Poster Abstracts67th Lindau Nobel Laureate Meeting25 – 30 June 2017

# T First Author Title

Catalysis – Photocatalysis

1 A Ki Chang Kwon Anion Engineering of Molybdenum Disulfide (MoS2)Thin Film Catalysts for E�cient Solar Water Splitting

2 B Xinyi Chia Chalcogen E�ect of Platinum Dichalcogenides on Electrochemistry and Electrocatalysis

3 C Thomas L. Gianetti Toward a Useful Catalytic Transformation of N2O

4 B Dayne F. Swearer The Best of Both Worlds: ‘Antenna-Reactor’ Nanostructures for Plasmonic Photocatalysis

5 A Biswajit Mondal CO2 Reduction to CO by Iron Porphyrins: Electrochemical and Spectroscopic Investigation of the Mechanism

Metal Organic Frameworks

6 C In-Hyeok Park Photo-Cycloaddition Reaction inside Metal-Organic Frame works: Formation of Isotactic and Syndiotactic Organic Polymers

7 B Ivo Stassen Chemical vapor deposition of nanoporous metal-organic frameworks

Perovskite Photovoltaics

8 A Amita Ummadisingu

Mechanism of perovskite film formation and the e�ect of light

9 B Il Jeon Carbon-Sandwiched Perovskite Solar Cell

10 C Abhishek Swarnkar Luminescence and Solar Cells from Colloidal Cesium Lead Halide (CsPbX3) Perovskite Nanocrystals

Nanoparticles

11 A Chenjie Zeng Precision at the nanoscale:On the structure and property evolution of gold nanoclusters

12 B Yolanda Salinas Polyphosphazene-based biodegradable bridged silicananoparticles, the future drug nanocarriers

Supramolecular Chemistry, Photoswitching, Polymers

13 C Michael M. Lerch Understanding Donor-Acceptor Stenhouse Adducts

14 A Michael Kathan Controlling Chemical Reactivity with Light

15 B Frank Biedermann Supramolecular Sensing Ensembles: More Information through Communication

16 C Alice Chang Manipulating the ABCs of Self-Assembly viaLow-χ Block Polymer Design

POSTER OVERVIEW

# T First Author Title

Methods and Method Development for Studying/Building Biological Systems

17 B Elisa D’Este Nanoscale organization of subcortical actin in the nervous system

18 A Vini Gautam Optoelectronic materials as biointerfaces for neuroprosthetics

19 C Chenge Li Dynamic multi-color protein labeling in living cells

20 A Aditi Borkar Bringing functional order to disordered complexes of HIV-1transactivation process

21 C Cécile Echalier Hybrid hydrogels as synthetic matrices for tissue engineering

22 B Marija Liutkute Monitoring co-translational folding in real-time

23 C Zibo Chen Watson-Crick style programmable protein interaction specificity

24 A Hiroko Yamashita Development of Helical Cell Penetrating PeptidesUsing Non-proteinogenic Amino Acids

Surfaces – Biofilms

25 A Noemí Encinas NoBios: Super-liquid repellent coatings to prevention protein adsorption and bacterial adhesion

DNA, RNA, Ribosome

26 C Zohar Eyal Structural insights into Staphylococcus aureus ribosome in complex with antibiotic, mRNA and tRNAs

27 B Shintaro Aibara The translating human mitochondrial ribosome in action – snapshots observed by cryo-EM

28 C Raktim N. Roy Ribosome Inactivating Peptides and the conserved mechanism of inhibition

29 A Victor Pui-Yan Ma Decoding the physical aspect of T cell activation and long term functions by DNA based force probes

30 B Magdalena Zdrowowicz

Trojan horse therapy of cancerModified nucleosides as photo/radiosensitizers of DNA damage

POSTER OVERVIEW

Poster Presentation Time Slots

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Wednesday, 28 June 2017 13.45-14.45

Thursday, 29 June 2017 13.45-14.45

Tuesday, 27 June 2017 13.45-14.45

POSTER PLAN

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Colored by Topic AreaSee preceding pages for details.

Colored by Presentation Time

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Wednesday, 28 June 2017 13.45-14.45

Thursday, 29 June 2017 13.45-14.45

Tuesday, 27 June 2017 13.45-14.45

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PostersThe posters will be on display in the primary school gym on Tues-day and Wednesday from 13.00 - 19.00 hrs and on Thursday from 13.00 - 16.30 hrs.

Poster PresentationsThe poster authors will be present at their posters in the primary school gym to present and explain their posters during the times stated on the left page.

Poster FlashesThe research presented on the poster will also be presented in a 90 minute poster �ash session, where every presenter may show a ma-ximum of two slides and has two minutes of time. The poster �ash takes place on Monday at 16.30 hrs at the city theatre. Posters will be presented in the order shown on the preceding pages.

Poster AwardsThis brochure includes a voting sheet. Please put your voting sheet in one of the boxes or return it to the Young Scientists Desk by Thursday, 29 June 2017, 16.30 hrs, at the latest. The winners will be announced during the boat trip on Friday, 30 June 2017.

Poster Setup• All poster walls have a useable area of 120 cm width and 150 cm

height. We recommend posters in size A0 (84,1 x 118,9 cm).• Posters may be set up between 13.00 and 15.00 hrs on Monday,

26 June 2017. • Posters have to be provided by the authors; no on-site printing is

available. Tape and �xing pins are available in the poster area. • Posters have to be placed on designated walls – please refer to

the poster number published in this brochure.• Posters have to be removed by the presenters immediately after

the poster session on Thursday, i.e. from 16.30 – 17.00 hrs. Posters not removed will not be stored.

INFORMATION

Anion Engineering of Molybdenum Disulfide (MoS2)

Thin Film Catalysts for Efficient Solar Water Splitting Ki Chang Kwon, Seokhoon Choi, Ho Won Jang

Seoul National University, Department of Materials Science and Engineering

1 Gwanak-ro, Daehak-dong, Gwanak-gu, Seoul 08826, Republic of Korea

We synthesized transferrable and transparent anion engineered MoS2 thin-film catalysts through a simple thermolysis method by using a [(NH4)2MoS4] solution precursor and powder precursors with different S/P weight ratios as shown in Figure 1 [1]. The sulfur-doped molybdenum phosphide (S:MoP, S/P ratio = 0.33) thin film catalyst, which was composed of cheap and earth abundant elements, could provide an onset potential as low as 1 mA/cm2 at 0.285 V vs. a reversible hydrogen electrode and a photocurrent density as high as 33.13 mA/cm2 at 0 V for a S:MoP/p-type Si heterojunction photocathode. The structure of the synthesized S:MoP thin film changed from the two-dimensional van der Waals structure to a three-dimensional hexagonal structure by the introduction of phosphorus atoms in the MoS2 thin film. According to the band energy diagram of the p-n heterojunction between S:MoP and a p-Si photocathode, this structural transition facilitated the easy transportation of photogenerated electrons to the surface from the p-Si light absorber. The density functional theory calculations indicated that the surface active S:MoP thin film catalyst could easily absorb hydrogen as compared to the relatively surface inactive MoS2 because of its low hydrogen adsorption Gibbs free energy [2].

Figure 1. Synthesis of anion engineered MoS2 thin film catalyst using chemical vapor deposition technique. Photoelectrochemical catalytic activity of synthesized thin film catalysts on p-type Si photocathode with various ratio of sulfur to phosphorus amounts. References

[1] K. C. Kwon, S. Choi, K. Hong, C. W. Moon, Y.-S. Shim, D. H. Kim, T. Kim, W. Sohn, J.-M. Jeon, C.-H. Lee, K. T. Nam, S. Han, S. Y. Kim, H. W. Jang, Energy & Environmental Science 9, 2240-2248 (2016).

[2] R. Ye, P. Angel-Vicente, Y. Liu, M. J. Arellano-Jimenez, Z. Peng, T. Wang, Y. Li, B. I. Yakobson, S.-H. Wei, M. J. Yacaman, J. M. Tour, Advanced Materials, 28, 1427-1432 (2016).

Catalysis – Photocatalysis1

Anion Engineering of Molybdenum Disulfide (MoS2)

Thin Film Catalysts for Efficient Solar Water Splitting Ki Chang Kwon, Seokhoon Choi, Ho Won Jang

Seoul National University, Department of Materials Science and Engineering

1 Gwanak-ro, Daehak-dong, Gwanak-gu, Seoul 08826, Republic of Korea

We synthesized transferrable and transparent anion engineered MoS2 thin-film catalysts through a simple thermolysis method by using a [(NH4)2MoS4] solution precursor and powder precursors with different S/P weight ratios as shown in Figure 1 [1]. The sulfur-doped molybdenum phosphide (S:MoP, S/P ratio = 0.33) thin film catalyst, which was composed of cheap and earth abundant elements, could provide an onset potential as low as 1 mA/cm2 at 0.285 V vs. a reversible hydrogen electrode and a photocurrent density as high as 33.13 mA/cm2 at 0 V for a S:MoP/p-type Si heterojunction photocathode. The structure of the synthesized S:MoP thin film changed from the two-dimensional van der Waals structure to a three-dimensional hexagonal structure by the introduction of phosphorus atoms in the MoS2 thin film. According to the band energy diagram of the p-n heterojunction between S:MoP and a p-Si photocathode, this structural transition facilitated the easy transportation of photogenerated electrons to the surface from the p-Si light absorber. The density functional theory calculations indicated that the surface active S:MoP thin film catalyst could easily absorb hydrogen as compared to the relatively surface inactive MoS2 because of its low hydrogen adsorption Gibbs free energy [2].

Figure 1. Synthesis of anion engineered MoS2 thin film catalyst using chemical vapor deposition technique. Photoelectrochemical catalytic activity of synthesized thin film catalysts on p-type Si photocathode with various ratio of sulfur to phosphorus amounts. References

[1] K. C. Kwon, S. Choi, K. Hong, C. W. Moon, Y.-S. Shim, D. H. Kim, T. Kim, W. Sohn, J.-M. Jeon, C.-H. Lee, K. T. Nam, S. Han, S. Y. Kim, H. W. Jang, Energy & Environmental Science 9, 2240-2248 (2016).

[2] R. Ye, P. Angel-Vicente, Y. Liu, M. J. Arellano-Jimenez, Z. Peng, T. Wang, Y. Li, B. I. Yakobson, S.-H. Wei, M. J. Yacaman, J. M. Tour, Advanced Materials, 28, 1427-1432 (2016).

Chalcogen Effect of Platinum Dichalcogenides on Electrochemistry and Electrocatalysis

Xinyi Chia a, Adriano Ambrosi a, Petr Lazar b, Zdeněk Sofer c, Jan Luxa c, Martin Pumera a

a School of Physical and Mathematical Sciences, Nanyang Technological University,

21 Nanyang Link, Singapore 637371, Singapore. b Regional Centre of Advanced Technologies and Materials, Palacký University Olomouc,

tř.17. Listopadu 12, 771 46 Olomouc, Czech Republic. c Department of Inorganic Chemistry, University of Chemistry and Technology Prague,

Technická 5, 166 28 Prague, Czech Republic.

To date, research in layered transition metal dichalcogenides (TMDs) is skewed towards Group 6 TMDs [1] while other groups in the TMD family remain in obscurity. This work unravels the electrochemistry of the Group 10 TMDs; specifically the platinum (Pt) dichalcogenides comprising PtS2, PtSe2 and PtTe2. Substituting the chalcogen atom from sulfur with selenium, and then with tellurium, dramatically modifies the electronic property of the Pt dichalcogenide [2-4]. Upon progressing down the chalcogen group, the paradigm shift in the electronic property of the Pt dichalcogenide from semiconducting in PtS2; semimetallic, in PtSe2 and to metallic in PtTe2, kindles interest in their charge transfer and catalytic attributes. We draw parallels between the chalcogen type (S, Se and Te) and the electrochemical and electrocatalytic properties of Pt dichalcogenides. Towards the goal of electrochemical activation, we evaluate the efficacy of an oxidative and reductive treatment in promoting their charge transfer and electrocatalytic properties. Using density functional theory (DFT) calculations, the electrochemical and catalytic behaviors of Pt dichalcogenides are rationalized to hinge on their electronic structures. In terms of charge transfer, all Pt dichalcogenides are successfully activated when subject to an electro-reductive treatment. Accelerated heterogeneous electron transfer (HET) rates are evident in electrochemically reduced Pt dichalcogenides. The electrocatalytic attributes of the Pt dichalcogenides for hydrogen evolution reaction (HER) unveil an interesting trend of PtTe2 > PtSe2> PtS2 whereby the HER catalytic property increases down the chalcogen group. Moreover, Pt dichalcogenides are effectively activated for HER such that reduced PtS2 and oxidized PtTe2

exhibit improved HER performance compared to before treatment. PtSe2 manifests enhanced HER properties when electrochemically oxidized or reduced. These different electrochemical responses of Pt dichalcogenides to attain activation largely stem from their intrinsic electronic structures. Among all electro-activated Pt dichalcogenides, PtS2 demonstrates most accentuated improvement as a HER electrocatalyst with 50 % decline in HER overpotential at -10 mA cm-2. Knowledge on Pt dichalcogenides provides insights into TMD electrochemistry and their applications; in particular, for the inadequately represented Group 10 TMDs. [1] S. Wu, Z. Zeng, Q. He, Z. Wang, S. J. Wang, Y. Du, Z. Yin, X. Sun, W. Chen, H. Zhang, Small 8, 2264-2270, (2012). [2] G. Y. Guo, W. Y. Liang, Journal Physics C: Solid State Physics 19, 995-1008, (1986). [3] S. Soled, A. Wold, O. Gorochov, Materials Research Bulletin 11, 927-932, (1976). [4] F. Hulliger, Journal of Physics and Chemistry of Solids 26, 639-645, (1965).

Catalysis – Photocatalysis 2

The Best of Both Worlds: ‘Antenna-Reactor’ Nanostructures for

Plasmonic Photocatalysis

Dayne F. Swearer1, Hossein Robatjazi1, Linan Zhou1, Chao Zhang1, Rowan K. Leary2, Sadegh Yazdi1, Hangqi Zhao1, Paul A. Midgley2, Peter Nordlander1, Emilie Ringe1, Naomi J. Halas1

1 Rice University, 6100 Main Street, Houston, TX 77005, USA

2 University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS, U.K.

Developing materials that can efficiently harvest solar radiation and drive chemical reactions is one route to realize the wide scale adoption of solar-driven chemical manufacture. This achievement could help wean the chemical industry off of fossil fuels, a major source of global energy consumption and anthropogenic atmospheric pollution. Yet this has been a challenge, since transition metal nanoparticles traditionally used in heterogeneous catalysis do not effectively couple with light. On the other hand, plasmonic metals such as Au, Ag, and Al, interact strongly with light but are often unsuitable to drive diverse chemical reactions on their surfaces. We are developing a new platform of modular ‘antenna-reactor’ nanostructures that combine the best of both worlds: a plasmonic ‘antenna’ and catalytic ‘reactors’ into a single structure with optimized optical and catalytic properties [1]. We utilize aluminum nanocrystals (AlNCs) as plasmonic antennae because Al is the most abundant metal in the Earth’s crust, and sustains strong plasmon resonances throughout the ultraviolet, visible, and near infrared regions of the electromagnetic spectrum [2]. The AlNCs are decorated with 3-5 nm islands of transition metals, of which over a dozen varieties have been synthesized [3]. AlNCs have a 2-4 nm self-limiting native oxide layer that passivates the underlying crystal, and acts as a thin physical barrier between the antenna and reactor. Material characterization using high-resolution electron microscopy, energy dispersive X-ray spectroscopy, and electron tomography revealed the morphological details and true 3D nature of these materials; important for understanding structure-function relationships within this new class of photocatalyst. The close proximities between the antenna and reactor results in significant absorption enhancements in the catalytic materials. This increased absorption in the optically lossy catalytic metal leads to high hot-carrier distributions within the materials, which leads to new mechanistic pathways that show potential for selective chemical transformations. For example, on Al-Pd, hydrogenation of acetylene resulted in significantly increased selectivity of ethylene production over ethane. Similarly, CO2 reduction to CO was achieved on Al-Cu2O with 99.97% selectivity over CH4, which is the main product under traditional thermal conditions.

This interdisciplinary work shines light on the fundamentals of plasmon-mediated chemistry, nanomaterial synthesis and characterization, heterogeneous catalysis, electron transfer processes, and nanoscale optics. The modularity in material design and the growing library of photocatalyzed reactions using antenna-reactor nanostructures may one day allow for light-driven chemistry to make the food, medicine, and materials of tomorrow.  [1] Swearer, D. F. et al. Proc. Natl. Acad. Sci. 113, 8916–8920 (2016). [2] Knight, M. W. et al. ACS Nano 8, 834–40 (2014). [3] Swearer, D.F. et al. Submitted. (2017)

Electron tomogram of a single Al-Ru nanoparticle, rendered in 3D, where Ru islands are color coded by diameters between 1-6 nm.

Toward a Useful Catalytic Transformation of N2O

Thomas L. Gianetti, Hansjörg Grützmacher

ETH Zürich, Department of Chemistry and Applied Biosciences,

Vladimir Prelog Weg 1, 8093 Zürich, Switzerland

Nitrous oxide (N2O) gases have been recently identified as the largest global ozone depleting agents and as the 3rd largest emitted greenhouse gases worldwide and 300 times more powerful than CO2.[1] N2O is naturally produced via nitrification and denitrification of nitrate during nitrogen cycle, but is also an industrial waste. N2O emission has increased significantly during industrialization as a result of agricultural soil management, N-fertilizer use, livestock waste management, mobile & stationary fossil fuel, combustion and industrial processes. Its transformation to less harmful chemicals is of particular interest but very challenging, since even if thermodynamically unstable, nitrous oxide is kinetically inert.[2] We have successfully design low valent and reactive organometallic species containing group 9 metals (Rh[3] and Co[4]) that activate and catalytically transform, under mild conditions, this environmentally unfriendly molecules to valuable chemicals.

[1] a) A. R. Ravishankara, J. S. Daniel, R. W. Portmann, Science 326, 123-125, (2009). b) J. Hansen, M. Sato, Proc. Natl. Acad. Sci. USA. 101, 16109-16114, (2004). [2] a) E. Eger, I., II. In Nitrous Oxide N2O, Elsevier: New York, 1985. b) K. Severin Chem. Soc. Rev. 44, 6375-6386, (2015). [3] T. L. Gianetti, S. P. Annen, G. Santiso-Quinones, M. Reiher, M. Driess, H. Grützmacher, Angew. Chem. Int. Ed. 55, 1886-1890, (2016). [4] T. L. Gianetti, R. E. Rodriguez-Lugo, J. Harmer, M. Trincado, M. Vogt, G. Santiso-Quinones, H. Grützmacher, Angew. Chem. Intl. Ed. 55, 15323-15328, (2016).

