is part of an ongoing ments, and nations. biomolecular and cellular processes. scientific debate whether solvent dynamics influences, or even "enslaves" the dynamics The Cluster of Excellence RESOLV (Ruhr But: Is there any water in living cells? This of biomolecules or, more speculative, whe- Explores Solvation: EXC 1069) is funded may seem like a strange question, but ther solvent fluctuations actually contribute by the Federal Ministry of Education and water as defined by its well-known ther- to biomolecular (mal)function, e.g. in biolo- Research and by the state North Rhine- modynamic and chemical properties may gical assembly, protein-substrate binding or Westphalia within the framework of the not exist within cells. With a cytoplasmic even enzymatic transformations. German Excellence Initiative. 6

Novel research infrastructure for Solvation Science

Prof. Dr. Martina Havenith-Newen; ZEMOS – Center for Molecular Spectroscopy and Simulation of Solvent-driven Processes

mical laboratories. In attractive for young scientists to start their addition, in ZEMOS we own research groups. Please contact the will integrate three core ZEMOS team ([email protected]) if you are facilities, each of which interested to apply for a research grant and will provide a specific are interested in more information on the technology platform opportunities in Bochum. for the scientists. The © ZEMOS, RUB distinct groups will ZEMOS aims to be an internationally lea- have access to a major ding institution for Solvation Science at the The Ruhr-Universität Bochum (RUB) is computer cluster in house. Scientific and Ruhr-Universität Bochum. The new center implementing a new research infrastruc- technical staff will support the researchers. will bundle the expertise of more than ture on campus for a novel research field: The architecture is set-up such that it ser- 20 research groups of RUB, Max Planck the investigation of solvation processes. ves to facilitate the collaboration between Institutes ("Kohlenforschung", Mülheim, Solvation – dissolving of a chemical subs- the different scientific disciplines and and "Eisenforschung", Düsseldorf), and the tance – is one of the most basic processes communication between the scientists by Fraunhofer Institute "UMSICHT" (Oberhau- in chemistry, in chemical engineering, and integration of communication zones next sen). It will intensively and immediately in biology. ZEMOS (German: "Zentrum für to the offices. collaborate with international world-class molekulare Spektroskopie und Simula- tion solvensgesteuerter Prozesse") is an essential part of the collaborative research project RESOLV (Ruhr Explores Solvation), a Cluster of Excellence funded by the DFG. The German Science Council (German: Wis- senschaftsrat (WR)) recommended funding the research building with 44 M€ in 2011. The new building with a total area of 3.891 square meters will offer space for about 100 scientists ranging from chemists, biochemists to engineers. The Foundation Stone Ceremony took place on May 26th 2014. The construction is making good progress and is planned to be completed by spring 2016. © Pressestelle der RUB The research within ZEMOS is dedicated to three cross-linked topics: Thus, ZEMOS will become an efficient institutions in this research field, including incubator platform for research dedica- research groups located in Cambridge, A. Understanding and Exploiting Solvation ted to Solvation Science. It is particular Berkeley, Yale, and at the Israeli Weizmann in Chemical Processes Institute. B. Connecting Solvation Dynamics with Biomo- www.rub.de/zemos lecular Function C. Ion Solvation and Charge Transfer at Interfaces

The attractive scientific infrastructure within the ZEMOS building will host special Laser laboratories for spectroscopy, microscopy and high pressure studies as well as analytical, biophysical and che- © ZEMOS, RUB 7

Electrochemistry: From bioelectrochemistry to electrocatalysis

Prof. Dr. Wolfgang Schuhmann; Analytical Chemistry – Center for Electrochemical Sciences (CES)

The Schuhmann group does research based transfer from FAD-containing enzymes to to an important field of research [6]. The on a number of electrochemical methods polymer bound redox relays with suitable development of novel detection modes and especially microelectrochemical me- adapted low potential. By using phenothia- in SECM by integrating potential-pulse thods. Main research topics are focusing zine derivatives as polymer-bound redox sequences allowed for the visualization of on electrocata lysis for energy conversion, relays novel redox polymers were obtained local catalytic activity for oxygen consump- high-throughput materials characterization which are able to accept electrons from tion or for local impedance measurements for solar energy con version, bioelectroche- FAD-containing enzymes at potentials as based on AC perturbations [7], the determi- mistry for biofuel cells, DNA assays and low as -200 mV vs Ag/AgCl allowing to nation of the onset potential of catalysts biosensors, as well as microelectroche- increase the open circuit voltage of related for the oxygen evolution reactions and the mistry for the elucidation of local processes biofuel cells by about 200 mV [1]. visualization of the activity of catalysts for in Li-ion and Zn/air batteries. oxygen reduction. The concept of electrode positioning was extended to the implementation of a scanning-droplet cell which allows high-throughput characterization of catalyst materi als or materials for solar energy conversion [8].

Electrocatalysis

Conversion of energy and sustainable energy production and distribution is of high impor tance. This implies on the one hand to develop new analytical tools for the evaluation of the catalytic activity of electrocatalysts but even more importantly to repla- ce scarce nobel-metal based catalysts by abundant materials. Moreover, the surface area of electrodes has to be substantially Fig. 1: Research fields of the Schuhmann group. enlarged to allow for high reaction rates. These topics were addressed by de signing Biosensors and biofuel cells The design of specifically adapted redox po- carbon nanotube based materials, three- lymers was further used to wire the protein dimensional hierarchical carbon nanotube Main focus are non-manual enzyme complexes photosystem 1 and photosys- composites with high electrical conducti- immobilization techniques using electro- tem 2 from algae to electrodes allowing vity, nitrogen-doped carbon nanotubes [9], chemically in duced strategies based on light-induced electron-transfer reactions [2] noble-metals supported on nitrogen doped electrodeposition polymers. The application and the design of a semi-artificial Z-sche- carbon nanotubes as well as pyrolysis of of this type of polymers was explored for me analogue of photosynthesis [3]. Recently, nitrogen-containing metal complexes such the design of biosensors and biofuel cells. the concept of the design of suitable redox as porphyrins or pyrolysis of nitrogen-con- Strategies to bind specifically designed polymers was ex tended to the entrapment taining polymers [10]. In addition to the Os-complexes to the polymer backbone of hydrogenases. It could be shown that investigation of oxygen reduction and oxy- were developed and corresponding redox the design of a viologen-based redox poly- gen evolution catalysts chlorine evolution polymers were applied for the optimization mer is able to protect hydrogenases from was intensively studied and new mechanis- of reagentless biosensors and biofuel cells. both high-potential deactivation as well as tic insights especially on gas-bubble depar- The development of suitable redox poly- from damage by molecular oxygen [4]. New ture [11] could be provided. mers for biofuel cell cathodes or anodes concepts for the visualization of DNA hybri- aims to adjust the redox potential of the dization were proposed [5]. Lithium-ion batteries polymer bound redox relays to those of the active sites of the enzymes for enabling Scanning electrochemical In addition to energy conversion and ener- highest possible current densities and microscopy (SECM) gy storage in chemical bonds, energy sto- open-circuit voltage. This was combined rage using batteries is of high importance. with the application of three-dimensionally In SECM the convolution between informa- It became evident, that the available test structured carbon nanotube based electro- tion about local electrochemical reactivity cells did not allow to obtain reliable infor- de sur faces for enhancing enzyme loading and the tip-to-sample distance has to be mation using electrochemical impedance and consequently power output. The most overcome. Application of SECM for the spectroscopy nor on the formation of the difficult aspect is seen in the electron visualization of biological activity evolved solid electrolyte interphase formed due to 8

[7] A. Bandarenka, A. Maljusch, K. Eckhard, W. Schuhmann, J. Phys. Chem. C 118 (2014) 8952–8959. Localised impedance measurements for electrochemical surface science [8] K. Sliozberg, R. Meyer, A. Ludwig, W. Schuhmann, ChemPlusChem. 80 (2015) 136-140. A combinatorial study of photoelectrochemical properties of Fe-W-O thin films. [9] S. Kundu, T. C. Nagaiah, W. Xia, Y. Wang, S. Dommele, J. Bitter, M. Santa, G. Grundmeier, M. Bron, W. Schuhmann, M. Muhler, J. Phys. Chem. C 113 (2009) 14302-14310. Electrocatalytic activity and stability of nitrogen-containing car- Fig. 2: The Schuhmann group in May 2014. bon nanotubes in the oxygen reduction reaction. electrolyte decomposition. Therefore, new (2013) 14233-14236. A Photosystem 1 [10] J. Masa, W. Xia, I. Sinev, A. Zhao, Z. Sun, S. measuring cells for impedance spectrosco- based photocathode and a Photosystem Grützke, P. Weide, M. Muhler, W. Schuh- py in sealed battery cells were developed 2 based photoanode combined to a Z- mann, Angew. Chem. Int. Ed. 53 (2014)

and a SECM was integrated within a glove scheme-mimic for biophotovoltaics 8508 –8512. MnxOy/NC and CoxOy/NC box to allow for in-situ investigation of the [4] N. Plumere, O. Rüdiger, A. Alsheikh nanoparticles embedded in a nitrogen- formation of the solid-electrolyte interpha- Oughli, R. Williams, J. Vivekananthan, S. doped carbon matrix for high perfor- se [12]. Pöller, W. Schuhmann, W. Lubitz, Nature mance bifunc tional oxygen electrodes. Chem. 6 (2014) 822-827. A redox hyd- [11] X. Chen, A. Maljusch, R. A. Rincón, A. Bat- Selected References rogel protects hydrogenase from high tistel, A. S. Bandarenka, W. Schuhmann, potential deactivation and oxygen da- Chem. Comm. 50 (2014) 13250-13253. [1] D. Leech, P. Kavanagh, W. Schuhmann, mage. Local visualization of catalytic activity at Electrochim. Acta 84 (2012) 223– 234. [5] M. Gebala, W. Schuhmann, Phys. Chem. gas evolving electrodes using frequency- Enzymatic fuel cells: Recent progress. Chem. Phys. 14 (2012) 14933-14942. dependent scanning electrochemical [2] A. Badura, T. Kothe, W. Schuhmann, M. Understanding properties of electrified microscopy Rögner, Energy Environ. Sci. 4 (2011) interfaces as a prerequisite for label-free [12] G. Zampardi, E. Ventosa, F. La Mantia, W. 3263-3274. Wiring photosynthetic enzy- DNA hybridization detection. Schuhmann, Chem. Comm. 49 (2013) mes to electrodes [6] A. Schulte, W. Schuhmann, Angew. 9347-9349. In-situ visualization of Li-ion [3] T. Kothe, N. Plumeré, A. Badura, M. M. Chem. Int. Ed. 46 (2007) 8760-8777. intercalation and formation of the solid Nowaczyck, D. A. Guschin, M. Rögner, W. Single-cell microelectrochemistry electrolyte interphase on TiO2 based Schuhmann, Angew. Chem. Int. Ed. 52 paste electrodes using scanning electrochemical microscopy

Wolfgang Schuhmann obtained his diploma de- and the Humboldt Foundation and in 2011 he gree in chemistry from the University in Karlsruhe, received the Katsumi-Niki-Award of the Internatio- Germany (1982) and his PhD from the Technical nal Society of Electrochemistry (ISE) and in 2012 he University of Munich (1986). After finishing his was appointed Fellow of the International Society habilitation thesis at the Technical University of of Electrochemistry (ISE). In 2014 he received the Munich in 1993, he was appointed professor for Howard Fellowship of the University of New South Analytical Chemistry at the Ruhr-Universität Bo- Wales, Sydney. He is the member of several edito- chum in 1996. In 2000 he received the Biosensors rial boards (ChemPlusChem, Biosensors & Bioelec- & Bioelectronics Award. In 2005 he was appointed tronics, Electroanalysis,) and chair of the board of Fellow of the Royal Society of Chemistry (FRSC). In ChemElectroChem. He published more than 450 2008 he was awarded with the Julius-von-Haast publications in international peer-reviewed scien- Fellowship of the Royal Society of New Zealand tific journals. 9

Analytical Chemistry – Biointerfaces: Understanding biological adhesion processes

Prof. Dr. Axel Rosenhahn; Analytical Chemistry – Biointerfaces

The Rosenhahn group aims on understan- Functional interfaces include the development of non-toxic anti- ding the interaction of microorganisms fouling coatings [2,4,5] and surfaces for tissue and cells with surfaces and its implication Functional interfaces with full control of engineering [6]. for biofouling and biomedical research. their chemical composition, elasticity, hy- Surface modification in conjunction with dration, morphology, hydrodynamics and Surface analysis surface characterization is used to correlate charge are prepared by self-assembly. Mo- surface properties with biological response. nolayers based on thiol and gold chemistry Before biological testing all interfaces are To gain a deeper insight into the structure are excellent tools to test the impact of a characterized by state of the art surface and dynamics of surface colonization by specific surface chemistry on adhesion [1,2]. analysis. Spectral ellipsometry, contact microorganisms, microfluidic assays, 3D Thicker polymer chemistries are prepared angle goniometry, surface IR spectroscopy, tracking techniques, and X-ray imaging are by dipping-robot assisted layer by layer SEM+EDX, fluorescence microscopy and XPS developed and applied. deposition [3] and reversible-deactivation are applied to characterize the chemistry radical polymerization. Key applications and properties at the interface. 10

Biological adhesion Selected publications nitors and leukemia cells with respect to CD44 mediated rolling versus adherence The functional interfaces are applied to [1] S. Bauer, M. Arpa-Sancet, J. Finlay, M. behavior on hyaluronic acid coated sur- investigate adhesion of microorganisms, Callow, J. Callow and A. Rosenhahn, faces Biomaterials, 2014, 35, 1411-1419. marine organisms and cells. To test the foul Adhesion of marine fouling organisms [7] S. Maleschlijski, S. Bauer, N. Aldred, A. S. release potential of surfaces, microfluidic on hydrophilic and amphiphilic polysac- Clare and A. Rosenhahn, Classification of adhesion assays of bacteria and diatoms charides Langmuir, 2013, 29, 4039-4047. the pre-settlement behaviour of barnac- are applied. More complex organisms like [2] A. Rosenhahn, S. Schilp, J. Kreuzer and le cyprids Royal Society of Interfaces A, green and brown algae, barnacles and M. Grunze, The role of "inert" surface 2014, 12, 20141104. mussels are tested in collaboration with chemistry in marine biofouling preven- [8] S. M. Vater, S. Weiße, S. Maleschlijski, C. partners from marine biology. To mecha- tion Physical Chemistry Chemical Physics, Lotz, F. Koschitzki, T. Schwartz, U. Obst nistically understand surface colonization, 2010, 12, 4275-4286. and A. Rosenhahn, Swimming Behavior holographic and stereoscopic 3D tracking [3] M. Arpa Sancet, M. Hanke, Z. Wang, S. of Pseudomonas aeruginosa Studied by techniques are developed and applied [7,9]. Bauer, C. Azucena, H. Arslan, M. Heinle, Holographic 3D Tracking PLoS ONE, 2014, In biomedical research our focus is on the H. Gliemann, C. Wöll and A. Rosenhahn, 9, e87765. CD44-HA interaction [6]. The catch-bond Surface anchored metal-organic frame- [9] A. Rosenhahn and G. H. Sendra, Surface mediated interaction and its relevance for works as stimulus responsive antifouling Sensing and Settlement Strategies of hematopoiesis, leukemia and cancer is coatings Biointerphases, 2013, 8, 29. Marine Biofouling Organisms Biointer- studied. [4] L. Xiao, J. Li, S. Mieszkin, A. Di Fino, A. phases, 2012, 7, 63. S. Clare, M. E. Callow, J. A. Callow, M. [10] M. Beckers, T. Senkbeil, T. Gorniak, M. X-ray spectromicroscopy Grunze, A. Rosenhahn and P. A. Levkin, Reese, K. Giewekemeyer, S. C. Gleber, T. and coherent scattering Slippery Liquid-Infused Porous Surfaces Salditt and A. Rosenhahn, Chemical Con- Showing Marine Antibiofouling Proper- trast in Soft X-Ray Ptychography Physical X-ray spectromicroscopy at synchrotron ties ACS Applied Materials & Interfaces, Review Letters, 2011, 107, 208101. sources combines high spatial resolution 2013, 5, 10074-10080. with chemical specificity at high penetra- [5] L. Xiao, S. Thompson, M. Röhrig, M. E. tion depth [10]. This renders the technique Callow, J. A. Callow, M. Grunze and A. Ro- ideal to study biological systems and senhahn, Hot embossed microtopogra- adhesion processes. Local chemistry and phic gradients reveal morphological cues elemental distributions are correlated with that guide the settlement of zoospores spatially resolved vibrational spectroscopy Langmuir, 2013, 29, 1093. (Raman and IR) to understand distribution [6] M. Hanke, I. Hoffmann, C. Christophis, of metals in organelles and biofoulers. In M. Schubert, V. T. Hoang, A. Zepeda- addition, X-ray scattering provides insight Moreno, N. Baran, V. Eckstein, P. Wuchter, into the ultrastructure of organelles and A. Rosenhahn and A. D. Ho, Differences microorganisms. between healthy hematopoietic proge-

Axel Rosenhahn has been Professor for Analytical worked at the Institute of Functional Interfaces at Chemistry at the Ruhr-University Bochum since the Karlsruhe Institute of Technology on microbial 2012. He received his chemistry diploma at the interactions with surfaces. (More information at University of Bonn and completed his Ph.D. in www.rub.de/biointerfaces) 2000 in the Physical Chemistry Department under the supervision of K. Wandelt. Moving to the Ma- terials Sciences Division of the Lawrence Berkeley National Laboratory he worked at the Advanced Light Source as postdoc with C.S. Fadley. In 2002 he joined the Applied Physical Chemistry group of M. Grunze to do his habilitation on Biointerfaces and coherent imaging. Between 2009 and 2012 he

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Center for Electrochemical Sciences (CES)

Sabine Seisel, Wolfgang Schuhmann

water splitting, catalysts for oxygen reduc- for interferences such as oxygen to allow tion/oxidation, (bio)fuel cells, and biosen- for on-site quantification without sample sors are performed. Members of CES are preparation [2]. In light to electricity conver- participating in a number of joint research sion, the immobilization of photosynthetic projects funded by BMBF, DFG, Helmholtz proteins requires electron mediators with Society and EU. redox potentials adjusted to the one of the protein to achieve fast electron transfer at low overpotential [3]. The use of redox hydrogels as immobilization matrix have As one winner of the HighTech.NRW com- recently yielded photocurrents [4] and petition the Center for Electrochemical voltages [3] that raise the expectation to Sciences (CES) of the Ruhr-Universität Bo- eventually achieve practical efficiency from chum has been founded in October 2009 biophotovoltaic devices. Redox enzymes by the Ruhr-Universität Bochum and the may also play a role as substitute for noble Max-Planck-Institut für Eisenforschung metals in chemical fuel to electricity con- Düsseldorf, with additional financial sup- version. In this case, the main issue is the port by ThyssenKrupp Steel. CES is regarded stability of the biocatalysts. We have shown as a Center of Excellence with the task to that the electron mediator can be designed ensure international competitive research to protect the catalyst from various degra- in all aspects of modern electrochemistry dation processes to achieve stability over at the highest standard. The key missions weeks unter constant turn-over conditions [5] of the center are the coordination of large- Young research group for H2 oxidation in biofuel cell . scale research projects of its members and “Molecular Nanostructures” establishing cooperations with external [1] M. Swoboda, J. Henig, H.-M. Cheng, partners from industry as well as other The group of Dr Plumeré is essentially D. Brugger, D. Haltrich, N. Plumeré, M. research institutions. involved in the design of electron relays Schlierf, ACS Nano, 2012, 6(7), 6364- to bridge redox proteins and electrodes 6369. Research facilities for sensing and energy conversion. Redox [2] N. Plumeré, J. Henig and W. H. Campbell enzymes have extreme activities and selec- Analytical Chemistry, 2012, 84, 2141- A modern electrochemistry laboratory has tivities for various reactions and are hence 2146. been built up and equipped with various attractive for technological applications. [3] V. Hartmann, T. Kothe, S. Pöller, E. El- potentiostats including different elec- We use synthetic chemistry to build redox Mohsnawy, M. M. Nowaczyk, N. Plumeré, trochemical cells, electrochemical quartz interfaces on electrode surface to accom- W. Schuhmann, M. Rögner Phys. Chem. micro (eQCM) balances, impedance spec- modate the target biomolecules with Chem. Phys., 2014, 16, 11936 - 11941. troscopy, scanning electrochemical micro- respect to their properties and intended [4] T. Kothe, S. Pöller, F. Zhao, P. Fortgang, scopy (SECM), scanning electron microsco- applications. The main projects involve M. Rögner, W. Schuhmann, N. Plumeré py (eSEM), atomic force microscopy (AFM) , biosensing, biophotovoltaics and biofuel Chemistry - A European Journal, 2014, surface plasmon resonance (SPR), raman cells. In each of these cases the redox pro- 20, 11029 – 11034. spectroscopy (SERS) and dynamic light teins are connected to the electrodes via [5] N. Plumeré, O. Rüdiger, A. Alsheikh scattering. The electrochemical electron mediators. For example, in nitrate Oughli, R. Williams, J. Vivekananthan, S. equipment, SECM as well as AFM can biosensing, the mediators with high affi- Pöller, W. Schuhmann, W. Lubitz Nature also be operated under inert atmospheres nity for an enzyme that selectively reduces Chemistry, 2014, 6, 822–827. [1] (H2O/O2 free or O2 free in a glove box) offe- nitrate are associated to a scavenger ring a unique facility for the investigation of water or oxygen sensitive systems. To promote young researchers, young research groups have been established within CES offering them full access to all equipment.

Research activities

At CES research activities on different areas of electrochemistry such as among others Li-ion-batteries, semiconductors, photo- electrochemistry, photoelectrochemical 12

Dr. Nicolas Plumeré studied chemistry at the Uni- Prof. Wilbur H. Campbell (NECi, Lake Linden, MI, versity of Strasbourg (France) and the University of USA), he started as a junior group leader at the the West of Scotland, Glasgow (UK). He obtained Center for Electrochemical Sciences (CES) at the his PhD in inorganic chemistry in 2009 from the Ruhr-Universität Bochum (Germany) in 2010. He University of Tuebingen (Germany). The main is coauthor of 30 publications dealing with elec- focus of his thesis was on synthesis and electro- trochemical biosensors, energy conversion based chemistry of redox-active nanoparticles. He was on biomolecules and redox-active materials. The awarded a DFG fellowship for his PhD as well as a research activities of his group at CES focus on DAAD fellowship for a research visit at the San Jose the development of new strategies for efficient State University (CA, USA). After a postdoctoral electrical connectivity between redox enzymes and stay in the field of bioelectrochemistry for sensing electrodes. applications (USDA fundings) at the laboratory of

Young research group “Semicon- battery, with 1.73 V operating potential, interface [5]; amorphous semiconductor/ ductor & Energy Conversion” working in near-neutral environment, and liquid junction theory. containing non-toxic and low-cost components has been developed [2]. The battery [1] J. Stojadinovi´c, A. Dushina, R. Trócoli, F. La shows a significantly improved stability Mantia, ChemPlusChem, 2014, 79, 1507- (more than 100 cycles), and could be a 1511. promising substitute of lead acid batteries [2] R. Trócoli, F. La Mantia, ChemSusChem, for several applications. The group of "Semi- DOI: 10.1002/cssc.201403143. conductor & Energy Conversion" works also [3] R. Trócoli, A. Battistel, F. La Mantia, Chem. on other aspects of applied and experimen- Eur. J., 2014, 20, 9888-9891. tal electrochemistry: lithium recovery from [4] J. Stojadinovi´c, S. Weiss, F. La Mantia, brine and seawater [3]; recovery of heavy Electrochim. Acta, 2014, 127, 153-158. metals from wastewater; membranes and [5] A. Battistel, F. La Mantia, Anal. Chem., Fig. 1: Cycle life and efficiency of the novel separators for alkaline electrolyzers [4]; elec- 2013, 85, 6799-6805. zinc-ion battery. It operates at 1.73 V. tron- and ion-transfer at the solid/liquid

The group "Semiconductor & Energy Con- version" focuses its research in the field of aqueous metal-ion batteries for electrochemical energy storage of grid power. Al- though aqueous batteries are cheaper than their organic counterparts, the electrochemical stability of the former is limited to 1.23 V. At this aim, the depedence of the electrochemical stability of the electrolytes on the components (salt and additives) was investigated [1]. By chosing the proper salts and additives, it was possible to rise the electrochemical stability window of water up to 2.2 V. Based on this, a novel zinc-ion

Fabio La Mantia has obtained his master degree in Dr. La Mantia moved to Stanford University (Cali- chemical engineering at the University of Palermo fornia) where he was involved in research related (Italy) in 2004, with the thesis entitled “Characte- to the development of new materials for batte- rization of Thin Amorphous Semiconducting Films ries, both aqueous and organic, as well as super- by EIS and Differential Admittance”. From 2005 to capacitors based on carbon nanotubes. Since June 2008 he has undertaken the doctoral studies at 2010, Dr. Fabio La Mantia has been leader of the the Eidgenössische Technische Hochschule Zürich group “Semiconductor & Energy Conversion” at and Paul-Scherrer Institut (Switzerland), which the Center for Electrochemical Sciences - CES at the have been focused on lithium-ion batteries, and Ruhr-Universität Bochum (Germany), which deals in particular the characterization of such systems with several aspects of fundamental and applied by means of differential mass spectrometry and electrochemistry in the field of energy conversion. electrochemical impedance spectroscopy. In 2008, 13

Bioinorganic and Medicinal Inorganic Chemistry

Prof. Dr. Nils Metzler-Nolte and Dr. Ulf-Peter Apfel; Chair of Inorganic Chemistry I – Bioinorganic Chemistry

Research at the Chair of Bioinorganic Chemistry revolves around the synthesis of new biologically relevant metal complexes and their bioconjugates. These compounds are investigated for their properties as drug candidates, as biosensors, tools for molecular biotechnology, and as functional mimics for metalloenzymes. Our research is very often inspired by questions of medicinal or biological relevance.

The groups at the Chair of Inorganic Chemistry I utilize the unique properties of metal complexes for the detection of biological targets, manipulation of drug interactions, and mimicking of biological systems. Fig. 2: Targeting of bacterial membranes with poly-valent peptide conjugates leads to new Targeted Antitumor Agents antibiotic drug candidates with excellent activity even against multi-resistant strains (MRSA).

While numerous metal compounds possess The group has developed a unique com- activity of anti-microbial peptides (AMPs) strong anti-proliferative activity against bination of synthetic methods for the by substitution with metal complexes. many cells, their use as actual drugs is preparation of metal-peptide conjugates Derivatization of a short hexameric AMP by limited by their poor selectivity. Research in even with very sensitive metal complexes. metallocenes (such as ferrocene and ruthe- the Metzler-Nolte group aims to improve Furthermore, the group is specialized on nocene carboxlic acid derivatives) yielded the selectivity of metal-based anticancer the investigation of the metal complexes’ not only more active derivatives in general. drug candidates for cellular targeting by spectroscopic properties, in conjunction Moreover, depending on the nature of the attaching them to biological signalling mo- with cell biological investigations in our metallocene and its position within the lecules like peptides. The peptides are de- own cell culture lab. peptide sequence, we could optimize the rived from sequences known for enhanced activity of such conjugates to otherwise and / or cell-type specific uptake (e.g. TAT Metal-Based Antibiotics resistant strains and achieve good activity peptides or octreotate), or for intra-cellular even against MRSA (Fig. 2). delivery (such as nuclear or mitochondrial Since the discovery of modern antibiotics localization, Fig. 1). such as the penicillins in the first half of the In collaboration with microbiologists, the last century, bacterial infections mechanism of action of our new metal- that would have been fatal only containing AMPs was elucidated, and the 100 years ago can be success- metallocene-peptide lead structure was fully treated at relatively low thoroughly optimized by chemical modi- cost. On the other hand, even fications. In a different project, we have in developed countries with synthesized new metal complexes with a

excellent healthcare facilities, Re(CO)3 fragment as promising anti-micro- the fight against bacterial bial agents. Again, membrane interaction infections is a continuous was demonstrated to be crucial for the endeavor. Resistance against mode of action. many common antibiotics develops rapidly as evidenced by Tools for Molecular Biotechnology the upsurge of multi-resistant bacteria (MRSA) in the last two In addition to their medicinal activity, many decades. Therefore, there is an metal complexes also provide unique spec- urgent need for new classes of troscopic properties and reactivity, which antibiotics. To match this need, can be applied to study biological problems metal-containing compounds or manipulate biological molecules such as hold particular promise. In DNA, RNA or proteins. The Metzler-Nolte Fig. 1: Metallocene-peptide conjugates for intra-cellular the Metzler-Nolte group, we group has developed Re(I) complexes as pro- nuclear localization of metal complexes. have successfully modified the mising probes for cellular imaging (Fig. 3). 14

Fig. 3: The particular photophysical properties of Rhenium complexes can be exploited for cellular imaging.

