This file was created by the TYPO3 extension publications --- Timezone: CEST Creation date: 2026-05-20 Creation time: 17:04:20 --- Number of references 95 article gao_mechanochemical_2026 The cyclobutane motif is a versatile force-reactive moiety enabling diverse mechanophores and their associated functions in polymer mechanochemistry. For example, the cyclobutane core has been applied in the context of stress-responsive polymers, self-healing materials, and self-sensing nanocomposites. However, leveraging the cyclobutane structure for the development of nucleobase- and nucleoside-derived mechanophores remains unexplored. Here, we introduce a pyrimidine dimer mechanophore based on a cyclobutane core (CPD), formed via photoinduced [2 + 2] cycloaddition of thymine under ultraviolet B (UVB) irradiation. Upon ultrasound exposure, the polymer-centered CPD undergoes formal cycloelimination. To better understand the individual mechanochemical contributions of the four possible CPD stereoisomers upon force input, we employ the CoGEF and FM-PES methods and compare the results. Experimental and computational methods suggest that the syn-diastereomers cleave preferentially compared to their anti-counterparts under mechanical force. 2026 4 17 2041-6539 10.1039/D6SC02165D Chemical Science 17 The Royal Society of Chemistry Xiang Gao Gurudas Chakraborty Felix Joel Urhahne Marcus Lantzius-Beninga Regina Lennarz Jilin Fan Kara Stappert Jan Meisner Robert Göstl Andreas Herrmann article barmin_microbubble_2025 Microbubbles (MB) are widely used as contrast agents for ultrasound (US) imaging and US-enhanced drug delivery. While the majority of studies utilize commercial MB formulations, increasing experimental evidence indicates that distinct MB features critically determine their diagnostic and therapeutic performance. Here, it is shown that shell stiffness engineering of poly(alkyl cyanoacrylate) (PACA) MB, via introducing monomers with varying alkyl chain lengths and glass transition temperatures, preserves a narrow size distribution ≈2–3 µm, while enhancing MB drug loading, in vitro sonoporation capability, and in vitro and in vivo acoustic responses. All-atom molecular dynamics simulations and spectroscopic experiments demonstrate that MB shell engineering increases drug diffusion rates in the shell, maximizing the loading capacity of the formulations. Atomic force microscopy demonstrates that the stiffness of the MB shell can be tailored by more than ten-fold, boosting sonoporation and imaging performance. Altogether, the work provides new insights into the control of polymeric MB structure and performance via dedicated shell engineering, promoting applications in US imaging and therapy. 2026 1 27 1 1521-4095 10.1002/adma.202507655 Advanced Materials 38 e07655 6 alkyl cyanoacrylate, drug delivery, microbubbles, sonoporation, ultrasound Roman A. Barmin MirJavad Moosavifar Elena Rama Julia Blöck Anne Rix Vladislav S. Petrovskii Rustam A. Gumerov Jens Köhler Michael Pohl Céline Bastard Stephan Rütten Laura Charlton Vu Ngoc Khiêm Fabio Domenici Thomas Lisson Ekaterina Savina Rui Zhang Jasmin Baier Susanne Koletnik Vasileios Koutsos Mikhail Itskov Gaio Paradossi Georg Schmitz Tina Vermonden Laura De Laporte Robert Göstl Andreas Herrmann Igor I. Potemkin Fabian Kiessling Twan Lammers Roger M. Pallares article aydonat_efficient_2025 The development of efficient methods for nitrile syntheses is a challenge due to the current reliance on toxic cyanide sources, metal catalysts and their associated waste products, and harsh conditions that limit functional group compatibility. Here, we show a metal- and complex reagent-free strategy for the conversion of aldehydes to nitriles through carbamoylaldoxime intermediates. Therefore, we synthesize aldoximes from several aldehydes using hydroxylamine, which in turn are reacted with dimethylcarbamoyl chloride (DMCC) to afford N,N-dimethylcarbamoyloximes. Subsequent heating cleanly produces the desired nitriles as well as volatile CO2 and HNMe2 through a pericyclic syn elimination. This approach relies on widely available commercial chemicals, proceeds with broad functional group tolerance, and minimizes the need for extensive purification of the nitrile product. 2025 12 17 1 1521-3765 10.1002/chem.202502629 Chemistry – A European Journal 31 e02629 71 aldehydes, carbamates, cyanides, nucleophilic addition-elimination, rearrangement Simay Aydonat Davide Campagna Robert Göstl article blank_moving_2025 2025 9 1 2976-8683 10.1039/D5MR90024G RSC Mechanochemistry 2 627-630 5 Kerstin G. Blank Robert Göstl article fan_polymer_2025 The flow-induced activation of mechanophores embedded in linear polymers by ultrasound (US) suffers from slow mechanochemical conversions at the commonly used frequency of 20 kHz and in many cases remains ineffective with higher MHz frequencies. Here, we present polymeric microbubbles (PMBs) as a platform that accelerates the mechanochemical activation of several mechanophores under both 20 kHz and MHz irradiation. MHz irradiation generated by biocompatible high-intensity focused US (HIFU). Through their pressure-sensitive gas core, PMBs act as acousto-mechanical transducers for the transformation of sound energy into stretching and compression forces as well as fracturing the polymer shell by the volume oscillation of PMB. We investigate three different mechanophores among which one flex-activation derivative was unexpectedly activated by US. Through a combination of experiments and computation, we find that PMBs likely exert compressive force onto the copolymerized mechanophores rather than the typical elongational forces solvated chain fragments experience in flow. We thereby underscore the mechanochemical properties of the PMB platform and its versatility for accelerated mechanochemical transformations with a perspective on biomedical applications. 2025 6 25 1 2041-1723 10.1038/s41467-025-60667-8 Nature Communications 16 5380 1 Polymers, Design, synthesis and processing, Mechanical properties Publisher: Nature Publishing Group Jilin Fan Regina Lennarz Kuan Zhang Ahmed Mourran Jan Meisner Mingjun Xuan Robert Göstl Andreas Herrmann article asya_optical_2025 Polymer deformation spans 7–10 orders of magnitude in length scales, making its analysis a significant challenge. Optical force probes (OFPs), functional molecular motifs in polymer mechanochemistry, enable the study of mechanical properties by undergoing force-activated optical changes, such as absorption, fluorescence, or chemiluminescence. This review highlights OFPs integrated within polymer materials, focusing on their mechanical properties, optical methods for force elucidation, and the insights they provide. Special attention is given to high-resolution microscopy combined with OFPs, enabling qualitative and quantitative imaging of material damage and failure at unprecedented spatial resolution. While binary OFPs respond at critical strain thresholds, ideal for detecting permanent damage and stress hotspots, continuum OFPs track strain proportionally through reversible optical mechanisms, providing dynamic, real-time strain mapping. Together, these systems advance material diagnostics, offering complementary capabilities to study stress distribution, improve durability predictions, and understand polymer failure mechanisms. 2025 4 17 1 2692-4560 10.1002/agt2.70014 Aggregate 6 e70014 4 failure, damage, polymer mechanochemistry, optical force probes Berçin V. Asya Sitao Wang Eric Euchler Vu Ngoc Khiêm Robert Göstl article hahmann_sequence-specific_2025 Nucleic acids, such as DNA, are integral components of biological systems in that they steer many cellular processes and biotechnological applications. In addition, their monomer-precise sequence and accurately predictable structure render them an excellent model for exploring fundamental problems in nanotechnology and polymer science. In the field of polymer mechanochemistry, predetermined breaking points, called mechanophores, are used to endow macromolecules with chain-scission selectivity when subjected to external forces. However, this approach entails cumbersome chemical synthesis and limited outcome analysis. Here, we show the mechanophore-free, near-nucleotide-precise scission of nicked double-stranded DNA in a combined experimental and computational approach. We leverage next-generation sequencing to achieve monomer-level precision in assessing chain scission. Additionally, we monitor and control the scission distribution on the polymer’s backbone. Our research highlights the potential of DNA as a model polymer in the field of polymer mechanochemistry. 