3 Catalysis – Photocatalysis

The Best of Both Worlds: ‘Antenna-Reactor’ Nanostructures for

Plasmonic Photocatalysis

Dayne F. Swearer1, Hossein Robatjazi1, Linan Zhou1, Chao Zhang1, Rowan K. Leary2, Sadegh Yazdi1, Hangqi Zhao1, Paul A. Midgley2, Peter Nordlander1, Emilie Ringe1, Naomi J. Halas1

1 Rice University, 6100 Main Street, Houston, TX 77005, USA

2 University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS, U.K.

Developing materials that can efficiently harvest solar radiation and drive chemical reactions is one route to realize the wide scale adoption of solar-driven chemical manufacture. This achievement could help wean the chemical industry off of fossil fuels, a major source of global energy consumption and anthropogenic atmospheric pollution. Yet this has been a challenge, since transition metal nanoparticles traditionally used in heterogeneous catalysis do not effectively couple with light. On the other hand, plasmonic metals such as Au, Ag, and Al, interact strongly with light but are often unsuitable to drive diverse chemical reactions on their surfaces. We are developing a new platform of modular ‘antenna-reactor’ nanostructures that combine the best of both worlds: a plasmonic ‘antenna’ and catalytic ‘reactors’ into a single structure with optimized optical and catalytic properties [1]. We utilize aluminum nanocrystals (AlNCs) as plasmonic antennae because Al is the most abundant metal in the Earth’s crust, and sustains strong plasmon resonances throughout the ultraviolet, visible, and near infrared regions of the electromagnetic spectrum [2]. The AlNCs are decorated with 3-5 nm islands of transition metals, of which over a dozen varieties have been synthesized [3]. AlNCs have a 2-4 nm self-limiting native oxide layer that passivates the underlying crystal, and acts as a thin physical barrier between the antenna and reactor. Material characterization using high-resolution electron microscopy, energy dispersive X-ray spectroscopy, and electron tomography revealed the morphological details and true 3D nature of these materials; important for understanding structure-function relationships within this new class of photocatalyst. The close proximities between the antenna and reactor results in significant absorption enhancements in the catalytic materials. This increased absorption in the optically lossy catalytic metal leads to high hot-carrier distributions within the materials, which leads to new mechanistic pathways that show potential for selective chemical transformations. For example, on Al-Pd, hydrogenation of acetylene resulted in significantly increased selectivity of ethylene production over ethane. Similarly, CO2 reduction to CO was achieved on Al-Cu2O with 99.97% selectivity over CH4, which is the main product under traditional thermal conditions.

This interdisciplinary work shines light on the fundamentals of plasmon-mediated chemistry, nanomaterial synthesis and characterization, heterogeneous catalysis, electron transfer processes, and nanoscale optics. The modularity in material design and the growing library of photocatalyzed reactions using antenna-reactor nanostructures may one day allow for light-driven chemistry to make the food, medicine, and materials of tomorrow.  [1] Swearer, D. F. et al. Proc. Natl. Acad. Sci. 113, 8916–8920 (2016). [2] Knight, M. W. et al. ACS Nano 8, 834–40 (2014). [3] Swearer, D.F. et al. Submitted. (2017)

Electron tomogram of a single Al-Ru nanoparticle, rendered in 3D, where Ru islands are color coded by diameters between 1-6 nm.

Toward a Useful Catalytic Transformation of N2O

Thomas L. Gianetti, Hansjörg Grützmacher

ETH Zürich, Department of Chemistry and Applied Biosciences,

Vladimir Prelog Weg 1, 8093 Zürich, Switzerland

Nitrous oxide (N2O) gases have been recently identified as the largest global ozone depleting agents and as the 3rd largest emitted greenhouse gases worldwide and 300 times more powerful than CO2.[1] N2O is naturally produced via nitrification and denitrification of nitrate during nitrogen cycle, but is also an industrial waste. N2O emission has increased significantly during industrialization as a result of agricultural soil management, N-fertilizer use, livestock waste management, mobile & stationary fossil fuel, combustion and industrial processes. Its transformation to less harmful chemicals is of particular interest but very challenging, since even if thermodynamically unstable, nitrous oxide is kinetically inert.[2] We have successfully design low valent and reactive organometallic species containing group 9 metals (Rh[3] and Co[4]) that activate and catalytically transform, under mild conditions, this environmentally unfriendly molecules to valuable chemicals.

[1] a) A. R. Ravishankara, J. S. Daniel, R. W. Portmann, Science 326, 123-125, (2009). b) J. Hansen, M. Sato, Proc. Natl. Acad. Sci. USA. 101, 16109-16114, (2004). [2] a) E. Eger, I., II. In Nitrous Oxide N2O, Elsevier: New York, 1985. b) K. Severin Chem. Soc. Rev. 44, 6375-6386, (2015). [3] T. L. Gianetti, S. P. Annen, G. Santiso-Quinones, M. Reiher, M. Driess, H. Grützmacher, Angew. Chem. Int. Ed. 55, 1886-1890, (2016). [4] T. L. Gianetti, R. E. Rodriguez-Lugo, J. Harmer, M. Trincado, M. Vogt, G. Santiso-Quinones, H. Grützmacher, Angew. Chem. Intl. Ed. 55, 15323-15328, (2016).

4Catalysis – Photocatalysis

CO2 Reduction to CO by Iron Porphyrins: Electrochemical and Spectroscopic Investigation of the Mechanism

Biswajit Mondal, Atanu Rana, Pritha Sen, Dibyajyoti Saha, Abhishek Dey*

Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, 2A & 2B Raja S.C. Mullick Road, Jadavpur, Kolkata-700032

E-mail: icbm@iacs.res.in, icad@iacs.res.in

Improved electrocatalysts for the CO2 reduction (CDR) are critical for the advancement of renewable energy research.[1] Iron porphyrins are one of the excellent catalysts for the electro- and photocatalytic reduction of CO2.[2] Our present study reveals that the reduction of CO2 by an iron porphyrin complex with a hydrogen bonding distal pocket involves at least two intermediates.[3] The resonance Raman data of intermediate I, which could only be stabilized at −95°C, indicates that it is a Fe(II)–CO2

2– adduct and is followed by an another intermediate II at −80°C where the bound CO2 in intermediate I is protonated to form a Fe(II)–COOH species. While the initial protonation can be achieved using weak proton sources like MeOH and PhOH, the facile heterolytic cleavage of the C–OH bond in intermediate II requires strong acids. However, the pKa of this externally added acid is the key to selective CO2 reduction over proton reduction and hence strong acid under electrocatalytic condition prior to the formation of intermediate-II may lead to oxidation of iron(0) to afford proton reduction. A series of iron porphyrins that varies in terms of the distal H-bonding pocket are further studied and possess turnover frequencies (TOFs) from ranging from 1.0 s−1 to an unprecedented value of 104 s−1. These TOFs correlate with the H-bonding ability of the distal superstructure of these iron porphyrin complexes. DFT studies show that the intermediate–I is less activated for iron porphyrin complexes bearing internal H-bonding donor residues compared to the complexes where the intermediate-I is stabilised by columbic interaction. However, these H-bonding donor residues are helpful in activating the externally added acid (without changing the pKa of the acid) required to cleave the C-OH bond of the intermediate-II. This analysis thus provides detailed understanding of the CDR barriers helpful to develop a better iron porphyrin based CO2 electroreduction catalyst.

[1] J. Qiao , Y. Liu , F. Hong , J. Zhang, Chem Soc Rev., 43, 631 (2014).

[2] (a) C. Costentin, S. Drouet, G. Passard, M. Robert, J-M. Savéant, Science, 338, 90 (2012).

(b) C. Costentin, G. Passard, M. Robert, J-M. Savéant, Proc. Natl. Acad. Sci. (USA), 111, 14990 (2014).

[3] B. Mondal, A. Rana, P. Sen, A. Dey, J. Am. Chem. Soc., 137, 11214 (2015).

Photo-Cycloaddition Reaction inside Metal-Organic Frameworks: Formation of Isotactic and Syndiotactic Organic Polymers

In-Hyeok Park,ab Shim Sung Lee,*a and Jagadese J. Vittal*b

aDepartment of Chemistry, Gyeongsang National University, Jinju 52828, South Korea bDepartment of Chemistry, National University of Singapore, 117543, Singapore

The tacticity control of the organic polymers is one of the important issues both in academic and industrial areas. We obtained the isotactic organic polymer inside a 3D Zn(II) metal-organic fraomework (MOF-1) based on a mixture of bpeb and H2bdc through the photo-induced [2+2] cycloaddition reaction as a first case [1]. While a bent H2obc ligand was used instead of the linear H2bdc ligand, we obtained the syndiotactic organic polymer inside a 3D Zn(II) MOF-2 [2]. In the 6-fold interpenetrated MOF-1, the bpeb ligands show a herringbone-type slip-stacked pattern which results in the formation of the isotactic organic polymer in metal-oragano-polymeric framework (MOPF-1, see below). Since the MOF-2 was photo-inactive, upon heating the bpeb ligand with trans,trans,trans-conformation undergoes pedal motion to trans,cis,trans-conformation and yield the MOPF-2 containing 2D network fused with the syndiotactic organic polymer. We also found that the both prepared organic polymers with different tacticities in the single crystal form are depolymerized reversibly by cleaving the cyclobutane rings upon heating.

[1] I.-H. Park, A. Chanthapally, Z. Zhang, S. S. Lee, M. J. Zaworotko, J. J. Vittal, Angew. Chem. Int. Ed. 53, 414–419 (2014). [2] I.-H. Park, R. Medishetty, H.-H. Lee, C. E. Mulijanto, H. S. Quah, S. S. Lee, J. J. Vittal, Angew. Chem., Int. Ed. 54, 7313–7317 (2015).

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5 Catalysis – Photocatalysis

CO2 Reduction to CO by Iron Porphyrins: Electrochemical and Spectroscopic Investigation of the Mechanism

Biswajit Mondal, Atanu Rana, Pritha Sen, Dibyajyoti Saha, Abhishek Dey*

Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, 2A & 2B Raja S.C. Mullick Road, Jadavpur, Kolkata-700032

E-mail: icbm@iacs.res.in, icad@iacs.res.in

Improved electrocatalysts for the CO2 reduction (CDR) are critical for the advancement of renewable energy research.[1] Iron porphyrins are one of the excellent catalysts for the electro- and photocatalytic reduction of CO2.[2] Our present study reveals that the reduction of CO2 by an iron porphyrin complex with a hydrogen bonding distal pocket involves at least two intermediates.[3] The resonance Raman data of intermediate I, which could only be stabilized at −95°C, indicates that it is a Fe(II)–CO2

2– adduct and is followed by an another intermediate II at −80°C where the bound CO2 in intermediate I is protonated to form a Fe(II)–COOH species. While the initial protonation can be achieved using weak proton sources like MeOH and PhOH, the facile heterolytic cleavage of the C–OH bond in intermediate II requires strong acids. However, the pKa of this externally added acid is the key to selective CO2 reduction over proton reduction and hence strong acid under electrocatalytic condition prior to the formation of intermediate-II may lead to oxidation of iron(0) to afford proton reduction. A series of iron porphyrins that varies in terms of the distal H-bonding pocket are further studied and possess turnover frequencies (TOFs) from ranging from 1.0 s−1 to an unprecedented value of 104 s−1. These TOFs correlate with the H-bonding ability of the distal superstructure of these iron porphyrin complexes. DFT studies show that the intermediate–I is less activated for iron porphyrin complexes bearing internal H-bonding donor residues compared to the complexes where the intermediate-I is stabilised by columbic interaction. However, these H-bonding donor residues are helpful in activating the externally added acid (without changing the pKa of the acid) required to cleave the C-OH bond of the intermediate-II. This analysis thus provides detailed understanding of the CDR barriers helpful to develop a better iron porphyrin based CO2 electroreduction catalyst.

[1] J. Qiao , Y. Liu , F. Hong , J. Zhang, Chem Soc Rev., 43, 631 (2014).

[2] (a) C. Costentin, S. Drouet, G. Passard, M. Robert, J-M. Savéant, Science, 338, 90 (2012).

(b) C. Costentin, G. Passard, M. Robert, J-M. Savéant, Proc. Natl. Acad. Sci. (USA), 111, 14990 (2014).

[3] B. Mondal, A. Rana, P. Sen, A. Dey, J. Am. Chem. Soc., 137, 11214 (2015).

Photo-Cycloaddition Reaction inside Metal-Organic Frameworks: Formation of Isotactic and Syndiotactic Organic Polymers

In-Hyeok Park,ab Shim Sung Lee,*a and Jagadese J. Vittal*b

aDepartment of Chemistry, Gyeongsang National University, Jinju 52828, South Korea bDepartment of Chemistry, National University of Singapore, 117543, Singapore

The tacticity control of the organic polymers is one of the important issues both in academic and industrial areas. We obtained the isotactic organic polymer inside a 3D Zn(II) metal-organic fraomework (MOF-1) based on a mixture of bpeb and H2bdc through the photo-induced [2+2] cycloaddition reaction as a first case [1]. While a bent H2obc ligand was used instead of the linear H2bdc ligand, we obtained the syndiotactic organic polymer inside a 3D Zn(II) MOF-2 [2]. In the 6-fold interpenetrated MOF-1, the bpeb ligands show a herringbone-type slip-stacked pattern which results in the formation of the isotactic organic polymer in metal-oragano-polymeric framework (MOPF-1, see below). Since the MOF-2 was photo-inactive, upon heating the bpeb ligand with trans,trans,trans-conformation undergoes pedal motion to trans,cis,trans-conformation and yield the MOPF-2 containing 2D network fused with the syndiotactic organic polymer. We also found that the both prepared organic polymers with different tacticities in the single crystal form are depolymerized reversibly by cleaving the cyclobutane rings upon heating.

[1] I.-H. Park, A. Chanthapally, Z. Zhang, S. S. Lee, M. J. Zaworotko, J. J. Vittal, Angew. Chem. Int. Ed. 53, 414–419 (2014). [2] I.-H. Park, R. Medishetty, H.-H. Lee, C. E. Mulijanto, H. S. Quah, S. S. Lee, J. J. Vittal, Angew. Chem., Int. Ed. 54, 7313–7317 (2015).

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6Metal Organic Frameworks

Chemical vapor deposition of nanoporous metal-organic frameworks

Ivo Stassen, Timothée Stassin, Alex Cruz, Rob Ameloot

KU Leuven — University of Leuven, Centre for Surface Chemistry and Catalysis

Leuven Chem&Tech, Celestijnenlaan 200F, 3001 Leuven, Belgium

Metal-organic frameworks (MOFs) are crystalline nanoporous materials built from metal-containing nodes and multitopic organic linkers interconnected by coordinate bonds. These materials show potential for integration in as thin film in (opto)electronic devices because of their record-high specific surface area, versatile organic-inorganic structure and guest-accessible pore space. Applications of these materials are foreseen for instance in chemical sensors, low-k dielectrics, resistive memories and energy conversions. Film deposition methods are crucial to leverage MOFs in these fields. Conventional chemical solution deposition procedures, typically adapted from powder preparation routes, are often incompatible with the fabrication of these devices [1]. Recently, we demonstrated a chemical vapor deposition (CVD) process that yields thin films of these materials, with a uniform and controlled thickness, even on challenging device structures such as high-aspect ratio features [2]. This procedure was the first demonstrated vapor-phase deposition method for any type of microporous crystalline network solid, and marks a milestone in their thin film processing and characterization. The ‘MOF-CVD’ method consists of two steps: a metal oxide deposition step and a vapor-solid reaction step (Figure 1a). For the first step, well-established methods such as atomic-layer deposition or evaporation can be used. The second step comprises evaporation of the MOF linker and the reaction with the metal oxide film in a (thermal) chemical vapor deposition chamber. Here, we implemented both steps of the MOF-CVD process as a reliable, scalable and fully automated process, using an all-purpose vacuum deposition system. Following this integration, we were able to study the formation of MOF thin films (Fig. 1b) using in situ characterization by X-ray diffraction, spectroscopic ellipsometry and quartz crystal microbalance at different conditions in terms of temperature, pressure and dosing (Fig. 1c). The results of our ongoing study are utilized to gain insights into the remarkable properties of the vapor-solid reaction: the self-terminating nature of the conversion process, the catalytic role of the water that is released from the metal oxide during reaction with the linker and the occurrence of epitaxial growth when making both steps part of a repeated cycle. Following these routes, new opportunities for tunable layer-by-layer deposition of nanoporous materials and composites are identified.

Figure 1. a) Two steps of the developed MOF-CVD method. b) Atomic force microscopy image of a polycrystalline MOF-CVD film c) In situ X-ray diffraction reveals the intricacies of the crystallization process (blue arrows indicate the reflections of the desired MOF phase).

[1] I. Stassen, D. De Vos and R. Ameloot, Chem. - Eur. J. 22, 14452-14460 (2016). [2] I. Stassen, M. Styles, G. Grenci, H. V. Gorp, W. Vanderlinden, S. D. Feyter, P. Falcaro, D. D. Vos, P. Vereecken and R. Ameloot, Nat. Mater. 15, 304-310 (2016).

a) b) c)

Metal Organic Frameworks7

Mechanism of perovskite film formation and the effect of light

Amita Ummadisingu1 and Michael Grätzel1

1Laboratory of Photonics and Interfaces (LPI), Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne (EPFL)

Station 6, CH-1015 Lausanne, Switzerland

In recent years, perovskites have emerged as excellent candidates for use as light harvesters in solar cells. Various deposition methods such as sequential deposition and the anti-solvent methods have been developed for the preparation of perovskite solar cells, with major effort focused on achieving high performance [1]. However, factors controlling the final film morphology in perovskite formation in these deposition methods are little understood, as the fundamental mechanisms are still unclear. This gap in knowledge leads to batch-to-batch inconsistencies in the morphology and thereby the device performance. Using fluorescence microscopy, scanning electron microscopy and cathodo-luminescence measurements, we identify the stages of the sequential deposition reaction. We demonstrate the unexpectedeffect of illumination on the nucleation in the sequential deposition method and unravel the underlying mechanism through photo-electrochemistry. Furthermore, we show that the lighteffect is present even in the anti-solvent method, the route used for the fabrication of high-efficiency solar cells. Our results establish that illumination is a major factor in various deposition methods and that it should always be considered while preparing perovskite films. We show that light is an efficient and convenient way to control the perovskite morphology for opto-electronic applications [2].

[1] M. Gratzel, Nature Materials 13, 838-842 (2014).

[2] A. Ummadisingu et al., Nature, In press (2017).