These complexes can be attached to pepti- the metals as well as the catalytic potential Chem. Rev. 104 (2004) 5931-5986. des for the imaging of intracellular organel- of the complexes, spectro-electrochemical [3] M. Patra, M. Wenzel, P. Prochnow, V. Pier- les such as mitochondria and the endoplas- methods, Mößbauer as well as EPR spectro- roz, G. Gasser, J. E. Bandow, N. Metzler- matic reticulum. We are also using metal scopy are applied. Nolte "An organometallic structure- conjugates with analogues of nucleic acids activity relationship study reveals

(so-called peptide nucleic acids or PNA) as the essentail role of a Re(CO)3 moiety artificial nucleases for the sequence-spe- in the activity against gram-positive cific cleavage of RNA and DNA. In collabo- pathogens including MRSA" Chem. Sci. 6 ration with researchers in Canada and at (2015) 214-224 RUB, we have also used such PNA conju- [4] M. Wenzel, A. I. Chiriac, A. Otto, D. gates with redox-active metal complexes Zweytick, C. May, C. Schumacher, R. Gust, as sequence-specific electrochemical DNA H. B. Albada, M. Penkova, U. Krämer, R. sensors. Complementary DNA sequences Erdmann, N. Metzler-Nolte, S. K. Straus, could be detected with high sensitivity and E. Bremer, D. Becher, H. Brötz-Oesterhelt, excellent mismatch discrimination. Fig. 4: Schematic representation of bime- H.-G. Sahl, J. E. Bandow, "Small Cationic

tallic Ni-Mo/Fe complexes for selective CO2 Antimicrobial Peptides Delocalize Peri- Metalloenzyme mimics: binding and reduction to CO. pheral Membrane Proteins" Proc. Natl.

Bioinspired CO2 activation Acad. Sci. USA 111 (2014) E1409–E1418. and hydrogen generation Hydrogen is a promising candidate for [5] H. B. Albada, F. Wieberneit, I. Dijkgraaf, energy storage and transportation. An J. H. Harvey, J. L. Whistler, R. Stoll, N. The research work of Dr. Apfel's group inexpensive and robust catalyst is required Metzler-Nolte, R. H. Fish "The Chemose- (Emmy-Noether Fellow) is focused on that makes the transformation of water lective Reactions of Tyrosine-Containing

the multi-electron reduction of CO2 and into hydrogen possible. Nature uses a G-Protein-Coupled Receptor Peptides

protons, and developing functional model powerful enzymatic system to transform with [Cp*Rh(H2O)3](OTf)2, Including 2D compounds for these metalloenzymes. protons into hydrogen – the hydrogenases. NMR Structures and the Biological Con- Although easily performed in nature, the In collaboration with groups at RUB and sequences" J. Am. Chem. Soc. 134 (2012)

selective and reversible reduction of CO2 to abroad, both the Apfel and Metzler-Nolte 10321 – 10324. CO under mild conditions is a fundamental groups are exploring ways to manipula- [6] S. D. Köster, H. Alborzinia, S. Can, I. challenge for chemists. In a novel bio- te the enzymatic performance of [FeFe] Kitanovic, S. Wölfl, R. Rubbiani, I. Ott, P. inspired approach, the group aims at the hydrogenases by implementing artificial, Riesterer, A. Prokop, K. Merz, N. Metzler- synthesis of heterobimetallic, low-valent tailored mimics into the natural enzymatic Nolte "A Spontaneous Gold(I)-Azide and low-coordinate Fe/Ni-complexes which environment, and by devising completely Alkyne Cycloaddition Reaction Yields are supported by tripodal ligands that will new enzyme mimics. Gold-Peptide Bioconjugates which enable a selective, direct electrochemical Overcome Cisplatin Resistance in a p53-

2-electron reduction of CO2 to exclusively Selected Publications Mutant Cancer Cell Line" Chem. Sci. 3 afford CO (Fig. 4). The direct multi-electron (2012) 2062 – 2072. reduction allows for lowering of the over- [1] G. Gasser, I. Ott, N. Metzler-Nolte "Or- [7] S. I. Kirin, I. Ott, R. Gust, W. Mier, T. Wey- potential and an increase of rate constants ganometallic Anticancer Compounds" J. hermüller, N. Metzler-Nolte, "Cellular for this important process. As a principal Med. Chem. 54 (2011) 3-25. Uptake Quantification of Metallated method to investigate the bonding proper- [2] D. R. van Staveren, N. Metzler-Nolte "Bio- Peptide and Peptide Nucleic Acid (PNA)

ties of CO2, the communication between organometallic Chemistry of Ferrocene", Bioconjugates by Atomic Absorption 15

Spectroscopy" Angew. Chem. Int. Ed. 47 Coey, M. Rudolph, J. G. Vos, R. Tacke, W. Assembly of the [FeFe] Hydrogenase: (2008) 955–959. Weigand "Models for the Active Site in Synthetic Mimics in a Biological Shell" [8] F. Noor, A. Wüstholz, R. Kinscherf, N. [FeFe] Hydrogenase with Iron-Bound ChemBioChem 14 (2013) 2237-2238. Metzler-Nolte "A cobaltocenium peptide Ligands Derived from Bis-, Tris-, and [12] R. Goy, L. Bertini, C. Elleouet, H. Görls, bioconjugate shows enhanced cellular Tetrakis(mercaptomethyl)silanes" Inorg. G. Zampella, J. Talarmin, L. De Gioa, P. uptake and nuclear localization" Angew. Chem. 14 (2010) 10117-10132. Schollhammer, U.-P. Apfel, W. Weigand Chem. Int. Ed. 44 (2005) 2429–2432. [10] U.-P. Apfel, W. Weigand "Efficient Activa- "A sterically stabilized FeI–FeI semi-rota- [9] U.-P. Apfel, D. Troegel, Y. Halpin, S. Tschier- tion of the Greenhouse Gas CO2" Angew. ted conformation of [FeFe] hydrogenase lei, U. Uhlemann, H. Görls, M. Schmitt, Chem. Int. Ed. 50 (2011) 4262-4264. subsite model" Dalton Trans. 44 (2015) J. Popp, P. Dunne, M. Venkatesan, M. [11] U.-P. Apfel, W. Weigand "Biomimetic 1690-1699.

Nils Metzler-Nolte is full professor of Inorganic Che- Ruhr-University Bochum in 2006. He has served mistry at RUB since 2006. He studied chemistry at as Dean of the University-wide graduate school the Universities of Hamburg, Freiburg, and Munich. from 2009 – 2012 and was Vice President for Early After a PhD in main group chemistry in 1994 and a Career Researchers and International Affairs of the postdoc period with Prof. M. L. H. Green in Oxford University. Prof.. Metzler-Nolte was Speaker of the he started his independent research on Bioorgano- DFG-funded Research Unit "Biological Function of metallic Chemistry at the Max-Planck-Institut für Organometallic Compounds" and is currently Coun- Strahlenchemie (today: MPI for Chemical Energy cil Member of the Society of Biological Inorganic Conversion) in Mülheim in 1996. He was appointed Chemistry. He serves on the international advisory professor for Pharmaceutical and Bioinorganic boards of several journals and is Associate Editor Chemistry at the University of Heidelberg in 2000, for Dalton Transactions. He is Chair-Elect for the and full professor of Inorganic Chemistry at the Gordon Conference on Metals in Medicine in 2016.

Ulf-Peter Apfel received his Diploma (2007) and by the DFG with an Emmy-Noether grant by the PhD (2010) from the Friedrich-Schiller-Universität German Science Foundation (DFG). Jena with W. Weigand as a fellow of the Studi- enstiftung des deutschen Volkes. Subsequently, he spent 2 years at the Massachusetts Institute of Technology as a Feodor-Lynen-fellow with S. J. Lippard. In 2013 he started his independent career as a group leader at the Ruhr-University Bochum, supported by the Fonds der Chemischen Industrie (Liebig fellowship). Since 2014 he is supported

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Synergy between synthesis, computational chemistry and materials development

Prof. Dr. Roland A. Fischer, Jun. Prof. Dr. Radim Beranek, Prof. Dr. Anjana Devi, PD Dr. Rochus Schmid

The main domain of research is on molecu- particular Cp* = pentamethylcyclopenta- Negishi, G. Frenking, R. A. Fischer, A No- lar chemistry with a perspective of develo- dienyl). [1] Recently we moved to study the vel Concept for the Synthesis of Multiply q+ ping new materials with different func- surface reactivity of such Hume Rothery Doped Gold Clusters [(M@AunM’m)Lk] , tionalities for a wide range of applications inspired molecular clusters with respect to Angew. Chem. Int. Ed. 2014, 53, 4327. which includes homogeneous and hetero- applications in nanocatalysis (e.g. selective geneous catalysis, photocatalysis, micro and multiple bond hydrogenation (Figure 1) and Research Group optoelectronics, sensing etc. The research transferred our chemistry towards multiply Metalorganic Frameworks: activities at the Chair of Inorganic Chemistry heterometal atom doped gold clusters. [2,3] Head: Prof. Dr. Roland A. Fischer II are rather diverse and segmented into four This work is currently funded with the Pri- areas namely, organometallic chemistry, ority Program 1708 of the German Research Metal-organic frameworks, MOFs, are a fas- coordination chemistry and metal-organic Foundation, "Materials Synthesis near Room cinating and novel class of porous materials frameworks (MOFs), nanomaterials in bulk, Temperature". with giant specific surface areas and pore thin films and nanostructures including photoactive materials and in computational materials chemistry. The main objective is to understand how the structure, composition, reactivity of materials are related to chemical and physical functionality.

Research Group Organometallics: Head: Prof. Dr. Roland A. Fischer and Akad. Rat Dr. Christian Gemel

The field of nanotechnology experienced an immense progress within the past two decades. Amongst various kinds of nanomaterials, especially intermetallic clusters and nanoparticles have been in the focus of research, for example to study the transiti- onal region between molecular compounds and the solid state. However, compositio- nal control of bimetallic clusters turns out

to be challenging, especially when the two Fig. 1: Synthesis and reactivity of [(Cp*AlCu)6H4] (Cu: orange; Al: pale blue; C: grey, N: deep metals are of a very different nature. The blue). [2] "Organometallics subgroup" focuses on the investigation of transition metal main Selected Publications volumes, which are formed by linking metal

group metal (nano)clusters AaBb of a defi- ion containing nodes with organic linkers to ned composition (a/b). Their compositions [1] S. González-Gallardo, T. Bollermann, R. three dimensional networks. MOFs feature and structures mimic situations known A. Fischer, R. Murugavel, Cyclopentadi- zeolite-like architectures, are crystalline from classic intermetallic solid state com- ene Based Low-valent Group 13 Metal but in contrast to zeolites are structurally pounds such as Hume-Rothery and Laves Compounds: Ligands in Coordination responsive and uniquely tuneable with Phases. The current research is focused on Chemistry and Link between Metal Rich respect to the chemistry of the internal this exact spot, the synthesis of ligand- Molecules and Intermetallic Materials, coordination space for host/guest inter- protected molecular intermetallic clusters Chem. Rev. 2012, 112, 3136. actions. MOFs are interesting for various left of the Zintl-border with B representing [2] C. Ganesamoorthy, J. Weßing, C. Kroll, applications ranging from gas storage group 12 or 13 metals (i.e. B = Zn, Cd; Al, Ga, R. W. Seidel, C. Gemel, R. A. Fischer, The and catalysis to sensing and microelectro-

In). Since as early as 1990, we have been Intermetalloid Cluster [(Cp*AlCu)6H4], nics. We have been contributing to MOF

working on the development of a tool-box Embedding a Cu6 Core Inside an Octa- materials research since 2005 in the areas [1] for the reliable, wet-chemical synthesis of hedral Al6 Shell: Molecular Models of of catalysis (“metals@MOFs”), MOF thin such compounds based on the coordination Hume–Rothery Nanophases, Angew. films for integration in devices, [2] flexible chemistry of low-coordinated organo main Chem. Int. Ed. 2014, 53, 7943. MOFs and functionalized MOFs for selective group species R-B towards transition metal [3] A. Puls, P. Jerabek, W. Kurashige, M. Förs- gas adsorption and separation. [3] Recently,

centers A (R = CH3, bulky aryl, alkyl and in ter, T. Bollermann, M. Winter, C. Gemel, Y. it was realized that the presence of various 17

structural defects (vacancies, dislocations, Research Group device geometries. In all these processes, etc.) within MOFs affects their chemical Inorganic Materials Chemistry: the precursor plays a pivotal role. The Inor- and physical properties quite drastically. Head: Prof. Dr. Anjana Devi ganic Materials Chemistry (IMC) research The targeted implementation of specific group specializes in the development of defects by synthetic means as well as the The downscaling of device dimensions novel precursor chemistries and their evalu- understanding of the defect structure over and the constraints posed on materials ation for the fabrication of nanostructured various length scales has become a new selection and properties for technological functional materials [1, Figure 3]. The principle and important topic. [4,5] A Horizon 2020 applications especially in the area of micro- concept of research is to transform molecu- Research Grant has been recently awarded electronics and optoelectronics, motivates les (precursors) to materials and investigate by the European Commission to highlight materials chemists to look out for new ma- the influence of precursor chemistry on the the collaborative investigations on Defect terials with enhanced functionalities. The material characteristics. The application of Network Materials (www.defnet-etn.eu). research activities of the Inorganic Materi- the functional materials is directed in the field of microelectronic, optoelectronics, photovoltaics, sensors, catalysis, spintronics etc. While group IV metal oxides namely,

ZrO2 and HfO2 exhibit a wide range of functional properties which make them very promising for technological applications ranging from high dielectric constant (k) material in complementary metal oxide semiconductor (CMOS) technology to optical fibers, sensors, thermal barrier coatings

waveguides etc., TiO2 is an interesting class of material, very well investigated for several applications that include UV Fig. 2: Schematic representation of selective guest adsorption in flexible (breathing) Metal- protection, photocatalysis, pigments, dye- Organic Frameworks triggered by the implementation of dangling alkylether side groups (red) sensitized solar cells etc. Rare earth (RE) [3] pinned to the organic linkers (blue) which connect the metal ion (cluster) nodes (yellow). oxides (e.g. Y2O3, Sc2O3, Gd2O3, Dy2O3, Er2O3) are very appealing for use in microelectro- Selected Publications als Chemistry group, encompasses the field nics, optoelectronics, magnetic devices etc. of fabrication of nanostructured materials and rare earth nitrides (GdN, DyN, ErN) are [1] M. Meilikhov, K. Yusenko, D. Esken, S. Tur- using vapor and solution based processes. being projected to be highly promising for ner, R. A. Fischer, Metals@MOFs: Loading This includes metalorganic chemical vapor spintronic based devices. Recently, the re- MOFs with Metal Nanoparticles for hybrid deposition (MOCVD), atomic layer depositi- search focus of IMC has been directed into functions, Eur. J. Inorg. Chem. 2010, 3701. on (ALD) and chemical solution deposition the field of transparent conducting oxides [2] A. Bétard, R. A. Fischer, Metal-Organic (CSD) of various functional materials such (TCOs) that include ZnO, In2O3 and Ga2O3 Frameworks Thin Films: From Funda- as metals, metal oxides and metal nitrides. nanostructures and barrier coatings such

mentals to Applications, Chem. Rev. These processes are compatible with other as TiO2, Al2O3 and SiO2 for polymer surfaces. 2012, 112, 1055. device fabrication processes and especially The research project on plasma enhanced [3] A. Schneemann, S. Henke, I. Schwedler, R. for high throughput coatings on complex ALD of barrier coatings on polymer surfaces A. Fischer, Targeted Manipulation of Me- tal–Organic Frameworks To Direct Sorption Properties, ChemPhysChem 2014, 5, 823. [4] O. Kozachuk, I. Luz, F. X. Llabrés i Xame- na, H. Noei, M. Kauer, H. B. Albada, E. D. Bloch, B. Marler, Y. Wang, M. Muhler, R. A. Fischer, Multifunctional, Defect- Engineered Metal–Organic Frameworks with Ruthenium Centers: Sorption and Catalytic Properties, Angew. Chem. Int. Ed. 2014, 53, 7058. [5] Z. Fang, J. P. Dürholt, M. Kauer, W. Zhang, C. Lochenie, B. Jee, B. Albada, N. Metzler- Nolte, A. Pöppl, B. Weber, M. Muhler, Y. Wang, R. Schmid, R. A. Fischer, Structural Complexity in Metal–Organic Frame- works: Simultaneous Modification of Open Metal Sites and Hierarchical Poro- Fig. 3: (left to right) Schematic of an ALD process, ALD reactor, application of Gd-tris-guanidi-

sity by Systematic Doping with Defective nate in combination with H2O for the ALD of high quality Gd2O3 thin films and characterizati- [2] Linkers, J. Am. Chem. Soc. 2014, 136, 9627. on of the Gd2O3 layers by GI-XRD, HRTEM and electrical characteristics. 18

is currently funded by the German Science Foundation (DFG-SFB-TR-87).

As CVD and ALD processes are in the main stream of future technology development, one of the missions of the group is to train young researchers in this field. In this context two European level training networks under the FP7 programme of the EU were installed and coordinated at RUB (www. enhance-itn.eu and www.rapid-itn.eu), especially addressing the research themes that are of direct interest to research and development.

Selected Publications

[1] A. Devi, Old Chemistries for New Appli- cations: Perspectives for development of precursors for MOCVD and ALD applications. Coord. Chem. Rev. 2013, 257, 23. [2] A. P. Milanov, K. Xu, A. Laha, E. Bugiel, R. Ranjith, D. Schwendt, H. J. Osten, H. Pa- rala, R. A. Fischer, A. Devi, Growth of crys-

talline Gd2O3 thin films with high quality Fig. 4: (a) The concept of hybrid photoanodes for water oxidation: thin layer of porous nanoc- interface on Si(100) by low temperature rystalline hybrid light absorber loaded with a water oxidation cocatalyst by photoelectroche-

H2O assisted atomic layer deposition, J. mical deposition allows for visible light-induced oxidation of water to oxygen at moderate Am. Chem. Soc. 2010, 132, 36. bias potentials. [1] (b) Within the EU-funded 4G-PHOTOCAT project, metal oxide co-catalysts are [3] A. P. Milanov, T. Thiede, A. Devi, R. A. deposited onto the surface of TiO2 photocatalyst in order to catalyze surface redox reactions

Fischer, Homoleptic Gadolinium Gua- and enhance charge separation; the redox co-catalyst modified TiO2 photocatalysts show [2] nidinate: A single source precursor for enhanced degradation rates of organic pollutants as compared to unmodified TiO2 . metalorganic chemical vapor deposition of gadolinium nitride thin films, J. Am. drogen production through water splitting, Research Group Chem. Soc. 2009, 131, 17062. degradation of harmful pollutants, or Computational Materials Chemistry: [4] M. Krasnopolski, C. G. Hrib, R. W. Seidel, selective photooxidation reactions). In Head: PD Dr. Rochus Schmid M. Winter, H.-W. Becker, D. Rogalla, R. A. the field of solar water splitting, the group Fischer, F. T. Edelmann, A. Devi, Homolep- has been recently developing a novel class Embedded into the experimental environ- tic gadolinium amidinates as precursors of photoanodes for solar water splitting ment of the Chair of Inorganic Chemistry for MOCVD of oriented gadolinium nit- utilizing visible-light photoactive inorga- II, the CMC group is both developing and ride (GdN) thin films, Inorg. Chem. 2013, nic/organic hybrid materials coupled to applying computational methods in close 52, 286. metal oxide co-catalysts for water oxida- collaboration with experimental partners. [5] M. Banerjee, R. W. Seidel, M. Winter, tion (Figure 4a) [1]. Within the EU-funded The research focuses on specific problems H.-W. Becker, D. Rogalla, A. Devi, Novel 4G-PHOTOCAT project, novel composite in materials science by theoretical methods ȕ-ketoiminato complexes of zirconium; photocatalysts for solar detoxification of in order to shed light on atomistic details. synthesis, characterization and evaluati- water are being developed (Figure 4b) [2]. The majority of such problems consist of

on for solution based processing of ZrO2 large systems with many atoms, which thin films, Dalton Trans. 2014, 43, 2384. Selected Publications means that often multiple length and time scales have to be covered in a theoretical Research Group [1] M. Bledowski, L. Wang, S. Neubert, simulation. As a consequence it is usually Photoactive Materials: D. Mitoraj, R. Beranek, Improving the impossible to solve these problems by Head: Jun. Prof. Dr. Radim Beranek Performance of Hybrid Photoanodes employing the most accurate quantum for Water Splitting by Photodeposition mechanical methods available in a direct The research of the Beranek group is fo- of Iridium Oxide Nanoparticles. J. Phys. and "brut-force" way. Instead, clever com- cused on development of chemistry-based Chem. C 2014, 118, 18951. binations of approximate methods with approaches to solar energy conversion, par- [2] S. Neubert, P. Pulisova, C. Wiktor, P. Wei- different resolution need to be combined in ticularly the synthesis and characterization de, B. Mei, D. A. Guschin, R. A. Fischer, order to succeed. Such multiscale simula- of novel hybrid and composite materials M. Muhler, R. Beranek, Enhanced pho- tion methods need to be developed and for use in photochemical systems capable tocatalytic degradation rates at rutile tuned for any materials science problem,

of harnessing solar energy to drive useful TiO2 photocatalysts modified with redox since in each case different approximations chemical transformations (for example, hy- co-catalysts,Catal. Today 2014, 230, 97. can or cannot be used. 19

[3] (a) (b)

Fig. 5: (a) Derivation of force field parameters from non-periodic model systems on the example of MOF-5. (b) Computed acetate terminated [111] surface of HKUST-1. [5]

The current main research target is the rithm global search strategy the Reversed M. Tafipolsky, S. Amirjalayer, R. Schmid, simulation of metal-organic frameworks Topological Approach (RTA) was developed A First Principles derived Force Field for (MOFs), in close interaction with the ex- to predict even experimentally unknown Copper Paddle-Wheel based Metal- perimental work in the Fischer group. The MOF structures [4]. Even the most stable Organic Frameworks, J. Phys. Chem. C novel porous materials are mostly too large surface structure of the prototypical MOF 2010, 114, 14402-14409. for periodic DFT methods. In addition, a key HKUST-1 could be determined by such a [4] S. Bureekaew, V. Balwani, S. Amirjalayer, property is their "softness" and flexibility, force field model [5] (see Figure 5b). Recently, R. Schmid, Isoreticular isomerism in which makes parameterized molecular defects within MOFs with a potential use 4,4-connected paddle-wheel metal–or- mechanics models the method of choice in catalysis have been investigated by QM/ ganic frameworks: structural prediction for configurational sampling. However, for MM methods. by the reverse topological approach, the coordination compound type nodes, CrystEngComm 2015, 17, 344-352. accurate parameter sets are not available. Selected Publications [5] S. Amirjalayer, M. Tafipolsky, R. Schmid, Over the years the CMC group has develo- Surface Termination of the Metal-Orga- ped a systematic parameterization method [1] S. Bureekaew, S. Amirjalayer, M. Tafipols- nic Framework HKUST-1: A Theoretical to close this gap. By evolutionary strategies, ky, C. Spickermann, T. K. Roy, R. Schmid, Investigation, J. Phys. Chem. Lett. 2014, force field parameters are derived from first MOF-FF - A flexible first principles 5, 3206−3210. principles reference data (Figure 5a). The derived Force Field for Metal-Organic resulting MOF-FF represents the first con- Frameworks, Phys. Stat. Sol. B 2013, 250, sistent and accurate force field for this class 1128-1141. of materials [1]. These force fields have been [2] S. Amirjalayer, M. Tafipolsky, R. Schmid, used to predict the diffusion of guest mo- Molecular Dynamics Simulation of Ben- lecules through the pores [2], or the curious zene Diffusion in MOF-5: Importance of shrinking of the materials with increasing Lattice Dynamics, Angew. Chem. Int. Ed. temperature [3]. Again, with a genetic algo- 2007, 46, 463-466.

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Roland A. Fischer studied chemistry at Technische he moved to Ruhr-Universität Bochum where Universität München (TUM) and received his Dr. he took the Chair of Inorganic Chemistry II. He rer. nat. in 1989 under the guidance of Wolfgang has been Vice Rector of RUB for teaching affairs A. Herrmann. After a postdoctoral collaboration (2000-2002), Dean of the Faculty of Chemistry and with Herb D. Kaesz at the University of California, Biochemistry (2005-2007) and Speaker of the Ruhr Los Angeles (UCLA), he returned to TUM in 1990, University Research School (2006-2009). Currently where he obtained his Habilitation in 1995. In he is member of the Editorial Board of Angewand- 1996 he was appointed Associate Professor at te Chemie and member of the DFG Senate commis- Ruprecht-Karls Universität Heidelberg. In 1998 sion of Collaborative Research Centers.