2025 4 10 1 2451-9294, 2451-9308 10.1016/j.chempr.2024.11.014 Chem 11 102376 4 mechanophores, ultrasound, nucleic acids, molecular dynamics, polymer mechanochemistry, SDG12: Responsible consumption and production, DNA mechanochemistry, next-generation sequencing, nicked DNA, SDG11: Sustainable cities and communities Publisher: Elsevier Johannes Hahmann Boris N. Schüpp Aman Ishaqat Arjuna Selvakumar Robert Göstl Frauke Gräter Andreas Herrmann article Force-activated functional groups in polymers may inform the design of future smart materials in which mechanical events trigger productive chemistry. The availability of such mechanochemically active tools (mechanophores) is perpetually increasing, but the limited understanding of mechanochemical reactivity complicates the identification of new molecular motifs that render reactive groups accessible by force. Here, we expand the chemical scope of our previously reported carbamoyloxime mechanophore motif from latent secondary to tertiary amines by harnessing the reactivity of transient nitrogen-centred radicals formed in the mechanochemical reaction pathway. Carbamoyloximes are modified with an N-pentenyl substituent which undergoes a consecutive intramolecular 5-exo-trig ring-closing reaction with an aminyl radical generated upon force-induced homolytic scission of the mechanophore, thereby enabling the hitherto unexplored mechanochemical activation of latent tertiary amines. We therefore show that carbamoyloxime mechanophores are nitrogen-centred mechanoradical generators expanding the chemical space of polymer mechanochemistry. 2025 3 1 1 10.1039/D4MR00099D RSC Mechanochemistry 2 240-245 2 Sonja Storch Davide Campagna Simay Aydonat Robert Göstl article aydonat_accelerated_2024 Current approaches to the discovery of mechanochemical reactions in polymers are limited by the interconnection of the zero-force and force-modified potential energy surfaces since most mechanochemical reactions are force-biased thermal reactions. Here, carbamoyloximes are developed as a mechanophore class in which the mechanochemical reaction rates counterintuitively increase together with the thermal stability. All carbamoyloxime mechanophores undergo force-induced homolytic bond scission at the N–O bond, and their mechanochemical scission rate increases with the degree of substitution on the α-substituent. Yet, carbamoylaldoximes react to both heat and light with a pericyclic syn elimination, while carbamoylketoximes undergo thermal decomposition at high temperature and photochemical homolytic scission only from the triplet state. Thereby, the mechanochemical and thermal reaction trajectories are separated, and the thermal stability increases alongside the mechanochemical reaction kinetics. This approach may play an important role in the future of systematic mechanochemical reaction discovery. 2024 11 20 1 0002-7863 10.1021/jacs.4c13319 Journal of the American Chemical Society 146 32117-32123 46 Publisher: American Chemical Society Simay Aydonat Davide Campagna Sourabh Kumar Sonja Storch Tim Neudecker Robert Göstl article Responsive Polymere ändern ihre Materialeigenschaften und reagieren über programmierte molekulare Prozesse auf Umwelteinflüsse. Solche Materialdesigns standen dieses Jahr im Fokus vieler Anwendungen: Sie verbessern die Rezyklierbarkeit, führen zu selbstreguliertem Abbau und Selbstheilung, transportieren Wirkstoffe und setzen sie frei oder ahmen biologische Systeme mit komplexen Signalverarbeitungsabläufen und adaptiven Strukturen nach. Für eine nachhaltige Kunststoffwirtschaft bleiben zudem leitfähige Polymere und biobasierte Monomere wichtig. 2024 10 1 10.1002/nadc.20244142791 Nachrichten aus der Chemie 72 52-59 10 Robert Göstl Sonja Storch article broschinski_mechanochemical_2024 Optical force probes (OFPs) are mechanochemically latent sensors that visualize stress and strain at the molecular level by changing their optical properties upon force-induced bond scission. Yet, the incorporation of mechanochemical responsivity into established fluorophore motifs is difficult, which is why red- and near-infrared (NIR)-excited OFPs are rarely reported. Here, an approach to solve this issue is presented, relying on triplet–triplet annihilation photon upconversion (TTA UC). OFPs based on Diels–Alder adducts of anthracene and maleimide are used as latent annihilators, and a phthalocyanine derivative is used as the triplet sensitizer. By incorporation of the annihilator motif in the center of linear polymer chains and subsequent ultrasonication, the latent annihilator is mechanochemically activated. In combination with the sensitizer and red excitation, TTA UC leads to yellow emission only after mechanochemical bond scission but not in its pristine form. Thereby, mechanochemically activated TTA UC is demonstrated with excitation energies as low as that of NIR light. 2024 9 27 1 10.1021/acsaom.4c00024 ACS Applied Optical Materials 2 1764–1769 1 9 Christian Broschinski Felix Majer Siyang He Alexander J. C. Kuehne Robert Göstl article The ultrasound (US)-induced activation of mechanophores embedded in linear polymers (LPs) is the most widely employed technique to realize chemical function by polymer mechanochemistry. However, the commonly used US frequency in this context is around 20 kHz, producing strong inertial cavitation limiting biomedical applicability. Herein, 20 kHz US and 1.5 MHz high-intensity focused US (HIFU) are investigated to drive disulfide mechanophore activation and mechanochemical polymer chain scission in network core-structured star polymers (NCSPs). It is found that the efficiency of activating disulfide mechanophores in NCSPs using 1.5 MHz HIFU irradiation is similar to the efficiency achieved with 20 kHz sonication. This is quantified by ‘turn on’ sensor molecules leveraging the Michael addition of the mechanochemically generated thiol groups and subsequent retro Diels–Alder reaction to release a fluorophore. Moreover, the anticancer drug doxorubicin (Dox) covalently loaded into NCSPs is efficiently released by 1.5 MHz HIFU. Finally, an in vitro study of drug release from NCSPs is performed, demonstrating the potential of HIFU-activated polymer mechanochemistry for sonopharmacology. 2024 8 8 1 10.1002/smsc.202400082 Small Science 4 2400082 8 Jilin Fan Mingjun Xuan Kuan Zhang Rostislav Vinokur Lifei Zheng Robert Göstl Andreas Herrmann article ishaqat_vivo_2024 Polymer mechanochemistry utilizes mechanical force to activate latent functionalities in macromolecules and widely relies on ultrasonication techniques. Fundamental constraints of frequency and power intensity have prohibited the application of the polymer mechanochemistry principles in a biomedical context up to now, although medical ultrasound is a clinically established modality. Here, a universal polynucleotide framework is presented that allows the binding and release of therapeutic oligonucleotides, both DNA- and RNA-based, as cargo by biocompatible medical imaging ultrasound. It is shown that the high molar mass, colloidal assembly, and a distinct mechanochemical mechanism enable the force-induced release of cargo and subsequent activation of biological function in vitro and in vivo. Thereby, we introduce a platform for the exploration of biological questions and therapeutics development steered by mechanical force. 2024 8 8 1 1521-4095 10.1002/adma.202403752 Advanced Materials 36 2403752 32 In vivo, Polymer Mechanochemistry, Rolling Circle Amplification, sonogenetics, Sonopharmacology Aman Ishaqat Johannes Hahmann Cheng Lin Xiaofeng Zhang Chuanjiang He Wolfgang H. Rath Pardes Habib Sabri E. M. Sahnoun Khosrow Rahimi Rostislav Vinokur Felix M. Mottaghy Robert Göstl Matthias Bartneck Andreas Herrmann article Ultrasound (US) activation of mechanophores in polymers that initiates cascade chemical reactions is a promising strategy for on-demand molecule release. However, the typical US frequency used for mechanochemistry is around 20 kHz, producing inertial cavitation that exceeds the tolerance threshold of biological systems. Here, high-intensity focused US (HIFU) as a mechanical stimulus is introduced to drive the activation of disulfide mechanophores in hyperbranched star polymers (HBSPs) and microgels (MGLs). The mechanism of molecular release is attributed to the thiol-disulfide exchange reaction and subsequent intramolecular cyclization. We reveal that HBSPs and MGLs effectively transduce HIFU as mechanical input to chemical output, demonstrated by the quantification of the release of fluorescent umbelliferone (UMB). Moreover, an in vitro study of drug release is carried out using camptothecin as the model drug, which is covalently loaded in MGLs, demonstrating the potential of our system for controlled drug delivery to cancer cells. 