Chemical vapor deposition of nanoporous metal-organic frameworks

Ivo Stassen, Timothée Stassin, Alex Cruz, Rob Ameloot

KU Leuven — University of Leuven, Centre for Surface Chemistry and Catalysis

Leuven Chem&Tech, Celestijnenlaan 200F, 3001 Leuven, Belgium

Metal-organic frameworks (MOFs) are crystalline nanoporous materials built from metal-containing nodes and multitopic organic linkers interconnected by coordinate bonds. These materials show potential for integration in as thin film in (opto)electronic devices because of their record-high specific surface area, versatile organic-inorganic structure and guest-accessible pore space. Applications of these materials are foreseen for instance in chemical sensors, low-k dielectrics, resistive memories and energy conversions. Film deposition methods are crucial to leverage MOFs in these fields. Conventional chemical solution deposition procedures, typically adapted from powder preparation routes, are often incompatible with the fabrication of these devices [1]. Recently, we demonstrated a chemical vapor deposition (CVD) process that yields thin films of these materials, with a uniform and controlled thickness, even on challenging device structures such as high-aspect ratio features [2]. This procedure was the first demonstrated vapor-phase deposition method for any type of microporous crystalline network solid, and marks a milestone in their thin film processing and characterization. The ‘MOF-CVD’ method consists of two steps: a metal oxide deposition step and a vapor-solid reaction step (Figure 1a). For the first step, well-established methods such as atomic-layer deposition or evaporation can be used. The second step comprises evaporation of the MOF linker and the reaction with the metal oxide film in a (thermal) chemical vapor deposition chamber. Here, we implemented both steps of the MOF-CVD process as a reliable, scalable and fully automated process, using an all-purpose vacuum deposition system. Following this integration, we were able to study the formation of MOF thin films (Fig. 1b) using in situ characterization by X-ray diffraction, spectroscopic ellipsometry and quartz crystal microbalance at different conditions in terms of temperature, pressure and dosing (Fig. 1c). The results of our ongoing study are utilized to gain insights into the remarkable properties of the vapor-solid reaction: the self-terminating nature of the conversion process, the catalytic role of the water that is released from the metal oxide during reaction with the linker and the occurrence of epitaxial growth when making both steps part of a repeated cycle. Following these routes, new opportunities for tunable layer-by-layer deposition of nanoporous materials and composites are identified.

Figure 1. a) Two steps of the developed MOF-CVD method. b) Atomic force microscopy image of a polycrystalline MOF-CVD film c) In situ X-ray diffraction reveals the intricacies of the crystallization process (blue arrows indicate the reflections of the desired MOF phase).

[1] I. Stassen, D. De Vos and R. Ameloot, Chem. - Eur. J. 22, 14452-14460 (2016). [2] I. Stassen, M. Styles, G. Grenci, H. V. Gorp, W. Vanderlinden, S. D. Feyter, P. Falcaro, D. D. Vos, P. Vereecken and R. Ameloot, Nat. Mater. 15, 304-310 (2016).

a) b) c)

Mechanism of perovskite film formation and the effect of light

Amita Ummadisingu1 and Michael Grätzel1

1Laboratory of Photonics and Interfaces (LPI), Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne (EPFL)

Station 6, CH-1015 Lausanne, Switzerland

In recent years, perovskites have emerged as excellent candidates for use as light harvesters in solar cells. Various deposition methods such as sequential deposition and the anti-solvent methods have been developed for the preparation of perovskite solar cells, with major effort focused on achieving high performance [1]. However, factors controlling the final film morphology in perovskite formation in these deposition methods are little understood, as the fundamental mechanisms are still unclear. This gap in knowledge leads to batch-to-batch inconsistencies in the morphology and thereby the device performance. Using fluorescence microscopy, scanning electron microscopy and cathodo-luminescence measurements, we identify the stages of the sequential deposition reaction. We demonstrate the unexpectedeffect of illumination on the nucleation in the sequential deposition method and unravel the underlying mechanism through photo-electrochemistry. Furthermore, we show that the lighteffect is present even in the anti-solvent method, the route used for the fabrication of high-efficiency solar cells. Our results establish that illumination is a major factor in various deposition methods and that it should always be considered while preparing perovskite films. We show that light is an efficient and convenient way to control the perovskite morphology for opto-electronic applications [2].

[1] M. Gratzel, Nature Materials 13, 838-842 (2014).

[2] A. Ummadisingu et al., Nature, In press (2017).

Perovskite Photovoltaics 8

Carbon-Sandwiched Perovskite Solar Cell Il Jeon, Esko Kauppinen, Yutaka Matsuo, Shigeo Maruyama

The University of Tokyo

7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

Since Miyasaka and colleagues adopted perovskite semiconductors into photovoltaic devices,[1] perovskite solar cells (PSCs) have received much attention on account of high power conversion efficiency (PCE)[2,3]. Their reported PCEs have soared rapidly in the last five years, and now some certified efficiencies exceed 20%[4,5]. However, there remains critical shortcomings, prominently high-cost and stability[6]. Numerous research groups have been working on these issues[9-11].

Here, we report PSCs in which the lead halide perovskite layer (CH3NH3PbI3) is sandwiched by C60 and single-walled CNTs (SWCNTs) as the solution to both stability and cost (inset figure). Such carbon sandwich approach enabled low-cost fabrication by removing expensive metal electrodes. The new device structure not only allowed room temperature process, but also long-term stability by preventing vapor penetration and charge trapping. Air-processed PSCs with a configuration of ITO/C60/ CH3NH3PbI3 /CNT were tested in the stability and cost perspectives by adding three mainstream hole-transporting materials (HTM), namely, 2,2’,7,7’-tetrakis (N,N-di-p-methoxyphenylamino) -9,9’-spirobifluorene (spiro-OMeTAD), poly [bis(4-phenyl) (2,4,6-trimethylphenyl) amine] (PTAA), and poly (3-hexylthiophene-2,5-diyl) (P3HT). Their efficiency, cost, and stability were compared and analyzed throughout this work. As the result, the encapsulated devices showed high stability against both air and light, retaining high PCE for more than 2000 hours, and achieved 95% cost-down according to our cost analyses.

[1] A. Kojima et al., J. Am. Chem. Soc. 131, 6050–6051, (2009). [2] M. Green et al., Nat. Photonics 8, 506–514, (2014). [3] S. H. Im et al., Energy Environ. Sci. 8, 1602–1608, (2015). [4] X. Li, et al., Science 353, 58–62, (2016). [5] J. Seo, et al., Acc. Chem. Res. 49, 562–572, (2016). [6]J. H. Noh, et al., Nano Lett. 13, 1764–1769, (2013).

[7] W. A. Laban, et al., Energy Environ. Sci. 6, 3249-3253 (2013). [8] L. Etgar, et al., J. Am. Chem. Soc. 134, 17396–17399, (2012). [9] J. Liu, et al., Energy Environ. Sci. 7, 2963–2967, (2014). [10] A. Mei, et al., Science 345, 295–298, (2014). [11] J. You, et al., Nat. Nanotechnol. 11, 75–81, (2015).

Perovskite

SWCNT + HTM

C60

Glass

C60

GlassITO

Perovskite Photovoltaics

Luminescence and Solar Cells fromColloidal Cesium Lead Halide (CsPbX3) Perovskite Nanocrystals

Abhishek Swarnkar,1,2 Ashley R. Marshall,2 Erin M. Sanehira,2 Ramya Chulliyil,3 Vikash Kumar Ravi,1Arindam Chowdhury,3 Joseph M. Luther,2* Angshuman Nag1*

1Department of Chemistry, Indian Institute of Science Education and Research (IISER) Pune 411008, India2Chemical and Materials Science, National Renewable Energy Laboratory (NREL), Golden, CO 80401, USA

3Department of Chemistry, Indian Institute of Technology Bombay Powai, Mumbai 400076, India

*Corresponding authors’ e-mails: AN: angshuman@iiserpune.ac.in JML: joey.luther@nrel.gov

In this presentation, I will discuss about a new class of luminescent nanocrystal (NC), namely colloidal CsPbX3 (where X= Br and I) NCs. These NCs are being explored extensively as an interesting variety of defect-tolerant materials, wherein high efficiencies of optical and optoelectronic processes can be achieved even in the presence of surface defects. This defect-tolerant nature arises mainly because of the unique electronic band structure of these perovskites.1 Without any surface modifications, these NC has high photoluminescence (PL) quantum yield (QY) (~90% in case of CsPbBr3 NCs and ~55% in case of CsPbI3 NCs)2,3 along with exceptionally high terahertz (THz) charge carrier mobility of ~4500 cm2V-1S-1

with large diffusion length of > 9.2 µm.3 Single NC PL studies suggest reduced blinking in CsPbBr3 NCs, along with similarity of spectral width between the single-NC PL and ensemble PL.2 Luminescence from films of weakly quantum confined ~11 nm CsPbBr3 NCs does not suffer from the vexing problems of self-absorption and Förster resonance energy transfer (FRET) unlike the traditional CdSe based cQDs where PL peaks get red-shifted on depositing film.2

Based on above all advantageous optoelectronic properties, stable solar cell from CsPbI3 NCs has been fabricated. CsPbI3 is an all-inorganic analogue to the hybrid organic cation halide perovskites.4 However, the cubic phase of bulk CsPbI3 is only stable at high temperature, preventing its adoption within the community. I will describe formation of cubic phase CsPbI3 QD films, phase stable for months in ambient air, with long-range electronic transport, leading to the fabrication of the first colloidal perovskite QD solar cells with an open-circuit voltage of 1.23 V and power conversion efficiency of 10.77 %.4 These devices also function as light emitting diodes (LEDs) with low turn-on voltage and tunable emission. The synthesis of normally unstable material phases stabilized through colloidal QD synthesis provides another mechanism formaterials design for photovoltaics, LEDs, and other applications. All these optoelectronic behaviors of CsPbX3perovskite NCs are advantageous, and therefore, CsPbX3NC can be a better candidate for optoelectronics.

References:1. Swarnkar, A.; Ravi, V. K.; Nag, A. ACS Energy Lett. [Invited Perspective], 2017, under minor revision.2. Swarnkar, A.; Chulliyil, R.; Ravi, V. K.; Irfanullah, M.; Chowdhury, A.; Nag, A. Angew. Chem., Int. Ed.

2015, 54, 15424-154283. Yettapu, G. R.; Talukdar, D.; Sarkar, S.; Swarnkar, A.; Nag, A.; Ghosh, P.; Mandal, P. Nano Lett. 2016, 16,

4838-48484. Swarnkar, A.; Marshall, A. R.; Sanehira, E. M.; Chernomordik, B. D.; Moore, D. T.; Christians, J. A.;

Chakrabarti, T.; Luther, J. M. Science 2016, 354, 92-95.

9

Carbon-Sandwiched Perovskite Solar Cell Il Jeon, Esko Kauppinen, Yutaka Matsuo, Shigeo Maruyama

The University of Tokyo

7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

Since Miyasaka and colleagues adopted perovskite semiconductors into photovoltaic devices,[1] perovskite solar cells (PSCs) have received much attention on account of high power conversion efficiency (PCE)[2,3]. Their reported PCEs have soared rapidly in the last five years, and now some certified efficiencies exceed 20%[4,5]. However, there remains critical shortcomings, prominently high-cost and stability[6]. Numerous research groups have been working on these issues[9-11].

Here, we report PSCs in which the lead halide perovskite layer (CH3NH3PbI3) is sandwiched by C60 and single-walled CNTs (SWCNTs) as the solution to both stability and cost (inset figure). Such carbon sandwich approach enabled low-cost fabrication by removing expensive metal electrodes. The new device structure not only allowed room temperature process, but also long-term stability by preventing vapor penetration and charge trapping. Air-processed PSCs with a configuration of ITO/C60/ CH3NH3PbI3 /CNT were tested in the stability and cost perspectives by adding three mainstream hole-transporting materials (HTM), namely, 2,2’,7,7’-tetrakis (N,N-di-p-methoxyphenylamino) -9,9’-spirobifluorene (spiro-OMeTAD), poly [bis(4-phenyl) (2,4,6-trimethylphenyl) amine] (PTAA), and poly (3-hexylthiophene-2,5-diyl) (P3HT). Their efficiency, cost, and stability were compared and analyzed throughout this work. As the result, the encapsulated devices showed high stability against both air and light, retaining high PCE for more than 2000 hours, and achieved 95% cost-down according to our cost analyses.

[1] A. Kojima et al., J. Am. Chem. Soc. 131, 6050–6051, (2009). [2] M. Green et al., Nat. Photonics 8, 506–514, (2014). [3] S. H. Im et al., Energy Environ. Sci. 8, 1602–1608, (2015). [4] X. Li, et al., Science 353, 58–62, (2016). [5] J. Seo, et al., Acc. Chem. Res. 49, 562–572, (2016). [6]J. H. Noh, et al., Nano Lett. 13, 1764–1769, (2013).

[7] W. A. Laban, et al., Energy Environ. Sci. 6, 3249-3253 (2013). [8] L. Etgar, et al., J. Am. Chem. Soc. 134, 17396–17399, (2012). [9] J. Liu, et al., Energy Environ. Sci. 7, 2963–2967, (2014). [10] A. Mei, et al., Science 345, 295–298, (2014). [11] J. You, et al., Nat. Nanotechnol. 11, 75–81, (2015).

Perovskite

SWCNT + HTM

C60

GlassITO

Luminescence and Solar Cells fromColloidal Cesium Lead Halide (CsPbX3) Perovskite Nanocrystals

Abhishek Swarnkar,1,2 Ashley R. Marshall,2 Erin M. Sanehira,2 Ramya Chulliyil,3 Vikash Kumar Ravi,1Arindam Chowdhury,3 Joseph M. Luther,2* Angshuman Nag1*

1Department of Chemistry, Indian Institute of Science Education and Research (IISER) Pune 411008, India2Chemical and Materials Science, National Renewable Energy Laboratory (NREL), Golden, CO 80401, USA

3Department of Chemistry, Indian Institute of Technology Bombay Powai, Mumbai 400076, India

*Corresponding authors’ e-mails: AN: angshuman@iiserpune.ac.in JML: joey.luther@nrel.gov

In this presentation, I will discuss about a new class of luminescent nanocrystal (NC), namely colloidal CsPbX3 (where X= Br and I) NCs. These NCs are being explored extensively as an interesting variety of defect-tolerant materials, wherein high efficiencies of optical and optoelectronic processes can be achieved even in the presence of surface defects. This defect-tolerant nature arises mainly because of the unique electronic band structure of these perovskites.1 Without any surface modifications, these NC has high photoluminescence (PL) quantum yield (QY) (~90% in case of CsPbBr3 NCs and ~55% in case of CsPbI3 NCs)2,3 along with exceptionally high terahertz (THz) charge carrier mobility of ~4500 cm2V-1S-1

with large diffusion length of > 9.2 µm.3 Single NC PL studies suggest reduced blinking in CsPbBr3 NCs, along with similarity of spectral width between the single-NC PL and ensemble PL.2 Luminescence from films of weakly quantum confined ~11 nm CsPbBr3 NCs does not suffer from the vexing problems of self-absorption and Förster resonance energy transfer (FRET) unlike the traditional CdSe based cQDs where PL peaks get red-shifted on depositing film.2

Based on above all advantageous optoelectronic properties, stable solar cell from CsPbI3 NCs has been fabricated. CsPbI3 is an all-inorganic analogue to the hybrid organic cation halide perovskites.4 However, the cubic phase of bulk CsPbI3 is only stable at high temperature, preventing its adoption within the community. I will describe formation of cubic phase CsPbI3 QD films, phase stable for months in ambient air, with long-range electronic transport, leading to the fabrication of the first colloidal perovskite QD solar cells with an open-circuit voltage of 1.23 V and power conversion efficiency of 10.77 %.4 These devices also function as light emitting diodes (LEDs) with low turn-on voltage and tunable emission. The synthesis of normally unstable material phases stabilized through colloidal QD synthesis provides another mechanism formaterials design for photovoltaics, LEDs, and other applications. All these optoelectronic behaviors of CsPbX3perovskite NCs are advantageous, and therefore, CsPbX3NC can be a better candidate for optoelectronics.

References:1. Swarnkar, A.; Ravi, V. K.; Nag, A. ACS Energy Lett. [Invited Perspective], 2017, under minor revision.2. Swarnkar, A.; Chulliyil, R.; Ravi, V. K.; Irfanullah, M.; Chowdhury, A.; Nag, A. Angew. Chem., Int. Ed.

2015, 54, 15424-154283. Yettapu, G. R.; Talukdar, D.; Sarkar, S.; Swarnkar, A.; Nag, A.; Ghosh, P.; Mandal, P. Nano Lett. 2016, 16,

4838-48484. Swarnkar, A.; Marshall, A. R.; Sanehira, E. M.; Chernomordik, B. D.; Moore, D. T.; Christians, J. A.;

Chakrabarti, T.; Luther, J. M. Science 2016, 354, 92-95.

Perovskite Photovoltaics 10

Precision at the nanoscale:

On the structure and property evolution of gold nanoclusters

Chenjie Zeng, Rongchao Jin

Department of Chemistry, Carnegie Mellon University 4400 Fifth Avenue, Pittsburgh, PA, 15213, US

Chemists are often regarded as “architects”, who are capable of building up complex molecular structures in the ultrasmall world. However, compared with organic chemistry, nanochemistry dealing with nanoparticles in the size range from 1 to 100 nm is less precise in terms of synthesis, composition, and structure. Such an imprecise nature of nanochemistry has impeded rational control and in-depth understanding of structures and properties of nanomaterials.

My graduate research focused on the thiolate-protected gold nanoclusters, which had recently emerged as a paradigm of atomically precise nanomaterials [1]. In this poster, I will first discuss how to synthesize atomically precise gold nanoclusters containing ~10 to ~1000 gold atoms (i.e. 1 to 3 nm), as well as their total structure determination by single-crystal X-ray diffraction. Then, I will show how the precise nature of these nanomaterials allows me to discover, decipher and understand many intriguing nanoscale phenomena, including the transformation chemistry at the nanoscale [2], periodicities in nanoclusters [3], a supermolecular origin of “magic sizes” [4], and the emergence of hierarchical structural complexity in the nanoparticle system [5].

[1] R. Jin, C. Zeng, M. Zhou, Y. Chen, Chem. Rev.116, 10346-10413 (2016). [2] C. Zeng, C. Liu, Y. Pei, R. Jin, ACS Nano 7, 6138-6145 (2013). [3] C. Zeng, Y. Chen, K. Iida, K. Nobusada, K. Kirschbaum, K. J. Lambright, R. Jin, J. Am. Chem. Soc. 138, 3950-3953 (2016). [4] C. Zeng, Y. Chen, C. Liu, K. Nobusada, N. L. Rosi, R. Jin, Sci. Adv. 1, e1500425 (2015). [5] C. Zeng, Y. Chen, K. Kirschbaum, K. J. Lambright, R. Jin, Science 354, 1580-1584 (2016).