Christian Gemel studied chemistry at the Institu- Prof. Roland Fischer at Ruhr University Bochum in te of Inorganic Chemistry, Vienna University of 2001 and was soon after appointed as Akademi- Technology (Austria). He obtained his PhD in 1997 sche Rat at the Chair of Inorganic Chemistry II. under the supervision of Prof. Karl Kirchner in the field of stoichiometric and catalytic organometallic chemistry of Ruthenium. After two postdoctoral research stays with Prof. Ken Caulton (Indiana Uni- versity, Bloomington) and Prof. Richard Poerschke (MPI Mülheim), he joined the research group of

Anjana Devi obtained B.Sc. and M.Sc. from Manga- Fischer at the Ruhr University Bochum (Germany). lore University followed by PhD from the Indian In- In 2002 she was appointed as a Junior Professor stitute of Science (IISc), Bangalore (India). In 1998, and in 2011 as a professor at the Ruhr University she moved to Germany for post doctoral research Bochum and is currently heading the Inorganic with a fellowship awarded by the Alexander von Materials Chemistry Research Group in the Faculty Humboldt foundation (AvH) (1998). Her post doc- of Chemistry and Biochemistry. toral research focused on metalorganic chemical vapor deposition of group III nitrides which was carried out in the research group of Prof. Roland

Radim Beránek studied chemistry at the Institute Research Award for Young European Scientists of of Chemical Technology in Prague (Czech Republic), The European Society for Quantum Solar Energy and obtained his PhD in inorganic chemistry from Conversion and has been a member of the Global the University of Erlangen-Nürnberg (Germany), Young Faculty of the Mercator Foundation (2011- working under the supervision of Prof. Horst 2013). Currently he is the coordinator of the colla- Kisch. In 2010 he joined the Faculty of Chemistry borative EU-FP7 project "4G-PHOTOCAT" (309636). and Biochemistry at the Ruhr University Bochum (Germany) as a Junior Professor and head of the Photoactive Materials Group. He received the 2008

Dr. Rochus Schmid studied chemistry at the Techni- mistry”. He is leading the Computational Materials cal University Munich (TUM) and received his PhD Chemistry research group at the Chair of Inorganic in the group of Wolfgang A. Herrmann in 1997. Chemistry II, and is focusing on multiscale simula- After a postdoctoral stay with Prof. Tom Ziegler at tion methods using first principles parameterized the University of Calgary (Canada) he returned to force fields for porous coordination polymers and the TUM in 1999. In 2003 he joined the group of other hybrid materials. Prof. Roland A. Fischer at the Ruhr-University Bo- chum, where he finished his Habilitation in 2009 on the topic “Atomistic Models in Materials Che- 17 2013

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Ionotropic Glutamate Receptors: Structure, Function, Regulation and Modulation

Prof. Dr. Michael Hollmann | Department of Biochemistry I - Receptor Biochemistry

Structure, function, regulation, and modu- Functional analysis of like receptors), in heterologous systems lation of ionotropic glutamate receptors delta-type glutamate receptors did not reveal functional ion channels is investigated by molecular biological, activatable by any glutamatergic agonist. electrophysiological, proteinbiochemical Delta-type glutamate receptors form a By transplanting the ion pores of GLRs in and immunocytochemical methods. We separate subfamily of glutamate receptors mammalian glutamate receptors we could analyze structural and functional properties that comprises two subunits, GluD1 and show that those Arabidopsis GLR ion chan- of members of the extended protein family GluD2, that have not been shown to bind nels indeed are functional domains [6]. We of ionotropic glutamate receptors as well as glutamate, and for which the activating then proceeded to analyze full-length GLRs their many interacting proteins in hetero- agonist remains unknown. Their member- in the Xenopus oocyte expression system logous expression systems such as Xenopus ship in the glutamate receptor family is pu- and were able to demonstrate that at least laevis oocytes and HEK293 cells. In our stu- rely based on sequence homology conside- one of the twenty genes, AtGLR1.4, is a dies we include vertebrate (23 known genes) rations, and many groups favor the theory receptor activated by hydrophobic amino as well as invertebrate glutamate receptors that these receptors are not meant to work acids such as methionine, tryptophane, ty- such as those of Caenorhabditis elegans (15 as ion channels. We managed to demons- rosine, phenylalanine, and leucine [7]. When genes) and lately also plant glutamate re- trate via ligand binding domain transplan- the AtGLR1.4 gene is knocked out, seedlings ceptor homologs like those 20 genes found tation between delta receptors and kainate of Arabidopsis do not respond to methioni- in Arabidopsis thaliana. receptors that delta receptors indeed have ne any longer. a functional ion channel domain [4,5]. After cloning the first glutamate receptor in For reasons still unknown and currently We currently analyze additional AtGLR 1989 [1], discovering the calcium permeabili- investigated, however, this channel domain subunits to see if they also can also act as ty of certain heteromeric glutamate recep- does not receive activating signals from the biosensors for certain amino acids. tor subunit combinations [2] and clarifying receptor’s ligand binding site. the correct transmembrane topology of glutamate receptor subunits [3], the group Plant glutamate receptor homologs of Michael Hollmann currently focuses as biosensors for certain amino acids on the little-known delta-type glutamate receptors of mammals, the pressure-sensi- The sequencing of the Arabidopsis thali- tivity of NMDA receptors, plant glutamate ana genome, finished by the year 2000, receptor homologs, the modulation of revealed the presence of an astonishing 20 ionotropic glutamate receptor function genes that looked like mammalian gluta- by auxiliary proteins, and the analysis of mate receptors in terms of their primary autoantibodies to glutamate receptors in sequence as well as their predicted trans- humans. membrane topology. However, expression of these proteins, termed GLRs (glutamate-

Fig. 2: The Arabidopsis thaliana glutamate- like receptor subunit AtGLR1.4 responds to hydrophobic amino acids and threonine Fig. 1: Glutamate does not bind to the GluD2 receptor’s own (red) ligand domain and thus does when expressed in oocytes. Upon knock-out not open the ion channel. If the GluD2 ligand binding domain is replaced by the (blue) kainate of the plasmamembrane-expressed AtGLR1.4, receptor ligand binding domain, the GluD2 receptor’s ion pore opens and allows current. plants become unresponsive to methionine. 23

Glutamate receptors are trafficked and functionally modulated by auxiliary proteins

TARPs (transmembrane AMPA receptor regulatory proteins) were discovered about 10 years ago through a coincidental observation in a mutant mouse strain. This observation revealed the protein stargazin, the first member of a family of eventually six proteins later named TARPs, to be an essential protein that facilitates the traf- ficking of the AMPA receptor subtype of glutamate receptors to the plasma membrane in cerebellar granule cells. Interestin- receptors does not necessarily indicate the chimeras and mutants. European Jour- gly, stargazin also modulates the biophysi- existence of a neurological disorder. Further nal of Neuroscience 37(10): 1620-1630. cal functions of these receptors. We investi- analysis will have to show how widespread [6] D. Tapken and M. Hollmann (2008). Ara- gated the family of TARP proteins and could these autoantibodies are, and why they are bidopsis thaliana glutamate receptor ion show that each TARP has its own profile of being produced. channel function demonstrated by ion functional modulation and its own set of pore transplantation. Journal of Molecu- AMPA receptor subunits and variants that Selected Publications lar Biology 383(1): 36-48. it modulates [8]. We later showed that TARP [7] D. Tapken, U. Anschütz, L.-H. Liu, T. transfection into cortical organotypic slices [1] M. Hollmann, A. O’Shea-Greenfield, S.W. Huelsken, G. Seebohm, D. Becker, and via a gene gun leads to an upregulation of Rogers, and S. Heinemann (1989). Clo- M. Hollmann (2013). A putative plant AMPA receptors which in turn modulates ning by functional expression of a mem- glutamate receptor emerges as an ion the dendritic arborization in pyramidal neu- ber of the glutamate receptor family. channel gated by multiple multiple hyd- rons as well as their spine morphology [9]. Nature 342: 643-648. rophobic amino acids. Science Signaling We currently investigate a host of other [2] M. Hollmann, M. Hartley, and S. Hei- 6(270, ra47): 1-11. known and potential auxiliary glutamate nemann (1991). Calcium permeability [8] S. Kott, M. Werner, C. Körber and M. receptor proteins that serve to fine-tune of KA-AMPA-gated glutamate receptor Hollmann (2007). Electrophysiological the functional properties of these impor- channels depends on subunit compositi- properties of AMPA receptors are diffe- tant excitatory neurotransmitter receptors. on. Science 252: 851-853. rentially modulated dependent on the [3] M. Hollmann, C. Maron, and S. Heine- associated member of the TARP family. Autoantibodies against NMDA mann (1994). N-Glycosylation site tag- Journal of Neuroscience 27(14): 3780- receptors in neuropathy patients ging suggests a three transmembrane 3789. and normal people domain topology for the glutamate [9] M.I.K. Hamad, A. Jack, O. Klatt, M. Lor- receptor GluR1. Neuron 13: 1331-1343. kowski, T. Strasdeit, S. Kott, C. Sager, M. Autoantibodies against glutamate re- [4] S.M. Schmid, S. Kott, C. Sager, T. Hülsken, Hollmann, and P. Wahle (2014). Type-I ceptors have been found in a number of and M. Hollmann (2009). The glutama- TARPs promote dendritic growth of early disease states, among others Rasmussen’s te receptor subunit delta2 is capable postnatal neocortical pyramidal cells encephalitis and certain neuropathies. of gating its intrinsic ion channel as in organotypic cultures. Development While investigating blood samples from revealed by ligand binding domain 141(8): 1737-1748. multiple sclerosis patients, we discovered transplantation. Proceedings of the Nati- [10] J. Trippe, K. Steinke, A. Orth, P.M. Faust- that even normal people have an asto- onal Academy of Sciences, USA 106(25): mann, M. Hollmann, and C.G. Haase nishingly high probability to carry auto- 10320-10325. (2014). Autoantibodies to glutamate antibodies against glutamate receptors of [5] A. Orth, D. Tapken and M. Hollmann receptor antigens in multiple sclerosis the NMDA receptor subtype [10]. Thus, the (2013). The delta subfamily of glutamate and Rasmussen´s encephalitis. Neuro- appearance of autoantibodies to glutamate receptors: Characterization of receptor immunomodulation 21(4): 189-194.

Michael Hollmann has been a Full Professor of the Salk Institute for Biological Studies in La Jolla, Biochemistry at the Ruhr University Bochum since California, USA. He returned to Germany on a 1999. He studied biochemistry in Tübingen and Heisenberg Fellowship and set up his independent received his PhD from the University of Tübingen research group at the Max Planck Institute for for a project carried out at the Max Planck Insti- Experimental Medicine in Göttingen, where he tute of Biophysical Chemistry in Göttingen, under received his Habilitation in Biochemistry from the the supervision of Wilfried Seifert (1988). He spent Medical Faculty of the University of Göttingen in six years (1988-1994) as a Postdoctoral Research 1998. For more details see www.ruhr-uni-bochum. Associate with the late Stephen F. Heinemann at de/bc1. 24

Molecular Neurobiochemistry: Towards protection and regeneration of brain neurons

Prof. Dr. Rolf Heumann (Department of Biochemistry II – Senior research group Molecular Neurobiochemistry, Faculty of Chemistry and Biochemistry)

The Heumann group investigates and of neurons and their fiber growth during with enhanced Ras activity were generated exploits the intracellular signaling mecha- ontogenetic development by limiting from synRas-derived stem cells. Phospha- nisms of extracellular ligands to regulate neurotrophic supply from target tissue that tidyl-inositol kinase was involved in the survival, neurotransmitter synthesis and has to be innervated. By introduction of molecular mechanism of signaling for connectivity in brain neurons. The group permanently activated Ras protein into the Ras-mediated protection against neuro- established that the universal intracellular cytoplasm of deprived neurons we could toxin-induced neuronal degeneration. signaling protein Ras GTPase regulates fibre demonstrate that Ras protein mimics the Yet, in these Ras-activated dopaminergic growth and synaptic activity in response intracellular signaling mechanism of neuro- neurons formation of synaptic contacts and to environmental sensory stimuli through trophins promoting neuronal survival and normal functions of sodium and potassium transient activation of downstream protein fiber outgrowth. Conversely, intracellular channels involved in action potentials were phosphorylation cascades. The group inves- inhibition of Ras activity by function blo- preserved. These results suggest that Ras tigates if neuronal cell death and axonal cking Fab-fragments prevented neurotro- activity could be a target for pharmaco- degeneration can be counteracted by Ras ac- phic factor induced effects. Thus, the afore logical stabilization of neurons in neuro- tivity in neurodegenerative diseases such as mentioned 2nd messenger mechanism of degenerative diseases such as Parkinson’s Parkinson’s disease. Dopaminergic neurons neurotrophic factors was identified [2]. disease [6]. derived from neural stem cells are protected from toxic treatment by Ras activation, Proinflammatory cytokines enhan- while formation of synaptic contacts and ce regeneration of sensory axons normal functions of sodium and potassium channels involved in action potentials are Interleukin-6 is a multifunctional cytokine preserved as shown in collaboration with mediating inflammatory reactions, immu- the Dietzel group. ne response and pain. By applying electrophysiological, morphological, biochemical A 2nd messenger is required and behavioral methods in mice lacking the for the biological activity gene coding for interleukin-6 we showed of nerve growth factor. that this cytokine is essential to enhance sensory functions in regenerating axons Extracellular ligands such as steroid hor- Fig. 1: In the synRas mouse model expression after peripheral nerve lesion [7]. mones regulate cellular protein expressi- of a Ras gene with point mutation from gly- on by penetrating the cell membrane to cine to valine in amino acid 12 permanently Ras homolog enriched bind to cytoplasmic or nuclear receptors enhances Ras activity in brain neurons. in brain (Rheb) that then modify promoter transcription activity of the nuclear DNA. Alternatively, Neuroprotection Rheb is a homolog of Ras GTPase that regu- ligands bind to their cognate cell surface in the synRas mouse model lates cell growth, proliferation, and regene- receptors thereby inducing transmembrane ration via mammalian target of rapamycin signaling cascades either directly across In order to investigate the in vivo function (mTOR). Because of the well established po- the membrane at the inner cytosolic face of neuronal Ras activity we have generated tential of activated Ras to promote survival, of the plasma membrane or after receptor a transgenic mouse model expressing per- the ability of Rheb signaling to phenocopy mediated endocytosis. We demonstrated manently activated Val12 Ras, selectively in Ras was investigated. Unexpectedly, Rheb- that a protein regulating neuronal survival neurons [3]. Using this model named synRas mTOR activation not only promoted normal and fiber outgrowth, named nerve growth mice (Figure 1) we showed that neuronal cell growth but also enhanced apoptosis in factor, is taken up into the cell, yet induces Ras activity is involved in the dynamics of response to diverse toxic stimuli via an apo- its neurotrophic effects by triggering an dendritic spine formation of brain neurons, ptosis signalling regulated kinase mediated intracellular transmembrane receptor in the regulation of synapse number and mechanism. Pharmacological regulation of mediated mechanism [1]. their efficiency [4] and in the suppression of the Rheb/mTORC1 pathway using rapa- adult neurogenesis in the hippocampus. mycin should take the presence of cellular Actication of Ras prevents neuronal This Ras-induced modulation of adult stress into consideration, as this may have cell death induced by deprivation neurogenesis was associated with changes clinical implications [8]. of neurotrophic factors in short term memory processes [5]. Fur- thermore, activation of Ras could prevent Neurotrophic factors interact with their co- mechanical lesion-induced degeneration gnate Trk receptors to regulate the number of motor neurons. Dopaminergic neurons 25

Selected Publications [6] Chakrabarty K, Serchov T, Mann SA, Diet- [7] Zhong, J., Dietzel, I.D., Wahle, P., Kopf, zel ID, Heumann R. 2007 Enhancement M., and Heumann, R. 1999 Sensory im- [1] Heumann R, Schwab M and Thoenen of dopaminergic properties and protec- pairments and delayed regeneration of H. 1981 A 2nd messenger required for tion mediated by neuronal activation sensory axons in interleukin-6-deficient nerve growth factor biological activity. of Ras in mouse ventral mesencephalic mice. J Neurosci 19, 4305–4313 Nature 292, 838–840. neurones. European Journal of Neurosci- [8] Karassek S, Berghaus C, Schwarten M, [2] Borasio, G.D., John, J., Wittinghofer, A., ence 25, 1971-1981. Goemans CG, Ohse N, Kock G, et al. 2010 Barde, Y.A., Sendtner, M., and Heumann, Ras homolog enriched in brain (Rheb) R. 1989 Ras p21-protein promotes survi- enhances apoptotic signaling. J Biol val and fiber outgrowth of cultured em- Chem 285, 33979 - 33991. bryonic neurons. Neuron 2, 1087–1096. [3] Heumann R, Goemans C, Bartsch D, Lingenhohl K, Waldmeier PC, Hengerer B, et al. 2000 Transgenic activation of Ras in neurons promotes hypertrophy and protects from lesion-induced degeneration. J Cell Biol 151,1537-1548. [4] Arendt T, Gartner U, Seeger G, Barma- shenko G, Palm K, Mittmann T, et al. 2004 Neuronal activation of Ras regulates synaptic connectivity. European Journal of Neuroscience 19, 2953-2966. [5] Manns, M., Leske, O., Gottfried, S., Bichler, Z., Lafenetre, P., Wahle, P., and Heumann, R. 2011 Role of neuronal ras activity in adult hippocampal neurogenesis and cognition. Front Neurosci 5:18 Fig. 2: The Heumann and Dietzel groups in December 2013.

Rolf Heumann is an expert in molecular neurosci- full professor of Biochemistry at the Ruhr-Univer- ence and biochemistry. He studied Microbiology sity Bochum (RUB). From 2006 to 2015 he was the (1975) and performed his PhD thesis at the Max- director of RUBION which is a service unit of RUB Planck-Institute for Biochemistry, Martinsried, offering scientific, technical and administrative Germany, under the guidance of Bernd Hamprecht service for ionbeams and radionuclides. Currently, (1978). In 1979 he switched to the Institute for he continues his research as a senior professor of Psychiatry at the Max-Planck-Institute in Martins- his molecular neurobiochemistry group at the ried. There he established and supervised a project RUB. group named “Dynamics and Stabilisation of Neural Structures”. In 1988, he finished his Habili- tation. From 1991 to 2012 he was the head of the Department of Molecular Neurobiochemistry as a 26

Electrobiochemistry: Molecular Regulation of Voltage-Gated Transmembrane Ion Currents Underlying Fast Signaling in Living Cells

Prof. Dr. Irmgard Dietzel-Meyer (Department of Biochemistry II – Electrobiochemistry of Neural Cells, Faculty of Chemistry and Biochemistry)

The Dietzel group studies the molecular regulation of the expression of voltage-gated ion currents underlying neuronal excitability, the molecular mechanisms leading to cytokine-induced damage of immature oligoden- drocytes and is involved in the development of Scanning Ion Conductance Microscopy.

Voltage-gated ion currents underlying neuronal excitability

Informations are processed in biological systems by transient stimulus-induced reversals of the potential difference across cell membranes, called action potentials. The propagation speed of these action potentials depends on the current density Fig. 4: Phase contrast picture of a cultured Retzius cell from the medicinal leech. The inset in carried through voltage-gated Na+ channels the phase contrast picture delineates a growth cone, the surface of which is shown in the in the membranes, which in turn depends enlarged display at the right after tracing its contours with a Scanning Ion Conductance on the open probability, single channel Microscope. conductance and membrane density of opened Na+ channels. Our experiments postnatal rats. Further investigations zing antibodies against fibroblast growth showed, that exposure to the thyroid provided evidence, that this is not a direct factor-2 (Figure 3). Apart from providing hormone triiodo-L-thyronin (T3) for several effect, but requires the secretion of soluble an explanation for changes in mental days increases the Na+current density in factors from neuronal satellite cells and speed observed during dysfunctions of the hippocampal and cortical neurons from that this effect can be blocked by neutrali- thyroid gland our results suggest that the surrounding satellite cells can modulate neuronal excitability by secreting proteins that influence the number of available Na+ channels in the membranes [1].

Scanning Ion Conductance Microscopy

Scanning ion conductance microscopy (SICM) is a scanning probe technique especially suited for long-term monitoring of topographical changes of delicate surfaces of the membranes of living cells. Topogra- phical representations are generated by mapping surfaces of equal resistance changes sensed by an electrolyte filled glass pi- pette approaching an insulating surface. By introducing a back-step recording mode we have refined this method to reproducibly monitor the entire soma contours of living cells with up to 50 repeated scans at a lateral resolution of 1μm steps and quantify cell volumes with errors of less than 10% Fig. 3: Cascades involved in the regulation of voltage activated Na+ currents by thyroid hormo- [2]. Using this method we demonstrated ne (red traces) with respect to currents recorded from untreated control cells (blue traces) as that during saltatory migration of oligo- measured using the whole cell patch clamp technique. dendrocyte precursor cells frontal volume 27

changes precede accelerated migration[3]. postnatal hippocampal neurons requires [4] Dietzel, I., Heinemann, U. & Lux, H. D. Our observations confirm the hypothesis secretion of soluble factors from glial 1989. Relations between slow extracel- that water fluxes through the somata are cells. Mol. Endocrinol 23, 1494–1504. lular potential changes, glial potassium involved in generating the directed forces [2] Thatenhorst, D., Rheinlaender, J., Schäf- buffering, and electrolyte and cellular driving the propulsion of the cell nucleus. fer, T. E., Dietzel, I. D. & Happel, P. 2014 Ef- volume changes during neuronal hyper- fect of sample slope on image formation activity in cat brain. Glia 2, 25–44. Selected Publications in scanning ion conductance microscopy. [5] Dietzel, I. D., Drapeau, P. & Nicholls, J. G. Analytical Chemistry 86, 9838–9845. 1986 Voltage dependence of 5-hyd- [1] Niederkinkhaus, V., Marx, R., Hoffmann, [3] Happel, P., Möller, K., Schwering, N. K. & roxytryptamine release at a synapse G. & Dietzel, I. D. 2009. Thyroid hormone Dietzel, I. D. 2013. Migrating oligodendro- between identified leech neurones in (T3)-induced up-regulation of voltage- cyte progenitor cells swell prior to soma culture. J.Physiol.(Lond.) 372, 191–205. activated sodium current in cultured dislocation. Scientific Reports 3, 1806.

Irmgard D. Dietzel studied physics at the RWTH induced volume changes of glial cells[4]. Following Aachen and developed her interest in synchroniza- postdoctoral work on the presynaptic regulation tion of nerve cells during her Diploma thesis at the of transmitter release in the laboratory of J. G. Ni- Institute of Physical Chemistry under the guidance cholls[5] (at Stanford University and the Biocenter of U. F. Franck. To investigate the role of extracellu- in Basel, funded by the award of an Otto Hahn- lar potassium in inducing epileptiform neuronal hy- Medal of the Max-Planck Society), she returned peractivity she joined the department of Neurophy- to the group of H.D. Lux at the MPI for Psychiatry siology at the Max-Planck-Institute for Psychiatry in to investigate the ontogenetic development of Munich, then headed by H.D. Lux in 1978. Together voltage-activated ion currents. After obtaining her with U. Heinemann she discovered shrinkages of the “Habilitation” for Physiology at the LMU Munich extracellular space during epilepsy-like neuronal at 1992 she joined the Department of Molecular hyperactivity due to electrolyte and water-flux Neurobiochemistry at the Ruhr-University. 28

Biomolecular Spectroscopy: NMR to study the structure and function of medically-relevant proteins

Prof. Dr. Raphael Stoll | Faculty of Chemistry and Biochemistry, Ruhr University of Bochum, Germany

Our research focuses in the main on medi- being hazardous to health. To date, it had a lower-energy form of GTP. These switch cally-relevant proteins, specifically those been assumed that bisphenol A produces proteins are crucial for transmitting signals involved in the development of cancerous a harmful effect by binding to hormone within the cell. We could demonstrate that tumours, in order to better understand the receptors. But recently, we have discovered bisphenol A binds to two different small causes of the condition and propose more that the substance also affects the so-called GTPases, K-Ras and H-Ras, thereby preven- effective treatment strategies. Examp- small GTPases (Fig. 1) [5]. ting the exchange of GDP for GTP (Fig. 2). les include oncogenic proteins, tumour suppressors as well as proteins involved in Various organisations have pointed out malignant melanoma, to name but a few. that bisphenol A may be hazardous to Other current areas of investigation also health: the Federal Institute for Risk Assess- cover the structure, function, dynamics and ment (Bundesinstitut für Risikoforschung), interaction of proteins associated with the the European Food Safety Authority, the US transduction of physiological signals. Food and Drug Administration (FDA), the US National Institutes of Health (NIH) and Biochemistry seeks to understand life at a Fig. 1: Bisphenol A binds to the switch the US-American Breast Cancer Founda- molecular level by examining the relation- protein K-Ras, which is vital for cell growth tion. However, those organisations have ship between the structure and function processes and plays a role in tumourigenesis. not yet provided a final assessment of the of biomolecules, such as nucleic acids and A HADDOCK model of K-Ras/GDP in complex substance’s hazardous potential. Never- lipids. To achieve this, we use a variety of with bisphenol A is shown. theless, the European Commission banned techniques, particularly biomolecular NMR the use of bisphenol A in the manufacture spectroscopy, in order to determine the Small GTPases are enzymes that occur in of baby bottles in 2011. Academic studies three-dimensional structures and dynamics two states within the cell: in the active indicate that the substance may increase of biomolecules as well as how they inter- form when bound to the GTP molecule; and the risk of cardiovascular diseases, breast act with each other and other molecules in in the inactive form when bound to GDP, and prostate cancer as well as neuronal solution at near-physiological conditions. diseases. The non-profit organisation Ger- Cancer cells are hallmarked by the ability to man Cancer Aid (Deutsche Krebshilfe e. V.) divide unrestrictedly, posing an often lethal has funded this project. threat to an organism. Thus, the development of selective small antagonistic ligands Selectively modifying hormones tailored to bind to crucial protein targets is through metal complexation paramount to be able to treat cancer effec- and using them as medicinal tively. In order to achieve this goal, the mole- substances cular mechanism of a potential therapeutic effect needs to be elucidated at atomic re- Together with Prof. Metzler-Nolte and his solution. In particular, we would like to un- co-workers from our faculty at the Ruhr derstand structure-function-relationships University of Bochum as well as Berkeley of MDM2/p53 [1], Ras as well as Rheb GTPa- we have used metal complexes to modify ses [2], and the melanoma inhibitory activity peptide hormones and could determine the (MIA) protein [3]. In addition, our research ef- three-dimensional structure of the resul- forts include an "SAR by NMR"-like approach ting metal-peptide compounds for the first in order to develop potential lead structures time (Fig. 3). These hormones – enkephalin of small molecular antagonists for these and somatostatin – influence the sensation medically-relevant proteins [4]. of pain and tumour growth. In this collaborative study we have analysed the peptide Bisphenol A is a suspected health hormone encephalin, which is important hazard contained in some plastics, for the sensation of pain, and octreotide because it also impairs the function [6]. The latter is a synthetic derivative of the of GTPases growth hormone somatostatin, approved Fig. 2: Top panel: Sos-mediated nucleotide as a medicinal substance and already used Bisphenol A impairs the function of proteins exchange assay. Effect of bisphenol A on Sos- in the treatment of certain tumours. that are vital for growth processes in cells. mediated K-Ras activation. Bottom panel: The substance, short BPA, is contained in Model of K-Ras[green]/Sos[blue] (PDB code many plastic products and is suspected of 1BKD) superimposed with bisphenol A [red]. 29

their effect changes, for example pain [2] Karassek, S., Berghaus, C., Schwarten, tolerance is lowered, or tumour growth M., Goemans, C.G., Ohse, N., Kock, G., inhibited. Interestingly, the reaction with Jockers, K., Neumann, S., Gottfried, S., the metal complex was highly selective. Herrmann, C., Heumann, R., Stoll, R. Although the hormones consist of hund- (2010) Ras homolog enriched in brain reds of atoms, the rhodium compound (Rheb) enhances apoptotic signaling. J. was always found to be coordinated by the Biol. Chem., 285, 33979-33991. Fig. 3: Using NMR spectroscopy, we have aromatic carbon ring system of the tyrosine [3] Stoll, R., Bosserhoff, A. (2008). Extracel- determined the three-dimensional structure - the phenol moiety. lular SH3 domain containing proteins of the metal-peptide complexes. The metal – features of a new protein family. Curr atom, rhodium (shown in magenta), binds The future goal is to develop other metal- Protein Pept Sci., 9, 221-226. to the peptides’s amino acid tyrosine, more containing, peptide-like substances subs- [4] Shuker, S.B., Hajduk, P.J., Meadows, R.P., specifically to the phenol group (carbon tances based on the basic studies on these Fesik. S.W. (1996). Discovering high- atoms are shown in green, nitrogen atoms basic studies as these could modulate the affinity ligands for proteins: SAR by NMR. in blue, and oxygen atoms in red, whereas effect of naturally occurring peptide hor- Science, 274, 1531-1534. hydrogen atoms have been omitted for clari- mones and, for example, be used as a novel [5] Schöpel, M., Jockers, K.F.G., Düppe, P.M., ty). The second circular carbon structure that remedy for pain or cancer. The German Autzen, J., Potheraveedu, V.N., Ince, S. Tuo is also shown in green above the rhodium Research Foundation (SFB 642 and Research Yip, K., Heumann, R. Herrmann, C., Scher- atom represents a 1,2,3,4,5-Pentamethylcy- Unit 630) and the Research Department kenbeck, J., Stoll, R. (2013). Bisphenol A clopentadienyl group (Cp*). Through metal for Interfacial Systems Chemistry at RUB binds to Ras proteins and competes with coordination, rhodium is bound between the supported the work. Guanine Nucleotide exchange: implica- two carbon rings. The gray net symbolizes tions for GTPase-selective antagonists. the surface of the molecule. Selected Publications Journal of Medicinal Chemistry, 56, 9664-9672. Peptide hormones consist of amino acids [1] Stoll, R., Renner, C., Hansen, S., Palme, [6] Bauke Albada, H., Wieberneit, F., Dijk- and they convey bodily sensations such as S., Klein, C., Belling, A., Zeslawski, W., graaf, I., Harvey, J.H., Whistler, J.L., Stoll, pain and hunger, but they also transmit Kamionka, M., Rehm, T., Mühlhahn, P., R., Metzler-Nolte, N., Fish, R.H. (2012). growth signals. One example of this is Schumacher, R., Hesse, F., Kaluza, B., The chemoselective reactions of tyrosine- insulin, which is important for the control Voelter, W., Engh, R.A., Holak, T.A. (2001). containing G-protein-coupled receptor 3 2 of blood sugar levels. Upon interaction with Chalcone derivatives antagonize interac- peptides with [Cp*Rh(H2O) ](OTf) , specific receptors, the G-protein-coupled tions between the human oncoprotein including 2D NMR structures and the receptors, peptide hormones transport MDM2 and p53. Biochemistry, 40, 336- biological consequences. Journal of the messages to cells. The hormones can be 344. American Chemical Society, 134, 10321- specifically chemically modified so that 10324.