2024 8 1 1 10.31635/ccschem.024.202403876 CCS Chemistry 6 1895-1907 1 8 Jilin Fan Kuan Zhang Mingjun Xuan Xiang Gao Rostislav Vinokur Robert Göstl Lifei Zheng Andreas Herrmann article aydonat_leveraging_2024 Over 8 billion tons of plastic have been produced to date, and a 100% reclamation recycling strategy is not foreseeable. This review summarizes how the mechanochemistry of polymers may contribute to a sustainable polymer future by controlling the degradation not only of de novo developed designer polymers but also of plastics in existing waste streams. The historical development of polymer mechanochemistry is presented while highlighting current examples of mechanochemically induced polymer degradation. Additionally, theoretical and computational frameworks are discussed that may lead to the discovery and better understanding of new mechanochemical reactions in the future. This review takes into account technical and engineering perspectives converging the fields of trituration and polymer mechanochemistry with a particular focus on the fate of commodity polymers and potential technologies to monitor mechanochemical reactions while they occur. Therefore, a unique perspective of multiple communities is presented, highlighting the need for future transdisciplinary research to tackle the high-leverage parameters governing an eventually successful mechanochemical degradation approach for a circular economy. 2024 4 1 1 1349-0540 10.1038/s41428-023-00863-9 Polymer Journal 56 249-268 1 4 Polymerization mechanisms, Mechanical properties, Engineering, Physical chemistry, Techniques and instrumentation Simay Aydonat Adrian H. Hergesell Claire L. Seitzinger Regina Lennarz George Chang Carsten Sievers Jan Meisner Ina Vollmer Robert Göstl article rath_mechanochemical_2024 Controlling the activity of DNAzymes by external triggers is an important task. Here a temporal control over DNAzyme activity through a mechanochemical pathway with the help of ultrasound (US) is demonstrated. The deactivation of the DNAzyme is achieved by hybridization to a complementary strand generated through rolling circle amplification (RCA), an enzymatic polymerization process. Due to the high molar mass of the resulting polynucleic acids, shear force can be applied on the RCA strand through inertial cavitation induced by US. This exerts mechanical force and leads to the cleavage of the base pairing between RCA strand and DNAzyme, resulting in the recovery of DNAzyme activity. This is the first time that this release mechanism is applied for the activation of catalytic nucleic acids, and it has multiple advantages over other stimuli. US has higher penetration depth into tissues compared to light, and it offers a more specific stimulus than heat, which has also limited use in biological systems due to cell damage caused by hyperthermia. This approach is envisioned to improve the control over DNAzyme activity for the development of reliable and specific sensing applications. 2024 2 23 1 2198-3844 10.1002/advs.202306236 Advanced Science 11 2306236 1 8 ultrasound, nucleic acids, polymer mechanochemistry, DNAzymes Wolfgang H. Rath Robert Göstl Andreas Herrmann article izak-nau_brownian_2024 Magnetic nanoparticles (NPs) are widely employed for remote controlled molecular release applications using alternating magnetic fields (AMF). Yet, they intrinsically generate heat in the process by Néel relaxation limiting their application scope. In contrast, iron oxide NPs larger than ≈15 nm react to AMF by Brownian relaxation resulting in tumbling and shaking. Here, such iron oxide NPs are combined with polymer shells where the shaking motion mechanically agitates and partially detaches the polymer chains, covalently cleaves a fraction of the polymers, and releases the prototypical cargo molecules doxorubicin and curcumin into solution. This heat-free release mechanism broadens the potential application space of polymer-functionalized magnetic NP composites. 2024 1 25 1 1613-6829 10.1002/smll.202304527 Small 20 2304527 1 4 magnetic nanoparticles, polymer composites, brownian relaxation Emilia Izak-Nau Louisa P. Niggemann Robert Göstl article xuan_polymer_2023 Polymer mechanochemistry is a promising technology to convert mechanical energy into chemical functionality by breaking covalent and supramolecular bonds site-selectively. Yet, the mechanochemical reaction rates of covalent bonds in typically used ultrasonication setups lead to reasonable conversions only after comparably long sonication times. This can be accelerated by either increasing the reactivity of the mechanoresponsive moiety or by modifying the encompassing polymer topology. Here, a microbubble system with a tailored polymer shell consisting of an N2 gas core and a mechanoresponsive disulfide-containing polymer network is presented. It is found that the mechanochemical activation of the disulfides is greatly accelerated using these microbubbles compared to commensurate solid core particles or capsules filled with liquid. Aided by computational simulations, it is found that low shell thickness, low shell stiffness and crosslink density, and a size-dependent eigenfrequency close to the used ultrasound frequency maximize the mechanochemical yield over the course of the sonication process. 2023 11 23 1 1521-4095 10.1002/adma.202305130 Advanced Materials 35 2305130 1 47 ultrasound, polymer mechanochemistry, microbubbles, disulfide mechanophore, inertial cavitation Mingjun Xuan Jilin Fan Vu Ngoc Khiêm Miancheng Zou Kai-Oliver Brenske Ahmed Mourran Rostislav Vinokur Lifei Zheng Mikhail Itskov Robert Göstl Andreas Herrmann article he_photoinduced_2023 The serial connection of multiple stimuli-responses in polymer architectures enables the logically conjunctive gating of functional material processes on demand. Here, a photoswitchable diarylethene (DAE) acts as a crosslinker in poly(N-vinylcaprolactam) microgels and allows the light-induced shift of the volume phase-transition temperature (VPTT). While swollen microgels below the VPTT are susceptible to force and undergo breakage–aggregation processes, collapsed microgels above the VPTT stay intact in mechanical fields induced by ultrasonication. Within a VPTT shift regime, photoswitching of the DAE transfers microgels from the swollen to the collapsed state and thereby gates their response to force as demonstrated by the light-gated activation of an embedded fluorogenic mechanophore. This photoinduced mechanical cloaking system operates on the polymer topology level and is thereby principally universally applicable. 2023 10 12 1 1521-4095 10.1002/adma.202305845 Advanced Materials 35 2305845 1 41 photoswitches, mechanical properties, mechanochemistry, microgels Siyang He Simon Schog Ying Chen Yuxin Ji Sinan Panitz Walter Richtering Robert Göstl article gostl_trendbericht_2023 Der Wunsch nach einer geschlossenen Kreislaufwirtschaft befeuert die Forschung an biobasierten Polymeren und an Materialien mit maßgeschneiderten Lebenszyklen. Auch die Forschung an Energiespeichern bleibt wichtig. Ungebrochener Beliebtheit erfreuen sich zudem biomedizinische Materialien, von Polymertherapeutika bis zu Hydrogelen mit besonderer Struktur. 2023 9 29 1868-0054 10.1002/nadc.20234132417 Nachrichten aus der Chemie 71 48--54 1 10 Robert Göstl article desai_transformative_2023 Drug delivery systems (DDS) are designed to temporally and spatially control drug availability and activity. They assist in improving the balance between on-target therapeutic efficacy and off-target toxic side effects. DDS aid in overcoming biological barriers encountered by drug molecules upon applying them via various routes of administration. They are furthermore increasingly explored for modulating the interface between implanted (bio)medical materials and host tissue. Herein, an overview of the biological barriers and host-material interfaces encountered by DDS upon oral, intravenous, and local administration is provided, and material engineering advances at different time and space scales to exemplify how current and future DDS can contribute to improved disease treatment are highlighted. 