Nanoparticles

Polyphosphazene-based biodegradable bridged silica nanoparticles, the future drug nanocarriers

Yolanda Salinas, Ian Teasdale and Oliver Brüggemann

Institute of Polymer Chemistry, Johannes Kepler University Linz,

(Altenberger Straße 69, 4040 Linz, Austria) Silica based organic-inorganic hybrid materials have set a precedent in terms of controlled drug release within the area of nanomedicine [1]. In this particular field, the evolution of new administration mechanisms has to deal with biodistribution, pharmacokinetics and cell uptake control, but must also be proven to be eliminated or excreted from the organism [2]. Indeed this has been a major hurdle in nanomedicines reaching the clinic and it has become commonly accepted in the community in recent years that the development of fully biodegradable materials is required to avoid the concerns of accumulation of retained materials, in particular for long-term use or high dose therapies such as chemotherapy. There are many nanocarriers accepted by the FDA, such as liposomes [3], polymeric micelles [4], or nanogels [5]. However, poor structural integrity or drug loading and release control are considerable disadvantages with such systems. To address the issue of degradation and hence clinical translation, the design of silica based nanoparticles incorporating biodegradable organic species into the mesoporous silica frameworks is required [6]. Polyphosphazenes are promising candidates [7] as they are known to have a highly tunable chemical nature, and thus small alterations can lead to a wide spectrum of degradation rates. Hence, we developed potential degradable hybrid mesoporous nanoparticles (also known as periodic mesoporous organosilica materials or PMOs) [8] containing phosphazene moieties as an alternative organic units, inserted as silsesquioxane frameworks, that under hydrolytic conditions could degrade on demand to excretable and harmless low molecular weight units (phosphates and ammonia). The chemical foundations and characterization of this novel class of materials were carried out to evaluate the morphology of silica-based nanoparticles (structural porous uniformity, functionalization orthogonality and biocompatibility). Furthermore, the effect of the introduction of different phosphazene units was investigated that can be hydrolyzed under specific physiological conditions, disassembling the nanoparticles. [1] Y. Zhang, B. Y W. Hsu, C. Ren, X. Li, J. Wang, Chemical Society Reviews 44, 315-335, (2015). [2] R. Duncan, J. Controlled Release 190, 371-380, (2014). [3] A. Puri, K. Loomis, B. Smith, J.-H Lee, A. Yavlovich, E. Heldman, R. Blumenthal, Critical reviews in therapeutic drug carrier systems 26, 523-580, (2009). [4] Z. Ahmad, A. Shah, M. Siddiq, H.-B. Kraatz, RSC Advances 4, 17028-17038, (2014). [5] R. T. Chacko, J. Ventura, J. Zhuang, S. Thayumanavan, Advanced Drug Delivery Reviews 64, 836-851, (2012). [6] J. Lu, M. Liong, Z. Li, J. I. Zink, F. Tamanoi, Small 6, 1794-1805, (2010). [7] S. Rothemund, I. Teasdale, Chemical Society Reviews 45, 5200-5215, (2016). [8] T. Asefa, M. J. MacLachlan, N. Coombs, G. A. Ozin, Nature 402, 867-871, (1999).

11

Precision at the nanoscale:

On the structure and property evolution of gold nanoclusters

Chenjie Zeng, Rongchao Jin

Department of Chemistry, Carnegie Mellon University 4400 Fifth Avenue, Pittsburgh, PA, 15213, US

Chemists are often regarded as “architects”, who are capable of building up complex molecular structures in the ultrasmall world. However, compared with organic chemistry, nanochemistry dealing with nanoparticles in the size range from 1 to 100 nm is less precise in terms of synthesis, composition, and structure. Such an imprecise nature of nanochemistry has impeded rational control and in-depth understanding of structures and properties of nanomaterials.

My graduate research focused on the thiolate-protected gold nanoclusters, which had recently emerged as a paradigm of atomically precise nanomaterials [1]. In this poster, I will first discuss how to synthesize atomically precise gold nanoclusters containing ~10 to ~1000 gold atoms (i.e. 1 to 3 nm), as well as their total structure determination by single-crystal X-ray diffraction. Then, I will show how the precise nature of these nanomaterials allows me to discover, decipher and understand many intriguing nanoscale phenomena, including the transformation chemistry at the nanoscale [2], periodicities in nanoclusters [3], a supermolecular origin of “magic sizes” [4], and the emergence of hierarchical structural complexity in the nanoparticle system [5].

[1] R. Jin, C. Zeng, M. Zhou, Y. Chen, Chem. Rev.116, 10346-10413 (2016). [2] C. Zeng, C. Liu, Y. Pei, R. Jin, ACS Nano 7, 6138-6145 (2013). [3] C. Zeng, Y. Chen, K. Iida, K. Nobusada, K. Kirschbaum, K. J. Lambright, R. Jin, J. Am. Chem. Soc. 138, 3950-3953 (2016). [4] C. Zeng, Y. Chen, C. Liu, K. Nobusada, N. L. Rosi, R. Jin, Sci. Adv. 1, e1500425 (2015). [5] C. Zeng, Y. Chen, K. Kirschbaum, K. J. Lambright, R. Jin, Science 354, 1580-1584 (2016).

12

Polyphosphazene-based biodegradable bridged silica nanoparticles, the future drug nanocarriers

Yolanda Salinas, Ian Teasdale and Oliver Brüggemann

Institute of Polymer Chemistry, Johannes Kepler University Linz,

(Altenberger Straße 69, 4040 Linz, Austria) Silica based organic-inorganic hybrid materials have set a precedent in terms of controlled drug release within the area of nanomedicine [1]. In this particular field, the evolution of new administration mechanisms has to deal with biodistribution, pharmacokinetics and cell uptake control, but must also be proven to be eliminated or excreted from the organism [2]. Indeed this has been a major hurdle in nanomedicines reaching the clinic and it has become commonly accepted in the community in recent years that the development of fully biodegradable materials is required to avoid the concerns of accumulation of retained materials, in particular for long-term use or high dose therapies such as chemotherapy. There are many nanocarriers accepted by the FDA, such as liposomes [3], polymeric micelles [4], or nanogels [5]. However, poor structural integrity or drug loading and release control are considerable disadvantages with such systems. To address the issue of degradation and hence clinical translation, the design of silica based nanoparticles incorporating biodegradable organic species into the mesoporous silica frameworks is required [6]. Polyphosphazenes are promising candidates [7] as they are known to have a highly tunable chemical nature, and thus small alterations can lead to a wide spectrum of degradation rates. Hence, we developed potential degradable hybrid mesoporous nanoparticles (also known as periodic mesoporous organosilica materials or PMOs) [8] containing phosphazene moieties as an alternative organic units, inserted as silsesquioxane frameworks, that under hydrolytic conditions could degrade on demand to excretable and harmless low molecular weight units (phosphates and ammonia). The chemical foundations and characterization of this novel class of materials were carried out to evaluate the morphology of silica-based nanoparticles (structural porous uniformity, functionalization orthogonality and biocompatibility). Furthermore, the effect of the introduction of different phosphazene units was investigated that can be hydrolyzed under specific physiological conditions, disassembling the nanoparticles. [1] Y. Zhang, B. Y W. Hsu, C. Ren, X. Li, J. Wang, Chemical Society Reviews 44, 315-335, (2015). [2] R. Duncan, J. Controlled Release 190, 371-380, (2014). [3] A. Puri, K. Loomis, B. Smith, J.-H Lee, A. Yavlovich, E. Heldman, R. Blumenthal, Critical reviews in therapeutic drug carrier systems 26, 523-580, (2009). [4] Z. Ahmad, A. Shah, M. Siddiq, H.-B. Kraatz, RSC Advances 4, 17028-17038, (2014). [5] R. T. Chacko, J. Ventura, J. Zhuang, S. Thayumanavan, Advanced Drug Delivery Reviews 64, 836-851, (2012). [6] J. Lu, M. Liong, Z. Li, J. I. Zink, F. Tamanoi, Small 6, 1794-1805, (2010). [7] S. Rothemund, I. Teasdale, Chemical Society Reviews 45, 5200-5215, (2016). [8] T. Asefa, M. J. MacLachlan, N. Coombs, G. A. Ozin, Nature 402, 867-871, (1999).

Nanoparticles

Understanding Donor-Acceptor Stenhouse Adducts

Michael M. Lerch,† Mariangela Di Donato,# Andrea Lapini,# Alessandro Iagatti,# Laura Bussotti,# Sander J. Wezenberg,† Wiktor Szymanski,†,‡ Paulo Foggi, Wybren Jan Buma,% Ben L. Feringa*,†

† Centre for Systems Chemistry, Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands; ‡ Department of Radiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands; % Van’t Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098XH Amsterdam, The Netherlands; # LENS (European Laboratory for Non Linear Spectroscopy), via N. Carrara 1, 50019 Sesto Fiorentino, Italy.

Tel: +31 (0)50 363 4661; E-mail: m.m.lerch@rug.nl

Molecular photoswitches[1] have been used in material science, supramolecular chemistry and biology. Developing novel applications, especially in the realm of molecular biology, evokes certain challenges on the properties of photoswitches in use.[2] Thus tight control over molecular and photoswitching characteristics is essential for successful applications.

Herein we present in-depth studies on the photoswitching mechanism of the recently reported donor-acceptor Stenhouse adducts (DASAs).[3] Investigation of a photogenerated, thermally-unstable intermediate unravels the actinic step to consist of a Z/E-isomerization[4] followed by a thermally controlled conrotatory 4π-electrocyclization. Ultrafast visible and infra-red pump-probe experiments enable a comprehensive understanding of DASA photoswitching in different solvents. Our results bode well for the development of new design principles of more efficient DASAs and have immediate effects on applications of DASAs.

References: [1] a) Molecular switches, Feringa, B. L., Browne, W. R., Eds.; Wiley-VCH: Weinheim,

2011; b) Brieke, C.; Rohrbach, F.; Gottschalk, A.; Mayer, G.; Heckel, A. Angew. Chem., Int. Ed., 51, 8446, (2012).

[2] a) Lerch, M.M.; Hansen, M.J.; van Dam, G.M.; Szymanski, W.; Feringa, B.L. Angew. Chem., Int. Ed. 55, 10978, (2016); b) Russew, M.-M.; Hecht, S. Adv. Mater. 22, 3348, (2010).

[3] a) Helmy, S.; Leibfarth, F. A.; Oh, S.; Poelma, J. E.; Hawker, C. J.; Read de Alaniz, J. J. Am. Chem. Soc. 136, 8169, (2014); b) Helmy, S.; Oh, S.; Leibfarth, F. A.; Hawker, C. J.; Read de Alaniz, J. J. Org. Chem. 79, 11316, (2014).

[4] Lerch, M.M.; Wezenberg, S.J.; Szymanski, W.; Feringa, B.L. J. Am. Chem. Soc. 138, 6344, (2016)

Controlling Chemical Reactivity with Light

M. Kathan,1 F. Eisenreich,1 C. Jurissek,1 P. Kovaříček,1 A. F. Thünemann,2 and S. Hecht1

1Department of Chemistry & IRIS Adlershof, Humboldt-Universität zu Berlin, Brook-Taylor-

Str. 2, 12489 Berlin, Germany 2Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205 Berlin,

Germany

Remote-controlling chemical reactions in a non-invasive and reversible fashion is the key for

chemists to design materials and chemical processes that can be adapted to the environment

where and when requested. Light is the ideal stimulus for this task, as it is a tunable energy

source that can be applied with high spatial and temporal precision. Diarylethene-type

photoswitches are perfect candidates to translate this stimulus into chemical information, as

both photoisomers differ greatly in their electronic structure while not being thermally

interconvertable. We use these features to create a system, in which the reactivity of aldehyde

functionalities can be reversibly modulated by light illumination, allowing for the control over

imine-exchange kinetics. This concept was applied to a siloxane-based dynamic covalent

polymer network, whose intrinsic properties such as color, texture and the ability to self-heal

can be reversibly altered with sunlight.[1] Beyond kinetic control, some applications require

thermodynamic trapping of a defined state, which can be achieved by coupling a thermal

equilibrium to the initial photoevent. By exploiting a light-induced tautomerization, we are

able to switch the polymerization of lactide as well as the condensation reaction between a

carbonyl group and amines completely on and off.[2] In the future, this approach has the

potential to reversibly shift a chemical equilibrium by fueling a reaction with light energy,

which is possible due to the unique ability of photoswitches to bypass and thus beat

microscopic reversibility.[3]

[1] M. Kathan, P. Kovaříček, C. Jurissek, A. Senf, A. Dallmann, A. F. Thünemann, and S.

Hecht, Angew. Chem. Int. Ed. 55, 13882–13886, (2016).

[2] Unpublished results.

[3] M. Kathan, S. Hecht, Chem. Soc. Rev., submitted.

Supramolecular Chemistry, Photoswitching, Polymers13

Understanding Donor-Acceptor Stenhouse Adducts

Michael M. Lerch,† Mariangela Di Donato,# Andrea Lapini,# Alessandro Iagatti,# Laura Bussotti,# Sander J. Wezenberg,† Wiktor Szymanski,†,‡ Paulo Foggi, Wybren Jan Buma,% Ben L. Feringa*,†

† Centre for Systems Chemistry, Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands; ‡ Department of Radiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands; % Van’t Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098XH Amsterdam, The Netherlands; # LENS (European Laboratory for Non Linear Spectroscopy), via N. Carrara 1, 50019 Sesto Fiorentino, Italy.

Tel: +31 (0)50 363 4661; E-mail: m.m.lerch@rug.nl

Molecular photoswitches[1] have been used in material science, supramolecular chemistry and biology. Developing novel applications, especially in the realm of molecular biology, evokes certain challenges on the properties of photoswitches in use.[2] Thus tight control over molecular and photoswitching characteristics is essential for successful applications.

Herein we present in-depth studies on the photoswitching mechanism of the recently reported donor-acceptor Stenhouse adducts (DASAs).[3] Investigation of a photogenerated, thermally-unstable intermediate unravels the actinic step to consist of a Z/E-isomerization[4] followed by a thermally controlled conrotatory 4π-electrocyclization. Ultrafast visible and infra-red pump-probe experiments enable a comprehensive understanding of DASA photoswitching in different solvents. Our results bode well for the development of new design principles of more efficient DASAs and have immediate effects on applications of DASAs.

References: [1] a) Molecular switches, Feringa, B. L., Browne, W. R., Eds.; Wiley-VCH: Weinheim,

2011; b) Brieke, C.; Rohrbach, F.; Gottschalk, A.; Mayer, G.; Heckel, A. Angew. Chem., Int. Ed., 51, 8446, (2012).

[2] a) Lerch, M.M.; Hansen, M.J.; van Dam, G.M.; Szymanski, W.; Feringa, B.L. Angew. Chem., Int. Ed. 55, 10978, (2016); b) Russew, M.-M.; Hecht, S. Adv. Mater. 22, 3348, (2010).

[3] a) Helmy, S.; Leibfarth, F. A.; Oh, S.; Poelma, J. E.; Hawker, C. J.; Read de Alaniz, J. J. Am. Chem. Soc. 136, 8169, (2014); b) Helmy, S.; Oh, S.; Leibfarth, F. A.; Hawker, C. J.; Read de Alaniz, J. J. Org. Chem. 79, 11316, (2014).

[4] Lerch, M.M.; Wezenberg, S.J.; Szymanski, W.; Feringa, B.L. J. Am. Chem. Soc. 138, 6344, (2016)

Controlling Chemical Reactivity with Light

M. Kathan,1 F. Eisenreich,1 C. Jurissek,1 P. Kovaříček,1 A. F. Thünemann,2 and S. Hecht1

1Department of Chemistry & IRIS Adlershof, Humboldt-Universität zu Berlin, Brook-Taylor-

Str. 2, 12489 Berlin, Germany 2Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205 Berlin,

Germany

Remote-controlling chemical reactions in a non-invasive and reversible fashion is the key for

chemists to design materials and chemical processes that can be adapted to the environment

where and when requested. Light is the ideal stimulus for this task, as it is a tunable energy

source that can be applied with high spatial and temporal precision. Diarylethene-type

photoswitches are perfect candidates to translate this stimulus into chemical information, as

both photoisomers differ greatly in their electronic structure while not being thermally

interconvertable. We use these features to create a system, in which the reactivity of aldehyde

functionalities can be reversibly modulated by light illumination, allowing for the control over

imine-exchange kinetics. This concept was applied to a siloxane-based dynamic covalent

polymer network, whose intrinsic properties such as color, texture and the ability to self-heal

can be reversibly altered with sunlight.[1] Beyond kinetic control, some applications require

thermodynamic trapping of a defined state, which can be achieved by coupling a thermal

equilibrium to the initial photoevent. By exploiting a light-induced tautomerization, we are

able to switch the polymerization of lactide as well as the condensation reaction between a

carbonyl group and amines completely on and off.[2] In the future, this approach has the

potential to reversibly shift a chemical equilibrium by fueling a reaction with light energy,

which is possible due to the unique ability of photoswitches to bypass and thus beat

microscopic reversibility.[3]

[1] M. Kathan, P. Kovaříček, C. Jurissek, A. Senf, A. Dallmann, A. F. Thünemann, and S.

Hecht, Angew. Chem. Int. Ed. 55, 13882–13886, (2016).

[2] Unpublished results.

[3] M. Kathan, S. Hecht, Chem. Soc. Rev., submitted.

Supramolecular Chemistry, Photoswitching, Polymers 14

67th Lindau Nobel Laureate Meeting (2017 Chemistry)

Supramolecular Sensing Ensembles: More Information through Communication

Frank Biedermanna

a Institute of Nanotechnology (INT), Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany. E-mail: frank.biedermann@kit.edu

The detection of spectroscopically silent analytes in water is often accomplished by utilization of reactive probes that form chromophoric analyte-dye conjugates. Unfortunately, similar but distinctly different analytes usually do not provide unique spectroscopic features, such that chromatographic separation steps have to be employed, causing significant additional costs and hinder application in remote areas. Supramolecular indicator-dye displacement assays can overcome certain limitations of reactive-probes, e.g., they allow for an in situ detection of even non-functionalizable analytes and are of great utility for reaction monitoring. However, their analyte differentiation capabilities are again restricted. Here, we present new strategies involving supramolecular sensing ensembles that allow for largely improved analyte differentiation through spectroscopic fingerprints. We show that this strategy is applicable to both non-covalent analyte-receptor binding schemes and to reactive-probe assays. As opposed to contemporary sensing strategies, our approach capitalizes on induced spectroscopic changes that are resulting from, (A) the direct “communication” of the analyte with a suitable dye in a confined receptor cavity, or (B) from analyte-induced structural changes of supramolecular dye-aggregates, leading to an altered dye-dye “communication”. (see Figure 1) Examples that will be shown include the differentiation of peptides, monitoring of enzymatic reactions and drug permeation through membranes, and detection of neurotransmitters in biological fluids.[1-3] Furthermore, it is shown how the commonly encountered affinity-challenge for artificial receptors in aqueous media can be overcome by taking advantage of “high-energy” water release from hydrophobic cavities (a.k.a. the non-classical hydrophobic effect).[4, 5]

Figure 1: Schematic representation of supramolecular sensing strategies which enable in situ analyte identification through unique spectroscopic fingerprints. [1] S. Sinn, F. Biedermann, and L. De Cola, Chem. Eur. J. 23 (2017). [2] F. Biedermann, D. Hathazi, and W. M. Nau, Chem. Commun. 51 (2015). [3] F. Biedermann, and W. M. Nau, Angew. Chem. Int. Ed. 53 (2014). [4] F. Biedermann, and H.-J. Schneider, Chem. Rev. 116 (2016). [5] F. Biedermann, W. M. Nau, and H.-J. Schneider, Angew. Chem. Int. Ed. 53 (2014).