Raphael Stoll is Professor of Biomolecular Spectro- his PhD from the Technical University of Munich in scopy in the Faculty of Chemistry and Biochemistry the year 2000. After a stay as a research associate at the Ruhr University of Bochum. He is also a foun- at The Scripps Research Institute, CA, USA funded ding member of the SFB 642 that has been establis- by first a DAAD- and then an Emmy-Noether hed in 2004, and was a member of the EU-funded fellowship, he initially joined the Ruhr-University of INTCHEM consortium. From 1990 until 1996, he Bochum as Juniorprofessor in 2003. studied Physiological Chemistry and Biochemistry For further details please refer to the following at the Universities of Tübingen, Germany, and Ox- web page: www.rub.de/bionmr ford, UK, as a fellow of the „Studienstiftung” and DAAD. Supported by a fellowship from the FCI, he carried out his doctoral research at the Max Planck Institute for Biochemistry in Munich and received

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Chemistry Education: Scientific ways of thinking and working

Prof. Dr. Katrin Sommer, Lehrstuhl für Didaktik der Chemie

Our research activities centre around the un- One example of such a model experiment from aluminium. The different units can derstanding of chemical procedures. There is the determination of the sodium chloride also be used in school chemistry lessons. is a particular focus on model experiments fraction in shampoo. The influence of so- and on didactic concepts for out-of-school dium chloride on the viscosity of shampoo After six years experience in the project, we learning environments that provide learners can be used to determine the sodium chlo- can state: The common laboratory visit is with opportunities to encounter chemical ride fraction in a shampoo (Fig. 1). a fix date in the families’ leisure program. ways of working and thinking. Experiments 70% of parent-child dyads attend seven or allow learners to carry out chemical proce- KEMIE – Kinder erleben more of the nine units. It has been shown dures and use scientific ways of thinking to mit ihren Eltern Chemie [4] that parents rate the relevance of science in gain insights into the science of Chemistry. their everyday life higher after they atten- School and university students as well as in- Is it possible to make parents and their ded the project. So far, the research focus terested lay people are the target audiences children feel that experiencing “scientific has been on the outcomes of the project. A of our research. Thus, our research contri- inquiry“ together is just as usual and new research project investigates parent- butes to the field of science communication everyday as a visit to the football pitch? child-communication during the project. across university, schools and the public. You can find a potential answer to this question disguised in five letters: "How it is to be a researcher" Model experiments K – E – M – I – E is the acronym for "Kinder ("Forscherwelt", Henkel) in the Chemistry classroom Erleben Mit Ihren Eltern Chemie"(Kids experience chemistry with their parents). This research area covers the potential Children (Grades 3 to 6) and their parents of model experiments in the Chemistry (Fig. 2) can take part in this project. The classroom. It is based on a profound dis- project is a series of nine consecutive units tinction between experiments and model with monthly topics; each unit takes three experiments that allows classifying model hours. experiments systematically and determi- ning their degree of modelling. The core idea of the project is to make the participants acquainted with various as- Particular model experiments are being pects of scientific inquiry. These stretch from Fig. 2: Parent and child determine the sugar used to investigate in how far secondary observation and measurements to cont- concentration of mulled wine for kids using school students identify the analogies rolling variables and testing hypotheses. a self-made hydrometer. between the original and the model expe- Chemical methods are introduced through riment. The results will be used to provide a curriculum following an upward spiral of „Forscherwelt“ is an educational initiative recommendations for the development of complexity. This way, the chemical methods set up by Henkel to introduce children up model experiments that will support stu- serve as a guiding structure. The examples to the age of 10 to the fascinating world dents in bridging the gap between model are taken from every day life, for example a of science. In 2010 Henkel asked us to and original. self-heating can, creams and packing made develop and implement a didactic concept for the out-of-school learning environment „Forscherwelt“. With Henkel as a research- focused company, it seemed only natural to put the research process and the research environment at the heart of the didactic concept for the "Forscherwelt". This core idea is reflected in the title of the concept: “How it is to be a researcher” [5].

The didactic concept includes the following aspects of scientific inquiry: Scientific methods and critical testing, analysis and inter- pretation of data, science and questioning (especially the ability to identify and formu- late questions) and creativity. It is important to introduce the children to the scientific work place because children believe that Fig. 1: Relation between viscosity (determined using a self-constructed falling ball viscometer) scientists are people who work alone, but and sodium chloride fraction. the world of work looks very different. 31

A strong focus on research processes and ist im Shampoo? Analytik einmal anders. environments asks for authenticity. Authen- In: Unterricht Chemie 24 (2013) 137, S. ticity can only be created when the comple- 24-30. te didactic concept evolves from Henkel’s [3] Wieczorek, R.; Sommer, K.: Demons- research topics. And this exactly what it trating the Antioxidative Capacity of does. The contents in the „Forscherwelt“ are Substances with Lightsticks. In: Journal of the research topics of Henkel (adhesives, chemical education 88 (2011) 4, S.468- washing/cleaning and cosmetics) and also 469. one more topic which is important for the [4] Sommer, K.; Russek, A.; Kleinhorst, H.; whole economy: sustainability. It is really a Kakoschke, A.; Efing, N.: KEMIE – Kinder didactic challenge to simplify and select the erleben mit ihren Eltern Chemie. Chem- research topics of this global company in a kon 20 (2013) 5, S.209-352 (Sonderheft). way that will bring them to life for eight- to [5] Sommer, K.; Kakoschke, A.; Schindler, ten-year-old children (see also: http://www. S.; Buchwald, M.; Russek, A.; Schäfer, henkel-forscherwelt.de/berg-des-wissens/ A.; Steff, H.; Krupp, U.: "Wie ein Forscher weitere-unterrichtsdownloads/). Fig. 3: Question-and-answer session with sein" – das didaktische Konzept für eine children and Tore Podola, an expert from Bildungsinitiative in einem Forschungs- Experts at Henkel play a special role in the Henkel’s adhesives department Science com- unternehmen und dessen Umsetzung. In: didactic concept. They are key to concep- munication – Public outreach in the RESOLV Chemkon 19 (2012) 3, S.131-136. tualizing the learning units as well as to Cluster of Excellence. [6] Sommer, K.; Aufdemkamp, G.: Rund ums implementing them. During the concept Aluminium – Schülerlabor und Tandem- phase, the experts introduce their fields faculty of Chemistry and Biochemistry and fortbildung. In: Chemie in unserer Zeit of research – from the composition of get first-hand insights into their work with 43 (2009) 6, S.408-416. products across product control and quality fluorescence microscopy. During the day, [7] Sommer, K.; Strippel, Ch.; Schaffer, S.; management to packing and marketing. the students also engage with new ways Wieczorek, R.: Umgang mit fachmetho- All the experts are prepared to give short of science communication by producing dischen Begriffen in Versuchsvorschriften. talks to the children to offer them authen- videos about their experiments. In: Beiträge zur Qualitativen Inhaltsana- tic insights into their topics (Fig. 3). This lyse (2013) Bd. 21. close collaboration between experts and We also develop a special exhibition on the [8] Metzger, S.; Sommer, K.: "Kochrezept" educators in conceptualizing and delive- work of the cluster for the wider public. oder Experimentelle Methode – Eine ring activities in an out-of-school learning This exhibition will also be used to investi- Standortbestimmung von Schülerex- environment marks a new route of creating gate the public’s understanding of current perimenten unter dem Gesichtspunkt learning environments. research, particularly the understanding der Erkenntnisgewinnung. In: MNU 63 of the role of questions for guiding the re- (2010) 1, S.4-11. Currently, didactic concepts are being search project and the selection of research [9] Sommer, K.; Andreß, St.; Kakoschke, developed to engage students and the methods. A.; Wieczorek, R.; Hanisch, S.; Hanss, J.: public with the research of the RESOLV Vanillezucker oder Vanillinzucker? In: Cluster of Excellence. One-day projects for Selected Publications Chemkon 16 (2009) 1, S.19-30. students aim to breach the gap between [10] Sommer, K.; Lorke, J.; Mattiesson, Ch. the students’ subject knowledge and the [1] Sommer, K.; Klein, M.; Steff, H.; Pfeifer, P.: (Hrsg.): Publizieren in Zeitschriften für research methods used by scientists from Modellexperimente – Zwischen Anschau- Forschung und Unterrichtspraxis – Ein the cluster. In one project, students first ungselement und Erkenntnisgewinnung. Element der Wissenschaftskommunika- carry out experiments to learn about the In: Unterricht Chemie 23 (2012) 132, tion in den Fachdidaktiken und Bildungs- potential of combining fluorescence and S.2-9. wissenschaften. Klinkhardt-Verlag, Bad microscopy to investigate living organisms. [2] Schröder, Th. P.; Schäfer, A.; Schmiedel, P.; Heilbrunn 2015. Later in the day, they visit scientists at the Kluthke, K.; Sommer, K.: Wieviel Kochsalz

Katrin Sommer is Professor of Chemistry Education Habilitation in Chemistry Education (University of (Ruhr-University Bochum, since 2004), further Erlangen-Nuremberg, 2004). For more details, see positions: Vice-Dean of the Professional School of www.rub.de/didachem Education at Ruhr-University Bochum (since 2011), head of Alfried Krupp School Laboratory (since 2012). First Staatsexamen (1995) and Second Staatsexamen (1997) in Chemistry and Biology for secondary schools, PhD scholarship “Studien- stiftung des deutschen Volkes” (German National Academic Foundation), PhD in Chemistry Educa- tion (University of Erlangen-Nuremberg, 2000), 32

Systems Chemistry: Self-Replication and Self-Assembly

Prof. Dr. Günter von Kiedrowski, Lehrstuhl für Organische Chemie I

Self-replication and self-assembly are two of side ABC are brought into close spatial pro- Organic Replicator Systems the major principles without which life could ximity facilitating covalent ligation to yield

not exist. The emergence of self-replicating the template duplex C2. The latter needs Small organic replicators facilitate the systems on the early earth is generally be- to decompose to start a new autocatalytic study of self-replication using simpler lieved to have taken place before the advent cycle. Typically, the autocatalytic growth of molecules and complexes suitable for of instructed protein synthesis based on a template molecules is parabolic as a con- computational studies at the DFT level. [5] complex translation machinery. Whether sequence of the interplay of autocatalysis Kinetic monitoring by 1H NMR allows to the origin of self-replication is identical to and product inhibition (Fig. 1). observe both structural and dynamic chan- the origin of the hypothetical RNA world or ges which result in much deeper insight whether it existed at an earlier stage of evo- Parabolic growth was also observed in compared to methods such as HPLC moni- lution is an open question that has stimula- more complex systems in which autocata- toring. Autocatalytic growth of template ted chemists to search for chemical systems lytic and crosscatalytic ligation pathways molecules is typically observed both in the capable of making copies of themselves via compete for the formation of self-com- sigmoidal increase of NMR signal inten- autocatalytic reaction networks. Their in- plementary and complementary template sities and in a characteristic shifting of vestigation, utilization and integration into products. [2] Exponential growth was achie- chemical shifts. The latter source of infor- even more complex dynamic super systems ved by utilizing surface immobilization of mation is useful for the analysis of reaction defines the field of systems chemistry. templates as a means to prevent product systems which include equilibration steps inhibition. [3] More recently, the natural occurring rapidly on the NMR time scale. Self-Replicating Oligonucleotides 3’-5’-phosphordiester linkage was replaced We developed the method of "kinetic NMR by an isosteric 3’-5’-disulfide linkage (Fig. titration" to simulate and fit time series of The first successful demonstration of non- 2), whose formation exhibits the fastest both chemical shifts and NMR integrals for enzymatic self-replication was achieved by ligation chemistry so far developed for arbitrary reaction models. [7] This enabled chemical ligation of two trideoxynucleoti- oligonucleotide systems. [9] Self-replication a facile extraction of rate and equilibri- des A and B yielding a self-complementary was also demonstrated for peptide nucleic um parameters at various temperatures hexadeoxynucleotide template C. [1] Autoca- acids [10] which have been discussed as and allowed to construct experimentally talysis resulted from a pathway embedding potential RNA precursors. derived enthalpy and entropy profiles for a the reaction sequence series of organic replicators which could be compared with theory.

A + B + C ÅÆ ABC Æ C2 ÅÆ 2 C Self-Assembling where ABC is a termolecular complex, Trisoligonucleotides

and C2 a template duplex held together by reversible base pairing. As the result of Self-assembly is nature’s key recipe to templating, the reactive ends of A and B in- create structural complexity on the nano to micrometer scale. The ribosome is an example for a functional nanoarchitecture which may be viewed as a threedimensio- nally defined array of 51 modular proteins Fig. 2: Overlay of a standard B-DNA model positioned by the rRNA scaffold. We deve- with B-DNA containing a 3’-5’-disulfide link loped biomimetic approaches towards the instead of a 3’-5’-phosphordiester link. 3D-nanoscaffolding of modular functions based on trisoligonucleotides [4,8], viz. synthetic 3-arm junctions in which either the 3’-ends or the 5’-ends of three oligonucleotides are connected by a suitable linker. Maximal instruction was employed as a design principle to generate noncovalent 3D-nanoobjects in which both, the topology and the geometry is defined. Examples include dodecahedral nanoscaffolds com- Fig. 1: Visualization of parabolic growth posed from 20 trisoligos each bearing three kinetics by a Christmas tree. Time runs from individually defined sequences (Fig. 4). [8] the tip to the bottom. The number of rose Fig. 3: 1H NMR Shift shifting observed in bulbs in each layer increases with the square product and precursor signals during kinetic of the time, from 1 to 4, 9, 16, 25. monitoring of a minimal organic replicator. 33

modular functions such as multidentate [6] W.M. Pankau, S. Mönninghof, G. von Kie- thioether-based gold cluster labels (RUBi- drowski, Thermostable and monocon- Gold) [6] which were tailored for monocon- jugable gold clusters by gripping with a jugability and thermostability. dodecadentate thioether ligand, Angew. Chem. Int. Ed. 45, 2006, 1889-1891. Selected major publications [7] I. Stahl, G. von Kiedrowski, "Kinetic NMR titration": including chemical shift [1] G. von Kiedrowski, A self-replicating information in the kinetic analysis of hexadeoxynucleotide, Angew. Chem. 98, supramolecular reaction systems such Fig. 4: (a) Computer model of a DNA dode- 1986, 932-934; Angew. Chem. Int. Ed. as organic replicators, J. Am. Chem. Soc. cahedron self-assembled from a set of 20 Engl. 25, 1986, 932-935. 128, 2006, 14014-14015. trisoligonucleotides each containing three [2] D. Sievers, G. von Kiedrowski, Self-Repli- [8] J. Zimmermann, M. P. J. Cebulla, S. individual 15mer sequences connected at cation of Complementary Oligonucleoti- Mönninghoff, G. von Kiedrowski, Self- their 3’-ends by a C3h-symmetric linker. The des, Nature 369, 1994, 221-224. Assembly of a DNA Dodecahedron from [3] nanoobject contains 30 individual DNA du- A. Luther, R. Brandsch, G. von Kiedrowski, 20 Trisoligonucleotides with C3h Linkers, plexes and has a diameter of about 20 nm. Surface-promoted replication and expo- Angew. Chem. Int. Ed. 47, 2008, 3626- (b) AFM of dodecahedra absorbed on mica nential amplification of DNA analogues, 3630. reveal compressed objects with lateral sizes Nature 396, 1998, 245-248. [9] V. Patzke, J.S. McCaskill, G. von Kiedrow- larger than their vertical counterparts. [4] L. Eckardt, K. Naumann, W.M. Pankau, ski, DNA with 3’-5’-disulfide links: Rapid M. Rein, M. Schweitzer, N. Windhab, G. chemical ligation through isosteric It was demonstrated that the connectivity von Kiedrowski, Chemical Copying of replacement, Angew. Chem. Int. Ed. 53, information in the nanoscaffold junc- Connectivity, Nature 420, 2002, 286. 2014, 4222-4226. tions can be copied by chemical means. [4] [5] M. Kindermann, I. Stahl, M. Reimold, [10] T.A. Plöger, G. von Kiedrowski, A self- Chemical copying schemes may be seen W.M. Pankau, G. von Kiedrowski, Sys- replicating peptide nucleic acid, Org. in conjunction with "surface-promoted re- tems chemistry: Kinetic and computa- Biomol. Chem. 12, 2014, 6908-6914. plication and exponential amplification of tional analysis of a nearly exponential DNA analogues" (SPREAD) [3]. Applications organic replicator, Angew. Chem. Int. Ed. of such scaffolds include the positioning of 44, 2005, 6750-6755.

Günter von Kiedrowski studied chemistry at the on synthetic, kinetic and computational studies. University of Münster. He joined the Tietze group His work with D. Sievers has been included in a list at the University of Göttingen where he received of 35 favorite publications the Editors of Nature his Ph.D. in 1983. After a postdoctorate with L.E. selected when looking back to chemistry between Orgel at the Salk Institute in La Jolla he returned 1950 and 2000. to Göttingen in 1985 and became Associated Professor of Organic Chemistry at the University of Freiburg in 1993. In 1996 he followed a call to the Chair of Organic Chemistry I at RUB. His research interests aim at self-assembly and self-replication in organic and biomolecular systems with a focus

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Multidentate Halogen Bonding in Solution: Organocatalysis and Supramolecular Chemistry

Prof. Dr. Stefan M. Huber, Organic Chemistry I, RU Bochum

Our group aims to utilize halogen bonding Applications in catalysis While this first application was based on in catalysis and supramolecular chemistry. the stoichiometric use of the halogen- To this end, we synthesize polyfluorinated or While hydrogen-bonds have already been based Lewis acid, subsequently we have cationic polyiodinated compounds and per- successfully used in organocatalysis, appli- also successfully employed these kinds of form systematic studies on their interaction cations of halogen bonding in this field are activators in catalytic amounts. One such with organic substrates. These experimental extremely rare. Thus, our long-term goal is example is depicted in Scheme 2, which studies are accompanied by quantum-che- the development of halogen-bond based also features a neutral polyfluorinated mical calculations and the determination of enantioselective organocatalysis. Because halogen-bond donor (3) instead of the thermodynamic binding data. of the different electronic nature of the in- cationic one of Scheme 1. teraction compared to hydrogen-bonds, dif- Halogen-bonds are attractive non-covalent ferent substrate scopes and selectivities are Recently we could also apply this organo- interactions between electrophilic halogen to be expected in comparison to classical catalytic principle towards the activation substituents and Lewis bases: R-X -- LB non-covalent organocatalysts. In our stu- of typical organic substrates like carbonyl (X = Cl, Br, I / LB = Lewis base). They share dies, benchmark reactions are monitored groups. many similarities with the well-known by spectroscopic methods, typically NMR. hydrogen-bonds, but rely on bromine or Competition and reference experiments are Determination of thermodynamic iodine instead of hydrogen substituents. often conducted to determine which part data and benchmarking Reasonably strong halogen-bonds are only of the catalyst candidate is responsible for obtained when the halogen is attached the reactivity. Catalysts are then optimized The binding strength of halogen-bond to a very electronegative group, e.g. a perfor highest activity, or in the case of chiral based adducts in solution are determined fluorinated or cationic backbone. These compounds, highest enantioselectivity. by NMR titrations or calorimetric measure- interactions can be similar in strength to ments. For the latter, we employ isothermal hydrogen-bonds, but in contrast to the In a first proof-of-principle reaction, we titration calorimetry (ITC). These thermody- latter, feature a high directionality: the R-X could show that dicationic halogen-bond namic measurements form the basis for a -- LB angle is always close to 180°. In the donors (halogen-based Lewis acids) like 1 rational optimization of our halogen-bond last 25 years, halogen-bonds have been are able to activate the carbon-bromine donors. All our experimental projects are established as reliable building blocks for bond in a test substrate (benzhydryl bro- usually also accompanied by quantum the rational design of solid-state structures mide 2). Comparison experiments with chemical calculations. Semi-empirical me- ("crystal engineering"). In contrast, there non-iodinated reference compounds and thods are used to quickly identify suitable are only few examples of applications of additional tests provided strong indications catalyst candidates, while DFT calculations halogen-bonds in solution. that halogen-bonds are indeed the basis of serve to determine the binding strength this activation (Scheme 1). of non-covalent adducts and to model the Synthesis of multidentate mode of action of catalysts on the transiti- halogen-bond donors on state of benchmark reactions.

The basis of our experimental work is the design, synthesis, and characterization of halogenated organic compounds. As common structural motif, all target molecules feature at least two Lewis-acidic halogen substituents directed towards the same point in space. As backbone structures, polyfluorinated aromatics or cationic Fig. 1: Activation of benzhydryl bromide 2 by halogen-bond donor 1 as a benchmark case for heterocyclic moieties like imidazolium or the acceleration of organic transformations by halogen bonding. pyridinium groups are used. The syntheses are accomplished by established procedures or novel approaches when necessary. All compounds are characterized by various spectroscopic methods (most importantly NMR) and studied in the solid state by X-ray structural analyses.

Fig. 2: Catalytic use of halogen-bond donor 3 in a test reaction. 35

tion of a carbonyl compound by halogen bonding. Chem. Commun. 2014, 50, 6281-6284. [3] Stefan H. Jungbauer, Severin Schindler, Florian Kniep, Sebastian Walter, Lax- midhar Rout, Stefan M. Huber – Multi- dentate Halogen-Bond Donors as Lewis Acidic Activators or Catalysts in Halide Abstraction Reactions. Synlett 2013, 24, 2624-2628. [4] Florian Kniep, Stefan H. Jungbauer, Qi Zhang, Sebastian M. Walter, Severin Schindler, Ingo Schnapperelle, Eberhardt Herdtweck, Stefan M. Huber – Organo- catalysis by Neutral Multidentate Halo- gen-Bond Donors. Angew. Chem. Int. Ed. 2013, 52, 7028-7032. [5] Stefan M. Huber, Joseph D. Scanlon, Elisa Jimenez-Izal, Jesus M. Ugalde, Ivan Infante – On the directionality of halogen bonding. Phys. Chem. Chem. Phys. 2013, 15, 10350-10357. [6] Florian Kniep, Laxmidhar Rout, Sebastian M. Walter, Heide K. V. Bensch, Stefan H. Jungbauer, Eberhardt Herdtweck, Stefan M. Huber – 5-Iodo-1,2,3-triazolium- based multidentate halogen-bond donors as activating reagents. Chem. Commun. 2012, 48, 9299-9301. [7] Stefan M. Huber, Elisa Jimenez-Izal, Jesus M. Ugalde, Ivan Infante – Unexpected Trends in Halogen-Bond Based Non-Cova- Fig. 3: Multipoint interaction between a tridentate halogen-bond donor and a tridentate lent Adducts. Chem. Commun. 2012, 48, Lewis base. 7708-7710. [8] Sebastian M. Walter, Florian Kniep, Applications in Selected Publications Laxmidhar Rout, Franz P. Schmidtchen, supramolecular chemistry Eberhardt Herdtweck, Stefan M. Huber [1] Stefan H. Jungbauer, David Bulfield, – Isothermal Calorimetric Titrations on In parallel, we also utilize halogen-bond Florian Kniep, Christian W. Lehmann, Charge-Assisted Halogen Bonds: Role of based multipoint interactions for the de- Eberhardt Herdtweck, Stefan M. Huber Entropy, Counterions, Solvent, and Tem- sign of supramolecular donor-acceptor – Toward Molecular Recognition: Three- perature. J. Am. Chem. Soc. 2012, 134, pairs. While the initial characterization of Point Halogen Bonding in the Solid State 8507-8512. these species is usually performed in the and in Solution. J. Am. Chem. Soc. 2014, [9] Sebastian M. Walter, Florian Kniep, solid state (X-ray analysis), we ultimately 136, 16740-16743. Eberhardt Herdtweck, Stefan M. Huber strive to study and apply these interactions [2] Stefan H. Jungbauer, Sebastian M. Wal- – Halogen-Bond-Induced Activation of a in solution. ter, Severin Schindler, Laxmidhar Rout, Carbon-Heteroatom Bond. Angew. Chem. Florian Kniep, Stefan M. Huber – Activa- Int. Ed. 2011, 50, 7187-7191.