2023 8 08 1 2192-2659 10.1002/adhm.202301062 Advanced Healthcare Materials 12 2301062 1 20 biomaterials, drug delivery, biomedical engineering, drug targeting, nanomedicines Prachi Desai Anshuman Dasgupta Alexandros Marios Sofias Quim Peña Robert Göstl Ioana Slabu Ulrich Schwaneberg Thomas Stiehl Wolfgang Wagner Stefan Jockenhövel Julia Stingl Rafael Kramann Christian Trautwein Tim H. Brümmendorf Fabian Kiessling Andreas Herrmann Twan Lammers article zhou_fracture_2023 Glues are being used to bond, seal, and repair in industry and biomedicine. The improvement of gluing performance is hence important for the development of new glues with better and balanced property spaces, which in turn necessitates a mechanistic understanding of their mechanical failure. Optical force probes (OFPs) allow the observation of mechanical material damage in polymers from the macro- down to the microscale, yet have never been employed in glues. Here, the development of a series of ratiometric OFPs based on fluorescent-protein–dye and protein–protein conjugates and their incorporation into genetically engineered bio-glues is reported. The OFPs are designed to efficiently modulate Förster resonance energy transfer upon force application thereby reporting on force-induced molecular alterations independent of concentration and fluorescence intensity both spectrally and through their fluorescence lifetime. By fluorescence spectroscopy in solution and in the solid state and by fluorescence lifetime imaging microscopy, stress concentrations are visualized and adhesive and cohesive failure in the fracture zone is differentiated. 2023 4 20 1 1521-4095 10.1002/adma.202210052 Advanced Materials 35 2210052 1 16 proteins, polymer mechanochemistry, optical force probes, fluorescence lifetimes Yu Zhou Silvia P. Centeno Kuan Zhang Lifei Zheng Robert Göstl Andreas Herrmann article kung_mechanoresponsive_2023 We report the formation of metal-organic cage-crosslinked polymer hydrogels. To enable crosslinking of the cages and subsequent network formation, we used homodifunctionalized poly(ethylene glycol) (PEG) chains terminally substituted with bipyridines as ligands for the Pd6L4 corners. The encapsulation of guest molecules into supramolecular self-assembled metal-organic cage-crosslinked hydrogels, as well as ultrasound-induced disassembly of the cages with release of their cargo, is presented in addition to their characterization by nuclear magnetic resonance (NMR) techniques, rheology, and comprehensive small-angle X-ray scattering (SAXS) experiments. The constrained geometries simulating external force (CoGEF) method and barriers using a force-modified potential energy surface (FMPES) suggest that the cage-opening mechanism starts with the dissociation of one pyridine ligand at around 0.5 nN. We show the efficient sonochemical activation of the hydrogels HG3–6, increasing the non-covalent guest-loading of completely unmodified drugs available for release by a factor of ten in comparison to non-crosslinked, star-shaped assemblies in solution. 2023 3 28 1 1521-3765 10.1002/chem.202300079 Chemistry – A European Journal 29 e202300079 1 18 mechanochemistry, hydrogels, supramolecular chemistry, host-guest systems, palladium Robin Küng Anne Germann Marcel Krüsmann Louisa P. Niggemann Jan Meisner Matthias Karg Robert Göstl Bernd M. Schmidt article yildiz_sonopharmacology_2022 Active pharmaceutical ingredients are the most consequential and widely employed treatment in medicine although they suffer from many systematic limitations, particularly off-target activity and toxicity. To mitigate these effects, stimuli-responsive controlled delivery and release strategies for drugs are being developed. Fueled by the field of polymer mechanochemistry, recently new molecular technologies enabled the emergence of force as an unprecedented stimulus for this purpose by using ultrasound. In this research area, termed sonopharmacology, mechanophores bearing drug molecules are incorporated within biocompatible macromolecular scaffolds as preprogrammed, latent moieties. This review presents the novelties in controlling drug activation, monitoring, and release by ultrasound, while discussing the limitations and challenges for future developments. 2022 11 30 1 2041-6539 10.1039/D2SC05196F Chemical Science 13 13708--13719 1 46 Deniz Yildiz Robert Göstl Andreas Herrmann article baumann_regiochemical_2022 The attachment point of the polymer chain to a force-responsive molecular unit (mechanophore) is a decisive parameter determining bond scission rate and ultimately the mechanochemical reaction outcome. However, such regiochemical polymer substituent effects have not yet been investigated for 9-π-extended anthracene-maleimide Diels-Alder adducts. Here we combine three methods, namely ultrasonication, CoGEF computation, and flow activation, to understand the influence of the pulling point location on the mechanochemical reactivity of this mechanophore class. We find minor mechanochemical reactivity differences between the investigated constitutional mechanophore isomers. Concomitantly, our results highlight the capabilities and limitations of the employed experimental techniques for such delicate variances and raise the question whether these are relevant for mechanochemical applications in a material context. 2022 11 15 1 2642-4169 10.1002/pol.20220342 Journal of Polymer Science 60 3128--3133 1 22 mechanochemistry, DFT, fluorescence, flow Christoph Baumann Niamh Willis-Fox Davide Campagna Etienne Rognin Paul Marten Ronan Daly Robert Göstl article kharandiuk_mechanoresponsive_2022 In the context of controlled delivery and release, proteins constitute a delicate class of cargo requiring advanced delivery platforms and protection. We here show that mechanoresponsive diselenide-crosslinked microgels undergo controlled ultrasound-triggered degradation in aqueous solution for the release of proteins. Simultaneously, the proteins are protected from chemical and conformational damage by the microgels, which disintegrate to water-soluble polymer chains upon sonication. The degradation process is controlled by the amount of diselenide crosslinks, the temperature, and the sonication amplitude. We demonstrate that the ultrasound-mediated cleavage of diselenide bonds in these microgels facilitates the release and activates latent functionality preventing the oxidation and denaturation of the encapsulated proteins (cytochrome C and myoglobin) opening new application possibilities in the targeted delivery of biomacromolecules. 2022 10 05 1 2041-6539 10.1039/D2SC03153A Chemical Science 13 11304--11311 1 38 Tetiana Kharandiuk Kok Hui Tan Wenjing Xu Fabian Weitenhagen Susanne Braun Robert Göstl Andrij Pich article rasch_pyrene-based_2022 Excimer-containing polymers with supramolecular mechanochromism are an attractive and well-investigated class of mechanoresponsive materials. However, only recently steps toward mechanophore-like mechanochromic systems that are anchored within the parent polymer structure and that show defined optical transitions on the molecular scale have been reported. However, the multi-step syntheses of these constructs are tedious. Here we report the development of a series of pyrene-based macrocrosslinkers that display supramolecular mechanochromism and are readily synthesized from mostly commercial reagents. We incorporate the water-soluble macrocrosslinkers in hydrogel networks and demonstrate their reversible mechanochromic behavior in the elastic deformation regime. 2022 10 1 2625-1825 10.1055/s-0042-1757972 Organic Materials 4 170--177 1 4 Dustin Rasch Robert Göstl article campagna_mechanoresponsive_2022 Mechanophore sind molekulare Einheiten, die in Polymere eingebaut werden und auf Kraft mit konstitutionellen, konfigurativen oder konformationellen Bindungsumlagerungen reagieren, um Funktionalität zu ermöglichen. Bis heute wurden bereits einige chemisch latente Motive durch mechanochemische Methoden in Polymeren aktiviert, aber die Erzeugung sekundärer Amine blieb unerforscht. Hier berichten wir über Carbamoyloxime als mechanochemische Schutzgruppen für sekundäre Amine. Wir zeigen, dass Carbamoyloxime eine kraftinduzierte homolytische Bindungsspaltung an der N−O-Oximbindung in Polymeren eingehen und so das freie Amin erzeugen. Die Reaktion verläuft analog zu ihrem photochemischen Gegenstück über Carbamoyloxyl- und Aminylradikale. Schließlich wenden wir das Carbamoyloxim-Motiv in einer kraftaktivierten organokatalytischen Knoevenagel-Reaktion an. Wir glauben, dass diese Schutzgruppenstrategie universell für viele andere sekundäre und primäre Amine in Polymermaterialien angewendet werden kann. 2022 9 26 1 1521-3757 10.1002/ange.202207557 Angewandte Chemie 134 e202207557 1 39 Amine, Mechanochemie, Polymere, Organokatalyse, Photochemie Davide Campagna Robert Göstl article campagna_mechanoresponsive_2022 Mechanophores are molecular moieties that are incorporated into polymers and respond to force with constitutional, configurational, or conformational bond rearrangements to enable functionality. Up to today, several chemically latent motifs have been activated by polymer mechanochemical methods, but the generation of secondary amines remains elusive. Here we report carbamoyloximes as mechanochemical protecting groups for secondary amines. We show that carbamoyloximes undergo force-induced homolytic bond scission at the N−O oxime bond in polymers thus producing the free amine, as the reaction proceeds via the carbamoyloxyl and aminyl radicals, analogously to its photochemical counterpart. Eventually, we apply the carbamoyloxime motif in a force-activated organocatalytic Knoevenagel reaction. We believe that this protecting strategy can be universally applied for many other secondary and primary amines in polymer materials. 