Manipulating the ABCs of Self-Assembly via Low-χ Block Polymer Design

Alice B. Chang,† Christopher M. Bates,† Mark W. Matsen,‡ Robert H. Grubbs†

† Division of Chemistry and Chemical Engineering, California Institute of Technology1200 E. California Blvd., Pasadena, CA 91125, United States

‡ Department of Chemical Engineering, University of Waterloo200 University Ave. West, Waterloo, Ontario N2L 3G1, Canada

Molecular sequence and interactions dictate the mesoscale structure of all self-assembling soft materials. Block polymers harness this relationship to access a rich variety of nanostructured materials. Block polymer self-assembly typically translates molecular chain connectivity into mesoscale structure by exploiting incompatible blocks with large interaction parameters (χij). Contrary to this convention, we demonstrate that the converse approach, encoding low-χinteractions in ABC bottlebrush triblock terpolymers (χAC ≲ 0), promotes organization into a unique mixed-domain lamellar morphology which we designate LAMP. Transmission electron microscopy indicates that LAMP exhibits ACBC domain connectivity, in contrast to conventional three-domain lamellae (LAM3) with ABCB periods. Complementary small angle X-ray scattering experiments reveal a strongly decreasing domain spacing with increasing total molar mass. Self-consistent field theory reinforces these observations and predicts that LAMP

is thermodynamically stable below a critical χAC, above which LAM3 emerges. Both experiments and theory expose close analogies to ABA' triblock copolymer phase behavior, collectively suggesting that low-χ interactions between chemically similar or distinct blocks intimately influence self-assembly. These developments expand the vocabulary of block polymer design and open new avenues for manipulating the self-assembly of synthetic macromolecules.

NO O NO O

HN

O

O

NN N

O

O

NO O

O

O

O

NA NB NC

x y

z

LAMP

A A/C B C/A A

Polymer Synthesis Self-Assembly: New Morphology Unique Properties

15 Supramolecular Chemistry, Photoswitching, Polymers

67th Lindau Nobel Laureate Meeting (2017 Chemistry)

Supramolecular Sensing Ensembles: More Information through Communication

Frank Biedermanna

a Institute of Nanotechnology (INT), Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany. E-mail: frank.biedermann@kit.edu

The detection of spectroscopically silent analytes in water is often accomplished by utilization of reactive probes that form chromophoric analyte-dye conjugates. Unfortunately, similar but distinctly different analytes usually do not provide unique spectroscopic features, such that chromatographic separation steps have to be employed, causing significant additional costs and hinder application in remote areas. Supramolecular indicator-dye displacement assays can overcome certain limitations of reactive-probes, e.g., they allow for an in situ detection of even non-functionalizable analytes and are of great utility for reaction monitoring. However, their analyte differentiation capabilities are again restricted. Here, we present new strategies involving supramolecular sensing ensembles that allow for largely improved analyte differentiation through spectroscopic fingerprints. We show that this strategy is applicable to both non-covalent analyte-receptor binding schemes and to reactive-probe assays. As opposed to contemporary sensing strategies, our approach capitalizes on induced spectroscopic changes that are resulting from, (A) the direct “communication” of the analyte with a suitable dye in a confined receptor cavity, or (B) from analyte-induced structural changes of supramolecular dye-aggregates, leading to an altered dye-dye “communication”. (see Figure 1) Examples that will be shown include the differentiation of peptides, monitoring of enzymatic reactions and drug permeation through membranes, and detection of neurotransmitters in biological fluids.[1-3] Furthermore, it is shown how the commonly encountered affinity-challenge for artificial receptors in aqueous media can be overcome by taking advantage of “high-energy” water release from hydrophobic cavities (a.k.a. the non-classical hydrophobic effect).[4, 5]

Figure 1: Schematic representation of supramolecular sensing strategies which enable in situ analyte identification through unique spectroscopic fingerprints. [1] S. Sinn, F. Biedermann, and L. De Cola, Chem. Eur. J. 23 (2017). [2] F. Biedermann, D. Hathazi, and W. M. Nau, Chem. Commun. 51 (2015). [3] F. Biedermann, and W. M. Nau, Angew. Chem. Int. Ed. 53 (2014). [4] F. Biedermann, and H.-J. Schneider, Chem. Rev. 116 (2016). [5] F. Biedermann, W. M. Nau, and H.-J. Schneider, Angew. Chem. Int. Ed. 53 (2014).

Manipulating the ABCs of Self-Assembly via Low-χ Block Polymer Design

Alice B. Chang,† Christopher M. Bates,† Mark W. Matsen,‡ Robert H. Grubbs†

† Division of Chemistry and Chemical Engineering, California Institute of Technology1200 E. California Blvd., Pasadena, CA 91125, United States

‡ Department of Chemical Engineering, University of Waterloo200 University Ave. West, Waterloo, Ontario N2L 3G1, Canada

Molecular sequence and interactions dictate the mesoscale structure of all self-assembling soft materials. Block polymers harness this relationship to access a rich variety of nanostructured materials. Block polymer self-assembly typically translates molecular chain connectivity into mesoscale structure by exploiting incompatible blocks with large interaction parameters (χij). Contrary to this convention, we demonstrate that the converse approach, encoding low-χinteractions in ABC bottlebrush triblock terpolymers (χAC ≲ 0), promotes organization into a unique mixed-domain lamellar morphology which we designate LAMP. Transmission electron microscopy indicates that LAMP exhibits ACBC domain connectivity, in contrast to conventional three-domain lamellae (LAM3) with ABCB periods. Complementary small angle X-ray scattering experiments reveal a strongly decreasing domain spacing with increasing total molar mass. Self-consistent field theory reinforces these observations and predicts that LAMP

is thermodynamically stable below a critical χAC, above which LAM3 emerges. Both experiments and theory expose close analogies to ABA' triblock copolymer phase behavior, collectively suggesting that low-χ interactions between chemically similar or distinct blocks intimately influence self-assembly. These developments expand the vocabulary of block polymer design and open new avenues for manipulating the self-assembly of synthetic macromolecules.

NO O NO O

HN

O

O

NN N

O

O

NO O

O

O

O

NA NB NC

x y

z

LAMP

AA A/C B C/AC/A A

Polymer Synthesis Self-Assembly: New Morphology Unique Properties

16Supramolecular Chemistry, Photoswitching, Polymers

Nanoscale organization of subcortical actin in the nervous system

Elisa D’Este1, Dirk Kamin1, Francisco Balzarotti1, Fabian Göttfert1, Caroline Velte2, Mikael Simons2, and Stefan W. Hell1

1- Department of NanoBiophotonics, Max Plank Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Goettingen, Germany 2- Department of Cellular Neuroscience, Max Plank Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Goettingen, Germany Actin is a key component of the cellular cytoskeleton that forms a fine meshwork within the cytoplasm. Its organization in neurites of nerve cells was unclear for a long time, due to the low resolution of the microscopes and the lack of proper labelling tools for live imaging. Since its invention, super resolution microscopy (nanoscopy) tackled essential biological questions, and recently, it enabled the discovery of a ~190 nm periodic subcortical actin scaffold along the axons of fixed hippocampal neurons [1]. We used SiR-Actin, a new actin labelling probe, in combination with Stimulated Emission Depletion (STED) optical nanoscopy to detect the presence of this structure in living neurons. SiR-Actin is membrane permeable and fluorogenic, meaning that it fluoresces only when it is bound to its target, providing an excellent signal-to-noise ratio [2]. These features make it highly suitable for live-cell fluorescence nanoscopy. SiR-Actin permitted the identification of the actin subcortical scaffold in living cultured cells, both in the axons and along the dendrites of virtually every neuron type [3,4]. We additionally showed that this lattice persists in fixed sciatic nerve fibers, underneath the myelin coat, therefore indicating that myelination does not alter its structure. SiR-Actin revealed that oligodendrocyte precursors, which are the cells responsible for myelination in the central nervous system (CNS), also exhibit an actin pattern similar to the one found in neurons. We therefore wondered whether the periodic cytoskeleton plays a role in the assembly of nodes of Ranvier, where a tight connection between the myelinating glial cell and the axon is present, and the myelin coat is interrupted to allow the saltatory propagation of the action potential. At nodes of Ranvier of sciatic nerve fibers all the major components of these structures are periodically arranged, with a high degree of interdependence between the position of the axonal and the glial proteins [5]. Hence, the results indicate the presence of mechanisms that finely align the cytoskeleton of the axon with the one of the glial cells, and open up several questions related to the role of actin in the nervous system. Importantly, our work underscores the power of combining specific fluorescent probes with modern super resolution microscopy techniques. [1] K. Xu et al. Science 339, 452-456, (2013). [2] G. Lukinavicius et al. Nat Methods 11, 731-733, (2014). [3] E. D'Este et al. Cell Rep 10, 1246-1251, (2015). [4] E. D'Este et al. Sci Rep 6, 22741, (2016). [5] E. D'Este et al. Proc Natl Acad Sci U S A 114, E191-E199, (2017).

Methods and Method Development for Studying/Building Biological Systems

Optoelectronic materials as biointerfaces for neuroprosthetics

Vini Gautam

John Curtin School of Medical Research, The Australian National University, Acton – 2601, Australia.

Interfacing optoelectronic materials with neuronal cells provides a platform for understanding the formation and function of neuronal circuits in the brain. Here I will present two examples from my research where I have utilised optoelectronic materials to engineer the growth of neuronal circuits and stimulate their activity. I will first highlight the use of organic semiconductors as artificial photoreceptors for interfacing with the visual system. In these studies, I utilised the optoelectronic signals from organic semiconductor/electrolyte interface to stimulate neuronal cells and thereby elicit neuronal activity in a blind retinal tissue [1]. These results have implications for the development of all-organic retinal prosthetic devices. Next, I will give an overview of my current project, where I design nanoscale surface topography on biocompatible scaffolds to mimic the biophysical features in the brain’s extracellular matrix [2]. I use these scaffolds to guide the growth of neurons, understand the formation of neuronal circuits and evaluate the neuronal network activity in response to the biophysical properties of their surrounding environment (Figure 1). These results have implications for developing biocompatible scaffolds to regenerate neural circuits upon brain damage and injury. The results from these cross-disciplinary studies have ultimate applications in the development of novel neuroprosthetic interfaces and strategies for the treatment of neurodegenerative diseases. [1] V. Gautam et al. A Polymer Optoelectronic Interface Provides Visual Cues to a Blind Retina, Adv. Mater. 26, 1751-1756 (2014). [2] V. Gautam et al. Engineering highly interconnected neuronal networks on nanowire scaffolds, Nano Lett., in press (2017).

Figure 1. (Top) Functional Ca2+ imaging of neuronal cells and circuits on a semiconductor nanowire scaffold. (bottom) Ca2+ activity (ΔF/F) as a function of time at the marked dendrites and soma. (inset) SEM image of a neuron on a nanowire scaffold.

17

Nanoscale organization of subcortical actin in the nervous system

Elisa D’Este1, Dirk Kamin1, Francisco Balzarotti1, Fabian Göttfert1, Caroline Velte2, Mikael Simons2, and Stefan W. Hell1

1- Department of NanoBiophotonics, Max Plank Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Goettingen, Germany 2- Department of Cellular Neuroscience, Max Plank Institute of Experimental Medicine, Hermann-Rein-Straße 3, 37075 Goettingen, Germany Actin is a key component of the cellular cytoskeleton that forms a fine meshwork within the cytoplasm. Its organization in neurites of nerve cells was unclear for a long time, due to the low resolution of the microscopes and the lack of proper labelling tools for live imaging. Since its invention, super resolution microscopy (nanoscopy) tackled essential biological questions, and recently, it enabled the discovery of a ~190 nm periodic subcortical actin scaffold along the axons of fixed hippocampal neurons [1]. We used SiR-Actin, a new actin labelling probe, in combination with Stimulated Emission Depletion (STED) optical nanoscopy to detect the presence of this structure in living neurons. SiR-Actin is membrane permeable and fluorogenic, meaning that it fluoresces only when it is bound to its target, providing an excellent signal-to-noise ratio [2]. These features make it highly suitable for live-cell fluorescence nanoscopy. SiR-Actin permitted the identification of the actin subcortical scaffold in living cultured cells, both in the axons and along the dendrites of virtually every neuron type [3,4]. We additionally showed that this lattice persists in fixed sciatic nerve fibers, underneath the myelin coat, therefore indicating that myelination does not alter its structure. SiR-Actin revealed that oligodendrocyte precursors, which are the cells responsible for myelination in the central nervous system (CNS), also exhibit an actin pattern similar to the one found in neurons. We therefore wondered whether the periodic cytoskeleton plays a role in the assembly of nodes of Ranvier, where a tight connection between the myelinating glial cell and the axon is present, and the myelin coat is interrupted to allow the saltatory propagation of the action potential. At nodes of Ranvier of sciatic nerve fibers all the major components of these structures are periodically arranged, with a high degree of interdependence between the position of the axonal and the glial proteins [5]. Hence, the results indicate the presence of mechanisms that finely align the cytoskeleton of the axon with the one of the glial cells, and open up several questions related to the role of actin in the nervous system. Importantly, our work underscores the power of combining specific fluorescent probes with modern super resolution microscopy techniques. [1] K. Xu et al. Science 339, 452-456, (2013). [2] G. Lukinavicius et al. Nat Methods 11, 731-733, (2014). [3] E. D'Este et al. Cell Rep 10, 1246-1251, (2015). [4] E. D'Este et al. Sci Rep 6, 22741, (2016). [5] E. D'Este et al. Proc Natl Acad Sci U S A 114, E191-E199, (2017).

18

Optoelectronic materials as biointerfaces for neuroprosthetics

Vini Gautam

John Curtin School of Medical Research, The Australian National University, Acton – 2601, Australia.

Interfacing optoelectronic materials with neuronal cells provides a platform for understanding the formation and function of neuronal circuits in the brain. Here I will present two examples from my research where I have utilised optoelectronic materials to engineer the growth of neuronal circuits and stimulate their activity. I will first highlight the use of organic semiconductors as artificial photoreceptors for interfacing with the visual system. In these studies, I utilised the optoelectronic signals from organic semiconductor/electrolyte interface to stimulate neuronal cells and thereby elicit neuronal activity in a blind retinal tissue [1]. These results have implications for the development of all-organic retinal prosthetic devices. Next, I will give an overview of my current project, where I design nanoscale surface topography on biocompatible scaffolds to mimic the biophysical features in the brain’s extracellular matrix [2]. I use these scaffolds to guide the growth of neurons, understand the formation of neuronal circuits and evaluate the neuronal network activity in response to the biophysical properties of their surrounding environment (Figure 1). These results have implications for developing biocompatible scaffolds to regenerate neural circuits upon brain damage and injury. The results from these cross-disciplinary studies have ultimate applications in the development of novel neuroprosthetic interfaces and strategies for the treatment of neurodegenerative diseases. [1] V. Gautam et al. A Polymer Optoelectronic Interface Provides Visual Cues to a Blind Retina, Adv. Mater. 26, 1751-1756 (2014). [2] V. Gautam et al. Engineering highly interconnected neuronal networks on nanowire scaffolds, Nano Lett., in press (2017).

Figure 1. (Top) Functional Ca2+ imaging of neuronal cells and circuits on a semiconductor nanowire scaffold. (bottom) Ca2+ activity (ΔF/F) as a function of time at the marked dendrites and soma. (inset) SEM image of a neuron on a nanowire scaffold.

Methods and Method Development for Studying/Building Biological Systems

Dynamic multi-color protein labeling in living cells

Chenge Li1,2, Marie-Aude Plamont1,2, Hanna L. Sladitschek3, Vanessa Rodrigues1,2, Isabelle Aujard1,2, Pierre Neveu3, Thomas Le Saux1,2, Ludovic Jullien1,2, Arnaud Gautier1,2

1École Normale Supérieure, PSL Research University, UPMC Univ Paris 06, CNRS,

Département de Chimie, PASTEUR, 24 rue Lhomond, 75005 Paris, France 2Sorbonne Universités, UPMC Univ Paris 06, ENS, CNRS, PASTEUR, 75005 Paris, France

3Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstr. 1, D-69117 Heidelberg

Deciphering the complex mechanisms controlling cells and organisms requires effective imaging systems and fluorescent probes to observe and quantify biomolecules with high spatiotemporal resolution. A common strategy for imaging proteins is to fuse them to peptide or protein sequences that provide fluorescence, such as autofluorescent proteins and self-labeling tags that can be labeled specifically with chemical probes. Our lab recently developed Fluorescence-Activating and absorption-Shifting Tag (FAST), a small fluorogen-based reporter enabling to fluorescently label fusion proteins in living cells. FAST binds specifically the fluorogenic 4-hydroxy-3-methylbenzylidene rhodanine (HMBR), giving a bright green-yellow fluorescent complex. A unique fluorogen activation mechanism implying two spectroscopic changes, fluorescence quantum yield increase and absorption red shift, ensures selective labeling and high contrast.[1] Here, we report novel fluorogens exhibiting improved brightness and orange-red fluorescence when bound to FAST. These new fluorogens make FAST highly versatile because investigators can now adapt FAST's color to the observation channels available for their experiments, expanding considerably the field of applications of FAST. Beyond allowing multicolor imaging of FAST-tagged proteins in live cells, these fluorogens enable dynamic color switching because of FAST's reversible labeling. This unprecedented behavior allows selective detection of FAST-tagged proteins in cells expressing both green and red fluorescent species through two-color cross-correlation, opening exciting prospects to overcome spectral crowding and push the frontiers of multiplexed imaging.[2]

[1] M.-A. Plamont, E. Billon-Denis, S. Maurin, C. Gauron, F. M. Pimenta, C. G. Specht, J. Shi, J. Querard, B. Pan, J. Rossignol, K. Moncoq, N. Morellet, M. Volovitch, E. Lescop, Y. Chen, A. Triller, S. Vriz, T. Le Saux, L. Jullien, A. Gautier, Proc. Natl. Acad. Sci. U. S. A. 113, 497–502, (2016). [2] C. Li, M-A. Plamont, H. Sladitschek, V. Rodrigues, I. Aujard, P. Neveu, T. Le Saux, L. Jullien, A. Gautier, submitted, (2017).

Methods and Method Development for Studying/Building Biological Systems

Bringing functional order to disordered complexes of HIV-1 transactivation process

Aditi Borkar1, 2, 3,4, Michele Vendruscolo1, Matthias Geyer2, 3, Thomas A Steitz4 and Chris Dobson1

1Department of Chemistry, University of Cambridge, Cambridge, UK

2ImmunoSensation Excellence Cluster, University of Bonn, Bonn, Germany 3Institute of Innate Immunity, University Hospitals, University of Bonn, Bonn, Germany

4Department of Molecular Biochemistry and Biophysics, Yale University, USA

HIV hijacks the human transcription machinery to make multiple copies of its own genome. This process, known as transactivation (TAC), is crucial in the HIV infection cycle and has thus become the object of focused scientific attention in the past two decades - both for understanding its molecular mechanism and for the development of anti-HIV drugs. Numerous studies have revealed that the viral components of TAC – TAR RNA and Tat protein – are highly flexible and intrinsically disordered molecules respectively and undergo significant conformational changes while assembling into multipartite complexes. Such properties have impeded the formation of comprehensive and homogenous TAC complexes for high-resolution structural biology analyses. I have addressed this challenge by systematically probing the construction of stable TAC ribonucleoprotein complexes [1] in solution and am currently using this method for determining the structure and dynamics of the whole HIV-1 TAC by X-ray crystallography complemented by NMR spectroscopy.