Stefan M. Huber has been associate professor of ger in Erlangen, he started his independent career organic chemistry at the Ruhr University Bochum in 2009 at the Technical University of Munich. For since 2014. He studied chemistry at the Friedrich- more details, see: www.rub.de/oc1/huber (Picture: Alexander University Erlangen-Nuremberg and A. Heddergott). obtained his Ph.D. in organic chemistry with Ro- bert Weiss in 2007. Subsequently, he worked as a postdoctoral fellow with Christopher J. Cramer at the University of Minnesota (2007) and with Laura Gagliardi at the University of Geneva (2008). After a further short postdoctoral stay with Harald Grö- 36

Natural Product Research: Chemical, Enzymatic and Fermentative Synthesis of Medicinally Important Compounds

Prof. Dr. Frank Schulz ; Chemistry and Biochemistry of Natural Products; Organische Chemie 1

The Schulz group pursues different pro- The introduction of synthetic compounds towards the derivatization of the antibiotic jects to break up important limitations in into biosynthetic pathways combines the erythromycin A. current natural product research. Both the strength of both regimes. In precursor- limited availability and derivatization of dif- directed mutasynthesis, synthetic com- Limitations of biosynthesis are thus bro- ferent compounds are addressed, rendering pounds are accepted by wild-type enzymes ken up by enzyme engineering. A logical new compounds with diverse biological from a native producer organism and can extension of this is the partial synthesis of activities available. carry artificial functional groups into the further derivatives. These synthetic efforts corresponding compound. start from compounds obtained through Microbial Synthesis engineered biosynthesis and as well

Polyketides form a large family of natural products and many polyketides are applied for the treatment of diseases such as cancer or infections. [1] However, the large and polyfunctional structures of many polyketides complicate the derivatization that Fig. 2: Cultures of Streptomyces cinnamonensis yield specifically modified derivatives of preis required to develop them into clinically monensin when supplied with the synthetic malonic acid derivatives shown here. useful compounds. Biosynthetic pathways show an enormous capability of generating molecular complexity. Genetic engineering In many cases, enzymes from the biosyn- directly from interesting natural products of polyketide-producing bacteria is thus thetic reaction cascade do not accept a for projects within medicinal chemistry to used to direct the biosynthetic derivatizati- synthetic building block as substrate and identify new molecules with interesting on of polyketides, yielding compounds with the intended modified biosynthesis fails. antibacterial or anti-tumor activities. altered biological activities. We recently introduced the enzyme-direc-

Fig. 1: Via site-directed mutagenesis of key enzymes from the biosynthetic pathway, predictable redox derivatives of the parent compound pre- monensin are synthesized in the bacterium Streptomyces cinnamonensis. [2]

ted mutasynthesis as a concept to engineer Artificial Functionalization the substrate specificity of key enzymes of Natural Products from polyketide biosynthesis facilitate the acceptance of malonic acid-based building Biosynthetic pathways bring about blocks into a natural product. In a first stu- structural complexity but are inflexible in dy, organic synthesis, enzyme engineering comparison to synthetic organic chemistry. and fermentation technology are combined 37

Fig. 3: In enzyme-directed mutasynthesis, engineered enzymes are utilized inside a microbial producer to accept synthetic building blocks as substrates for the targeted derivatization of a natural product, in this case the antibiotic erythromycin A. [3]

Selected Publications

[1] U. Sundermann, S. Kushnir, F. Schulz, Nach. Chem. 2011, 59, 29-35. [2] S. Kushnir, U. Sundermann, S. Yahiaoui, A. Brockmeyer, P. Janning, F. Schulz, Angew. Chem. Int. Ed. 2012, 51, 10664- 10669. [3] a) U. Sundermann, K. Bravo-Rodriguez, S. Klopries, S. Kushnir, H. Gomez, E. Sanchez-Garcia, F. Schulz, ACS Chem. Biol. 2013, 8, 443-450; b) S. Klopries, U. Sundermann, F. Schulz, Beilstein J. O. C. 2013, 9, 664-674. [4] a) J. Arens, D. Bergs, M. Mewes, J. Merz, G. Schembecker, F. Schulz, Mycology 2014, 1-13; b) J. Arens, B. Engels, S. Klop- ries, S. Jennewein, C. Ottmann, F. Schulz, Chem. Commun. 2013, 49, 4337-4339. Fig. 4: Baker’s yeast is genetically engineered to produce fusicoccadiene (FCdiene) from the fungus Phomopsis amygdali. It carries several mutations in its primary metabolism (mevalonic acid pathway) to channel biosynthetic capability towards the targeted compound. [4]

Heterologous Fermentation bers of the terpenoids family of natural of Terpenes products. We express key enzymes towards terpenes in baker’s yeast to synthesize In many cases, natural sources do not preparative amounts of the corresponding provide enough material to investigate compounds in synthetically meaningful the promising biological activity of natural quantities. products. This is particularly true for mem-

Frank Schulz was appointed professor of organic Foundation of the Chemical Industry (FCI) and was chemistry at the Ruhr-University Bochum in au- later on appointed Beilstein-Professor of Organic tumn 2013. He received his diploma degree in che- Chemistry at the TU Dortmund. Research in his mistry in 2003 and the Dr. rer. nat. under supervi- group focuses on the derivatization of natural pro- sion of Manfred T. Reetz in 2007. Subsequently, he ducts using synthetic, fermentative and enzymolo- moved to the Department of Biochemistry at the gical approaches. University of Cambridge into the group of Peter F. Leadlay where he investigated the mechanism of stereospecificity in polyketide synthases. In 2009 he moved to the Max-Planck Institute of Molecular Physiology in Dortmund as Liebig Fellow of the 38

Physical Organic Chemistry: Understanding Reactions

Prof. Dr. Wolfram Sander, Lehrstuhl für Organische Chemie II

Chemistry is the science of changes of the hydroxyl radical and benzene. [1] The and studied during the past years. The matter, and thus chemical reactions are at reactions of these radicals are not only prediction weather or not QMT is involved the very heart of chemistry. The focus of the important for organic synthesis but also for in a chemical reaction is still challenging. research of the Sander groups is on the ex- tropospheric chemistry, combustion, and The work of the Sander group helps to ploration of reaction mechanisms, thus in- oxidation processes in living cells. find generalizable and predictive rules for vestigating details of reactive intermediates, tunneling reactions. their interactions and reactions. To achieve A combination of several radical centers this goal, modern methods of chemical results in polyradicals [3] such as the trime- Non-Covalent synthesis, spectroscopy, and computational thylenebenzene [4] shown in Figure 1. These Chemistry and Solvation chemistry are combined. The spectroscopic polyradicals show unusual reactivity and methods include matrix isolation spectro- magnetic properties and find applications The chemistry in condensed phase is scopy, time resolved spectroscopy, EPR, and as building blocks for organic magnetic dominated by non-covalent interactions, advanced IR spectroscopy. Unusual media materials. Molecular magnets with up to and therefore are of key importance for for performing reactions used by the group six unpaired electrons and septet electronic the understanding of chemical reactions. are solvents at extremely low temperature, ground states could been synthesized and An example is the unfolding of a peptide, rare gases such as neon, parahydrogen, or characterized. [5] that is governed by the interplay between amorphous water ice. internal and external hydrogen bonds. [8] A Tunneling in Chemistry detailed analysis allowed the scientists to From Radicals to unravel the solvent effects that control the Molecular Magnets While quantum mechanical tunneling conformation of peptides. (QMT) was recognized as a an interesting Radicals are formed by homolysis of che- phenomenon that might influence reaction mical bonds, and their reactivity strongly rates decades ago, it is still regarded as so- depends on substituents at the radical mehow exotic to most chemists. However, center. A prototype of a highly reactive more and more evidence is found that tun- radical is the phenyl radical, [1] a typical neling not only influences the kinetics, but V-radical, while the benzyl radical or the also the selectivity of chemical reactions. phenoxyl radical, [2] typical S-radicals, are far Low temperature spectroscopy is ideal to less reactive. Important reactions of these investigate tunneling, since the competing radicals include reactions with solvent thermal reactions are suppressed at low molecules, molecular oxygen and hydro- temperatures. [6-7] In particular, for hydrogen gen, carbonmonoxyde etc. An interesting Fig. 3: Crystal structure of a cyclic peptide finding was that the highly reactive phenyl that was synthesized for conformation radical is able to abstract hydrogen atoms studies. from water to form a complex between Solvent-solute interactions are in particular difficult to understand at the molecular level, and therefore this is studied within the framework of the Cluster of Excellence RE- SOLV using the tools of physical organic chemistry. Strong solvent effects are observed for all reactions where during the course of a reaction a charge-separation takes place. [9] Intriguing solvent effects were found for Fig. 2: Electron density difference plot before the solvation of highly reactive carbenes. and after a tunneling reaction. The colors Dilution of methanol in an inert medium at show how electron density is shifted during very low temperatures results in diffusion QMT. [6] controlled reaction while bulk methanol is completely inert at the same temperature. Fig. 1: Spin density distribution in trime- abstractions and hydrogenations with mo- [10] This demonstrates the high non-linearity thylene benzene (TMB). The molecule was lecular hydrogen large tunneling contribu- of solvent mixtures. This work resulted in synthesized in an argon matrix at 3 K and tions are observed. A number of tunneling the development of a new method for the investigated by IR, UV-vis, and EPR spectro- reactions, including both hydrogen and stabilization of highly reactive cations: isola- scopy. heavy atom tunneling, were discovered tion in amorphous water ice. 39

[4] P. Neuhaus, W. Sander, Isolation and characterization of the triradical 1,3,5-tri- methylenebenzene, Angew. Chem., Int. Ed. 2010, 49, 7277-7280. [5] W. Sander, D. Grote, S. Kossmann, F. Neese, 2,3,5,6-Tetrafluorophenylnitren- 4-yl: electron paramagnetic resonance spectroscopic characterization of a quartet-ground-state nitreno radical, J. Am. Chem. Soc. 2008, 130, 4396-4403. [6] S. Henkel, Y. A. Huynh, P. Neuhaus, M. Winkler, W. Sander, Tunneling rearrangement of 1-azulenylcarbene, J. Am. Chem. Soc. 2012, 134, 13204-13207. [7] P. Costa, W. Sander, Hydrogen Bonding Switches the Spin State of Diphenyl- carbene from Triplet to Singlet, Angew. Chem., Int. Ed. 2014, 53, 5122-5125. [8] C. Kolano, J. Helbing, M. Kozinski, W. San- der, P. Hamm, Watching hydrogen-bond dynamics in a beta-turn by transient two-dimensional infrared spectroscopy, Nature 2006, 444, 469-472. [9] M. Sajid, A. Lawzer, W. Dong, C. Rosorius, W. Sander, B. Schirmer, S. Grimme, C. G. Daniliuc, G. Kehr, G. Erker, Carbonylation reactions of intramolecular vicinal frus- trated phosphane/borane Lewis pairs, J. Fig. 4: The fluorenyl cation shown here is highly stabilized, and in methanol at room tempera- Am. Chem. Soc. 2013, 135, 18567-18574. ture shows a lifetime of only 5 picoseconds. In contrast, it is indefinitely stable in amorphous [10] P. Costa, M. Fernandez-Oliva, E. Sanchez- water ice at temperatures below 30 K. Garcia, W. Sander, The highly reactive benzhydryl cation isolated and stabilized Selected Publications [2] W. Sander, S. Roy, I. Polyak, J. M. Ramirez- in water ice, J. Am. Chem. Soc. 2014, 136, Anguita, E. Sanchez-Garcia, The phen- 15625-15630. [1] A. Mardyukov, E. Sanchez-Garcia, R. oxyl radical-water complex-a matrix Crespo-Otero, W. Sander, Interaction isolation and computational study, J. and reaction of the phenyl radical with Am. Chem. Soc. 2012, 134, 8222-8230. water: a source of OH radicals, Angew. [3] M. Winkler, W. Sander, Triradicals, Acc. Chem., Int. Ed. 2009, 48, 4804-4807. Chem. Res. 2014, 47, 31-44.

Wolfram Sander is a Professor of Organic Che- intermediates, organic high spin molecules, and mistry at the Ruhr-Universität Bochum (RUB). He non-covalently bound species using a variety of obtained his Ph.D. at the University of Heidelberg experimental and computational techniques. in 1982 and was a postdoctoral fellow at UCLA with Prof. O. L. Chapman from 1982 to 1984. He was Associated Professor at the Technische Universität Braunschweig from 1990 to 1993 before accepting his present position in 1993. In 2007 he received the Adolf-von-Baeyer Gold Medal of the German Chemical Society (GDCh). His main research interest in the field of Physical Organic Chemistry is the investigation of reactive 40

Metals in Catalysis and Self-Organization

Prof. Dr. Gerald Dyker / Organic Chemistry

The Dyker group’s research is focused on preparative Organic Chemistry, with special emphasis on the application of stoichiometric as well as catalytic organometallic methods.

The target structures range from extended S-systems to steroid frameworks and functionalized molecular cavities:

Gold- and Platinum-Catalyzed Chiral Transition Metal Complexes Domino Processes Based on pentaarylcyclopentadienes ru- Alkynes are effectively activated by gold- thenium complexes - chelated by a chiral and platinum chloride for the attack of va- oxazoline moiety – were developed, which rious carbon, oxygen and nitrogen nucleo- exhibit a second chiral center directly at the philes. [1] For an intramolecular process even metal. [8] ketones and aldehydes are nucleophilic enough to generate benzopyrylium intermediates, which can be readily trapped by cycloaddition reactions, f.i. for the synthesis Self-Organization of terpenoids and for building up a steroid of Molecular Cavities framework. [2-3] The straight forward synthesis of heliophenanthrone illustrates this A fourfold Sonogashira coupling reaction fascinating type of rearrangement. [4] with a chiral propargylic alcohol let to the formation of a functionalized calixarene, which formed hydrophilic channels with a helical symmetry in the crystal lattice. Thus point chirality is translated to helical chirality. [6] Agostic and Anagostic Interactions

While agostic interactions are often involved in transition metal catalyzed CH activation processes, the rare anagostic interactions may cause significant anisotro- pic downfield shifts in proton NMR spectra. Due to the through space interaction of hydrogen atoms with the electron sphere of chelated palladium salts the signal of aliphatic CH groups was registered at up to 8.5 ppm, the signals of aromatic CH- groups at up to 11.1 ppm. [9]

Functionalized For the self-organization of a pyridyloxy-ca- Pentaarylcyclopentadienes lixarene to hexameric supracycles the complexation of palladium dichloride under- A palladium-catalyzed multifold arylation neath the lower rim is crucial, triggering the opens up a new entry to sterically shielded geometric alignment of the pyridyl moieties cyclopentadienes. [5] as well as their electronic properties. [7] 41

Selected publications [4] G. Dyker, D. Hildebrandt, Total Synthesis [7] G. Dyker, M. Mastalerz, K. Merz, A Hexa- of Heliophenanthrone, J. Org. Chem. meric Supracycle from a Calix[4]arene, [1] G. Dyker, D. Hildebrandt, D. Kadzimirsz, 2005, 70, 6093-6096. Eur. J. Org. Chem. 2003, 4355-4362. K.Merz, Isoindoles and Dihydroisoquino- [5] G. Dyker, J. Heiermann, M. Miura, S. [8] M. Kanthak, A. Aniol, M. Nestola, K. lines by Gold-catalyzed Intramolecular Pivsa-Art, T. Satoh, M. Nomura, Palladium Merz, I. M. Oppel, G. Dyker, Chelated Hydroamination of Alkynes, Chem. Com- Catalyzed Arylation of Cyclopentadienes, Ruthenium Complexes of Functionalized mun. 2006, 661-662. Chemistry Eur. J. 2000, 6, 3426-3433. Pentaarylcyclopentadienes, Organome- [2] G. Dyker, D. Hildebrandt, J. Liu, K. Merz, [6] M. Mastalerz, H. J. E. Rivera, I. M. Oppel, tallics 2011, 30, 215-229. Gold(III)chloride Catalyzed Domino Pro- G. Dyker, Supramolecular single-stranded [9] S. Schöler, M. H. Wahl, N. I. C. Wurster, A. cesses with Intermediary Isobenzopyry- calix[4]arene helices—towards a crystal Puls, C. Hättig, G. Dyker, Bidentate Cycloi- lium Salts, Angew. Chem., Int. Ed. Engl. engineering approach of homochiral midate Palladium Complexes with aA- 2003, 42, 4399-4402. assemblies, CrystEngComm 2011, 13, liphatic and Aromatic Anagostic Bonds, [3] G. Dyker, D. Hildebrandt, A Gold-Cataly- 3979-3982 Chem. Commun. 2014, 50, 5909-5911. zed Domino Process to the Steroid Frame- work, J. Org. Chem. 2006, 71, 6728-6733.

Gerald Dyker studied chemistry at Dortmund versity in 1995 as associate professor of Organic University. After completing his dissertation on and Organometallic Chemistry. In 2000 he joined nitrogen and sulfur heterocycles in 1988 under the the Faculty of Chemistry and Biochemistry at the guidance of R. P. Kreher he developed ruthenium Ruhr-Universität Bochum. catalyzed reactions with B. M. Trost at Stanford University. As research chemist at Bayer AG, Monheim, he worked in the fields of veterinary pharmaceuticals and agricultural chemistry. He finished his habilitation at the Technical University of Braunschweig in 1994, moved to Duisburg Uni-

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Reactions of molecules on hybrid surfaces

Prof. Dr. Karina Morgenstern | Chair for Physical Chemistry I | Ruhr-Universität Bochum

The far reaching goal of the research in the lar switch in future molecular electronics; as in living organisms proceed in a humid group of Karina Morgenstern at the Chair mainly, but not exclusively, constitutional, environment. In our group, the structure for Physical Chemistry I is to modify metallic configurational, and geometric isomerisati- of water grown at different parameters on and dielectric surfaces on the nanoscale on reactions [4]. metallic and salt surfaces was investigated by systematically employing strain and with respect to formation, restructuring quantum-size effects and modify the im- The isomerisation is induced either by light with temperature and electron solvation [6]. mediate chemical environment in order to or by electrons, from the STM tip. Some With the aid of the tunnelling electrons we promote non-adiabatic reactions on these reactions are similar to those observed for also produced amorphous ice clusters from nanostructures into a desired direction. For the molecule in the gas phase, but some adsorbed water molecules, then crystal- this aim, the different parts of the system, are observed or even possible only on a lized the clusters, dissociated the water the support, the nanostructures, the adsorp- surface. The detailed investigation of the molecules, and finally oxidized the surface. tion of molecules on the support and on the isomerisation yield dependence on several nanostructures have to be characterized parameters gives insight into the underly- Combinations and understood in detail. The research is ing processes of the reaction [4]. A miniature mainly performed with scanning tunneling switch, consisting just of the reorientation The isomerisation reactions were repeated microscopy. of one single bond within a molecule has on NaCl layers [7], the water was attached to been recently realized [5]. several azobenzene derivatives [8]. In future, Geometrical and electronic structure of nanostructures

Model systems were utilized to gain a profound understanding of ripening phenomena on metallic surfaces. Effects of both quantum-size effects and strain were recently described for the systems NaCl/ Ag(111) [1] and Cu/Ag(100) [2].

Fig. 2: Electron induced rotation of a OH group of an adsorbed di-hydroxy-azobenzene adsorbed on Au(111).

Water we will investigate the influence of the solvent onto the reaction on the nanostruc- Water is all around us. It wets surfaces and tured surface. many reactions in the troposphere as well Selected publications

Fig. 1: Dependence of effective mass on [1] Size dependence of the dispersion island size for NaCl grown on Ag(111). Insets relation for the interface state between reveal electronic standing wave pattern in NaCl(100) and Ag(111), S. Heidorn, A. dI/dV maps of two islands of different sizes. Sabellek, K. Morgenstern, Nano Letters, 14, 13 (2014). Also the phonon structure of the surfaces is [2] Quantitative determination of a nano- investigated locally [3]. object's atom density without atomic resolution, C. Zaum, J. Meyer, K. Reuter, Functional molecules K. Morgenstern, Phys. Rev. B 90, 165418 on metal surfaces (2014); Anomalous Scaling in Heteroepi- taxial Islands Dynamics on Ag(100), Ch. Electronic switches are essential as basic Zaum, M. Rieger, K. Reuter, K. Morgen- components for storage and logical ope- stern, Phys. Rev. Lett. 107, 046101 (2011). rations. We investigated isomerisation [3] Local determination of the amount of reactions of single molecules adsorbed on Fig. 3: Extended water structure grown on integration of an atom into a crystal surfaces that have a potential as a molecu- Cu(111). surface, K. Volgmann, H. Gawronski, Ch. 43

Zaum, G. Rusina, S. Borisova, E. Chulkov, Karina Morgenstern, Nature Communi- cations 5, 5089 (2014). [4] Switching individual molecules by light and electrons: From isomerisation to chirality flip, K. Morgenstern, Prog. Surf. Sci. 86, 115 (2011). [5] Reorientation of a Single Bond within an Adsorbed Molecule by Tunneling Elect- rons, J. Henzl, K. Boom, K. Morgenstern, J. Am. Chem. Soc. 135, 11501 (2013). [6] Local Investigation of Femtosecond Laser Induced Dynamics of Water Nanoclus- ters on Cu(111), M. Mehlhorn, J. Carras- co, A. Michaelides, K. Morgenstern, Phys. Rev. Lett. 103, 026101 (2009); Electron Damage to Supported Ice Investigated by Scanning Tunneling Microscopy and Spectroscopy M. Mehlhorn, H. Gaw- ronski, K. Morgenstern, Phys. Rev. Lett. 101, 196101 (2008); Manipulation and Control of Hydrogen Bond Dynamics in Bovensiepen, M. Meyer, D. Kusmierek, K. 104, 216102 (2010). Adsorbed Ice Nanoclusters, H. Gawron- Morgenstern, M. Wolf, Phys. Rev. Lett. 98, [8] Using the first steps of hydration for the ski, J. Carrasco, A. Michaelides, K. Mor- 206105 (2007). determination of molecular conforma- genstern, Phys. Rev. Lett. 101, 136102 [7] Isomerization of an Azobenzene Deriva- tion of a single molecule, J. Henzl, K. (2008); Impact of Ice Structure on Ultra- tive on a Thin Insulating Layer by Inelas- Boom, K. Morgenstern, J. Am. Chem. Soc. fast Electron Dynamics in D2O Clusters tically Tunneling Electrons, A. Safiei, J. 136, 13341 (2014). on Cu(111); J. Stähler, M. Mehlhorn, U. Henzl, K. Morgenstern, Phys. Rev. Lett.

Karina Morgenstern has been full professor of Lausanne, Aarhus, and Berlin she finished her physical chemistry at the Ruhr-Universität Bochum Habilitation in Experimental Physics at the FU since 2012 after having been a full professor of Berlin in 2002, where she stayed with the aid of a solid state physics at the Leibniz University of Heisenberg fellowship till 2005. She received the Hannover from 2005 to 2012. She studied physics Günther-Leibfried-Preis of Forschungszentrums and computer science at the Friedrich-Wilhelm- Jülich in 1997 and the Hertha-Sponer-Preis of the Universität Bonn and the University of Tennesse in German Physical Society in 2002. Knoxville and received her PhD from the University in Bonn in 1993 having performed her thesis work predominantly at the Forschungszentrum Jülich and partly at the Universitet Aarhus in Denmark. After Postdoctoral stays at the Universities in

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Biophysical Chemistry: Protein Interactions

Prof. Dr. Christian Herrmann / Physical Chemistry 1, Ruhr-University Bochum

Proteins interacting with small molecules, Hofmeister type rankings of anions and ca- tached to the membrane surface through lipid membrane systems or other protein tions were established [2,3] (Fig. 1). In another hydrophobic anchors. Interferon-induced binding partners are characterized in terms study we were able to demonstrate that the human Guanylate Binding Protein 1 repre- of affinity and specificity as well as binding crowding effect on protein folding stability sents a multidomain protein (Fig. 3). We kinetics. In addition, the role of water and for some compounds is based on enthalpy have characterized its enzymology as well of co-solvents and co-solutes in defining the changes while other crowding compounds as structural changes which could be shown thermodynamic characteristics of the obove- exert their impact on protein stability by to be coupled to nucleotide binding and hy- mentioned interactions is investigated by shifting entropic contributions [4]. drolysis [7-10]. Most intriguingly, we observe employing biophysical techniques like micro- nucleotide dependent membrane attach- calorimetry, fluorescence stopped flow and Binding induced protein folding ment which may be crucial for the antipa- temperature jump. thogenic activity of this protein. Regulated turning on and off of enzymatic With the aim to understand biochemical activities and protein interactions is crucial processes on the molecular level our re- to many biological processes, e.g. cellular search work is devoted to the quantitative signal transduction. Our project aims at the characterization of protein complex forma- analysis of the changes of structure and dy- tion. Fundamental features are addressed namics of multi-protein complexes involved like the impact of the interaction of the in signaling in order to understand the mo- solvent with the protein surface as well as lecular mechanism of differentiation bet- the thermodynamics and kinetics of more ween multiple pathways. In particular, we Fig. 3: X-ray structure of human Guanylate complex biochemical systems like nucleoti- have investigated a family of proteins har- Binding Protein 1 revealing three protein dode dependent protein oligomerisation and boring a short helical domain which beco- mains. lipid membrane attachment. mes structured after homo- or heterodimer formation [5,6] (Fig. 2). In recent years intrin- Our research work is conducted in the Ionic co-solutes and crowding sically unfolded proteins have emerged as a framework of various cooperations within compounds in protein stability new biochemical feature which may adopt the excellence cluster RESOLV at the Ruhr- to a multitude of binding partners and the- University and within the SFB 642. Financial As we and others have shown for various ex- reby may fulfill various functions. support from Deutsche Forschungsgemein- amples the strength of interaction between schaft and from the 7th EU framework pro- proteins is strongly reduced by the addition Nucleotide dependent protein gramme is gratefully acknowledged. of salt to the solution the extent of which interactions at membranes depends on the number of charge based interactions on the protein surfaces. In our A large number of proteins is known to re- recent studies we could demonstrate that side within a lipid membrane or to be at- the nature of the salt may also have a strong impact on protein interaction and stability [1]. In particular, for a number of ionic liquid compounds employed as co-solutes in protein stability and enzymatic activity assays

Fig. 1: Thermograms from differential scanning calorimetry of ribonuclease A in the presence of various ionic liquid compounds (see Fig. 2: Folding of an alpha-helical domain induced by homodimer formation as indicated by CD ref. 2). spectroscopy at increasing protein concentrations from top to bottom at 222 nm (see ref. 5-6). 45

Selected Publications [5] D. Constantinescu, C. Makbul, A. Kotu- [8] A. Kerstan, T. Ladnorg, C. Grunwald, T. renkiene, M.B. Lüdemann, C. Herrmann, Vöpel, D. Zacher, C. Herrmann, C. Wöll, [1] D. Constantinescu, C. Herrmann, H. “Dimerization-induced folding of MST1 “hGBP1 as a model system investigated Weingärtner, “Patterns of Protein Unfol- SARAH and the influence of the intrin- by several surface techniques”, Biointer- ding and Protein Aggregation in Ionic Li- sically unstructured inhibitory domain: phases 5, 131-138 (2010) quids”, Phys. Chem. Chem. Phys. 12, 1756- low thermodynamic stability of mono- [9] A. Syguda, A. Kerstan, T. Ladnorg, F. Stü- 1763 (2010) mer”. Biochemistry 50, 10990-11000 ben, C. Wöll, C. Herrmann, “Immobiliza- [2] D. Constantinescu, H. Weingärtner, C. (2011) tion of biotinylated hGBP1 in a defined Herrmann, “Protein Denaturation by Io- [6] C. Makbul, D. C. Aruxandei, E. Hofmann, orientation on surfaces is crucial for nic Liquids and the Hofmeister Series: A D. Schwarz, E. Wolf, C. Herrmann, “Struc- uniform interaction with analyte prote- Case Study of Aqueous Solutions of Ri- tural and thermodynamic characteri- ins and catalytic activity”, Langmuir 28, bonuclease A”, Angew. Chem. Int. Ed. 46, zation of Nore1-SARAH: a small, helical 6411-6418 (2012) 8887-8889 (2007); Angew. Chem. 119, module important in signal transduction [10] T. Vöpel, C. S. Hengstenberg, T. O. Peulen, 9044-9046 (2007) networks”. Biochemistry 52, 1045-1054 Y. Ajaj, C. A. Seidel, C. Herrmann, J. P. Kla- [3] H. Weingärtner, C. Cabrele, C. Herrmann, (2013) re, “Triphosphate Induced Dimerization “How ionic liquids can help to stabilize [7] T. Vöpel, A. Syguda, N. Britzen-Laurent, of Human Guanylate Binding Protein 1 native proteins”, Phys. Chem. Chem. Phys. S. Kunzelmann, M. B. Lüdemann, C. Do- Involves Association of the C-Terminal 14, 415-426 (2012) vengerds, M. Stürzl, C. Herrmann, “Me- Helices: A Joint Double Electron-Electron [4] M. Senske, L. Törk, B. Born, M. Havenith, chanism of GTPase-activity-induced self- Resonance and FRET Study”. Biochemistry C. Herrmann, S. Ebbinghaus, “Protein sta- assembly of human guanylate binding 53, 4590-4600 (2014) bilization by macromolecular crowding protein 1”, J. Mol. Biol. 400, 63-70 (2010) through enthalpy rather than entropy”. J. Am. Chem. Soc. 136, 9036-9041 (2014).