2022 9 26 1 1521-3773 10.1002/anie.202207557 Angewandte Chemie International Edition 61 e202207557 1 39 Organocatalysis, Polymers, Photochemistry, Mechanochemistry, Amines Davide Campagna Robert Göstl article klok_force_2022 2022 8 10 10.1021/acspolymersau.2c00029 ACS Polymers Au 2 208--212 1 4 Harm-Anton Klok Andreas Herrmann Robert Göstl inbook niggemann_mechanoresponsive_2022 This chapter describes molecules that selectively react to force when embedded in polymer systems, so-called mechanophores. Such mechanophores are important tools for harnessing and understanding force-induced events within the field of polymer mechanochemistry. Due to the large portfolio of mechanophores and methods for their activation, which have been researched in recent years, many applications have been realized ranging from drug delivery, catalysis, and self-healing, to force-sensing. In this chapter, mechanisms of the force-induced activation of mechanophores are classified, methods for the exertion of force are summarized, and mechanophore applications and their detection using optical properties are described. 2022 7 08 978-1-83916-277-0 10.1039/9781839166136-00604 Chemoresponsive Materials 2 Royal Society of Chemistry Smart Materials Series 604--636 1 L. P. Niggemann Robert Göstl article xuan_mechanochemical_2022 Mechanochemistry uses mechanical force to break, form, and manipulate chemical bonds to achieve functional transformations and syntheses. Over the last years, many innovative applications of mechanochemistry have been developed. Specifically for the synthesis and activation of carbon-rich π-conjugated materials, mechanochemistry offers reaction pathways that either are inaccessible with other stimuli, such as light and heat, or improve reaction yields, energy consumption, and substrate scope. Therefore, this review summarizes the recent advances in this research field combining the viewpoints of polymer and trituration mechanochemistry. The highlighted mechanochemical transformations include π-conjugated materials as optical force probes, the force-induced release of small dye molecules, and the mechanochemical synthesis of polyacetylene, carbon allotropes, and other π-conjugated materials. 2022 7 06 1 2198-3844 10.1002/advs.202105497 Advanced Science 9 2105497 1 19 polymer mechanochemistry, carbon-rich materials, mechanosynthesis, trituration, π-conjugation Mingjun Xuan Christian Schumacher Carsten Bolm Robert Göstl Andreas Herrmann article zou_microgels_2022 The ultrasound-induced cleavage of covalent and non-covalent bonds to activate drugs (sonopharmacology) is a promising concept to gain control over the action of active pharmaceutical ingredients by an external trigger. Previously, linear polymer architectures bearing drug payloads were exploited for drug release by using the principles of polymer mechanochemistry. In this work, the carrier design is altered by the polymer topology to improve the ultrasound-triggered release of covalently anchored drugs from polymer scaffolds. We use microgels crosslinked by mechanoresponsive disulfides and copolymerized with Diels-Alder adducts of furylated payload molecules and acetylenedicarboxylate. Force-induced thiol formation induces a Michael-type addition liberating the payload from the microgels. The use of microgels significantly reduces sonication times compared to linear polymer chains and shields the cargo efficiently from non-triggered activation using ultrasound that produces inertial cavitation at a frequency of 20 kHz as model condition. 2022 6 15 1 2642-4169 10.1002/pol.20210874 Journal of Polymer Science 60 1864--1870 1 12 mechanochemistry, microgels, drug delivery, sonopharmacology Miancheng Zou Pengkun Zhao Jilin Fan Robert Göstl Andreas Herrmann article baumann_triazole-extended_2022 Optical force probes (OFPs) are force-responsive molecules that report on mechanically induced transformations by the alteration of their optical properties. Yet, their modular design and incorporation into polymer architectures at desired positions is challenging. Here we report triazole-extended anthracene OFPs that combine two modular ‘click’ reactions in their synthesis potentially allowing their incorporation at desirable positions in complex polymer materials. Importantly, these retain the excellent optical properties of their parent 9-π-extended anthracene OFP counterparts. 2022 6 1 0936-5214, 1437-2096 10.1055/s-0040-1720924 Synlett 33 875--878 1 9 cycloaddition, chromophores, fluorescence, polymers, Key words mechanochemistry Christoph Baumann Robert Göstl article izak-nau_mechanically_2022 Microgels (μgels) swiftly undergo structural and functional degradation when they are exposed to shear forces, which potentially limit their applicability in, e.g., biomedicine and engineering. Here, poly(N-vinylcaprolactam) μgels that resist mechanical disruption through supramolecular hydrogen bonds provided by (+)-catechin hydrate (+C) are synthesized. When +C is added to the microgel structure, an increased resistance against shear force exerted by ultrasonication is observed compared to μgels crosslinked by covalent bonds. While covalently crosslinked μgels degrade already after a few seconds, it is found that μgels having both supramolecular interchain interactions and covalent crosslinks show the highest mechanical durability. By the incorporation of optical force probes, it is found that the covalent bonds of the μgels are not stressed beyond their scission threshold and mechanical energy is dissipated by the force-induced reversible dissociation of the sacrificial +C bonds for at least 20 min of ultrasonication. Additionally, +C renders the μgels pH-sensitive and introduces multiresponsivity. The μgels are extensively characterized using Fourier-transform infrared, Raman and quantitative nuclear magnetic resonance spectroscopy, dynamic light scattering, and cryogenic transmission electron microscopy. These results may serve as blueprint for the preparation of many mechanically durable μgels. 2022 4 25 1 2198-3844 10.1002/advs.202104004 Advanced Science 9 2104004 1 12 colloids, mechanical properties, microgels, sacrificial bonds, optical force probes, shear force Emilia Izak-Nau Susanne Braun Andrij Pich Robert Göstl article huo_mechano-nanoswitches_2022 Current pharmacotherapy is challenged by side effects and drug resistance issues due to the lack of drug selectivity. Mechanochemistry-based strategies provide new avenues to overcome the related problems by improving drug selectivity. It is recently shown that sonomechanical bond scission enables the remote-controlled drug release from their inactive parent macromolecules using ultrasound (US). To further expand the scope of the US-controlled drug activation strategy, herein a mechano-responsive nanoswitch for the selective activation of doxorubicin (DOX) to inhibit cancer cell proliferation is constructed. As a proof-of-concept, the synthesis, characterization, and US-responsive drug activation evaluation of the mechano-nanoswitch, which provides a blueprint for tailoring nanosystems for force-induced pharmacotherapy is presented. 2022 4 25 1 2198-3844 10.1002/advs.202104696 Advanced Science 9 2104696 1 12 dimer, ultrasound, drug release, drug activation, nanoswitch Shuaidong Huo Zhihuan Liao Pengkun Zhao Yu Zhou Robert Göstl Andreas Herrmann article schulte_microgels_2022 Microgels are colloidal polymer networks with high molar mass and properties between rigid particles, flexible macromolecules, and micellar aggregates. Their unique stimuli-responsiveness in conjunction with their colloidal phase behavior render them useful for many applications ranging from engineering to biomedicine. In many scenarios either the microgel's mechanical properties or its interactions with mechanical force play an important role. Here, we firstly explain microgel mechanical properties and how these are measured by atomic force microscopy (AFM), then we equip the reader with the synthetic background to understand how specific architectures and chemical functionalities enable these mechanical properties, and eventually we elucidate how the interaction of force with microgels can lead to the activation of latent functionality. Since the interaction of microgels with force is a multiscale and multidisciplinary subject, we introduce and interconnect the different research areas that contribute to the understanding of this emerging field in this Tutorial Review. 