Fig 1: Free Energy landscape of the TAR:Tat recognition process

[1] Borkar AN, Bardaro MF, Camilloni C, Aprile FA, Varani G and Vendruscolo M (2016) Structure of a low-population binding intermediate in protein-RNA recognition. Proc Nat Acad Sci, 113(26), 7171–7176.

19

Dynamic multi-color protein labeling in living cells

Chenge Li1,2, Marie-Aude Plamont1,2, Hanna L. Sladitschek3, Vanessa Rodrigues1,2, Isabelle Aujard1,2, Pierre Neveu3, Thomas Le Saux1,2, Ludovic Jullien1,2, Arnaud Gautier1,2

1École Normale Supérieure, PSL Research University, UPMC Univ Paris 06, CNRS,

Département de Chimie, PASTEUR, 24 rue Lhomond, 75005 Paris, France 2Sorbonne Universités, UPMC Univ Paris 06, ENS, CNRS, PASTEUR, 75005 Paris, France

3Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstr. 1, D-69117 Heidelberg

Deciphering the complex mechanisms controlling cells and organisms requires effective imaging systems and fluorescent probes to observe and quantify biomolecules with high spatiotemporal resolution. A common strategy for imaging proteins is to fuse them to peptide or protein sequences that provide fluorescence, such as autofluorescent proteins and self-labeling tags that can be labeled specifically with chemical probes. Our lab recently developed Fluorescence-Activating and absorption-Shifting Tag (FAST), a small fluorogen-based reporter enabling to fluorescently label fusion proteins in living cells. FAST binds specifically the fluorogenic 4-hydroxy-3-methylbenzylidene rhodanine (HMBR), giving a bright green-yellow fluorescent complex. A unique fluorogen activation mechanism implying two spectroscopic changes, fluorescence quantum yield increase and absorption red shift, ensures selective labeling and high contrast.[1] Here, we report novel fluorogens exhibiting improved brightness and orange-red fluorescence when bound to FAST. These new fluorogens make FAST highly versatile because investigators can now adapt FAST's color to the observation channels available for their experiments, expanding considerably the field of applications of FAST. Beyond allowing multicolor imaging of FAST-tagged proteins in live cells, these fluorogens enable dynamic color switching because of FAST's reversible labeling. This unprecedented behavior allows selective detection of FAST-tagged proteins in cells expressing both green and red fluorescent species through two-color cross-correlation, opening exciting prospects to overcome spectral crowding and push the frontiers of multiplexed imaging.[2]

[1] M.-A. Plamont, E. Billon-Denis, S. Maurin, C. Gauron, F. M. Pimenta, C. G. Specht, J. Shi, J. Querard, B. Pan, J. Rossignol, K. Moncoq, N. Morellet, M. Volovitch, E. Lescop, Y. Chen, A. Triller, S. Vriz, T. Le Saux, L. Jullien, A. Gautier, Proc. Natl. Acad. Sci. U. S. A. 113, 497–502, (2016). [2] C. Li, M-A. Plamont, H. Sladitschek, V. Rodrigues, I. Aujard, P. Neveu, T. Le Saux, L. Jullien, A. Gautier, submitted, (2017).

Bringing functional order to disordered complexes of HIV-1 transactivation process

Aditi Borkar1, 2, 3,4, Michele Vendruscolo1, Matthias Geyer2, 3, Thomas A Steitz4 and Chris Dobson1

1Department of Chemistry, University of Cambridge, Cambridge, UK

2ImmunoSensation Excellence Cluster, University of Bonn, Bonn, Germany 3Institute of Innate Immunity, University Hospitals, University of Bonn, Bonn, Germany

4Department of Molecular Biochemistry and Biophysics, Yale University, USA

HIV hijacks the human transcription machinery to make multiple copies of its own genome. This process, known as transactivation (TAC), is crucial in the HIV infection cycle and has thus become the object of focused scientific attention in the past two decades - both for understanding its molecular mechanism and for the development of anti-HIV drugs. Numerous studies have revealed that the viral components of TAC – TAR RNA and Tat protein – are highly flexible and intrinsically disordered molecules respectively and undergo significant conformational changes while assembling into multipartite complexes. Such properties have impeded the formation of comprehensive and homogenous TAC complexes for high-resolution structural biology analyses. I have addressed this challenge by systematically probing the construction of stable TAC ribonucleoprotein complexes [1] in solution and am currently using this method for determining the structure and dynamics of the whole HIV-1 TAC by X-ray crystallography complemented by NMR spectroscopy.

Fig 1: Free Energy landscape of the TAR:Tat recognition process

[1] Borkar AN, Bardaro MF, Camilloni C, Aprile FA, Varani G and Vendruscolo M (2016) Structure of a low-population binding intermediate in protein-RNA recognition. Proc Nat Acad Sci, 113(26), 7171–7176.

Methods and Method Development for Studying/Building Biological Systems 20

Hybrid hydrogels as synthetic matrices for tissue engineering Cécile Echalier,1,2 Said Jebors,1 Baptiste Legrand,1 Hélène Van Den Berghe,1

Xavier Garric,1 Estelle Jumas-Bilak,3 Danièle Noël,4 Elizabeth Engel,5 Jean Martinez,1 Ahmad Mehdi,2 Gilles Subra,1

1 Institute of Biomolecules Max Mousseron (IBMM), 2 Institute Charles Gerhardt (ICGM), 3 HydroSciences, 4 Institute for Regenerative Medicine and Biotherapy (IRMB),

Montpellier, France. 5 Institute for BioEngineering of Catalonia (IBEC), Barcelona, Spain.

Hydrogels play a central role in the field of biomedical materials as extracellular matrix substitutes. They are of tremendous interest in reconstructive surgery and tissue engineering but also for drug delivery. One of the main challenges is to synthesize scaffolds in which cells will be able to proliferate, differentiate and behave like in their natural environment. In this context, hydrogel functionalization with bioactive molecules is of first importance in order to mimic natural tissues. Therefore, we developed a bottom-up approach to obtain tunable hydrogels through the sol-gel process.[1] This method is based on (bio)organic-inorganic hybrid blocks obtained by functionalization of synthetic polymers or bioactive molecules, such as peptides, with silyl groups (triethoxy- or hydroxydimethylsilanes). These hybrid blocks can be combined in desired ratio and engaged in the sol-gel process to yield multifunctional hydrogels. Hydrolysis and condensation of silylated precursors result in a three-dimensional covalent network in which molecules are linked through siloxane bonds. Gelation proceeds at 37°C at pH 7.4 in a physiological buffer. Interestingly, in contrast with existing strategies to get covalent gels, no toxic reagents are required, enabling the use of fragile biomolecules and even cells. First, we demonstrated that these hydrogels exhibited biological properties depending on the nature of the hybrid bioactive peptide introduced, promoting cell adhesion or displaying antibacterial activity. Secondly, a hybrid peptide whose sequence was inspired from natural collagen was synthesized and used to prepare hydrogels that enabled stem cell encapsulation with high viability.[2] Finally, the liquid hybrid solution could be used as a bio-ink and functional scaffolds could be 3D-printed.[3] Thus, this soft and biocompatible strategy opens the way to the biofabrication of extracellular matrix mimics. [1] C. Echalier et al., Chem. Mater. 28, 1261–1265 (2016). [2] C. Echalier et al., Materials Today, DOI: 10.1016/j.mattod.2017.02.001 (2017) [3] C. Echalier et al., RSC Adv. 7, 12231–12235 (2017).

Methods and Method Development for Studying/Building Biological Systems

Monitoring co-translational folding in real-time Liutkute M., Holtkamp W., Thommen M., Rodnina M.

Max Planck Institute for Biophysical Chemistry, department of Physical Biochemistry Am Fassberg, Göttingen 37075, Germany

One of the outstanding questions in the protein folding field is how proteins attain

their native three-dimensional structure during biosynthesis on the ribosome. Contrary to the well studied folding of isolated proteins in vitro, co-translational folding is vectorial, i.e., it starts as soon as the N-terminal part of protein emerges from the peptide exit tunnel of the ribosome. Numerous studies on stalled ribosome nascent chain complexes (RNC) suggested that protein domains fold into stable tertiary structures co-translationally and well before the C-terminal part of the polypeptide chain is synthesized. Nevertheless, the timing of these events in relation to translation is largely unknown [1].

To investigate co-translational folding of RnaseH we use a fully reconstituted in vitro translation system and selective site-specific labeling of the nascent chain with fluorescent probes in combination with limited proteolysis [2]. The limited proteolysis assay of RNC complexes with different lengths of RnaseH nascent chain showed that only full-length RnaseH forms a stable protease resistant intermediate while the peptide chain is still attached to the ribosome. Ribosome-tethered RnaseH is not catalytically active as determined by an enzyme activity assay [3]; only after release of full-length RnaseH from the ribosome it shows enzymatic activity, indicating that the native form is not folded on the ribosome.

To monitor folding in real-time we employ fluorescence resonance energy transfer (FRET) and introduce two fluorophores site specifically into the nascent chain [4]. We generated specific sites in the RnaseH sequence that enables us to specifically incorporate fluorescently labeled amino acids co-translationally and confirmed that the mutants are natively folded and catalytically active by far-UV circular dichroism spectroscopy and enzyme activity assays. The dyes come into close proximity when RnaseH folds into the native state. Two variants showed an increase in the FRET signal during translation. This signal occurs before any full-length RnaseH is produced suggesting the formation of a compact intermediate in the RnaseH co-translational folding trajectory. When the nascent chain was released with puromycin no further FRET changes were observed, indicating that the distance between dyes does not change during rearrangement into the native state.

Here we show that the high performance in vitro translation system can faithfully produce proteins that occupy their native fold. We can now monitor protein folding on the ribosome in real-time using rapid kinetics and fluorescence methods. With this powerful toolbox we wish to elucidate the general mechanisms of co-translational folding and understand how the ribosome affects the folding trajectory of RnaseH. 1. Balchin, D., M. Hayer-Hartl, and F.U. Hartl. Science, 2016. 353(6294). 2. Thommen, M., W. Holtkamp, and M.V. Rodnina. Curr Opin Struct Biol, 2016. 42: p. 83-

89. 3. Chen, Y., et al., Chembiochem, 2008. 9(3): p. 355-359. 4. Buhr, F., et al., Molecular Cell, 2016. 61(3): p. 341-351.

21

Hybrid hydrogels as synthetic matrices for tissue engineering Cécile Echalier,1,2 Said Jebors,1 Baptiste Legrand,1 Hélène Van Den Berghe,1

Xavier Garric,1 Estelle Jumas-Bilak,3 Danièle Noël,4 Elizabeth Engel,5 Jean Martinez,1 Ahmad Mehdi,2 Gilles Subra,1

1 Institute of Biomolecules Max Mousseron (IBMM), 2 Institute Charles Gerhardt (ICGM), 3 HydroSciences, 4 Institute for Regenerative Medicine and Biotherapy (IRMB),

Montpellier, France. 5 Institute for BioEngineering of Catalonia (IBEC), Barcelona, Spain.

Hydrogels play a central role in the field of biomedical materials as extracellular matrix substitutes. They are of tremendous interest in reconstructive surgery and tissue engineering but also for drug delivery. One of the main challenges is to synthesize scaffolds in which cells will be able to proliferate, differentiate and behave like in their natural environment. In this context, hydrogel functionalization with bioactive molecules is of first importance in order to mimic natural tissues. Therefore, we developed a bottom-up approach to obtain tunable hydrogels through the sol-gel process.[1] This method is based on (bio)organic-inorganic hybrid blocks obtained by functionalization of synthetic polymers or bioactive molecules, such as peptides, with silyl groups (triethoxy- or hydroxydimethylsilanes). These hybrid blocks can be combined in desired ratio and engaged in the sol-gel process to yield multifunctional hydrogels. Hydrolysis and condensation of silylated precursors result in a three-dimensional covalent network in which molecules are linked through siloxane bonds. Gelation proceeds at 37°C at pH 7.4 in a physiological buffer. Interestingly, in contrast with existing strategies to get covalent gels, no toxic reagents are required, enabling the use of fragile biomolecules and even cells. First, we demonstrated that these hydrogels exhibited biological properties depending on the nature of the hybrid bioactive peptide introduced, promoting cell adhesion or displaying antibacterial activity. Secondly, a hybrid peptide whose sequence was inspired from natural collagen was synthesized and used to prepare hydrogels that enabled stem cell encapsulation with high viability.[2] Finally, the liquid hybrid solution could be used as a bio-ink and functional scaffolds could be 3D-printed.[3] Thus, this soft and biocompatible strategy opens the way to the biofabrication of extracellular matrix mimics. [1] C. Echalier et al., Chem. Mater. 28, 1261–1265 (2016). [2] C. Echalier et al., Materials Today, DOI: 10.1016/j.mattod.2017.02.001 (2017) [3] C. Echalier et al., RSC Adv. 7, 12231–12235 (2017).

Monitoring co-translational folding in real-time Liutkute M., Holtkamp W., Thommen M., Rodnina M.

Max Planck Institute for Biophysical Chemistry, department of Physical Biochemistry Am Fassberg, Göttingen 37075, Germany

One of the outstanding questions in the protein folding field is how proteins attain

their native three-dimensional structure during biosynthesis on the ribosome. Contrary to the well studied folding of isolated proteins in vitro, co-translational folding is vectorial, i.e., it starts as soon as the N-terminal part of protein emerges from the peptide exit tunnel of the ribosome. Numerous studies on stalled ribosome nascent chain complexes (RNC) suggested that protein domains fold into stable tertiary structures co-translationally and well before the C-terminal part of the polypeptide chain is synthesized. Nevertheless, the timing of these events in relation to translation is largely unknown [1].

To investigate co-translational folding of RnaseH we use a fully reconstituted in vitro translation system and selective site-specific labeling of the nascent chain with fluorescent probes in combination with limited proteolysis [2]. The limited proteolysis assay of RNC complexes with different lengths of RnaseH nascent chain showed that only full-length RnaseH forms a stable protease resistant intermediate while the peptide chain is still attached to the ribosome. Ribosome-tethered RnaseH is not catalytically active as determined by an enzyme activity assay [3]; only after release of full-length RnaseH from the ribosome it shows enzymatic activity, indicating that the native form is not folded on the ribosome.

To monitor folding in real-time we employ fluorescence resonance energy transfer (FRET) and introduce two fluorophores site specifically into the nascent chain [4]. We generated specific sites in the RnaseH sequence that enables us to specifically incorporate fluorescently labeled amino acids co-translationally and confirmed that the mutants are natively folded and catalytically active by far-UV circular dichroism spectroscopy and enzyme activity assays. The dyes come into close proximity when RnaseH folds into the native state. Two variants showed an increase in the FRET signal during translation. This signal occurs before any full-length RnaseH is produced suggesting the formation of a compact intermediate in the RnaseH co-translational folding trajectory. When the nascent chain was released with puromycin no further FRET changes were observed, indicating that the distance between dyes does not change during rearrangement into the native state.

Here we show that the high performance in vitro translation system can faithfully produce proteins that occupy their native fold. We can now monitor protein folding on the ribosome in real-time using rapid kinetics and fluorescence methods. With this powerful toolbox we wish to elucidate the general mechanisms of co-translational folding and understand how the ribosome affects the folding trajectory of RnaseH. 1. Balchin, D., M. Hayer-Hartl, and F.U. Hartl. Science, 2016. 353(6294). 2. Thommen, M., W. Holtkamp, and M.V. Rodnina. Curr Opin Struct Biol, 2016. 42: p. 83-

89. 3. Chen, Y., et al., Chembiochem, 2008. 9(3): p. 355-359. 4. Buhr, F., et al., Molecular Cell, 2016. 61(3): p. 341-351.

Methods and Method Development for Studying/Building Biological Systems 22

Watson-Crick style programmable protein interaction specificity

Zibo Chen, Scott Boyken, Ben Groves, Robert Langan, Georg Seelig, David Baker

Department of Biochemistry, University of Washington 4000 15th Ave NE, Seattle, WA 98105. United States of America

In nature, structural specificity in DNA and proteins is encoded differently: In DNA, specificity arises from modular hydrogen bonds in the core of the double helix, whereas in proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Here, we describe a general approach for designing a wide range of protein homo-oligomers with specificity determined by modular arrays of central hydrogen-bond networks [1]. We use the approach to design dimers, trimers, and tetramers consisting of two concentric rings of helices, including previously not seen triangular, square, and supercoiled topologies. X-ray crystallography confirms that the structures overall (Figure 1), and the hydrogen-bond networks in particular, are nearly identical to the design models, and the networks confer interaction specificity in vivo. The ability to design extensive hydrogen-bond networks with atomic accuracy enables the programming of protein interaction specificity for a broad range of synthetic biology applications; more generally, our results demonstrate that, even with the tremendous diversity observed in nature, there are fundamentally new modes of interaction to be discovered in proteins.

Figure 1. The hydrogen bond networks confer specificity. (A) Crystal structure of a designed homodimer. The backbone can accommodate hydrogen bond networks at each of four repeating geometric cross sections. (B)Two possibilities for each cross section: hydrogen bond network, “A”, or hydrophobic, “X”. (C) Combinatorial designs using this two-letter combination were tested for interaction specificity using the yeast two-hybrid assay. Axis labels denote the network pattern; for example, “AXAX” indicates network A at cross sections 1 and 3, and X (hydrophobic) at the two others. Designs were fused to both DNA binding domain and the

activation domain constructs and binding measured by determining the cell growth rate [maximum change in optical density (∆OD) per hour]; darker cells indicate more rapid growth, hence stronger binding; values are the average of three biological replicates. [1] Scott E. Boyken, Zibo Chen, Benjamin Groves, Robert A. Langan, Gustav Oberdorfer, Alex Ford, Jason M. Gilmore et al. "De novo design of protein homo-oligomers with modular hydrogen-bond network–mediated specificity." Science 352, no. 6286 (2016): 680-687.