Christian Herrmann has been Professor for Physical Institute for Molecular Physiology in Dortmund un- and Biophysical Chemistry at Ruhr University Bo- til 2003. For more details see www.rub.de/proin chum since 2003. After studying chemistry he received his doctoral degree under the supervision of W. Knoche from the University in Bielefeld in 1991 as well as his habilitation in 2001. After a postdoctoral stay with T. Barman and F. Travers from 1991- 1993 at INSERM/CNRS in Montpellier he joined the department of Fred Wittinghofer at the Max Planck

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Physical Chemistry: From Microsolvation to Bulk Water Dynamics

Prof. Dr. Martina Havenith - Department of Physical Chemistry II, Ruhr University Bochum

The research of the Havenith group is deeply as the solvation of ions and biomolecules machine, allowing the successive solvation embedded within the Cluster of Excellence on a microscopic level. The research spans of solutes with single water molecules. A RESOLV. The majority of chemical reactions, a wide gap between the microsolvation of superfluid helium droplet creates an envi- including many that are central to important single molecules and bulk solvation of large ronment which facilitates the formation

industrial and virtually all biological proces- biomolecules in our laboratory. of (HCl)m(H2O)n clusters under controlled ses, take place in a liquid-state environment. conditions at 0.37 K. The droplets are for- The Havenith group has developed IR and THz The helium droplet – An ultracold med by expansion of high-pressure helium laser technologies to address solvation on trap for individual molecules gas through a small cooled nozzle into a a molecular scale. The group has pioneered vacuum; they have a temperature of 0.37 THz spectroscopy as a new tool to probe the The Havenith group has set up a high-reso- K and contain about 10,000 helium atoms collective hydration dynamics of ions and lution IR laser spectrometer and combined that are basically frictionless. These helium biomolecules. This has led to insights as to it with a suprafluid helium nanodroplet droplets serve as an ultracold trap, which the role of water in biological function and transcended the traditional view of water as an inert medium, acting solely as a passive spectator. Water molecules and the coupling of the protein to the solvent are now increasingly recognized as playing an active role in their own right. Recent experimental advances in combination with theoretical progress made in the Havenith group in this newly emerging field have shown the great potential “Solvation Science” has. Additionally, time resolved Kinetic THz absorption spectroscopy (KITA) has been developed in the group. KITA allows changes in the coupled protein/hydration dynamics during biological function to be probed in real time. Unraveling the microscopic contribution of water as an “active” solvent to fundamental biomolecular processes is a vital ingredient towards achieving an understanding of molecular recognition and, thus, a step towards to de novo enzyme synthesis. Within RESOLV, the Havenith group is dedicated to establishing “Solvation Science” as a research field in its own right.

Laser technology to probe solvation dynamics

The Havenith group has set up a number of state-of-the-art laser spectrometers, some of which are unique. This incorporates 3 Terahertz (THz) absorption spectrometers, including a high power (2W) p-Ge difference spectrometer, an infrared (IR)-near- field microscope in the chemical finger- print region and a high power IR Optical Parametric Oscillator for the high resolution IR spectroscopy of clusters embedded in superfluid helium nanodroplets. Within the last years, the group has used these cutting-edge laser technologies to explore Fig. 1: Aggregation induced dissociation of HCl. Shown is the cluster formation within the fundamental questions in chemistry such suprafluid helium nanodroplet upon successive pick up of single water molecules. 47

can catch single molecules, cool them This heterogeneous hydration, or more KITA – monitoring down to 0.37 K and retain them inside the specifically, a gradient of hydrogen bond real-time hydration dynamics cluster interior, where they bond one by dynamics towards the catalytic site of enzy- one to form molecular aggregates of well- mes is postulated to assist molecular recog- In Bochum, our group has set up the controlled sizes, or where reactions can nition. Up to now, the solvent has been an first-ever experiment able to observe take place at ultracold conditions (Figure 1). underestimated or even neglected element changes in solvation dynamics in real time Furthermore, the cold environment allows of the multilateral partnership that makes during biological function, namely kinetic one to obtain spectra with only a few quan- up biomolecular function. THz absorption spectroscopy (KITA), see tum levels populated. The spontaneous dis- + - sociation of HCl into (H3O) (H2O)n-1 and Cl is a classic textbook example: Combining IR laser techniques with the suprafluid helium apparatus means that acid formation can now be observed on the level of a step wise aggregation process. [1]

Terahertz laser spectroscopy – bulk water dynamics

Prof. Havenith’s group has pioneered THz absorption spectroscopy as a new, powerful tool able to study solute/solvent interaction. Using state of the art THz spectrometers, including a unique p-Ge spectrometer (2.4-2.7 THz), an FT spectrometer (50 - 500 cm-1), and time domain THz spectrometers Fig. 2: Schematic representation of the hydration funnel, i.e. the retardation of the hydrogen (0-2 THz) allowed the detection of subtle bond dynamics of the water molecule in an enzyme-substrate complex (the enzyme is shown changes in the dynamical orientation of in grey, the substrate in green, and the retarded water molecules in red) (left-hand side) and water molecules by giving direct access to for the insect antifreeze protein AFP III (the ice binding site with the regular spaced threonine collective water network dynamics. [2,3] is shown in yellow, and the retarded water molecules in red) (right-hand side).

Hydration funnel facilitates Antifreeze proteins keep fish Figure 3. [7] Dynamical processes such as substrate binding in enzymes alive in sub-zero surroundings protein folding are initiated by stopped- flow mixing and the subsequent changes Although it was initially thought that enzy- An important example for this new con- in solvation dynamics are mapped in real matic catalysis could be attributed to direct cept of assisted molecular binding by a time using a THz time domain spectrome- structural interactions between enzymes hydrogen dynamics funnel was given for ter. In a proof-of-principal experiment we and substrates, it is now becoming widely the ice-binding site of antifreeze proteins. could show that changes in water dynamics accepted that the functions of enzymes Antifreeze proteins are found in some considerably precede the acquisition of a are mediated by their dynamic character vertebrates and ensure their survival in native-like structure during protein folding. and by interactions with the solvent. In sub-zero environments, e.g. certain types We could map the changes in the low fre- particular, there is ongoing research aimed of fish in the Antarctic (Figure 2). Although quency spectrum during protein folding and at elucidating the dynamical features of the antifreeze activity of several types of enzyme/substrate docking. [4,5,6,7] protein-water coupling on the picose- antifreeze proteins has been characterized, cond timescale (corresponding to the THz the details of the mechanism at the mole- spectral range), as many processes in water cular level remained controversial. With the occur on this timescale. In joint THz spect- help of THz spectroscopy, CD spectroscopy roscopy and classical molecular dynamics and accompanying MD simulations, our simulation studies of model enzymes and group showed that the antifreeze activity human membrane type-1 matrix metallo- of AFPs can be attributed to two distinct proteinase a steep gradient of fast-to-slow molecular mechanisms: (i) a short-range di- coupled protein-water motions towards rect interaction of the protein surface with the active site and substrate was obser- the growing ice face and (ii) a long-range ved – the so-called “hydration funnel” (see interaction through protein-induced water Figure 2). It has been proposed that the dynamics extending up to 20 Å (5 – 7 water observed gradient may assist enzyme- shells) from the surface of the AFP protein. substrate interactions. [4,5] [6] These important findings could change the way in which enzymes and drugs are designed in the future. Fig. 3: Professor Havenith calibrating the KITA laser (Copyright: RUBIN, Foto: Nielinger). 48

Raman microscopy detailed images of the tissue and grants us Terahertz Absorption Spectroscopy in major insights into the structure of both conjunction with Molecular Dynamics Chemical microscopy is used in our group for healthy and diseased tissues. Simulations”, J. Am. Chem. Soc. 136, the label-free characterization of surfaces: 12800 (2014). For more details see www.rub.de/pc2 [5] M. Grossmann et al. “Correlated structu- Interfaces: We were able to characterize ral kinetics and retarded solvent dyna- local opto-mechanical forces generated Selected Publications mics at the metalloprotease active site”, within photosensitive azobenzene contai- Nature Structural & Molecular Biology ning polymer films by a red shift of the G [1] A. Gutberlet et al. “Aggregation Induced 18, 1102 (2011). [6] band of graphene. This graphene-based Dissociation of HCl (H2O)4 below 1K: The K. Meister et al. “Long-range protein–wa- nanoscopic gauge opens new possibilities Smallest Droplet of Acid”, Science 324, ter dynamics in hyperactive insect anti- to characterize opto-mechanical forces 1545 (2009). freeze proteins”, PNAS 110, 1617 (2013). generated within photosensitive polymer M. Letzner et al. “High resolution [7] S.J. Kim et al. “Real-time detection of films. [8] spectroscopy of HCl–water clusters: IR protein-water dynamics upon protein bands of undissociated and dissociated folding by Terahertz absorption”, Angew. Plasma medicine: Patients with chronic, clusters”, J. Chem. Phys., 139, 154304/1- Chem. Int. Ed. 47, 6486 (2008). non-healing wounds often suffer severe 11 (2013). [8] G. Di Florio et al. “Graphene multilayer physical and emotional stress, however, [2] U. Heugen et al. “Solute-induced as nano-sized optical strain gauge for treatment with so-called "cold plasma" can retardation of water dynamics probed polymer surface relief gratings”, Nano improve their condition considerably. It’s directly by THz spectroscopy”, PNAS 103, Letters 14, 5754 (2014). not yet known just how the plasma inter- 12301 (2006). [9] J. Sun et al. “Understanding THz Spectra acts on a molecular level with living cells or, [3] S. Funkner et al. “Watching the low of Aqueous Solutions: Glycine in Light indeed, tissues like our skin; this requires frequency motions in aqueous salt and Heavy Water”, J. Am. Chem. Soc. more scientific research. In our group, we solutions – the terahertz vibrational si- 136, 5031 (2014). utilize the confocal Raman microscopy gnatures of hydrated ions”, J. Am. Chem. [10] M. Heyden et al. “Dissecting the THz technique to examine living cells in their Soc. 134, 1030 (2012) spectrum of liquid water from first natural environment and determine their [4] V. Conti Nibali et al. “New Insights into principles via correlations in time and chemical composition without destroying the Role of Water in Biological Function: space”, PNAS 107, 12068 (2010). the tissue itself. This enables one to obtain Studying Solvated Biomolecules using

Martina Havenith-Newen received her Dr. rer. nat. 220 invited lectures. Prof. Havenith has received degree in physics from the Rheinische Friedrich-Wil- numerous prizes acknowledging her work such as helms-University, Bonn in 1990 and her Habilita- the Heisenberg Grant, the Bennigsen Foerder Prize, tion in experimental physics in 1997. She has been the Human Frontier Science Award and the Innova- Professor of Physical Chemistry at the Ruhr-Uni- tion Prize of the RUB. Recently she has been awar- versity in Bochum since 1998. Prof. Havenith is a ded a Visiting Miller Professorship at UC Berkeley, member of the North Rhine-Westphalian Academy USA in combination with the Gabor A. und Judith of Sciences, Humanities and Arts and the German K. Somorjai Visiting Miller Professorship Award. National Academy of Sciences Leopoldina. In her She is founder and coordinator of the DFG funded research she has developed new laser technologies Cluster of Excellence RESOLV as well as a Centre of to explore fundamental questions in chemistry. She Molecular Spectroscopy and Simulation of Solvent has pioneered THz spectroscopy as a new tool to Controlled Processes (ZEMOS) at the Ruhr-Univer- probe the collective hydration dynamics of biomo- sity. She is advancing the field Solvation Science, lecules, leading to new insights into the role of wa- which aims to provide a unifying framework for ter in biological function. She has published more understanding and predicting solvent processes. than 170 research papers and has given more than For more details, see www.rub.de/pc2.

Biopolymers in vivo – from the test tube into the cell

Jun.-Prof. Dr. S. Ebbinghaus, Lehrstuhl für Physikalische Chemie II

Most biopolymers like proteins, DNA, and ments. Therefore, special in-cell techniques Protein stability in the crowded cell RNA molecules function inside the cell. The are used and the results are interpreted by Ebbinghaus group is interested in study- comparative in vitro experiments in cell-like Compared to the test tube where most ing biomolecular structure, function and environments and dilute solutions (Fig. 1). biochemical studies are conducted, cells aggregation directly in cellular environ- are highly crowded. The macromolecular 49

[2] S. Ebbinghaus, A. Dhar, J.D. McDonald and M. Gruebele. Protein folding stability and dynamics imaged in a living cell. Nat. Methods, 7:319-323, 2010. [3] M. Senske, S. Büning, S. Ebbinghaus. Un- derstanding the ‘native’ solvent – from the test tube into the cell. Bunsenmaga- zin, 6:276–281, 2014. [4] M. Gao, K. Estel, J. Seeliger, R.P. Friedrich, Fig. 1: Sequential workflow of analyzing in vivo experiments by comparative in vitro studies. S. Dogan, E.E. Wanker, R. Winter and Different cosolute effects are systematically studied in vitro to mimic the cellular environment. S. Ebbinghaus. Modulation of human IAPP fibrillation: Cosolutes, crowders concentration reaches 400 mg per ml of and promote protein aggregation. Future and chaperones. Phys. Chem. Chem. cytosol meaning that 1/3 of the available studies will show how crowding effects Phys., Advance Article, DOI: 10.1039/ volume in the cell is occupied by macromo- act on the organism level (e.g. C. elegans) C4CP04682J, 2015 lecules. Biomolecules behave differently and how cells utilize the cellular milieu to [5] S. Ebbinghaus and M. Gruebele. Protein under such conditions. For example, mac- actively control biomolecular function. Folding Landscapes in the Living Cell. J. romolecular crowding effects can stabilize proteins in the cellular environment compared to aqueous solution [1,2,3] and prevent protein aggregation [4]. Moreover, the stability varies within the cytoplasm of a single living cell [5] or between different compartments [6]. A high heterogeneity was found between different cells of a cell population [7].

The physicochemical origin of Fig. 2: Stabilization of ubiquitin by macromolecular crowding is mediated by enthalpic rather macromolecular crowding effects than entropic effects. Reprinted with permission from reference [1]. Copyright 2014 American Chemical Society. A central dogma in crowding theories was that crowding effects are solely mediated by The group is currently funded by the Minis- Phys. Chem. Lett., 2:314-319, 2011. hard-core repulsions between the macromo- try of Innovation, Science and Research of [6] A. Dhar, K. Girdhar, D. Singh, S. Ebbing- lecules and therefore steric excluded volume the State of North Rhine-Westphalia (Rück- haus and M. Gruebele. Protein Stability effects. This ideal excluded volume effect kehrerprogramm), the Cluster of Excellence and Folding Kinetics in the Nucleus and results in an entropic stabilization of the pro- RESOLV (EXC 1069) funded by the German Endoplasmic Reticulum of Eucaryotic tein while the enthalpy remains unchanged. Research Foundation (DFG), and by the Cells. Biophys. J., 101:1-10, 2011. However, using artificial crowding agents International Graduate School of Neurosci- [7] A. Dhar, S. Ebbinghaus, Z. Shen, T. Mishra like Ficoll 70 our group has recently shown ence (Ruhr-University Bochum, Germany). and M. Gruebele. The diffusion coeffici- that crowding effects on protein stability can ent for PGK folding in eukaryotic cells. be primarily mediated by enthalpic effects Selected Publications Biophys. J., 99:69-71, 2010. (Fig. 2) [1]. In the cellular environment, exclu- [8] D. Gnutt, M. Gao, O. Brylski, M. Heyden ded volume effects are further compensated [1] M. Senske, L. Törk, B. Born, M. Havenith, and S. Ebbinghaus. Excluded volume ef- by unspecific interactions [8]. However, hyper- C. Herrmann, S. Ebbinghaus. Protein Sta- fects in the living cell. Angew. Chem. Int. tonic stress can evoke significant excluded bilization by Macromolecular Crowding Ed., Accepted Manuscript, DOI: 10.1002/ volume effects that lead to high compres- through Enthalpy rather than Entropy. anie.201409847R1 sion forces acting on biomolecules in cells J. Am. Chem. Soc., 136(25): 9036–9041, [8]. Such effects could endanger proteostasis 2014.

Simon Ebbinghaus has been a Junior Professor Havenith. For more details, see www.rub.de/pc2/ at the Ruhr-University Bochum (Department of ebbinghaus. Physical Chemistry II) since 2011. Before that, he worked as a Feodor Lynen Research Fellow with Martin Gruebele at the University of Illinois (Urbana-Champaign) from 2008 to 2010. He received his Ph.D. (Dr. rer. nat.) from the Ruhr-University Bochum in 2007 under the supervision of Martina 50

Ultrafast photochemistry: In hot pursuit of chemical reactions

Prof. Dr. Patrick Nürnberger, Workgroup “Ultrafast photochemistry”, Physical Chemistry II

The group is concerned with the develop- The adequate timing of a further pulse ted versus sequential reaction mecha- ment and application of a variety of advan- may also give access to reactions which nisms can be disclosed [6,7]. ced femtosecond spectroscopy techniques necessitate an excitation to a higher-lying in order to identify the intermediates and electronic state [3] or a re-excitation after These kinds of experiments provide products of photochemical reactions. The intersystem crossing to a triplet state. valuable information for photochemical research aims to unravel and control the applications: for instance, the Wolff rear- primary dynamics induced by laser light in When transient absorption is not sufficient rangement and subsequent processes (Fig. systems relevant for synthesis, lithography, to reveal complex photo-induced dynamics, 2) are key reactions in UV photolithography, biology, and other fields of application. coherent multidimensional electronic spec- which are completed within a few nanose- Special emphasis is put to the impact of the troscopy can be used to further separate conds in room-temperature solution [7]. solvent environment as well as the role of the signal contributions originating from A further example is the photo-induced excess energy with regard to photodynami- different processes. The information about ligand release in organometallic comple- cal processes. the excited species is then intrinsically pre- xes (Fig. 3) which is of vital importance to served and hence an intuitive visualization understand the biological activity of these Deciphering ultrafast processes of the route from reactant to product is compounds that are relevant for therapeu- possible, e.g. in case that several absorbing tic applications [8]. Femtosecond spectroscopy has become species are initially present in solution and a very powerful tool for the investigati- only some of them can perform a certain Control of photochemistry on of photophysical and photochemical photoreaction [4]. phenomena. The characteristic time scales Femtosecond laser pulses do not consist of of fluorescence, electronic and vibrational Light-triggered reaction sequences monochromatic light but exhibit a broad coupling, charge and energy transfer, and spectrum. With pulse-shaping techniques, many further processes can be determi- Many ultrafast studies investigate purely the temporal ordering of these spectral ned with high accuracy. In the common photophysical effects or the dynamics components and their relative phase can be approach, a pump pulse triggers the of excited species until a bond is broken, adjusted in a well-defined way, so that the reaction and a probe pulse at an adjustable i.e. up to the first photochemical step. laser pulse can be tailored to the properties time delay monitors the progression of the However, often a multifaceted reaction of the molecular system. Depending on the reaction. By virtue of the short duration of sequence will set in after the bond cleava- pulse shape, a desired reaction path can be the laser pulses, the dynamics are followed ge. Utilizing sensitive ultrafast transient enhanced whereas unfavorable ones may in real time, and also quantum-mechanical absorption spectroscopy with vibronic be suppressed. In this way, bond-forming events like coherent wavepacket motion excitation and mid-infrared probing [5], reactions among small molecules in an (Fig.1) can be induced and observed [1]. intermediate species and the time scales adsorbate can be controlled [9]. associated with their formation can be By employing a pulse shaper for mid-in- identified, and it is possible to decipher frared laser pulses [10], the impact of excess how the reaction sequence proceeds. Due energy in certain vibrational modes on the to the characteristic vibrational signatures photoreaction and the possibility to there- of the possible intermediates, competing by manipulate its outcome is explored. reaction pathways or the issue of concer- The solvent’s role in ultrafast reactions

In various experiments, the group addresses the influence of the environment on ultrafast processes in solution, especially the Fig. 1: Transient absorption signal due to reaction dynamics in solvent mixtures and coherent wavepacket dynamics after excita- in the presence of cosolutes. The role of the tion of a merocyanine dye in solution [1]. solvent may be crucial: on the one hand, it influences the speed, yield and pathway of Additional insight into the photochemical the reaction; on the other hand, the solvent dynamics of a system can be achieved may even take part in the reaction, e.g. by by multipulse approaches. In case of a Fig. 2: Ultrafast reaction sequence of the reacting with a carbene or ketene interme- reversible functionality, e.g. in a molecular photoinduced Wolff rearrangement in 5-dia- diate (Fig. 2). For ultrafast energy transfer photoswitch, a second pump pulse can zo-Meldrum’s acid (upper left). The ketene or its localization in a system with excitonic be employed to investigate how fast the intermediate reacts with a solvent molecule character, the dynamics in the molecule system can be driven back and forth [2]. to form an enol and an ester [7]. might compete with rearrangement of the 51

[3] S. Ruetzel, M. Kullmann, J. Buback, P. Nuernberger, T. Brixner, Tracing the steps of photoinduced chemical reactions in organic molecules by coherent two-dimensional electronic spectroscopy using triggered exchange, Phys. Rev. Lett. 2013, 110, 148305 [4] M. Kullmann, S. Ruetzel, J. Buback, P. Nuernberger, T. Brixner, Reaction dynamics of a molecular switch unveiled by coherent two-dimensional electronic spectroscopy, J. Am. Chem. Soc. 2011, 133, 13074 [5] J. Knorr, P. Rudolf, P. Nuernberger, A comparative study on chirped-pulse up- conversion and direct multichannel MCT detection, Opt. Express 2013, 21, 30693 [6] A. Steinbacher, S. Roeding, T. Brixner, P. Nuernberger, Ultrafast photofragment ion spectroscopy of the Wolff rearrangement in 5-diazo Meldrum's acid, Phys. Chem. Chem. Phys. 2014, 16, 7290 [7] P. Rudolf, J. Buback, J. Aulbach, P. Nuernberger, T. Brixner, Ultrafast mul- tisequential photochemistry of 5-diazo Meldrum's acid, J. Am. Chem. Soc. 2010, 132, 15213 Fig. 3: UV excitation of a metal carbonyl compound in solution leads to the release of one CO [8] P. Rudolf, F. Kanal, J. Knorr, C. Nagel, ligand (arrow), as observable by an infrared probe pulse [8]. J. Niesel, T. Brixner, U. Schatzschneider, P. Nuernberger, Ultrafast photochemistry solvent shell. Current projects are directed Selected publications of a manganese-tricarbonyl CO-releasing to elucidate this interplay between compe- molecule (CORM) in aqueous solution, J. ting reactions mediated by solute-solvent [1] S. Ruetzel, M. Diekmann, P. Nuernberger, Phys. Chem. Lett. 2013, 4, 596 interactions. C. Walter, B. Engels, T. Brixner, Photoiso- [9] P. Nuernberger, D. Wolpert, H. Weiss, merization among ring-open merocya- G. Gerber, Femtosecond quantum control Since 2012, the group is supported by the nines. I. Reaction dynamics and wave- of molecular bond formation, Proc. Natl. DFG within the Emmy-Noether program, packet oscillations induced by tunable Acad. Sci. USA 2010, 107, 10366 and since 2014 as part of the cluster of femtosecond pulses, J. Chem. Phys. 2014, [10] R. Maksimenka, P.Nuernberger, K.F. Lee, Excellence RESOLV (EXC1069). 140, 224310 A.Bonvalet, J.Milkiewicz, C.Barta, [2] J. Buback, M. Kullmann, F. Langhojer, M. Klima, T. Oksenhendler, P. Tournois, P. Nuernberger, R. Schmidt, F. Würthner, D. Kaplan, M. Joffre, Direct mid-infrared T. Brixner, Ultrafast bidirectional pho- femtosecond pulse shaping with a toswitching of a spiropyran, J. Am. Chem. calomel acousto-optic programmable Soc. 2010, 132, 16510 dispersive filter, Opt. Lett. 2010, 35, 3565

Patrick Nürnberger studied physics at the Julius- and Theoretical Chemistry in Würzburg, supported Maximilians-Universität Würzburg and at the by an Emmy-Noether grant from the Deutsche State University of New York at Stony Brook. He Forschungsgemeinschaft. In 2013, he finished his received a Master of Arts degree in physics from habilitation in physical chemistry. Since 2014, he SUNY Stony Brook in 2003, followed in 2004 by has been a professor for physical chemistry at the a diploma in physics and in 2007 by a doctoral Ruhr-Universität Bochum. For more details on his degree from JMU Würzburg under the supervision research, see www.rub.de/ag-nuernberger. of Gustav Gerber. From 2008 to 2010, he was a Leopoldina postdoctoral fellow at the Laboratoire d’Optique et Biosciences at Ecole Polytechnique in Palaiseau, France. Back in Germany, he set up a junior research group at the Institute for Physical 52

Heterogeneous redox catalysis: From fundamental insight to industrial application

Prof. Dr. Martin Muhler and Dr. Wei Xia, Laboratory of Industrial Chemistry, Ruhr-University Bochum, Germany.

The Laboratory of Industrial Chemistry thesis, and the synthesis of higher alcohols. multiwalled carbon nanotubes (CNTs) has performs fundamental research in the Oxidation catalysis focuses on the selec- become a major topic due to the numerous area of heterogeneous catalysis aiming at tive oxidation of propene and methanol, applications of CNTs in electrocatalysis. All developing catalysts based on mechanis- the oxidative dehydrogenation of hydro- the necessary bulk- and surface-sensitive tic insight. The scientific challenge is the carbons, and the selective oxidation of techniques for catalyst characterization are elucidation of the reaction mechanisms on alcohols in the gas phase and in the liquid available with a strong focus on sorption the atomic level and their interplay with phase. Recently, we entered the fields of techniques. the complex surface chemistry of hetero- electrocatalysis and heterogeneous photo- geneous catalysts, which usually consist catalysis. Liquid-phase oxidation and elec- For improving the catalysts we first of all of many phases and components, often trocatalysis require a deeper understanding study steady-state kinetics. Numerous present as X-ray amorphous nanoparticles of solvation-related phenomena. continuously operated flow set-ups with or layers. online analytics are available allowing us For the synthesis of catalysts a large re- to screen the parameter space efficiently The reactions investigated by Prof. Dr. pertoire of methods is available including under full computer control using LabVIEW. Martin Muhler belong to industrial redox chemical vapor deposition, spray drying The role of the various elementary steps is chemistry. Reduction catalysis comprises and co-precipitation. In recent years the ca- investigated by applying transient kinetic methanol synthesis, Fischer-Tropsch syn- talytic growth and surface modification of methods such as temperature-program-

Fig. 1: Knowledge-based approach to heterogeneous catalysis at the Laboratory of Industrial Chemistry. 53

med reactor operation, dosing pulses and concentration steps, and using isotopes. For these methods we strongly rely on fast online quantitative mass spectrometry. In addition, we try to gain as much spectroscopic information as possible using mainly FTIR and photoelectron spectroscopy. Re- cently, static and dynamic microcalorimetry have been developed into versatile tools to probe the surface properties quantitatively.