2022 4 19 1 1460-4744 10.1039/D2CS00011C Chemical Society Reviews 51 2939--2956 1 8 M. Friederike Schulte Emilia Izak-Nau Susanne Braun Andrij Pich Walter Richtering Robert Göstl article kung_release_2022 The design and manipulation of (multi)functional materials at the nanoscale holds the promise of fuelling tomorrow's major technological advances. In the realm of macromolecular nanosystems, the incorporation of force-responsive groups, so called mechanophores, has resulted in unprecedented access to responsive behaviours and enabled sophisticated functions of the resulting structures and advanced materials. Among the diverse force-activated motifs, the on-demand release or activation of compounds, such as catalysts, drugs, or monomers for self-healing, are sought-after since they enable triggering pristine small molecule function from macromolecular frameworks. Here, we highlight examples of molecular cargo release systems from polymer-based architectures in solution by means of sonochemical activation by ultrasound (ultrasound-induced mechanochemistry). Important design concepts of these advanced materials are discussed, as well as their syntheses and applications. 2022 3 22 1 1521-3765 10.1002/chem.202103860 Chemistry – A European Journal 28 e202103860 1 17 mechanochemistry, ultrasound, drug release, polymers, sonochemistry Robin Küng Robert Göstl Bernd M. Schmidt article stratigaki_confocal_2022 Brittle fracture often compromises the durability of glassy polymers. This can be mitigated by reinforcing the matrix with a filler, activating a range of toughening mechanisms. Therefore, it is desirable to better understand the mechanical response of polymer composites, but a direct visualization of the mechanical fate of second-phase inclusions upon material fracture was previously unavailable. Here, rubbery poly(hexyl acrylate) particles, cross-linked with an optical force probe (OFP), are dispersed within an epoxy matrix, the material is fractured, and particle–crack interactions are visualized with confocal laser scanning microscopy. The dual-fluorescence character of the OFPs allows the differentiation between particles that remain intact and those that are stressed beyond bond scission upon interaction with a propagating crack. The localized activation of OFPs reveals stress gradients within the particles and crack direction pathways, hence providing a new layer of information over fracture events in polymer composites. 2022 2 08 1 0024-9297 10.1021/acs.macromol.1c02366 Macromolecules 55 1060--1066 1 3 Maria Stratigaki Christoph Baumann Robert Göstl article meng_highly_2022 DNA-based gels are attractive materials as they allow intuitive rational design, respond to external physicochemical stimuli, and show great potential for biomedical applications. However, their relatively poor mechanical properties currently limit their technological application considerably as the latter requires mechanical integrity and tunability. With this work, a DNA organogel is reported that gels through supramolecular interactions, which induce mesophase ordering, and that exhibits exceptional stretchability, deformability, plasticity, and biocompatibility. Moreover, the nature of the supramolecular bond enables complete self-healing within 3 s. Most importantly, the DNA-based liquid crystalline organogels exhibit impressive ultimate tensile strengths above 1 MPa, stiffness higher than 20 MPa, and toughness up to 18 MJ m−3, rendering these materials the strongest among reported DNA networks. In addition, the facile access is demonstrated to composite DNA materials by blending magnetic nanoparticles with the organogel matrix giving access to magnetic field induced actuation. It is believed that these findings contribute significantly to the advancement of DNA gels for their use in smart materials and biomedical applications. 2022 1 20 1 1521-4095 10.1002/adma.202106208 Advanced Materials 34 2106208 1 3 plasticity, self-healing materials, organogels, {DNA} liquid crystals, magnetic response Zhuojun Meng Qing Liu Yi Zhang Jing Sun Chenjing Yang Hongyan Li Mark Loznik Robert Göstl Dong Chen Fan Wang Noel A. Clark Hongjie Zhang Andreas Herrmann Kai Liu article zou_activation_2022 The ultrasound-mediated activation of drugs from macromolecular architectures using the principles of polymer mechanochemistry (sonopharmacology) is a promising strategy to gain spatiotemporal control over drug activity. Yet, conceptual challenges limit the applicability of this method. Especially low drug-loading content and low mechanochemical efficiency require the use of high carrier mass concentrations and prolonged exposure to ultrasound. Moreover, the activated drug is generally shielded by the hydrodynamic coil of the attached polymer fragment leading to a decreased drug potency. Here we present a carrier design for the ultrasound-induced activation of vancomycin, which is deactivated with its H-bond-complementary peptide target sequence. We show that the progression from mechanophore-centered linear chains to mechanophore-decorated polymer brushes increases drug-loading content, mechanochemical efficiency, and drug potency. These results may serve as a design guideline for future endeavors in the field of sonopharmacology. 2022 1 18 1 10.1021/acsmacrolett.1c00645 ACS Macro Letters 11 15-19 1 Miancheng Zou Pengkun Zhao Shuaidong Huo Robert Göstl Andreas Herrmann article he_tailoring_2021 The correlation of mechanical properties of polymer materials with those of their molecular constituents is the foundation for their holistic comprehension and eventually for improved material designs and syntheses. Over the last decade, optical force probes (OFPs) were developed, shedding light on various unique mechanical behaviors of materials. The properties of polymers are diverse, ranging from soft hydrogels to ultra-tough composites, from purely elastic rubbers to viscous colloidal solutions, and from transparent glasses to super black dyed coatings. Only very recently, researchers started to develop tailored OFP solutions that account for such material requirements in energy (both light and force), in time, and in their spatially detectable resolution. We here highlight notable recent examples and identify future challenges in this emergent field. 2021 11 17 1 1521-3765 10.1002/chem.202102938 Chemistry – A European Journal 27 15889--15897 1 64 chemiluminescence, sensors, mechanochemistry, fluorescence, polymers Siyang He Maria Stratigaki Silvia P. Centeno Andreas Dreuw Robert Göstl article shi_mechanochemical_2021-1 The covalent attachment of cargo molecules (e.g., drugs and fluorophores) in β-position to a disulfide moiety through carbamate and carbonate bonds finds many applications in responsiverelease systems. Recently, we showed that the combination of this release process with polymer mechanochemistry-induced disulfide scission enabled the remote-controlled release of small molecule drugs and fluorophores from their inactive parent macromolecules using ultrasound. The nature of the linker bond largely governed the subsequent release kinetics, an aspect that has not been investigated so far. To compare the differences, we here employ disulfide-centered polymers releasing either hydroxyl- or amino-naphthalimides from their respective β-carbonate or -carbamate linkers by force-induced intramolecular 5-exo-trig cyclization. We present the synthesis, characterization, and cell imaging evaluation of three naphthalimides featuring colorimetric and green fluorescence turn-on upon release, allowing monitoring of the release process. We believe that the insights gained from these experiments would advance the tailoring of release rates for force-induced pharmacotherapy. 