Methods and Method Development for Studying/Building Biological Systems

Development of Helical Cell Penetrating Peptides Using Non-proteinogenic Amino Acids

Hiroko Yamashita1, Takashi Misawa2, Masaaki Kurihara2*, Yosuke Demizu2*

1Graduate School of Pharmaceutical Sciences, The University of Tokyo (1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan)

2National Institute of Health Sciences (1-18-1, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan)

In recent year, a group of therapeutic agents called ‘bio-pharmaceuticals’ gains power. Bio-pharmaceuticals are derived from proteins or substances produced by mammalian cells, viruses, or bacteria. These medicines are expected to provide highly effective cures with fewer side effects because of their specific target. However, bio-pharmaceuticals also have their drawbacks. One of them is low cell permeability arising from high hydrophilicity and molecular weight of these medicines. Cell penetrating peptides (CPPs) can propose one of effective solution. CPPs, which show high permeability toward various types of cells, are received much attention as an intracellular delivery tool of hydrophilic molecules. It is known that these peptides contain many cationic amino acid (Arg, Lys) residues [1], however, there are few reports which investigate the effect of CPPs secondary structures on their cell penetrating ability. So, it has been difficult to theoretically design novel CPPs having high cell permeability. Herein, we designed cationic a,a-disubstituted amino acids Api, ApiC2NH2, and ApiC2Gu, which can stabilize peptide helical structures. We also designed cationic proline derivatives ProNH2 and ProGu, which are expected to induce environmental responsive secondary structural change. Those cationic amino acids were introduced into nonaarginine (R9), the most commonly used CPP, at the 3rd, 6th, and 9th positions to give the peptides 1-5. We assessed these peptides’ secondary structures and cell membrane permeability. Peptides 1-3, forming stable helical structures entered into the cells more efficiently than random peptide R9 [2a]. Interestingly, the peptide 5, which changed its secondary structure from random to the helix corresponding to surrounding environment, also showed higher permeability than random peptides R9 and 4 [2b]. These results indicate that peptide helical structures improve the cellular permeability. These results provide useful guide for designing novel CPPs having higher permeability. In this study, we also investigated cytotoxicity, intracellular uptake pathway, and plasmid transportation capacity of these peptide. We presented these results in our poster as well. [1] S. Futaki, et. al., Biochemistry, 50, 612-619 (2007). [2] (a) H. Yamashita, T. Misawa, M. Kurihara, Y. Demizu, et. al., ChemBioChem, 17, 137-140 (2016); (b) H. Yamashita, T. Misawa, M. Kurihara, Y. Demizu, et. al., Sci. Rep., 6, 33003 (2016).

Figure 1 Chemical structures and cell membrane permeability of R9 and peptides 1-5.

23

Watson-Crick style programmable protein interaction specificity

Zibo Chen, Scott Boyken, Ben Groves, Robert Langan, Georg Seelig, David Baker

Department of Biochemistry, University of Washington 4000 15th Ave NE, Seattle, WA 98105. United States of America

In nature, structural specificity in DNA and proteins is encoded differently: In DNA, specificity arises from modular hydrogen bonds in the core of the double helix, whereas in proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Here, we describe a general approach for designing a wide range of protein homo-oligomers with specificity determined by modular arrays of central hydrogen-bond networks [1]. We use the approach to design dimers, trimers, and tetramers consisting of two concentric rings of helices, including previously not seen triangular, square, and supercoiled topologies. X-ray crystallography confirms that the structures overall (Figure 1), and the hydrogen-bond networks in particular, are nearly identical to the design models, and the networks confer interaction specificity in vivo. The ability to design extensive hydrogen-bond networks with atomic accuracy enables the programming of protein interaction specificity for a broad range of synthetic biology applications; more generally, our results demonstrate that, even with the tremendous diversity observed in nature, there are fundamentally new modes of interaction to be discovered in proteins.

Figure 1. The hydrogen bond networks confer specificity. (A) Crystal structure of a designed homodimer. The backbone can accommodate hydrogen bond networks at each of four repeating geometric cross sections. (B)Two possibilities for each cross section: hydrogen bond network, “A”, or hydrophobic, “X”. (C) Combinatorial designs using this two-letter combination were tested for interaction specificity using the yeast two-hybrid assay. Axis labels denote the network pattern; for example, “AXAX” indicates network A at cross sections 1 and 3, and X (hydrophobic) at the two others. Designs were fused to both DNA binding domain and the

activation domain constructs and binding measured by determining the cell growth rate [maximum change in optical density (∆OD) per hour]; darker cells indicate more rapid growth, hence stronger binding; values are the average of three biological replicates. [1] Scott E. Boyken, Zibo Chen, Benjamin Groves, Robert A. Langan, Gustav Oberdorfer, Alex Ford, Jason M. Gilmore et al. "De novo design of protein homo-oligomers with modular hydrogen-bond network–mediated specificity." Science 352, no. 6286 (2016): 680-687.

Development of Helical Cell Penetrating Peptides Using Non-proteinogenic Amino Acids

Hiroko Yamashita1, Takashi Misawa2, Masaaki Kurihara2*, Yosuke Demizu2*

1Graduate School of Pharmaceutical Sciences, The University of Tokyo (1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan)

2National Institute of Health Sciences (1-18-1, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan)

In recent year, a group of therapeutic agents called ‘bio-pharmaceuticals’ gains power. Bio-pharmaceuticals are derived from proteins or substances produced by mammalian cells, viruses, or bacteria. These medicines are expected to provide highly effective cures with fewer side effects because of their specific target. However, bio-pharmaceuticals also have their drawbacks. One of them is low cell permeability arising from high hydrophilicity and molecular weight of these medicines. Cell penetrating peptides (CPPs) can propose one of effective solution. CPPs, which show high permeability toward various types of cells, are received much attention as an intracellular delivery tool of hydrophilic molecules. It is known that these peptides contain many cationic amino acid (Arg, Lys) residues [1], however, there are few reports which investigate the effect of CPPs secondary structures on their cell penetrating ability. So, it has been difficult to theoretically design novel CPPs having high cell permeability. Herein, we designed cationic a,a-disubstituted amino acids Api, ApiC2NH2, and ApiC2Gu, which can stabilize peptide helical structures. We also designed cationic proline derivatives ProNH2 and ProGu, which are expected to induce environmental responsive secondary structural change. Those cationic amino acids were introduced into nonaarginine (R9), the most commonly used CPP, at the 3rd, 6th, and 9th positions to give the peptides 1-5. We assessed these peptides’ secondary structures and cell membrane permeability. Peptides 1-3, forming stable helical structures entered into the cells more efficiently than random peptide R9 [2a]. Interestingly, the peptide 5, which changed its secondary structure from random to the helix corresponding to surrounding environment, also showed higher permeability than random peptides R9 and 4 [2b]. These results indicate that peptide helical structures improve the cellular permeability. These results provide useful guide for designing novel CPPs having higher permeability. In this study, we also investigated cytotoxicity, intracellular uptake pathway, and plasmid transportation capacity of these peptide. We presented these results in our poster as well. [1] S. Futaki, et. al., Biochemistry, 50, 612-619 (2007). [2] (a) H. Yamashita, T. Misawa, M. Kurihara, Y. Demizu, et. al., ChemBioChem, 17, 137-140 (2016); (b) H. Yamashita, T. Misawa, M. Kurihara, Y. Demizu, et. al., Sci. Rep., 6, 33003 (2016).

Figure 1 Chemical structures and cell membrane permeability of R9 and peptides 1-5.

Methods and Method Development for Studying/Building Biological Systems 24

Structural insights into Staphylococcus aureus ribosome in complex with antibiotic, mRNA and tRNAs

Zohar Eyala, Donna Matzova, Miri Krupkina, Itai Wekselmana, Ella Zimmermana, Susanne Pauknerb, Tofayel Ahmedc, Satabdi Mishrac, Anat Bashana, Shashi Bhushanc,d and Ada Yonatha

a The Department of Structural Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel; b Nabriva Therapeutics AG, Vienna, Austria c School of Biological Sciences, Nanyang Technological University, 637551, Singapore. d NTU Institute of Structural Biology, Nanyang Technological University, 637551, Singapore The ribosome translates the genetic code into proteins in all living cells. As the ribosomes are essential for cell life, inhibiting their function will damage cell’s viability. In fact, about 40% of the antibiotics in clinical use target functional centers in the ribosome. With the increased use of antibiotics to treat bacterial infections, pathogenic strains have accumulated antibiotic resistance that is a major clinical threat.

Here we present the crystal structures of the large ribosomal subunit of Staphylococcus aureus, a Gram-positive versatile and aggressive pathogen, alongside its complex with a new potential high potency pleuoromutilin derivative, called BC-3205 [1].

By analyzing these crystal structures we identified some internal and peripheral unique structural motifs that may be potential candidates for improving known antibiotics and for the design of selective antibiotic drugs against Staphylococcus aureus.

We also present here our single-particle cryo-electron microscopy studies on the structure of the entire 70S ribosome complex with two tRNA molecules, mRNA chain and two antibiotics drugs that bind the small ribosomal subunit in two distinct functional sites.

1. Eyal, Z., et al., Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus. Proceedings of the National Academy of Sciences, 2015. 112(43): p. E5805-E5814.

NoBios: Super-liquid repellent coatings to prevention protein adsorption and bacterial adhesion

Noemí Encinas 1,*, Maxime Paven1, Lars Schmüser1,2, Ching-Yu Yang1,3, Florian Geyer1,

Maria D´Acunzi1, Jonas Reinholz1, Voller Mailänder1, Daniel Graham2, David G. Castner2, Tobias Weidner1,4, Doris Vollmer1, Hans Jürgen Butt1

1Physics at Interfaces Department,Max Planck Institute for Polymer Research, Mainz

2 Department of Chemical Engineering, University of Washington, Seattle,USA 3 Biological and Bio-inspired Materials Lab, National Tsing Hua University, Hsinchu, Taiwan

4 Department of Chemistry, Aarhus University, Aarhus, Denmark

*encinas@mpip-mainz.mpg.de Abstract Biofouling describes the agglomeration of microorganisms on surfaces mainly in contact with liquid. Free-floating cells freely swim and approach surfaces until they undergo irreversible attachment and start to develop well-formed colonies. These bacterial layers can be found on pipelines, hulls of boats or food packaging, leading to corrosion, increase on fuel consumption due to friction and food poisoning. Furthermore, when they form on medical devices nosocomial infections and failure due to clogging can take place. Accounting to the related economical losses and mortality related to biofilm formation new approaches battling this field have been proposed in the past years. The use of biocidal compounds (silver ions, quaternary ammonium salts) is one of the options. However, the increased resistance (up to a factor of 1000) of enclosed bacteria compared to free-floating cells as well as the possibility to restore films within hours make reasonable to focus on hindering or delaying the first adhesion events.

On this behalf, research within the NoBios project has been focused on super-liquid repellent surfaces as a platform to prevent biofilm formation. These surfaces prevent wetting by both water and low surface tension liquids thanks to the existence of a mobile air layer (Cassie-Baxter state) between solid features and liquid. We have used cutting-edge methods to evaluate the ability of such coatings to reduce protein (X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS)) adsorption below the technique detection limit, as well as to evaluate the attachment of bacterial cells and biofilm evolution (laser scanning confocal microscopy (LSCM)). Nano-structured candle-soot based coatings, flexible silicone nanofilaments and poly(dimethyl)siloxane brushes have been the main studied platforms, which we have proved to be able to importantly reduce the ubiquitous and undesirable biofilm formation.

[1] Costerton, J. W.; Stewart, P. S.; Greenberg, E. P. Science 284, 1318-1322, 1999. [2] Klevens, R. M. et al.; Public Health Rep 122, 160-166, 2007.. [3] Deng X., Mammen L., Butt H.-J., Vollmer D., Science 335, 67-70, 2012. [4] Paven M., Papadopoulos P., Schöttler S., Deng X., Mailänder V., Vollmer D., Butt H.-J., Nature Communication 4, 2013. [5] Wooh, S.; Encinas, N.; Vollmer, D.; Butt, H.-J.. Advanced Materials 1604637, 2017. [6] Schmüsser, L.; Encinas, N.; Paven, M..; Graham, D.; Castner, D.G.; Vollmer, D.; Butt, H.-J.; Weidner, T. Biointerphases 11:3, 031007, 2016. Editor’s Pick. [7] Schellenberger, F.; Encinas, N.; Vollmer, D.; Butt, H.-J.. Physical Review Letters 116, 096101, 2016. Editor’s Suggestion, Featured in Physics (L. Courbin, “Re-thinking superhydrophobicity”, Physics

Surfaces - Biofilms25

Structural insights into Staphylococcus aureus ribosome in complex with antibiotic, mRNA and tRNAs

Zohar Eyala, Donna Matzova, Miri Krupkina, Itai Wekselmana, Ella Zimmermana, Susanne Pauknerb, Tofayel Ahmedc, Satabdi Mishrac, Anat Bashana, Shashi Bhushanc,d and Ada Yonatha

a The Department of Structural Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel; b Nabriva Therapeutics AG, Vienna, Austria c School of Biological Sciences, Nanyang Technological University, 637551, Singapore. d NTU Institute of Structural Biology, Nanyang Technological University, 637551, Singapore The ribosome translates the genetic code into proteins in all living cells. As the ribosomes are essential for cell life, inhibiting their function will damage cell’s viability. In fact, about 40% of the antibiotics in clinical use target functional centers in the ribosome. With the increased use of antibiotics to treat bacterial infections, pathogenic strains have accumulated antibiotic resistance that is a major clinical threat.

Here we present the crystal structures of the large ribosomal subunit of Staphylococcus aureus, a Gram-positive versatile and aggressive pathogen, alongside its complex with a new potential high potency pleuoromutilin derivative, called BC-3205 [1].

By analyzing these crystal structures we identified some internal and peripheral unique structural motifs that may be potential candidates for improving known antibiotics and for the design of selective antibiotic drugs against Staphylococcus aureus.

We also present here our single-particle cryo-electron microscopy studies on the structure of the entire 70S ribosome complex with two tRNA molecules, mRNA chain and two antibiotics drugs that bind the small ribosomal subunit in two distinct functional sites.

1. Eyal, Z., et al., Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus. Proceedings of the National Academy of Sciences, 2015. 112(43): p. E5805-E5814.

26DNA, RNA, Ribosome

NoBios: Super-liquid repellent coatings to prevention protein adsorption and bacterial adhesion

Noemí Encinas 1,*, Maxime Paven1, Lars Schmüser1,2, Ching-Yu Yang1,3, Florian Geyer1,

Maria D´Acunzi1, Jonas Reinholz1, Voller Mailänder1, Daniel Graham2, David G. Castner2, Tobias Weidner1,4, Doris Vollmer1, Hans Jürgen Butt1

1Physics at Interfaces Department,Max Planck Institute for Polymer Research, Mainz

2 Department of Chemical Engineering, University of Washington, Seattle,USA 3 Biological and Bio-inspired Materials Lab, National Tsing Hua University, Hsinchu, Taiwan

4 Department of Chemistry, Aarhus University, Aarhus, Denmark

*encinas@mpip-mainz.mpg.de Abstract Biofouling describes the agglomeration of microorganisms on surfaces mainly in contact with liquid. Free-floating cells freely swim and approach surfaces until they undergo irreversible attachment and start to develop well-formed colonies. These bacterial layers can be found on pipelines, hulls of boats or food packaging, leading to corrosion, increase on fuel consumption due to friction and food poisoning. Furthermore, when they form on medical devices nosocomial infections and failure due to clogging can take place. Accounting to the related economical losses and mortality related to biofilm formation new approaches battling this field have been proposed in the past years. The use of biocidal compounds (silver ions, quaternary ammonium salts) is one of the options. However, the increased resistance (up to a factor of 1000) of enclosed bacteria compared to free-floating cells as well as the possibility to restore films within hours make reasonable to focus on hindering or delaying the first adhesion events.

On this behalf, research within the NoBios project has been focused on super-liquid repellent surfaces as a platform to prevent biofilm formation. These surfaces prevent wetting by both water and low surface tension liquids thanks to the existence of a mobile air layer (Cassie-Baxter state) between solid features and liquid. We have used cutting-edge methods to evaluate the ability of such coatings to reduce protein (X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS)) adsorption below the technique detection limit, as well as to evaluate the attachment of bacterial cells and biofilm evolution (laser scanning confocal microscopy (LSCM)). Nano-structured candle-soot based coatings, flexible silicone nanofilaments and poly(dimethyl)siloxane brushes have been the main studied platforms, which we have proved to be able to importantly reduce the ubiquitous and undesirable biofilm formation.

[1] Costerton, J. W.; Stewart, P. S.; Greenberg, E. P. Science 284, 1318-1322, 1999. [2] Klevens, R. M. et al.; Public Health Rep 122, 160-166, 2007.. [3] Deng X., Mammen L., Butt H.-J., Vollmer D., Science 335, 67-70, 2012. [4] Paven M., Papadopoulos P., Schöttler S., Deng X., Mailänder V., Vollmer D., Butt H.-J., Nature Communication 4, 2013. [5] Wooh, S.; Encinas, N.; Vollmer, D.; Butt, H.-J.. Advanced Materials 1604637, 2017. [6] Schmüsser, L.; Encinas, N.; Paven, M..; Graham, D.; Castner, D.G.; Vollmer, D.; Butt, H.-J.; Weidner, T. Biointerphases 11:3, 031007, 2016. Editor’s Pick. [7] Schellenberger, F.; Encinas, N.; Vollmer, D.; Butt, H.-J.. Physical Review Letters 116, 096101, 2016. Editor’s Suggestion, Featured in Physics (L. Courbin, “Re-thinking superhydrophobicity”, Physics

The translating human mitochondrial ribosome in action – snapshots observed by cryo-EM

Shintaro Aibara1,2, Angelika Modelska3, Alexey Amunts1,2

1 Science for Life Laboratory, Tomtebodavägen 23A, SE-171 65 Solna, Sweden.

2 Stockholms universitet, Institutionen för biokemi och biofysik, 106 91 Stockholm, Sweden.

3 Laboratory of Translational Genomics, Centre for Integrative Biology, University of Trento, via Sommarive 9, 38123, Povo, Trento, Italy.

The advent of the direct electron detector and improvements in computational tools has allowed near-atomic resolution structures to be determined by cryo-EM [1]. One of the milestones achieved during this exciting development were the structures of the mammalian mitochondrial ribosomes [2-3]. However to date, the structure of the translating human mitochondrial ribosome has remained elusive. We here present a 3.0 Å overall resolution of the human mitochondrial ribosome that were imaged in complex with a potential translational inhibitor using a Titan Krios equipped with a K2-Summit detector. By conventional classical methods within RELION such as exhaustive coarse or local fine-angular 3D classification [4], the dataset appeared to consist of one major and minor ratcheting state, and a further minor class with weak density for tRNA. However, using focused classification with signal subtraction [5], we were able to establish that this dataset consisted of three different tRNA bound states and one empty state of roughly equal distribution, each yielding a 3.6 Å resolution reconstruction. The classification strategy employed directly affecting the conclusions drawn from this dataset exemplify the importance of trying different ways and programs to classify data. Using the high-resolution ensemble map we were able to build a fully refined atomic model of the human mitochondrial 55S particle, correcting errors that were introduced previously in difficult regions. We observe that the P-site finger within the central-protuberance plays a central role in interacting the P-site tRNA, and becomes disordered when the site is unoccupied. mRNA was only observed in the class with both A&P-sites occupied, and this was accompanied with a previously unidentified factor binding onto the small subunit of the mitochondrial ribosome. These four reconstructions that were separated from an initial mixture provide insight at near-atomic resolution for the translational cycle within mitochondria.

[1] M. Eisenstein., Nat Meth 13, 19–22 (2016).