Dr. Wei Xia’s research focuses on nanostructured materials playing vital roles in energy conversion and storage. Carbon is essentially indispensible since it is the only material that is highly conductive and (electro-) chemically stable. Oxides, although often less conductive, can further improve the stability and surface reactivity of carbon. Research on these nanomaterials often covers morphology and agglomerate, porosity and surface area, phase compo- Fig. 2: Bifunctional electrocatalysts for the ORR and OER: NCNTs with Co-Mn spinels synthe- sition and structure, surface defects and sized by catalytic growth and oxidative cutting. functional groups, adsorption and desorp- tion, mass transfer, activity and selectivity, His research in electrocatalysis comprises the mental understanding on the surface che- corrosion and stability, electronic and ionic modification of carbon nanomaterials, the mistry, and the impact of materials proper- conductivity. development of hybrid materials, the funda- ties on electrocatalysis. Various surface and

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ler, "The role of carbonaceous deposits of Binary ZnO-Al2O3 Composites with in the activity and stability of Ni-based High Specific Surface Area"; 19 (2009) catalysts applied in the dry reforming 3914-3922. of methane", Catal. Sci. Technol. 4 (2014) [9] A. Zhao, J. Masa, W. Xia, A. Maljusch, M.- 3317-3328. G. Willinger, G. Clavel, K. Xie, R. Schlögl, [3] B. Mei, C. Wiktor, S. Turner, A. Pougin, G. W. Schuhmann, M. Muhler, "Spinel Mn- van Tendeloo, R. A. Fischer, M. Muhler, Co oxide in N-doped Carbon Nanotubes J. Strunk, Evidence for Metal-Support as Bifunctional Electrocatalyst Synthe-

Interactions in Au Modified TiOx/SBA -15 sized by Oxidative Cutting", J. Am. Chem. Materials Prepared by Photodeposition, Soc. 136 (2014) 7551–7554. ACS Catal. 3 (2013) 3041-3049. [10] M. Sanchez, P. Chen, T. Reinecke, M. Fig. 3: TEM image of Fe nanoparticles on [4] K. Kähler, M.C. Holz, M. Rohe, A.C. van Muhler, W. Xia, "The role of oxygen- and nitrogen-functionalized carbon nanotubes. Veen, M. Muhler, "Methanol oxidation nitrogen containing surface groups on as probe reaction for active sites in Au/ the sintering of iron nanoparticles on

bulk sensitive characterization techniques ZnO and Au/TiO2 catalysts", J. Catal. 299 carbon nanotubes in different atmos- are employed including X-ray photoelectron (2013) 162-170. pheres", ChemCatChem, 4 (2012) 1997- spectroscopy, Raman spectroscopy, physi- [5] M. Xu, H. Noei, K. Fink, M. Muhler, Y. 2004. sorption, chemisorption, temperature-pro- Wang, Ch. Wöll, "The Surface Science [11] P. Chen, F. Yang, A. Kostka, W. Xia, "Inter- grammed techniques, electron microscopy, Approach for Understanding Reactions action of cobalt nanoparticles with oxy- X-ray diffraction, thermogravimetry and elec- on Oxide Powders: The Importance of IR gen- and nitrogen-functionalized carbon trochemical methods like cyclic voltammetry, spectroscopy", Angew. Chem. Int. Ed. 51 nanotubes and impact on nitrobenzene rotating disc electrode voltammetry and (2012) 4731-4734. hydrogenation catalysis",ACS Catal. 4 electrochemical impedance spectroscopy. [6] B. Graf, H. Schulte, M. Muhler, "The For- (2014) 1478–1486. mation of Methane over Iron Catalysts [12] A. Zhao, J. Masa, W. Schuhmann, W. Selected Publications Applied in Fischer-Tropsch Synthesis: Xia, "Activation and Stabilization of A Transient and Steady State Kinetic Nitrogen-Doped CNTs as Electrocatalysts [1] G.W. Busser, B. Mei, A. Pougin, J. Strunk, Study", J. Catal. 276 (2010) 66-75. in the Oxygen Reduction Reaction at R. Gutkowski, W. Schuhmann, M.-G. [7] J. Strunk, K. Kähler, X. Xia, M. Comotti, F. Strongly Alkaline Conditions", J. Phys. Willinger, R. Schlögl, M. Muhler, "Photo- Schüth, Th. Reinecke, M. Muhler, Au/ZnO Chem. C 117 (2013) 24283–24291. deposition of Copper and Chromia on as Catalyst for Methanol Synthesis: The [13] P. Chen, L.M. Chew, W. Xia, "Carbon Gallium Oxide: The Role of Co-Catalysts role of oxygen vacancies, Appl. Catal., A nanotube-supported Pt nanoparticles in Photocatalytic Water Splitting", 359 (2009) 121-128. for selective olefin hydrogenation: the ChemSusChem 7 (2014) 1030-1034. [8] S. Kaluza, M. Muhler; "On the Precipitati- influence of the residual growth catalyst [2] H. Düdder, K. Kähler, B. Krause, K. Mette, on Mechanism and the Role of the Post- and the surface functional groups", J. S. Kuhl, M. Behrens, V. Scherer, M. Muh- Precipitation Steps During the Synthesis Catal. 307 (2013) 84-93.

Martin Muhler was appointed full Professor of In- From 1991-1996 he was the head of the group dustrial Chemistry at the Ruhr-University Bochum "Heterogeneous Catalysis" in the Physical Che- in 1996. He studied chemistry at the Ludwig- mistry Department of the FHI Berlin. In 1996, he Maximilians-University in Munich and received finished his habilitation in Industrial Chemistry at his Ph.D. in 1989 from the FU Berlin under the the TU Berlin. In 2013, he was elected Chairman of supervision of Prof. Dr. G. Ertl at the Fritz Haber In- the German Catalysis Society. stitute of the Max Planck Society in Berlin. He then joined the Department of Fundamental Research in Heterogeneous Catalysis at Haldor Topsøe A/S in Denmark as postdoctoral fellow for two years.

Wei Xia studied chemistry (B. Sc.) in Shanghai (Chi- the inventors competition in Northrhine-Westpha- na) and Halle-Wittenberg (M. Sc.) and received his lia for a method of modifying carbon nanotubes. Ph.D. in 2006 from the Ruhr-University Bochum. He spent one year as a Postdoctoral Research Associate at the Laboratory of Industrial Chemistry at the Ruhr-University Bochum and became the leader of the group “Carbon materials and electrocatalysis” in 2008. He received the invention prize of the Ruhr-University Bochum three times (2005, 2008 and 2010). In 2010 he received the prize of 55

Heterogeneous Catalysis: Relations between Structure and Performance of Catalysts

Prof. Dr. Wolfgang Grünert, Lehrstuhl Technische Chemie

The group’s research is focused on the elucidation of active site structures and promoting interactions in heterogeneous catalysts by combining reaction rate data with results of struc-tural studies, including in-situ and operando work. Reactions investigated are often related to environmental catalysis. Analytical expertise covers photoemission, low-energy ion scattering (LEIS) and X-ray absorption methods while other spectroscopic techniques and electrochemi-cal studies are contributed by cooperation partners (Prof. A. Brückner, Rostock, Prof. M. Bron, Halle, Prof. M. Muhler, Bochum)

In environmental catalysis, the group has been studying selective catalytic reduction (SCR) of nitrogen oxides with different reactants for two decades, but extended onto tree-way catalysis and low-temperature CO oxidation more recently.

SCR with ammonia

The group has significantly contributed to present-day knowledge on Fe zeolite catalysts, which are being commercialized for Diesel exhaust treatment according to Euro

Fig. 2: CO conversion over Au/TiO2 catalysts in different states of the surface as indicated by XAS and IR of adsorbed CO.

VI standards. This includes the finding that A project on standard SCR over traditional

SCR of NO and of NO/NO2 mixtures (“stan- V-W/TiO2 catalysts resulted in a new view dard” and “fast” SCR) proceed on different si- upon the origin of the promoting effect of tes and via different mechanisms on Fe zeo- tungsten and revealed unexpected thermal lites [1], and the rejection of a popular view effects on the behavior of these catalysts [6], according to which binary Fe-O-Fe pairs are which has been widely appreciated just in required to catalyze standard SCR [2]. Instead, industrial groups. the reaction proceeds on all exposed Fe sites that remain three-valent in the feed, with a Low-temperature CO oxidation particular contribution of oligomeric oxide [3, 4] clusters in the zeolite voids . Fast SCR is Metal-support interactions in Au/TiO2 CO catalyzed by a minority Fe site comprising oxidation catalysts were investigated with an isolated Fe ion stabilized in the +2 state model catalysts containing both compo- by two adjacent framework Al [3]. A popular nents as guests in a siliceous host (MCM- mechanistic concept according to which 48) [7]. The study resulted in the conclusion

standard SCR proceeds as a sequence of NO2 that epitactic relations between metal formation from NO with subsequent fast and support as observed in literature are SCR over Fe zeolites was rejected [4, 5] (Fig. irrelevant for CO oxidation, that the active Fig. 1: Comparison of rates for NO oxidation 1). Recent work is focused on the identifi- Au0 sites are in clusters of <1nm size, and and standard SCR over different Fe-ZSM-5 cation of active sites for NO oxidation and that most sites are poisoned, probably by catalysts proving irrelevance of the former on the utilization of the above-mentioned carbonate, under stationary conditions. In a for the reaction mechanism of the latter. sequence in hybrid catalysts. study with conventional Au/TiO2 catalysts, 56

it was observed that CO oxidation can Electrochemical Oxygen "SCR and NO oxidation over Fe-ZSM-5 – proceed with high rates also sites contai- Reduction (ORR) on the influence of the Fe content", Catal. ning cationic gold. After their complete Leached Pt Alloy Nanoparticles Today (2015) in press (doi:10.1016/j. conversion to Au0, the reaction proceeds cattod.2014.12.017). on the perimeter between the support and The ORR activity of Pt-X alloy nanoparticles [5] I. Ellmers, R.P. Vélez, U. Bentrup, A. Brück- positively charged Au0 clusters (cf. [8]), which is known to be enhanced by leaching the ner, W. Grünert, Oxidation and Selective are most likely oligomeric structures or less noble component via chemical or elec- Reduction of NO over Fe-ZSM-5 – How even atoms stabilized by oxygen vacancies trochemical treatments. The latter, superior related are these reactions? J. Catal. 311 in the support [9, 10] (Fig. 2). route was described to result on core-shell (2014) 199-211. nanoparticles with a multilayer Pt core co- [6] P.G.W.A. Kompio, A. Brückner, F. Hipler, G. Three-way catalysis vering an alloy core of original composition. Auer, E. Löffler, W. Grünert, "A new view Our multitechnique study on the structure on the relations between tungsten and

Reactions of three-way catalysis have been of chemically leached Pt-Cu particles, with vanadium in V2O5-WO3/ TiO2 catalysts studied with noble-metal substituted key impact of LEIS, revealed that the treat- for the selective reduction of NO with

perovskites to examine claims in literature ment affects the whole particles, resulting NH3", J. Catal. 286 (2012) 237-247. that these materials release Pd0 and resorb in a Pt monolayer covering a Cu-depleted [7] M.W.E. van den Berg, A. De Toni, M. Pd2+ on the time scale of O fluctuations alloy core. As these results challenge the Bandyopadhyay, H. Gies, W. Grünert,

in the exhaust of gasoline engines. While model established for electrochemically "CO oxidation with Au/TiO2 aggregates this claim was found unrealistic. Pd was leached particles in literature, detailed encapsulated in the mesopores of MCM- observed to form alloy phases with analyses with the given set of methods are 48: Model studies on activation, deacti- perovskite components (Fe, Co), which going on. vation and metal-support interaction",

are highly active in NO reduction and N2O Appl. Catal. A 391 (2011) 268-280. decomposition. At present, the potential of Selected Publications [8] M.F. Camellone, J.L. Zhao, L.Y. Jin, Y.M. gold as a component of three-way catalysts Wang, M. Muhler, D. Marx, Angew. is investigated. [1] M. Schwidder, S. Heikens, A. De Toni, S. Chem. Int. Ed. 52 (2013) 5780-5784. Geisler, M. Berndt, A. Brückner, W. Grü- [9] W. Grünert, D. Großmann, H. Noei, M.M.

Active sites of MoS2 nert, "The role of NO2 in the Selective Pohl, I. Sinev, A. De Toni, Y. Wang, M. Catalytic Reduction of Nitrogen Oxides Muhler, "Low-temperature CO Oxidation 3+ The catalytic activity of MoS2 in simple test over Fe-ZSM-5 Catalysts – Active Sites with TiO2-supported Au ions" Angew.

reactions (e.g. ethene hydrogenation) was for the Conversion of NO and of NO/NO2 Chem. Int. Ed. 53 (2014) 3245-3249. studied with materials made from different mixtures", J. Catal. 259 (2008) 96-103. [10] W. Grünert, D. Grossmann, H. Noei, M.M. precursors and activated with different [2] F. Heinrich, C. Schmidt, E. Löffler, M. Pohl, I. Sinev, A. De Toni, Y.M. Wang, M. treatments in order to relate activities to Menzel, W. Grünert, "Fe-ZSM-5 catalysts Muhler, "How different characterization the extent of coordinative unsaturation for the selective catalytic reduction of techniques elucidate the nature of the

at the Mo ion assessed via oxygen chemi- NO by isobutane - the problem of the ac- gold species in a polycrystalline Au/TiO2 sorption. All test reactions were found to tive sites", J. Catal. 212 (2002) 157-172. catalyst", Chem. Ing. Tech. 86 (2014) proceed also on surfaces that were unable [3] R. Pérez Vélez, I. Ellmers, H. Huang, U. 1883-1889. to adsorb oxygen [11]. This result is a highly Bentrup, V. Schünemann, W. Grünert, [11] T. Drescher, F. Niefindt, W. Bensch, W. debated contribution to an ongoing change A. Brückner, "Identifying active sites Grünert, "Sulfide Catalysis without co-

of paradigms in views on active sites of for fast NH3-SCR of NO/NO2 mixtures ordinatively unsaturated sites: Hydroge-

sulfide catalysts, from models requesting overFe-ZSM-5 by operando EPR and nation, cis-trans isomerisation and H2D2

multiple vacancies on Mo for hydrogenati- UV-vis spectroscopy", J. Catal. 316 (2014) scrambling over MoS2 and WS2", J. Am. on to models with saturated hydrogenation 103-111. Chem. Soc. 134 (2012) 18896-18899. sites, which had not yet been demonstra- [4] I. Ellmers, R. Pérez Vélez, U. Bentrup, ted in reality. W. Schwieger, A. Brückner, W. Grünert,

Wolfgang Grünert has been a professor for In- the Fritz-Haber Institute of the Max-Planck Society dustrial Chemistry at the Laboratory of Industrial in Berlin with R. Schlögl and 6 months at Liverpool Chemistry of Ruhr University Bochum since 1997. University with R. W. Joyner. In 1992, he received He studied Chemistry in Merseburg and received his habilitation degree from Technical University his PhD from the Technical University Leuna- Leuna-Merseburg. After shutdown of GDR Aca- Merseburg in 1975. He was a research assistant in demy of Sciences and a project-based transition the Central Institute of Organic Chemistry, Leipzig period, W. Grünert joined Ruhr University Bochum branch, of the GDR Academy of Sciences from as a senior researcher in 1994, where he became a 1975 to 1991, which included regular research full professor in 1997. periods at the Institute of Organic Chemistry of the Soviet Academy of Sciences in Moscow. After the Fall of the Wall, W. Grünert spent one year at ... präsentieren Sie zielgerecht Ihre Produkte und Dienstleistungen!

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Ab Initio Simulations: Chemical Reactions in the "Virtual Laboratory"

Dominik Marx, Lehrstuhl für Theoretische Chemie

Leitmotives of the Marx Group are, on the one hand, the development of novel quantum and quasi-classical simulation techniques for molecular many-body systems, and on the other, their application in terms of High-Performance Scientific Computing.

The general theme of our research consists in understanding structure, dynamics, and chemical reactions of complex molecular many-body systems. Our aim is to capture nature as closely as possible by theoretical means – the basic entities being nuclei and electrons. This implies that we have to use atomistic ab initio computer simulation techniques which are capable of including dynamics and quantum mechanics – of course only approximately. The notion "ab initio" or "first principles" means for us that we neither want to fit to experimental data nor do we want to adjust any parameters. The central working horse to turn these ideas into practical numerical tools are in particular the ab initio simulation methods going back to the ground-breaking ideas of Car and Parrinello (1985).

In Bochum, major methodological deve- Fig. 1: Snapshot of a HCl(H2O)4 cluster in superfluid helium. The bosonic exchange paths that lopments of the Marx group have been establish the superfluid fraction within the path integral formulation of quantum mechanics devoted to continuing the extension and are represented by blue ribbons, whereas the spheres represent the delocalized individual broadening of the "standard" Car-Parrinello atoms. method, for which a few highlights are given in the following. nello propagation scheme, which enables Walewski, is a method that allows us to the description of the dynamics of electro- solvate reactive molecular complexes in Nonadiabatic ab initio dynamics nic states that cannot be represented using superfluid helium droplets at sub-Kelvin a single Kohn-Sham determinant, has been temperatures [3]. It combines ab initio path In 2002, a general approach to go beyond developed starting in 2007 [2]. Using this integrals to treat chemically complex mo- the usual Born-Oppenheimer approximati- strategy, we have computed Heisenberg's lecular solutes with bosonic path integral on has been developed and implemented antiferromagnetic exchange coupling Monte Carlo sampling of the helium envi- in collaboration with Nikos Doltsinis. The obtained from a spin-projected, Hubbard- ronment to establish quantum mechanical basic idea of this nonadiabatic ab initio dy- corrected, two-determinant ground state. indistinguishability - as required by the namics technique [1] is to use Tully's surface Generating the time evolution of this Bose-Einstein quantum statistics of liquid hopping algorithm in combination with the quantity "on the fly" provides access to ma- 4He. This approach opens the doorway to so-called restricted open-shell Kohn-Sham gnetostructural dynamics, which arise from studying chemical reactivity in the absence Ansatz. This efficient approach "beyond the the intricate coupling of molecular motion of thermal energy, such as aggregation- Born-Oppenheimer approximation" allows and magnetic properties. More recently, the induced dissociation phenomena and us to study photochemical reactions with method has been extended toward spin- cryochemical reactions (Fig. 1). particular focus on laser-induced processes density constraint DFT to deal with cases in solutions or complex environments. where the +U correction fails. Mechanochemistry and molecular nanomechanics Spin-projected multideterminant Ab initio/bosonic ab initio dynamics path integral MD/MC Another field pioneered in Bochum is the general theory and computer simulation Together with Nisanth Nair and Eduard Among the most recent developments, of covalent mechanochemistry in collabo- Schreiner, a multi-determinant Car-Parri- together with Harald Forbert and Lukasz ration with Jordi Ribas-Arino [4]. In contrast 59

to thermochemistry, photochemistry or Catalysis and spectroscopy from THz spectroscopy [7] together with Gerald electrochemistry (where temperature, light ab initio molecular dynamics Mathias, Sergei Ivanov and Harald Forbert. or electricity are used to trigger reactions), mechanochemistry utilises mechanical Finally, successful ab initio molecular Much of the metholological development force to activate and control chemical dynamics based approaches have been of Dominik Marx and his coworkers is con- reactions [5]. Advances in this field impact developed for fields where radically diffe- tained in the Marx-Hutter monograph on on areas of application such as molecular rent methods have been used traditionally, "Ab Initio Molecular Dynamics" [8]. nanomechanics of single-molecule junc- which includes theoretical heterogeneous tions, functionalized surface coatings, and catalysis [6] with Bernd Meyer and Johannes Solvation Science mechanoenzymes (Fig. 2). Frenzel as well as theoretical infrared and The ever-growing family of ab initio simulation techniques, in conjunction with high- performance computing, is ideally suited to the investigation of disordered systems at finite temperatures; molecular liquids being a prime example of this. As such, this set of methods provides the most direct insight into the structure and dynamics of solvation shells, the impact of hydrogen bonding on the properties of aqueous solutions, and, most importantly, the influence of solvation on chemical reactivity [9,10] (Fig. 3).

Beyond science

The Marx group also provides fertile grounds for independent young investiga- tors to mature. Nikos Doltsinis and Bernd Meyer, who both habilitated in Bochum, are professors in the meantime. Currently, Jörg Behler is the head of a Heisenberg group as a Privatdozent subsequent to his Emmy Noether and Liebig Fellowships, whereas Fig. 2: Schematic of topological distortions of the Born-Oppenheimer potential energy lands- Michael Römelt just started to establish his cape underlying a thermal chemical reaction (left) as a result of applying tensile force (right). Otto Hahn research group. In addition, The- oretical Chemistry in Bochum traditionally attracts Humboldt Fellows and Awardees from all over the world.

Last but not least, the Marx group is very active in fostering graduate and postgra- duate training by co-organizing schools for PhD students and postdocs on computer simulation techniques together with the Jülich Supercomputing Centre (JSC at Forschungszentrum Jülich) on topics such as "Computational Trends in Solvation and Transport in Liquids" (2015), "Hierarchical Methods for Dynamics in Complex Molecu- lar Systems" (2012), "Multiscale Simulation Methods in Molecular Sciences" (2009), and "Computational Nanoscience: Do It Yourself!" (2006).

Fig. 3: Free energy landscape for the hydrolysis from GTP to GDP in explicit aqueous solution using a nucleoside triphosphate model, where the inset shows the transition state structure. 60

Selected Publications [5] J. Ribas-Arino, D. Marx, Covalent Mecha- [9] E. Schreiner, N. N. Nair, D. Marx, Influ- nochemistry: Theoretical Concepts and ence of Extreme Thermodynamic Con- [1] N. L. Doltsinis, D. Marx, Nonadiabatic Computational Tools with Applications ditions and Pyrite Surfaces on Peptide Car-Parrinello molecular dynamics, Phys. to Molecular Nanomechanics, Chem. Synthesis in Aqueous Media, J. Am. Rev. Lett. 2002, 88, 166402-1-4. Rev. 2012, 112, 5412-5487. Chem. Soc. (Communication) 2008, 130, [2] E. Schreiner, N. N. Nair, R. Pollet, V. Sta- [6] J. Frenzel, J. Kiss, N. N. Nair, B. Meyer, D. 2768-2770. emmler, D. Marx, Dynamical magneto- Marx, Methanol synthesis on ZnO from [10] D. Munoz-Santiburcio, C. Wittekindt, D. structural molecular dynamics (Feature Article), Marx, Nanoconfinement effects on hyd- properties of Anabaena ferredoxin, Proc. Phys. Status Solidi B 2013, 250, 1174- rated excess protons in layered materi- Natl. Acad. Sci. USA 2007, 104, 20725- 1190. als, Nat. Commun. 2013, 4, 2349-1-5. 20730. [7] S. D. Ivanov, A. Witt, D. Marx, Theoretical [3] L. Walewski, H. Forbert, D. Marx, Reactive spectroscopy using molecular dynamics: path integral quantum simulations of theory and application to CH+5 and its molecules solvated in superfluid helium, isotopologues (Perspective Article), Phys. Comput. Phys. Commun. 2014, 185, Chem. Chem. Phys. 2013, 15, 10270- 884-899. 10299. [4] J. Ribas-Arino, M. Shiga, D. Marx, Under- [8] D. Marx J. Hutter, Ab Initio Molecular standing Covalent Mechanochemistry, Dynamics: Basic Theory and Advanced Angew. Chem. Int. Ed. 2009, 48, 4190- Methods (Cambridge University Press, 4193. Cambridge 2009).

Dominik Marx studied chemistry and physics at on in Theoretical Physics at Universität Stuttgart Universität Mainz and the University of California (1998), before he received the chaired professor- at Irvine, where he worked with Max Wolfsberg on ship of Theoretical Chemistry at Ruhr-Universität isotope effects. In Mainz, he received his Diplom Bochum (1999). Several Chairs in Germany and in Chemistry (1990) working with Karl Heinzinger abroad, including the Coulson Chair of Theore- (MPI für Chemie) on MD simulations of non- tical Chemistry at Oxford in conjunction with a aqueous electrolyte solutions and his Ph.D. (1992) Professorial Fellowship at University College, were with Kurt Binder (Institut für Physik) on Quantum offered to him. Dominik Marx was fascinated from Monte Carlo simulations of phase transitions. early on by the multifaceted problems that are Thereafter, he worked as a Postdoctoral Fellow at posed by the physics and chemistry of complex IBM Zurich Research Laboratory (Rüschlikon) with molecular systems which can only be tackled using Michele Parrinello, as a staff scientist at MPI für utmost realistic computer simulation approaches. Festkörperforschung, and obtained the Habilitati-

Professional Support of Scientific Activities to obtain a better Understanding of Complex Chemical Systems

Prof. Dr. Wolfgang Schuhmann / Dr. Sabine Borgmann – Research Department „Interfacial Systems Chemistry“ (RD IFSC)

The Research Department „Interfacial Systems Chemistry“ (RD IFSC) is a research network located at Ruhr-Universität Bochum (RUB) in Germany. The Research Departments (RDs) of RUB are an integrated part of the institutional "Research Campus RUB" strategy promoting excellent research with a unique interdisciplinary approach. RDs function as large, collaborative research platforms which each span over several disciplines.

The RD IFSC was founded in 2009. Research performed in RD IFSC is related to chemistry and neighboring disciplines. The goal is to obtain a better understanding of complex chemical systems.

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Contact: www.rub.de/ifsc. 61

Quantum Chemistry

Prof. Dr. Christof Hättig, Fakultät für Chemie und Biochemie, Theoretische Chemie

The research of the Quantum Chemistry mophores (up to ca. 100 atoms). Examples Explicitly correlated wavefunctions group focuses on Computational Chemistry, which have been studied with CC2 range in particular on molecular and electronic from medium-sized molecules like amino- A serious limitation for the application of structure calculations with quantum chemi- benzonitriles [3] to substituted porphyrins [4] high-level electronic structure methods for cal methods ranging from density functio- and chlorophylls [5]. the prediction of thermochemical and spec- nal theory to explicitly correlated coupled cluster methods. The group applies these methods to a large variety of problems ranging from heterogenous catalysis and thermochemistry to linear and nonlinear electronic spectroscopy. Beside this, the group is involved in the development of the world-wide distributed TURBOMOLE program package.

The reseach in the Hättig group is concerned with the application and development of various computational chemistry methods for the prediction of molecular structures, interactions, properties and spectra, with emphasis on correlated wavefunction methods for electronic spectra and excited states in molecules. Its aim is to improve the understanding and prediction of experimental results with quantum chemical calculations and the implementation of robust and efficient computational chemistry methods, which are used by many Fig. 1: Molecular geometry of 4-(dimethyl-amino)-benzonitrile determined with CC2 for an groups at academic research institutions almost planar state, locally excited within the benzene ring, and a charge transfer state where and in industry [1]. the dimethyl-amino group is twisted by 90°.

Spectra and structure Solvation and environment effects troscopic properties of larger molecules is of excited states on electronic spectra their slow convergence with the atomic orbital basis sets which is caused by cusps in Electronically excited states have usually a Apart from laboratory measurements the many-electron wavefunction. In coope- complicated electronic structure, and often carried out in ultra high vacuum and the ration with the groups of W. Klopper (KIT), the molecular geometry is different from interstellar space molecules don’t appear D.P. Tew (Bristol) and A. Köhn (Stuttgart) the that in the ground state and difficult to as isolated species but in a chemical envi- Hättig group develops explicitly correlated predict. Chemical calculations are an im- ronment where the interaction with other so-called F12 Møller-Plesset perturbation portant tool for the understanding of the molecules influences their properties and theory and coupled-cluster methods which molecular spectra and the photochemical spectra [6]. The interaction between mole- tackle this problem by including functions reactivity of molecules. Modern electronic cules is of electric nature, but because of that depend on the interelectronic distan- structure methods, as e.g. density functio- the many possible ways how the electric ces in the wavefunction ansatz. This leads nal and coupled-cluster response methods interaction can become apparent, e.g. as in- to a large enhancement of the basis set allow to investigate excited states of re- teraction between electric dipole moments convergence [8] and allows to apply such latively large molecules, to predict their or as dispersion interaction the detailed methods to larger systems. spectra and to determine their equilibrium description of intermolecular interactions structures. The Hättig group applies for in terms of molecular properties is rather Pair natural orbital methods these investigations in addition to TDDFT complex. To predict and study the origin of mainly the CC2 method, for which the inhomogenous broadening of electronic To extend the applicability of wavefunction group has developed an efficient imple- spectra in solution and at interfaces the methods for thermochemistry and spect- mentation [2] which since 2002 is distribu- group became recently involved in the roscopic properties to larger systems and ted as part of the TURBOMOLE progam development of a polarizable embedding molecular structures at interfaces current package and is well-suited for applications scheme for the RI-CC2 approach [7]. research is concerned with the develop- on medium sized and large organic chro- ment of approaches that reduce the scaling 62

of the computational costs with the system Selected Publications volving E-ligated chlorophylss, Biochem. size. Based on recent advances for pair na- Biophys. Acta-Bioener., 2009, 1787, tural orbital (PNO) expansions it has been [1] P. Deglmann, A. Schäfer, C. Lennartz, 1254-1265. possible to develop CC2 and ADC(2) imple- Application of Quantum Calculations in [6] J. Kongsted, T.B. Pedersen, M. Strange, mentations for excitation energies [9] and the Chemical Industry – An Overview, A. Osted, A.E. Hansen, K.V. Mikkelsen, F. the explicitly correlated coupled-cluster Int. J. Quant. Chem. 2015, 3, 107-136. Pawlowski, P. Jørgensen, C. Hättig, Cou- singles-and-doubles CCSD[F12] model [10] [2] C. Hättig, F. Weigend, CC2 excitation pled cluster calculations of the optical with reduced computational scalings. energy calculations on large molecules rotation of S-propylene oxide in gas pha- using the resolution of the identity ap- se and solution, Chem. Phys. Lett, 2005, proximation, J. Chem. Phys. 2000, 113, 401, 385-392. 5154-5161. [7] T. Schwabe, K. Sneskov, J.M.H. Olsen, [3] C. Hättig, A. Hellweg, A. Köhn, Intramo- J. Kongsted, O. Christiansen, C. Hättig, lecular Charge-Transfer Mechanism in PERI-CC2: A Polarizable Embedded RI- Quinolidines: The Role of the Amino- CC2 Method, J. Chem. Theory Comput., Twist Angle, J. Am. Chem. Soc., 2006, 2012, 8, 3274-3283. 128, 15672-15682. [8] C. Hättig, W. Klopper, A. Köhn, D.P. Tew, [4] N.O.C. Winter, N.K. Graf, S. Leutwyler, C. Explicitly correlated electrons in molecu- Hättig, Benchmarks for 0-0 transitions les, Chem. Rev. 2012, 112, 4. of aromatic organic molecules: DFT/ [9] B. Helmich, C. Hättig, A pair natural orbi- B3LYP, ADC(2), CC2, SOS-CC2 and SCS- tal implementation of the coupled clus- CC2 compared to high-resolution gas- ter model CC2 for excitation energies, J.