2021 8 12 1 10.31635/ccschem.021.202101147 CCS Chemistry 3 2333--2344 1 11 bioimaging, mechanochemistry, polymers, drug delivery, sonopharmacology Zhiyuan Shi Qingchuan Song Robert Göstl Andreas Herrmann article rasch_gated_2021 The synthesis and manufacturing of multiresponsive polymer hydrogels using simple components is a notable challenge. Pyrene is an excimer-forming fluorophore mostly used as microenvironmental probe and for the localization of molecules in close proximity in artificial and biomaterials. Here we make use of the solvophobic preaggregation and photolysis properties of pyrene to construct multiresponsive hydrogels. We synthesize poly(ethylene glycol) (PEG) hydrogels from well-defined pyrene-substituted macro-cross-linkers and elucidate their intricate intra- and intermolecular excimer formation pathways. We find that controlling the water content of the hydrogels through the degree of swelling acts as a gating stimulus governing the photoinduced solvolysis of pyrenylmethyl esters from their poly(methacrylate) backbone. This allows the implementation of a simple transient photolithography process. We thus demonstrate that multiresponsive soft materials with complex optical and mechanical responses can be obtained with comparatively little synthetic effort. 2021 8 11 1 10.1021/acspolymersau.1c00011 ACS Polymers Au 1 59--66 1 1 Dustin Rasch Robert Göstl article huo_reversible_2021 Mechanical force applied by ultrasound in solution leads to the dissociation of DNA metallo-base-pair interactions when these motifs are functionalized with oligodeoxynucleotide sequences of sufficient length. The annealing and force-induced denaturing process is followed by the attachment of distance-sensitive fluorescent probes and is found to be reversible. 2021 7 27 1 1364-548X 10.1039/D1CC02402G Chemical Communications 57 7438--7440 1 60 Shuaidong Huo Yu Zhou Zhihuan Liao Pengkun Zhao Miancheng Zou Robert Göstl Andreas Herrmann article zhao_activation_2021 The regulation of enzyme activity is a method to control biological function. We report two systems enabling the ultrasound-induced activation of thrombin, which is vital for secondary hemostasis. First, we designed polyaptamers, which can specifically bind to thrombin, inhibiting its catalytic activity. With ultrasound generating inertial cavitation and therapeutic medical focused ultrasound, the interactions between polyaptamer and enzyme are cleaved, restoring the activity to catalyze the conversion of fibrinogen into fibrin. Second, we used split aptamers conjugated to the surface of gold nanoparticles ({AuNPs}). In the presence of thrombin, these assemble into an aptamer tertiary structure, induce {AuNP} aggregation, and deactivate the enzyme. By ultrasonication, the {AuNP} aggregates reversibly disassemble releasing and activating the enzyme. We envision that this approach will be a blueprint to control the function of other proteins by mechanical stimuli in the sonogenetics field. 2021 6 21 1 1521-3773 10.1002/anie.202105404 Angewandte Chemie International Edition 60 14707-14714 1 26 Polymer mechanochemistry, Nucleic acids, Ultrasound, Enzymes, Sonogenetics Pengkun Zhao Shuaidong Huo Jilin Fan Junlin Chen Fabian Kiessling Arnold J. Boersma Robert Göstl Andreas Herrmann article zhao_aktivierung_2021 Die Regulierung der Aktivität von Enzymen ist eine Methode zur Steuerung biologischer Funktionen. Wir berichten über zwei Systeme, die die ultraschallinduzierte Aktivierung von Thrombin ermöglichen, das für die sekundäre Hämostase wichtig ist. Erstens entwickelten wir Polyaptamere, die spezifisch an Thrombin binden können und dessen katalytische Aktivität hemmen. Mit Hilfe von Ultraschall, der Trägheitskavitation erzeugt, und therapeutisch-medizinischem fokussiertem Ultraschall lösen sich die Wechselwirkungen zwischen Polyaptamer und Enzym, wodurch die Aktivität zur Katalyse der Umwandlung von Fibrinogen in Fibrin wiederhergestellt wird. Zweitens verwendeten wir gespaltene Aptamere, die an die Oberfläche von Gold-Nanopartikeln ({AuNPs}) konjugiert sind. In Gegenwart von Thrombin assemblieren diese zu einer Aptamer-Tertiärstruktur, induzieren die Aggregation der {AuNPs} und deaktivieren das Enzym. Durch Behandlung mit Ultraschall lösen sich die {AuNP}-Aggregate reversibel, setzen das Enzym frei und aktivieren es. Wir glauben, dass dieser Ansatz eine Blaupause für die Steuerung der Funktion anderer Proteine durch mechanische Stimuli im Bereich der Sonogenetik sein wird. 2021 6 21 1 1521-3757 10.1002/ange.202105404 Angewandte Chemie 133 14829-14836 1 26 Enzyme, Ultraschall, Nukleinsäuren, Polymer-Mechanochemie, Sonogenetik Pengkun Zhao Shuaidong Huo Jilin Fan Junlin Chen Fabian Kiessling Arnold J. Boersma Robert Göstl Andreas Herrmann article ma_ultra-strong_2021 The development of biomedical glues is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, i.e. strong adhesion and adaption to remodeling processes in healing tissue. Here, we report a biocompatible and biodegradable protein-based adhesive with high adhesion strengths. The maximum strength reaches 16.5 ± 2.2 MPa on hard substrates, which is comparable to that of commercial cyanoacrylate superglue and higher than other protein-based adhesives by at least one order of magnitude. Moreover, the strong adhesion on soft tissues qualifies the adhesive as biomedical glue outperforming some commercial products. Robust mechanical properties are realized without covalent bond formation during the adhesion process. A complex consisting of cationic supercharged polypeptides and anionic aromatic surfactants with lysine to surfactant molar ratio of 1:0.9 is driven by multiple supramolecular interactions enabling such strong adhesion. We demonstrate the glue’s robust performance in vitro and in vivo for cosmetic and hemostasis applications and accelerated wound healing by comparison to surgical wound closures. 2021 6 14 1 2041-1723 10.1038/s41467-021-23117-9 Nature Communications 12 3613 1 Chao Ma Jing Sun Bo Li Yang Feng Yao Sun Li Xiang Baiheng Wu Lingling Xiao Baimei Liu Vladislav S. Petrovskii {Bin Liu} Jinrui Zhang Zili Wang Hongyan Li Lei Zhang Jingjing Li Fan Wang Robert Göstl Igor I. Potemkin Dong Chen Hongbo Zeng Hongjie Zhang Kai Liu Andreas Herrmann article kung_mechanochemical_2021 Supramolecular coordination cages show a wide range of useful properties including, but not limited to, complex molecular machine-like operations, confined space catalysis, and rich host–guest chemistries. Here we report the uptake and release of non-covalently encapsulated, pharmaceutically-active cargo from an octahedral Pd cage bearing polymer chains on each vertex. Six poly(ethylene glycol)-decorated bipyridine ligands are used to assemble an octahedral PdII6(TPT)4 cage. The supramolecular container encapsulates progesterone and ibuprofen within its hydrophobic nanocavity and is activated by shear force produced by ultrasonication in aqueous solution entailing complete cargo release upon rupture, as shown by NMR and GPC analyses. 2021 6 7 1 1521-3773 https://doi.org/10.1002/anie.202102383 Angewandte Chemie International Edition 60 13626--13630 1 24 host–guest systems, cage compounds, mechanochemistry, drug release, polymers Robin Küng Tobias Pausch Dustin Rasch Robert Göstl Bernd M. Schmidt article kung_mechanochemische_2021 Supramolekulare Koordinationskäfige zeigen ein breites Spektrum an nützlichen Eigenschaften, wie zum Beispiel komplexe maschinenartige Operationen, Katalyse in deren nanoskopischen Hohlräumen und umfangreiche Wirt-Gast-Chemie. Hier berichten wir über die Aufnahme und Freisetzung von nichtkovalent verkapselter, pharmazeutischer Fracht aus einem oktaedrischen Pd-Käfig, welcher an jedem Vertex Polymerketten trägt. Sechs Poly(ethylenglykol)-dekorierte Bipyridinliganden werden verwendet, um einen oktaedrischen PdII6(TPT)4-Käfig zu bilden. Der entstandene supramolekulare Wirt verkapselt Progesteron und Ibuprofen in seiner hydrophoben Nanokavität. Der Käfig wird mittels Scherkräfte aktiviert, die durch Ultraschall in wässriger Lösung erzeugt werden und zu einer vollständigen Freisetzung der Fracht bei Bindungsbruch führen, wie NMR- und GPC-Analysen zeigen. 