[2] A. Amunts et al., Science 348, 95–8 (2015)

[3] B.J Greber et al., Science 348, 303–8 (2015)

[4] Scheres, S.H.W., J. Struct. Biol. 180, 519–30 (2012)

[5] XC. Bai. eLife 4, e11182 (2015)

DNA, RNA, Ribosome

Ribosome Inactivating Peptides and the conserved mechanism of inhibition Raktim N. Roy1, Matthieu G. Gagnon1, Ivan B. Lomakin1, Tanja Florin2, Alexander S. Mankin2, Thomas A. Steitz1 1 Yale University, New Haven, CONNECTICUT, United States 2 Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, IL, USA Bacterial resistance to clinically used drugs is becoming a major public health concern. Proline-rich antimicrobial peptides (PrAMPs) have kindled renewed interests due to their targeted inhibitory effect on the bacterial protein synthesis, making them effective therapeutic leads, against human pathogens. Our crystal structures at less than 3 angstroms resolution for a set of PrAMPs, providing insights into their mode of ribosome inactivation and translation inhibition. These Ribosome Inactivating Peptides (RIPs) sterically interfere with the tRNAs in the A and P sites and also occlude the peptide exit tunnel of the bacterial ribosome. We purified 70S ribosomes from Thermus thermophilus, which were then co-crystallized with mRNA, tRNAs and RIPs. We used X-ray on all our crystals, containing the complexes to collect diffraction patterns, from which we solved the structures by molecular replacement methods. Our biochemical experiments show that the ribosome was effectively stalled during translation right after the initiation step, in presence of the RIPs. This inhibition was also equally potent in cellular environment and was reflected in corresponding hindered cell growth and MIC values in very low micro-molar ranges. We also found from the high-resolution structures, that all of these RIPs have a common mode of binding and their spatial architecture inside the Ribosome overlaps with the binding sites of three well-known classes of antibiotics; a feature that would markedly reduce the probability of appearance of drug resistance. These structures and the biochemical data will provide a strong platform for structure-based design of new-generation therapeutics against pathogenic microbes.

1. Roy RN, et al., (2015). The mechanism of inhibition of protein synthesis by the proline-rich peptide oncocin. Nat. Struct. Mol. Biol. 22(6): p. 466-9

2. Gagnon MG, Roy RN, Lomakin IB, Florin T, Mankin AS, Steitz TA (2016). Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibition. Nucleic Acids Res.44: 2439–2450.

27

The translating human mitochondrial ribosome in action – snapshots observed by cryo-EM

Shintaro Aibara1,2, Angelika Modelska3, Alexey Amunts1,2

1 Science for Life Laboratory, Tomtebodavägen 23A, SE-171 65 Solna, Sweden.

2 Stockholms universitet, Institutionen för biokemi och biofysik, 106 91 Stockholm, Sweden.

3 Laboratory of Translational Genomics, Centre for Integrative Biology, University of Trento, via Sommarive 9, 38123, Povo, Trento, Italy.

The advent of the direct electron detector and improvements in computational tools has allowed near-atomic resolution structures to be determined by cryo-EM [1]. One of the milestones achieved during this exciting development were the structures of the mammalian mitochondrial ribosomes [2-3]. However to date, the structure of the translating human mitochondrial ribosome has remained elusive. We here present a 3.0 Å overall resolution of the human mitochondrial ribosome that were imaged in complex with a potential translational inhibitor using a Titan Krios equipped with a K2-Summit detector. By conventional classical methods within RELION such as exhaustive coarse or local fine-angular 3D classification [4], the dataset appeared to consist of one major and minor ratcheting state, and a further minor class with weak density for tRNA. However, using focused classification with signal subtraction [5], we were able to establish that this dataset consisted of three different tRNA bound states and one empty state of roughly equal distribution, each yielding a 3.6 Å resolution reconstruction. The classification strategy employed directly affecting the conclusions drawn from this dataset exemplify the importance of trying different ways and programs to classify data. Using the high-resolution ensemble map we were able to build a fully refined atomic model of the human mitochondrial 55S particle, correcting errors that were introduced previously in difficult regions. We observe that the P-site finger within the central-protuberance plays a central role in interacting the P-site tRNA, and becomes disordered when the site is unoccupied. mRNA was only observed in the class with both A&P-sites occupied, and this was accompanied with a previously unidentified factor binding onto the small subunit of the mitochondrial ribosome. These four reconstructions that were separated from an initial mixture provide insight at near-atomic resolution for the translational cycle within mitochondria.

[1] M. Eisenstein., Nat Meth 13, 19–22 (2016).

[2] A. Amunts et al., Science 348, 95–8 (2015)

[3] B.J Greber et al., Science 348, 303–8 (2015)

[4] Scheres, S.H.W., J. Struct. Biol. 180, 519–30 (2012)

[5] XC. Bai. eLife 4, e11182 (2015)

Ribosome Inactivating Peptides and the conserved mechanism of inhibition Raktim N. Roy1, Matthieu G. Gagnon1, Ivan B. Lomakin1, Tanja Florin2, Alexander S. Mankin2, Thomas A. Steitz1 1 Yale University, New Haven, CONNECTICUT, United States 2 Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, IL, USA Bacterial resistance to clinically used drugs is becoming a major public health concern. Proline-rich antimicrobial peptides (PrAMPs) have kindled renewed interests due to their targeted inhibitory effect on the bacterial protein synthesis, making them effective therapeutic leads, against human pathogens. Our crystal structures at less than 3 angstroms resolution for a set of PrAMPs, providing insights into their mode of ribosome inactivation and translation inhibition. These Ribosome Inactivating Peptides (RIPs) sterically interfere with the tRNAs in the A and P sites and also occlude the peptide exit tunnel of the bacterial ribosome. We purified 70S ribosomes from Thermus thermophilus, which were then co-crystallized with mRNA, tRNAs and RIPs. We used X-ray on all our crystals, containing the complexes to collect diffraction patterns, from which we solved the structures by molecular replacement methods. Our biochemical experiments show that the ribosome was effectively stalled during translation right after the initiation step, in presence of the RIPs. This inhibition was also equally potent in cellular environment and was reflected in corresponding hindered cell growth and MIC values in very low micro-molar ranges. We also found from the high-resolution structures, that all of these RIPs have a common mode of binding and their spatial architecture inside the Ribosome overlaps with the binding sites of three well-known classes of antibiotics; a feature that would markedly reduce the probability of appearance of drug resistance. These structures and the biochemical data will provide a strong platform for structure-based design of new-generation therapeutics against pathogenic microbes.

1. Roy RN, et al., (2015). The mechanism of inhibition of protein synthesis by the proline-rich peptide oncocin. Nat. Struct. Mol. Biol. 22(6): p. 466-9

2. Gagnon MG, Roy RN, Lomakin IB, Florin T, Mankin AS, Steitz TA (2016). Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibition. Nucleic Acids Res.44: 2439–2450.

DNA, RNA, Ribosome 28

Trojan horse therapy of cancer Modified nucleosides as photo/radiosensitizers of DNA damage

Magdalena Zdrowowicz, Janusz Rak

Faculty of Chemistry, University of Gdansk Wita Stwosza 63, 80-308 Gdansk, Poland

The therapeutic effects of electromagnetic radiation used in cancer treatment are reduced by factors such as lack of oxygen caused by hypoxia or effective repair mechanisms. This fact calls for introducing sensitizers, i.e. substances that sensitize cells to radiation, in order to increase the efficiency of any radiation therapy. Modified nucleosides seem to be especially well suited for radiation-induced cell killing because of their specific features. The most unique property is the fact that they can substitute (at least some of them) native nucleosides in DNA without affecting its structure and function. Thus, the lethal effects are produced mainly as a result of interaction between radiation and nucleoside analogs incorporated into DNA [1].

One of the most promising radiosensitizer is 5-thiocyanato-2’-deoxyuridine (SCNdU). A combination of theoretical studies with negative ion photoelectron spectroscopy experiments demonstrated that the compound possesses properties required for efficient radiosensitizers [2]. Further studies of the degradation of SCNdU induced by excess electron attachment using low-temperature ESR, steady-state radiolysis at ambient temperature, and molecular modeling at the DFT level confirmed its sensitizing potential. Our results show that the electron attachment induced formation of two highly cytotoxic radicals: dU-S• and dU• and consequently two stable degradation products: dU-S-S-dU dimer and 2’-deoxyuridine [3]. Thus, our studies establish SCNdU as a potential radiosensitizer that could cause strand breaks and intra- /interstrand crosslinking as well as DNA-protein crosslinking via S-S dimer formation.

The modified nucleosides have also photosensitizing properties so they can be used in photodynamic anticancer therapies, based on the controlled destruction of the DNA molecule. Halogen derivatives of nucleobases are one of the most widely studied group of photosensitizing compounds. We demonstrated that 5-bromo-2’-deoxycytidine (BrdC) can serve as a potential DNA photosensitizer. Using the LC-MS method, denaturing PAGE electrophoresis and tandem MS/MS analysis coupled with the enzymatic digestion, two types of DNA damage were discovered in UV-irradiated BrdC-sensitized DNA: single strand breaks formed due to photoinduced electron transfer and intrastrand crosslinking [4].

[1] J. Rak, L. Chomicz, J. Wiczk, K. Westphal, M. Zdrowowicz, P. Wityk, M. Żyndul, S. Makurat, Ł. Golon, J. Phys. Chem. B 119, 8227-38, (2015).

[2] L. Chomicz, M. Zdrowowicz, F. Kasprzykowski, J. Rak, A. Buonaugurio, Y. Wang, K. Bowen, J. Phys. Chem. Lett. 4, 2853-57, (2013).

[3] M. Zdrowowicz, L. Chomicz, M. Żyndul, P. Wityk, J. Rak, T. Wiegand, C. Hanson, A. Adhikary, M. Sevilla, Phys. Chem. Chem. Phys. 17, 16907-16, (2015).

[4] M. Zdrowowicz, B. Michalska, A. Zylicz-Stachula, J. Rak, J. Phys. Chem B 118, 5009-16, (2014).

Decoding the physical aspect of T cell activation and long term functions by DNA based force probes

Victor Pui-Yan Maa and Khalid Salaitaa,b,*

a Department of Chemistry, Emory University, Atlanta GA 30322, United States b Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30322, United States * Corresponding author Email addresses: pui-yan.ma@emory.edu or k.salaita@emory.edu T lymphocytes play a central role in adaptive immunity by destroying infected or aberrant cells. At molecular level, T cell activation primarily occurs through interaction of T cell receptors (TCRs) on the T cell with major histocompatibility complex proteins displaying peptide (8-12 amino acids) antigens (pMHC) on the antigen-presenting cell (APC). This initial TCR-ligand binding triggers a series of downstream phosphorylation events that ultimately activate T cells. However, how this binding triggers a signal from the TCR remains a topic of debate, even though the TCR has been identified for more than 20 years. Recent single molecule force spectroscopy experiments using optical tweezer1 and bio-membrane force probe2 showed TCR is a mechanosensor – by converting externally applied forces into a biochemical signal upon ligation with its cognate ligands. However, whether T cells transmit intrinsic forces to cognate antigens when encountering APCs in intracellular environment, and whether the forces have specific functions in initial antigen recognition, TCR signal amplification and long term biological functions is unknown. To study these questions, we have developed DNA based force probes to study the physical aspect of T cell signaling. Our technique is capable of mapping piconewton (pN) tension of individual TCRs during activation with ~200 nm spatial and ~ms temporal resolution. We showed naïve T cells transmitted defined piconewton forces (~5 to 12 pN) to its cognate antigen during their initial encounter on both a gold coated substrate3 and supported lipid bilayer.4 Pharmacological ablation revealed the TCR forces are tightly coupled to the cytoskeleton. We further showed that antigen recognition by T cells is modulated by TCR forces – T cells displayed a dampened and poor specific responses to antigens when the forces are chemical abolished by cytoskeletal drugs or “physically filtered” by mechanically liable tension sensors. This work revealed T cells resort intrinsic mechanical energy transmitted by its cytoskeleton for antigen recognition and discrimination. To move further, ongoing research on how TCR forces affect long term functional outcomes of T cells (e.g. cytokine production, altered transcriptional and surface markers profiles) will be discussed.

References 1. S. T. Kim, K. Takeuchi, Z. Y. Sun, M. Touma, C. E. Castro, S. Fahmy, M. J. Lang, G. Wagner, E. L. Reinherz, J. Biol. Chem., 2009, 284, 31028 2. B. Liu, W. Chen, B. D. Evavold, C. Zhu, Cell, 2014, 157, 357 3. Y. Liu, L. Blanchfield, V. P.-Y. Ma, R. Andargachew, K. Galior, Z. Liu, B. D. Evavold, K. Salaita, Proc. Natl. Acad. Sci. USA, 2016, 113, 5610 4. V. P.-Y. Ma, Y. Liu, L. Blanchfield, H. Su, B. D. Evavold, K. Salaita, Nano Lett., 2016, 16, 4552

29 DNA, RNA, Ribosome

Trojan horse therapy of cancer Modified nucleosides as photo/radiosensitizers of DNA damage

Magdalena Zdrowowicz, Janusz Rak

Faculty of Chemistry, University of Gdansk Wita Stwosza 63, 80-308 Gdansk, Poland

The therapeutic effects of electromagnetic radiation used in cancer treatment are reduced by factors such as lack of oxygen caused by hypoxia or effective repair mechanisms. This fact calls for introducing sensitizers, i.e. substances that sensitize cells to radiation, in order to increase the efficiency of any radiation therapy. Modified nucleosides seem to be especially well suited for radiation-induced cell killing because of their specific features. The most unique property is the fact that they can substitute (at least some of them) native nucleosides in DNA without affecting its structure and function. Thus, the lethal effects are produced mainly as a result of interaction between radiation and nucleoside analogs incorporated into DNA [1].

One of the most promising radiosensitizer is 5-thiocyanato-2’-deoxyuridine (SCNdU). A combination of theoretical studies with negative ion photoelectron spectroscopy experiments demonstrated that the compound possesses properties required for efficient radiosensitizers [2]. Further studies of the degradation of SCNdU induced by excess electron attachment using low-temperature ESR, steady-state radiolysis at ambient temperature, and molecular modeling at the DFT level confirmed its sensitizing potential. Our results show that the electron attachment induced formation of two highly cytotoxic radicals: dU-S• and dU• and consequently two stable degradation products: dU-S-S-dU dimer and 2’-deoxyuridine [3]. Thus, our studies establish SCNdU as a potential radiosensitizer that could cause strand breaks and intra- /interstrand crosslinking as well as DNA-protein crosslinking via S-S dimer formation.

The modified nucleosides have also photosensitizing properties so they can be used in photodynamic anticancer therapies, based on the controlled destruction of the DNA molecule. Halogen derivatives of nucleobases are one of the most widely studied group of photosensitizing compounds. We demonstrated that 5-bromo-2’-deoxycytidine (BrdC) can serve as a potential DNA photosensitizer. Using the LC-MS method, denaturing PAGE electrophoresis and tandem MS/MS analysis coupled with the enzymatic digestion, two types of DNA damage were discovered in UV-irradiated BrdC-sensitized DNA: single strand breaks formed due to photoinduced electron transfer and intrastrand crosslinking [4].

[1] J. Rak, L. Chomicz, J. Wiczk, K. Westphal, M. Zdrowowicz, P. Wityk, M. Żyndul, S. Makurat, Ł. Golon, J. Phys. Chem. B 119, 8227-38, (2015).

[2] L. Chomicz, M. Zdrowowicz, F. Kasprzykowski, J. Rak, A. Buonaugurio, Y. Wang, K. Bowen, J. Phys. Chem. Lett. 4, 2853-57, (2013).

[3] M. Zdrowowicz, L. Chomicz, M. Żyndul, P. Wityk, J. Rak, T. Wiegand, C. Hanson, A. Adhikary, M. Sevilla, Phys. Chem. Chem. Phys. 17, 16907-16, (2015).

[4] M. Zdrowowicz, B. Michalska, A. Zylicz-Stachula, J. Rak, J. Phys. Chem B 118, 5009-16, (2014).

Decoding the physical aspect of T cell activation and long term functions by DNA based force probes

Victor Pui-Yan Maa and Khalid Salaitaa,b,*

a Department of Chemistry, Emory University, Atlanta GA 30322, United States b Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30322, United States * Corresponding author Email addresses: pui-yan.ma@emory.edu or k.salaita@emory.edu T lymphocytes play a central role in adaptive immunity by destroying infected or aberrant cells. At molecular level, T cell activation primarily occurs through interaction of T cell receptors (TCRs) on the T cell with major histocompatibility complex proteins displaying peptide (8-12 amino acids) antigens (pMHC) on the antigen-presenting cell (APC). This initial TCR-ligand binding triggers a series of downstream phosphorylation events that ultimately activate T cells. However, how this binding triggers a signal from the TCR remains a topic of debate, even though the TCR has been identified for more than 20 years. Recent single molecule force spectroscopy experiments using optical tweezer1 and bio-membrane force probe2 showed TCR is a mechanosensor – by converting externally applied forces into a biochemical signal upon ligation with its cognate ligands. However, whether T cells transmit intrinsic forces to cognate antigens when encountering APCs in intracellular environment, and whether the forces have specific functions in initial antigen recognition, TCR signal amplification and long term biological functions is unknown. To study these questions, we have developed DNA based force probes to study the physical aspect of T cell signaling. Our technique is capable of mapping piconewton (pN) tension of individual TCRs during activation with ~200 nm spatial and ~ms temporal resolution. We showed naïve T cells transmitted defined piconewton forces (~5 to 12 pN) to its cognate antigen during their initial encounter on both a gold coated substrate3 and supported lipid bilayer.4 Pharmacological ablation revealed the TCR forces are tightly coupled to the cytoskeleton. We further showed that antigen recognition by T cells is modulated by TCR forces – T cells displayed a dampened and poor specific responses to antigens when the forces are chemical abolished by cytoskeletal drugs or “physically filtered” by mechanically liable tension sensors. This work revealed T cells resort intrinsic mechanical energy transmitted by its cytoskeleton for antigen recognition and discrimination. To move further, ongoing research on how TCR forces affect long term functional outcomes of T cells (e.g. cytokine production, altered transcriptional and surface markers profiles) will be discussed.

References 1. S. T. Kim, K. Takeuchi, Z. Y. Sun, M. Touma, C. E. Castro, S. Fahmy, M. J. Lang, G. Wagner, E. L. Reinherz, J. Biol. Chem., 2009, 284, 31028 2. B. Liu, W. Chen, B. D. Evavold, C. Zhu, Cell, 2014, 157, 357 3. Y. Liu, L. Blanchfield, V. P.-Y. Ma, R. Andargachew, K. Galior, Z. Liu, B. D. Evavold, K. Salaita, Proc. Natl. Acad. Sci. USA, 2016, 113, 5610 4. V. P.-Y. Ma, Y. Liu, L. Blanchfield, H. Su, B. D. Evavold, K. Salaita, Nano Lett., 2016, 16, 4552

30DNA, RNA, Ribosome

Council for the Lindau Nobel Laureate Meetings Foundation Lindau Nobel Laureate Meetings

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