Fig. 2: Structure of a calix-4-arene · H2O phase data, Phys. Chem. Chem. Phys., Chem. Phys., 2013, 139, 084114. complex for which a binding energy of 2012, 15, 6623-6630. [10] G. Schmitz, C. Hättig, D.P. Tew, Explicitly 10.7 kcal/mol has been calculated with [5] T.S. Balaban, P. Braun, C. Hättig, A. Hell- correlated PNO-MP2 and PNO-CCSD and PNO-CCSD[F12] on 6 Xeon E5430 CPU cores weg, J. Kern, W. Saenger, A. Zouni, Prefe- their application to the S66 set and large within 170 h. rential pathways for light-trapping in- molecular systems.

Christof Hättig has been Professor for Theoretical a researcher at the Institute of Nanotechnology Chemistry at Ruhr-Universität Bochum since 2006. (INT) of the Forschungszentrum Karlsruhe (today He studied Chemistry at the University Bonn, KIT), Germany, in the group of R. Ahlrichs. In 2000 Germany, where he received his Ph. D. degree in he became head of an independent junior research Theoretical Chemistry in 1995. His thesis on the group at the INT and in 2003 he completed his development of a correlated wavefunction me- Habilitation in theoretical Chemstry at the Univer- thod for dispersion coefficients for intermolecular sity Karlsruhe (today KIT). During this time he star- interactions was supervised by Prof. Bernd A. Hess. ted to work on the development of approximate In 1996 he joined first as a postdoctoral research coupled-cluster methods for electronic spectra and associated and since 1997 as Forskingsadjunkt excited states in large molecules for which he re- (Assistant Research Professor) the Theoretical Che- ceived in 2004 the Hans G.A. Hellmann Prize of the mistry group at Aarhus University, Denmark, whe- Arbeitsgemeinschaft Theoretische Chemie. He is re he worked with P. Jørgensen on coupled-cluster member of the TURBOMOLE GmbH and since 2009 response methods for the calculation of nonlinear one of scientific coordinators of the TURBOMOLE optical properties. From 1999 to 2000 he has been program package.

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Theoretical Chemistry: Molecular Simulation

Prof. Dr. Lars Schäfer, Lehrstuhl für Theoretische Chemie

The Schäfer group is driven by the aim to cellular processes, yet often very little is understand life at the molecular level: can known about their structural organization. we describe biomolecular systems from the Improving the predictive power of compu- basic principles of chemistry and phy- ted protein-protein interactions is a long- sics? Molecular dynamics (MD) computer standing challenge. We study both soluble simulations can provide a deep and causal proteins and, often even more demanding, understanding of the structural dynamics membrane proteins [4,5]. As a prime example and energetics underlying biomolecular for a protein super-complex, we investigate processes, and are thus one of the most the molecular architecture of the major powerful tools to achieve this goal. histocompatibility complex (MHC) class I peptide loading complex (PLC), a key player The group is active in the development in the mammalian antiviral immune res- and application of simulation methods ponse, the rejection of organ transplants, for describing the structure and dynamics and cancer. Enabled by high-performance of large biomolecular assemblies on long parallel supercomputers and GPU compu- time scales. This requires efficient classical ting, we use atomistic MD simulations to molecular dynamics (MD) type simulations, Fig. 1: Snapshot from MD simulation of study the spontaneous association of the in which Newton’s equations of motion transporter associated with antigen proces- two central proteins in the PLC, tapasin and are iteratively solved in small time steps sing (TAP) embedded in a lipid nanodisc. TAP MHC-I (Fig. 2). Previously, due to the lack of and empirical potentials (force fields) are is shown in cyan and orange, whereas the structural data, the molecular mechanism employed for describing the interatomic nanodisc proteins and lipids are colored yel- of this protein complex remained elusive. interactions. In addition to using conven- low and grey, respectively. The red molecule Our simulations now provide for the first tional fully atomistic MD simulations, at the right is the ICP47 protein from herpes time a basis for an in-depth understanding the group also contributes to improving simplex virus, a high-affinity inhibitor of TAP. of its working mechanism. In addition, in the accuracy of computationally highly another project, the Schäfer group collabo- efficient coarse-grained approaches, as well tions between the different components rates with Boehringer Ingelheim Pharma as to the development of hybrid multiscale (proteins, lipids, solvent molecules) that GmbH & Co. KG on improving the aggrega- methods that combine different levels of govern the structure and dynamics – and tion behavior of biopharmaceuticals. resolution. In the following, we highlight a hence the function – of membrane protein few recent applications and methodologi- complexes. cal advancements. Solvation Science Membrane Proteins Water molecules can play a major role for Membrane proteins are not only of great molecular recognition processes, such as interest due to their intriguing chemical protein-protein and protein-ligand binding. and biophysical principles, but also because We investigate how water (and other (co-) of their pharmaceutical importance: about solvents) can modulate the thermodyna- half of all current drugs target membrane mics of biomolecular interactions. One proteins. We use MD simulations to probe focus is on serine protease inhibitors, in the free energy landscapes and corres- collaboration with Christian Herrmann ponding thermodynamic driving forces (Ruhr-University Bochum). Free energy behind the molecular mechanisms of these simulations provide detailed atomistic nano-machines. Recent work focused on insights into the molecular thermody- Fig. 2: MHC class-I/b2m (red and blue) and both secondary active transporters such as namics, including the origins of different tapasin (green) proteins, separated by a EmrE [1], and ATP binding cassette trans- enthalpic and entropic contributions to the layer of water molecules. Multi-microsecond porters such as ThiT [2] and the transporter free energy of binding, and the role of the all-atom MD simulations enable to study the associated with antigen processing (TAP) solvent. Together with microcalorimetry spontaneous encounter of these two binding [3]. Whereas the former two proteins were experiments, they open the way toward a partners. studied in a conventional lipid bilayer targeted and rational design of improved surrounding, the latter was embedded in a inhibitors. Multiscale Modeling so-called nanodisc, a special environment with several experimental advantages (Fig. Protein-Protein Interactions One of the major bottlenecks of today's 1). The simulations thus show how compu- atomistic MD simulations is the sampling tational techniques can probe the interac- Protein complexes are crucial for many problem: Due to the enormous computati- 64

onal costs, only processes at nanosecond to microsecond time scales (or faster) can be studied directly. To overcome this limitation, we develop computationally efficient hybrid multiscale approaches that combine atomistic and coarse-grained levels of resolution [6,7], in addition to our ongoing efforts to improve fast coarse-grained force fields [8,9]. The basic idea of hybrid modeling is to use models of different resolution in separate spatial domains, e.g., the protein and its direct surrounding are described by an atomistic force field, whereas a coarse- grained model is used for the remainder (Fig. 3). The aim is to trade off the size and complexity of the system against the efforts of a fully atomistic description. Successful implementation of such hybrid approaches enables to directly simulate large-scale self-assembly processes in ato- Fig. 3: Multiscale MD simulation of an atomistic protein (gold) surrounded by coarse-grained mic detail, with possible impact on related solvent. Supramolecular coarse-grained water molecules are shown in cyan, lipids in grey fields in which complex collective processes (lower right corner). play a role, such as material science and nanotechnology. cation complex TAP, J. Biol. Chem. 2014, [7] M. Gopal, A. B. Kuhn, L. V. Schäfer, Syste- 289, 33098. matic Evaluation of Bundled SPC Water Selected Publications [4] L. V. Schäfer, D. H. de Jong, A. Holt, A. J. for Biomolecular Simulations, Phys. Rzepiela, A. H. de Vries, B. Poolman, J. A. Chem. Chem. Phys. 2015, 17, 8393. [1] P. Lloris-Garcera, J. S. Slusky, S. Seppälä, Killian, S. J. Marrink, Lipid Packing Drives [8] S. O. Yesylevskyy, L. V. Schäfer, D. Sen- M. Prieß, L. V. Schäfer, G. von Heijne, In the Segregation of Transmembrane gupta, S. J. Marrink, Polarizable Water vivo Trp-scanning of the Small Multidrug Helices into Disordered Lipid Domains in Model for the Coarse-Grained MARTINI Resistance Protein EmrE confirms 3D Model Membranes, Proc. Natl. Acad. Sci. Force Field, PLoS Comput. Biol. 2010, 6, Structure Models, J. Mol. Biol. 2013, 425, USA 2011, 108, 1343. e1000810. 4642. [5] J. Domanski, S. J. Marrink. L. V. Schäfer, [9] D. H. de Jong, G. Singh, W. F. D. Ben- [2] M. Majsnerowska, I. Hänelt, D. Wun- Transmembrane Helices can Induce nett, C. Arnarez, T. A. Wassenaar, L. V. nicke, L. V. Schäfer, H.-J. Steinhoff, D. J. Domain Formation in Crowded Model Schäfer, X. Periole, D. P. Tieleman, and S. Slotboom, Substrate-induced Confor- Membranes, Biochim. Biophys. Acta - J. Marrink, Improved Parameters For The mational Changes in the S-component Biomembr. 2012, 1818, 984. Martini Coarse-Grained Protein Force ThiT from an Energy Coupling Factor [6] T. A. Wassenaar, H. I. Ingolfsson, M. Field, J. Chem. Theory Comput. 2013, 9, Transporter, Structure 2013, 21, 861. Prieß, S. J. Marrink, L. V. Schäfer, Mixing 687. [3] S. Eggensperger, O. Fisette, D. Parcej, L. V. Martini: Electrostatic Coupling in Hybrid Schäfer, R. Tampé, An annular lipid belt Atomistic/Coarse-grained Biomolecular is essential for allosteric coupling and Simulations, J. Phys. Chem. B 2013, 117, viral inhibition of the antigen translo- 3516.

Lars Schäfer has been appointed Professor of Mo- an independent research group leader at Goethe- lecular Simulation at the Ruhr-University Bochum University Frankfurt. For more details, see www. in February 2014. He studied chemistry at the molecular-simulation.org TU Braunschweig and did his Ph.D. with Helmut Grubmüller at the MPI for Biophysical Chemistry in Göttingen (2007), as a Ph.D. fellow of the Boehrin- ger Ingelheim Fonds. Subsequently, he received a Veni fellowship from the Netherlands Organisation for Scientific Research to work as a postdoc at the University of Groningen with Siewert Jan Marrink (2008-2012), and an Emmy-Noether grant from the Deutsche Forschungsgemeinschaft to work as 65

Large-Scale Molecular Dynamics Simulations of Complex Systems Employing Neural Network Potentials

PD Dr. Jörg Behler, Fakultät für Chemie und Biochemie, Lehrstuhl für Theoretische Chemie

The main topic of the Behler group is the Materials Science development and implementation of accurate and efficient potential-energy surfaces Neural network potentials (NNPs) are for complex systems using artificial neural able to describe all types of bonding from networks and electronic structure methods. covalent bonds via metallic bonding to These potentials are applied to study pro- dispersion interactions for equilibrium blems in materials science, heterogeneous and non-equilibrium configurations with catalysis and solvation. comparable accuracy making them ideal candidates for applications to materials Neural Network Potentials science. Questions, which have been Fig. 2: Model of a copper cluster supported studied to date, include the high-pressure at zinc oxide. The reliability of the results obtained in phase diagram of silicon [3], the graphite to computer simulations of chemical proces- diamond phase transition of carbon [6] as Water and Solvation ses strongly depends on the quality of the well as the phase change material GeTe [7]. underlying potential-energy surface. While Water is the most abundant solvent in electronic structure methods like density- Heterogenous Catalysis chemistry and of central importance for functional theory (DFT) provide an accurate many chemical processes from bioche- description of the atomic interactions, The investigation of the structure of "real mistry to the storage of energy in batteries. the high computational costs prevent the catalysts" including large-scale defects is For understanding reactions in solution investigation of many interesting problems. an important prerequisite to study catalytic and at the solid-liquid interface, reactive In recent years artificial neural networks, reaction mechanisms in detail. Employing water potentials, which are able to provide which are trained to first-principles data, neural networks, in the SFB 558 "Metal- a reliable description of other species like have become a valuable tool to construct Substrate Interactions in Heterogeneous ions and metal surfaces are required. NNPs, high-quality atomistic potentials (Fig. 1) [1-2]. Catalysis" we have been able to construct which we have developed in the context We have been able to extend the applica- a potential for the copper-zinc-oxygen of the DFG cluster of excellence RESOLV – bility of this method to high-dimensional system , which is an important industrial "Ruhr-Explores SOLVation" can be applied to structures containing thousands of atoms, catalyst for methanol synthesis (Fig. 2). This water clusters [10] as well as to liquid water which now enables the simulation of large potential can provide total energies diffe- (Fig. 3) and can be used to speed up ab condensed systems [3-5] with an accuracy ring only a few meV per atom from DFT. initio molecular dynamics simulations by close to ab initio molecular dynamics several orders of magnitude. simulations.

Input Hidden Hidden Output Layer Layer1 Layer2 Layer

Fig. 3: Simulation of liquid water using a neural network potential.

Fig. 1: Schematic structure of a neural network potential [1]. In this example the energy E is a function of three coordinates G1, G2 and G3 . 66

Selected Publications [7] G. C. Sosso, G. Miceli, S. Caravati, F. [9] N. Artrith, B. Hiller, J. Behler, Neural Net- Gilberti, J. Behler, M. Bernasconi, Fast work Potentials for Metals and Oxides [1] J. Behler, Neural network potential- Crystallization of the Phase Change – First Applications to Copper Clusters at energy surfaces in chemistry: a tool for Compound GeTe by Large-Scale Molecu- Zinc Oxide, Phys. Stat. Sol. B 2013, 250, large-scale simulations, Phys. Chem. lar Dynamics Simulations, J. Phys. Chem. 1191. Chem. Phys. 2011, 13, 17930. Lett. 2013, 4, 4241. [10] T. Morawietz, J. Behler, A Density-Func- [2] J. Behler, B. Delley, S. Lorenz, K. Reuter, M. [8] N. Artrith, J. Behler, High-Dimensional tional Theory Based Neural Network Po-

Scheffler, Dissociation of O2 at Al(111): Neural Network Potentials for Metal tential for Water Clusters Including van The Role of Spin Selection Rules, Phys. Surfaces: A Prototype Study for Copper, der Waals Interactions, J. Phys. Chem. A Rev. Lett. 2005, 94, 36104. Phys. Rev. B 2012, 85, 045439. 2013, 117, 7356. [3] J. Behler, M. Parrinello, Generalized Neural-Network Representation of High- Dimensional Potential-Energy Surfaces, Phys. Rev. Lett. 2007, 98, 146401. [4] J. Behler, Atom-Centered Symmetry Functions for Constructing High-Di- mensional Neural Network Potentials, J. Chem. Phys. 2011, 134, 074106. [5] J. Behler, Representing Potential-Energy Surfaces by High-Dimensional Neural Network Potentials, J. Phys.: Condens. Matter 2014, 26, 183001. [6] R. Z. Khaliullin, H. Eshet, T. D. Kühne, J. Behler, M. Parrinello, Nucleation Mecha- nism for the direct graphite-to-diamond phase transition, Nature Materials 2011, 10, 693.

Dr. Jörg Behler is the head of an independent moved to the group of Prof. Dominik Marx at the Junior Research Group at the Lehrstuhl für The- Ruhr-Universität Bochum, where he established oretische Chemie. He studied chemistry at the an independent Junior Research Group funded by Universität Dortmund and obtained his PhD at the a Liebig Fellowship of the Fonds der Chemischen Fritz-Haber Institut der Max-Planck Gesellschaft Industrie (2007-2008), an Emmy Noether Group of and the Technische Universität Berlin under the the DFG (2008-2014) and a Heisenberg Fellowship supervision of Prof. Matthias Scheffler (2004). For of the DFG (2014-). In 2013 he was awarded the his thesis he was awarded the Otto-Hahn medal of Hans G.A. Hellmann Prize of the Arbeitsgemein- the MPG. After a postdoctoral stay at the Fritz- schaft Theoretische Chemie. In 2014 he finished his Haber Institut with Dr. Karsten Reuter he joined Habilitation in theoretical chemistry. Homepage: the group of Prof. Michele Parrinello at the ETH http://www.theochem.rub.de/research/behler/ Zürich, USI Campus Lugano, in 2006. In 2007 he index.html

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Quantum Chemistry: Wavefunction-Based Electronic Structure Theory

Prof. emeritus Volker Staemmler, Lehrstuhl für Theoretische Chemie, Ruhr-Universität Bochum

The main research interest of Volker studied the adsorption of atoms (H, Cu), tron spectra (XPS) and NEXAFS (near edge

Staemmler’s group has been and still is the small molecules (H2, CO, NO, N2) on oxide X-ray absorption fine structure) spectra for development and application of advanced surface (Figure 1). The aim is to determi- C1s, N1s, and O1s core levels in isolated and computational methods for the description ne adsorption energies and geometries, adsorbed molecules, Zn2s and Zn2p core le- of the electronic structure of molecules in adsorbate-induced modifications of the vels in Zn metal and ZnO, and surface core open-shell and excited states using accurate surface, change of the molecular properties level shifts in MgO. In many cases accom- wavefunction-based quantum chemical ab upon adsorption, spectroscopic properties panying ab initio calculations are needed initio techniques. By an efficient treatment of adsorbed species. to understand and correctly interpret the of electron correlation effects in such states experimental X-ray spectra. an approximate coupled cluster program, Magnetic exchange coupling called MC-CEPA, could be developed, which in transition metal complexes Selected Publications has been successfully applied to various systems with complicated electronic struc- The magnetic properties of transition 1. R. Fink, V. Staemmler, A multi-configurati- tures, as for instance in transition metal metal complexes are characterized by the on reference CEPA method based on pair complexes. exchange coupling constant J, the g tensor natural orbitals, Theoret. Chim. Acta 87, and the zero-field splitting tensor D. Using 129-145 (1993) For all of the following applications the our open.-shell programs, in particular 2. P. Mach, J. Urban, V. Staemmler, Disso- own MC-CEPA program has been used. the MC-CEPA part, and including spin- ciative Electron Attachment to Methyl orbit coupling we were able to calculate Chloride. A Quasi-Diatomic Potential Spectroscopic properties the energies of the different spin states Curve for the Fragmentation of the Me- - of small molecules for several transition metal complexes tastable CH3Cl Anion, Chem. Phys. 356, and to extract the parameters J, g, and D. 164-170 (2009) Accurate open-shell quantum chemical In combination with ab initio molecular 3. V. Staemmler, Method of Local Incre- methods are needed for a proper descripti- dynamics we have determined the magne- ments for the Calculation of Adsorption on of spectroscopic properties, in particular tostructural dynamics of iron-sulfur cores Energies of Atoms and Small Molecules electronic excitation energies, as well as for in ferredoxin and Rieske proteins (Figure 2), on Solid Surfaces. 2. CO/MgO(001), J. the calculation of potential energy surfaces by calculating the fluctuations of the anti- Phys. Chem. A 115, 7153-7160 (2011) for elementary chemical reactions. Our ferromagnetic coupling constant J at finite 4. S. A. Fiethen, V. Staemmler, N. N. Nair, recent applications cover (a) ground and temperatures. J. Ribas-Arino, E. Schreiner, D. Marx, excited electronic states of small radicals, Revealing the Magnetostructural Dy- (b) molecular Rydberg states and (c) meta- namics of [2Fe-2S] Ferrodoxins from stable molecular anions and dissociative Reduced-Dimensionality Analysis of electron attachment. Antiferromagnetic Exchange Coupling Fluctuations, J. Phys. Chem. B 114, Adsorption of small 11612-11619 (2010) molecules on oxide surfaces 5. Y. K. Gao, F. Traeger, K. Kotsis, V. Staemm- ler, A Theoretical Study of the XP and The first decisive step in heterogeneous NEXAFS Spectra of Alanine: Gas Phase catalysis is the adsorption of the reac- Molecule, Crystal, and Adsorbate at the tants (atoms, radicals, small molecules) ZnO(10-10) Surface, Phys. Chem. Chem. on the solid surface of the catalyst. Using Phys, 13, 10709-10718 (2011) embedded cluster models combined with 6. C. J. Nelin, F. Uhl, V. Staemmler, P. S. quantum-chemical methods we have Bagus, Y. Fujimori, M. Sterrer, H. Kuhlen- Figure 2 beck, H.-J. Freund, Surface Core-Level Binding Energy Shifts for MgO(100), X-ray spectroscopy Phys. Chem. Chem. Phys. 16, 21953- 21956 (2014) X-ray spectroscopies of different kind are widely used experimentally to get element- specific information on the electronic structure of molecules. Such techniques are particularly important for adsorbates on solid surfaces. Our open-shell programs have been modified to calculate such spec- Figure 1 tra. Recent examples are X-ray photoelec- 68

Volker Staemmler is retired professor for Theore- Research Lab in San Jose, California (1975-1976, tical Chemistry at the Ruhr-University Bochum. with A. D. McLean) he finished his Habilitation in He studied physics in Göttingen, but switched to Bochum in 1975. He stayed at the Ruhr-University Quantum Chemistry for his diploma and PhD the- as research assistant and was appointed professor sis. He received his PhD in Göttingen under the su- for Theoretical Chemistry in 1980. Since this time pervision of Prof. W. A. Bingel in 1969. After post- he was teaching in Bochum and was involved as doctoral stays in Karlsruhe(1970-1973, with W. member and speaker in several priority programs Kutzelnigg), Naples (1972, with G. Del Re), Bochum and graduate schools. He retired in 2006, but is (1974-1976, with W. Kutzelnigg) and at the IBM still active in research as professor emeritus.

Physical Chemistry at High Presssures

Prof.em. Dr.rer.nat. Dr.hc(UA) Gerhard M. Schneider, Physical Chemistry 2

The main fields of research were physico- phases allows the separation of thermola- Science, Phys. Chem. Chem. Phys. 2004, 6, chemical investigations predominantly at bile and/or low-volatile substances and the 2285 - 2290. high pressures the accent being on phase determination of some physicochemical [2] G.M. Schneider, Aqueous solutions at behaviour and critical phenomena of fluid properties such as capacity ratios, diffusion pressures up to 2 GPa: gas-gas equilibria, mixtures as well as supercritical fluid coefficients, a.o. [4]. closed loops, high-pressure immiscibility, chromatography (SFC), investigations using salt effects and related phenomena, Phys. thermal methods (DTA, DSC), application of Thermal methods (DTA, DSC) Chem. Chem. Phys. 2002, 4, 845 - 852. pressure jump relaxation techniques, a.o. at high pressures [3] R. Grzanna, G.M. Schneider, High Pressure Investigations on Fluid Mixtures with a Phase equilibria and Selected substances (organic compounds, Diamond Anvil Cell: Liquid-Liquid Phase critical phenomena of highly liquid crystals, plastic crystals) were studied Equilibria and "High Pressure Immiscibi- compressed fluid mixtures by differential thermal analysis (DTA) up to liy" of the System 1-Butanol + 2-Methyl- 7 kbar and differential scanning calorimetry 2-propanol + Water up to 2.9 GPa, Z. Phys. The phase and critical behaviour of binary, (DSC) up to 5 kbar [5]. Chem. 1996,193, 41 - 47. ternary and more complex mixtures (lg, ll, [4] U, van Wasen, I. Swaid, G.M. Schneider, gg, ls etc.) between -200 °C and +400 °C Pressure jump relaxation Physikalisch-chemische Grundlagen und and at pressures up to 4 kbar was measu- studies at high pressures Anwendungen der Fluidchromatographie red, the investigations being of interest for (SFC), Angew. Chem. 1980, 92, 585 - 598. fluid extraction and supercritical fluid chro- Experimental setups for pressure jump [5] C. Schmidt, M. Rittmeier-Kettner, H. Be- matography (SFC) [1,2]. The measurements relaxation measurements up to 2 kbar were cker, J. Ellert, R. Krombach, G.M. Schnei- could be extended up to about 20 kbar by developed and used for investigations on der, Differential Thermal Analysis (DTA) diamond anvil techniques [3]. the kinetics of phase separation in fluid mix- and Differential Scanning Calorimetry tures and of chemical reactions in solution. (DSC) at high pressures. Experimental Supercritical Fluid techniques and selected results, Ther- Chromatography (SFC) Selected Publications mochimica Acta 1994, 238, 321 - 336.

The use of highly compressed gases in [1] G.M. Schneider, The continuity and family their critical temperature range as mobile concepts - useful tools in Fluid Phase

Gerhard M. Schneider was born in 1932. He received his the International Union of Pure and Applied Chemistry degrees in chemistry from the University of Göttingen (IUPAC) from 1981 to 1985 and Vice-President (1987 (Diploma, 1957; Doctorate, 1959) and completed his - 1989) and President (1989 - 1991) of the Physical Che- Habilitation at the University of Karlsruhe in 1965 mistry Division of IUPAC. In 1960 he received the Nernst where he held the positions of a Senior Researcher Prize of the Deutsche Bunsengesellschaft. He was Rossini (1961 - 1965) and a Lecturer (1965 - 1969). From 1969 Lecturer of IUPAC in 1990, Wilhelm-Jost Lecturer of the to 1997 he was Professor of Physical Chemistry at the Deutsche Bunsengesellschaft in 1995 and Lennard-Jones Ruhr-University Bochum where he supervised about 90 Lecturer .of the Royal Society of Chemistry in 2005. He diploma students and about 80 doctoral students, Since received the Dr.hc(UA) title from the Ukrainian State 1997 he is Emeritus Professor. He is author or coauthor Academy of Refrigeration, Odessa, in 2003. For more of about 300 scientific publications. He was Chairman details see Ber. Bunsenges. Phys. Chem. 1997, 101, 872 - of the Commission on Chemical Thermodynamics of 873; J. Supercritical Fluids 1998, 13, 1 - 3. Bei uns findest Du Deinen Traumberuf! www.opusmundi.de

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