2021 6 07 1 1521-3757 https://doi.org/10.1002/ange.202102383 Angewandte Chemie 133 13738--13742 1 24 Mechanochemie, Polymere, Käfigverbindungen, Wirkstofffreisetzung, Wirt-Gast-System Robin Küng Tobias Pausch Dustin Rasch Robert Göstl Bernd M. Schmidt article baumann_mehrfarbige_2021 Der Bruch von Polymermaterialien ist ein multiskaliger Prozess, der mit der Spaltung einer einzelnen molekularen Bindung beginnt und sich bis zu einer Bruchstelle im Festkörper ausbreitet. Die Quantifizierung der während dieses Prozesses gebrochenen Bindungen bleibt eine große Herausforderung, würde aber helfen, die Verteilung und Dissipation makroskopischer mechanischer Energie zu verstehen. Wir zeigen hier die Gestaltung und die Synthese von fluorogenen molekularen optischen Kraftsonden (Mechanofluorophoren), die das gesamte sichtbare Spektrum sowohl in Absorption als auch in Emission abdecken. Ihre dual-fluoreszenten Eigenschaften ermöglichen es, nicht gebrochene und gebrochene Bindungen in gelösten Polymeren und im Festkörper durch Fluoreszenzspektroskopie und -mikroskopie zu verfolgen. Wichtig ist, dass wir einen Ansatz entwickeln, um die absolute Anzahl und den relativen Anteil von intakten und gebrochenen Bindungen mit hoher lokaler Auflösung zu bestimmen. Wir gehen davon aus, dass unsere Mechanofluorophore in Kombination mit unserer Quantifizierungsmethodik eine quantitative Beschreibung von Versagensprozessen in Materialien von weichen Hydrogelen bis hin zu Hochleistungspolymeren ermöglichen werden. 2021 6 07 1 1521-3757 https://doi.org/10.1002/ange.202101716 Angewandte Chemie 133 13398--13404 1 24 Mechanochemie, Polymere, Fluoreszenz, Bruch, Mikroskopie Christoph Baumann Maria Stratigaki Silvia P. Centeno Robert Göstl article baumann_multicolor_2021 The fracture of polymer materials is a multiscale process starting with the scission of a single molecular bond advancing to a site of failure within the bulk. Quantifying the bonds broken during this process remains a big challenge yet would help to understand the distribution and dissipation of macroscopic mechanical energy. We here show the design and synthesis of fluorogenic molecular optical force probes (mechanofluorophores) covering the entire visible spectrum in both absorption and emission. Their dual fluorescent character allows to track non-broken and broken bonds in dissolved and bulk polymers by fluorescence spectroscopy and microscopy. Importantly, we develop an approach to determine the absolute number and relative fraction of intact and cleaved bonds with high local resolution. We anticipate that our mechanofluorophores in combination with our quantification methodology will allow to quantitatively describe fracture processes in materials ranging from soft hydrogels to high-performance polymers. 2021 6 07 1 1521-3773 https://doi.org/10.1002/anie.202101716 Angewandte Chemie International Edition 60 13287--13293 1 24 microscopy, mechanochemistry, fluorescence, polymers, fracture Christoph Baumann Maria Stratigaki Silvia P. Centeno Robert Göstl article gostl_machen_2021 Aduc-Preisträger Robert Göstl erforscht die Polymermechanochemie – einen eigenen Forschungszweig, der Polymersynthese, -analytik und Materialwissenschaften verknüpft. 2021 5 03 1868-0054 https://doi.org/10.1002/nadc.20214108893 Nachrichten aus der Chemie 69 78--79 1 5 Robert Göstl article shi_mechanochemical_2021 Drug delivery systems responsive to physicochemical stimuli allow spatiotemporal control over drug activity to overcome limitations of systemic drug administration. Alongside, the non-invasive real-time tracking of drug release and uptake remains challenging as pharmacophore and reporter function are rarely unified within one molecule. Here, we present an ultrasound-responsive release system based on the mechanochemically induced 5-exo-trig cyclization upon scission of disulfides bearing cargo molecules attached via β-carbonate linker within the center of a water soluble polymer. In this bifunctional theranostic approach, we release one reporter molecule per drug molecule to quantitatively track drug release and distribution within the cell in real-time. We use N-butyl-4-hydroxy-1,8-naphthalimide and umbelliferone as fluorescent reporter molecules to accompany the release of camptothecin and gemcitabine as clinically employed anticancer agents. The generality of this approach paves the way for the theranostic release of a variety of probes and drugs by ultrasound. 2021 2 11 1 2041-6539 10.1039/D0SC06054B Chemical Science 12 1668--1674 1 5 Zhiyuan Shi Qingchuan Song Robert Göstl Andreas Herrmann article sun_reversibly_2021 Light-responsive materials have been extensively studied due to the attractive possibility of manipulating their properties with high spatiotemporal control in a non-invasive fashion. This stimulated the development of a series of photo-deformable smart devices. However, it remained a challenge to reversibly modulate the stiffness and toughness of bulk materials. Here, we present bioengineered protein fibers and their optomechanical manipulation by employing electrostatic interactions between supercharged polypeptides (SUPs) and an azobenzene (Azo)-based surfactant. Photo-isomerization of the Azo moiety from the E- to Z-form reversibly triggered the modulation of tensile strength, stiffness, and toughness of the bulk protein fiber. Specifically, the photo-induced rearrangement into the Z-form of Azo possibly strengthened cation–π interactions within the fiber material, resulting in an around twofold increase in the fiber's mechanical performance. The outstanding mechanical and responsive properties open a path towards the development of SUP-Azo fibers as smart stimuli-responsive mechano-biomaterials. 2021 2 08 1 1521-3757 https://doi.org/10.1002/ange.202012848 Angewandte Chemie International Edition 133 3259--3265 1 6 azobenzene, supercharged polypeptides, mechanical behavior, photo-modulating, protein fibers Jing Sun Chao Ma Sourav Maity Fan Wang Yu Zhou Giuseppe Portale Robert Göstl Wouter H. Roos Hongjie Zhang Kai Liu Andreas Herrmann article huo_mechanochemical_2021 Pharmaceutical drug therapy is often hindered by issues caused by poor drug selectivity, including unwanted side effects and drug resistance. Spatial and temporal control over drug activation in response to stimuli is a promising strategy to attenuate and circumvent these problems. Here we use ultrasound to activate drugs from inactive macromolecules or nano-assemblies through the controlled scission of mechanochemically labile covalent bonds and weak non-covalent bonds. We show that a polymer with a disulfide motif at the centre of the main chain releases an alkaloid-based anticancer drug from its β-carbonate linker by a force-induced intramolecular 5-exo-trig cyclization. Second, aminoglycoside antibiotics complexed by a multi-aptamer RNA structure are activated by the mechanochemical opening and scission of the nucleic acid backbone. Lastly, nanoparticle–polymer and nanoparticle–nanoparticle assemblies held together by hydrogen bonds between the peptide antibiotic vancomycin and its complementary peptide target are activated by force-induced scission of hydrogen bonds. This work demonstrates the potential of ultrasound to activate mechanoresponsive prodrug systems. 2021 2 1 1755-4349 10.1038/s41557-020-00624-8 Nature Chemistry 13 131--139 1 2 Shuaidong Huo Pengkun Zhao Zhiyuan Shi Miancheng Zou Xintong Yang Eliza Warszawik Mark Loznik Robert Göstl Andreas Herrmann article zhou_controlling_2021 Ultrasound (US) produces cavitation-induced mechanical forces stretching and breaking polymer chains in solution. This type of polymer mechanochemistry is widely used for synthetic polymers, but not biomacromolecules, even though US is biocompatible and commonly used for medical therapy as well as in vivo imaging. The ability to control protein activity by US would thus be a major stepping-stone for these disciplines. Here, we provide the first examples of selective protein activation and deactivation by means of US. Using GFP as a model system, we engineer US sensitivity into proteins by design. The incorporation of long and highly charged domains enables the efficient transfer of force to the protein structure. We then use this principle to activate the catalytic activity of trypsin by inducing the release of its inhibitor. We expect that this concept to switch “on” and “off” protein activity by US will serve as a blueprint to remotely control other bioactive molecules. 2021 1 18 1 1521-3773 https://doi.org/10.1002/anie.202010324 Angewandte Chemie International Edition 60 1493--1497 1 3 enzymes, mechanochemistry, ultrasound, protein engineering, fluorescence Yu Zhou Shuaidong Huo Mark Loznik Robert Göstl Arnold J. Boersma Andreas Herrmann article zhou_kontrolle_2021 Ultraschall (US) erzeugt mittels Kavitation mechanische Kräfte, die Polymerketten in Lösung dehnen und brechen. Diese Art der Polymer-Mechanochemie wird für synthetische Polymere, nicht aber für Biomakromoleküle verwendet, obwohl US biokompatibel ist und gemeinhin für die medizinische Therapie sowie für die Bildgebung in vivo eingesetzt wird. Die Möglichkeit, die Aktivität von Proteinen durch US zu kontrollieren, wäre daher ein wichtiger Meilenstein für diese Disziplinen. Hier zeigen wir die ersten Beispiele für die selektive Aktivierung und Deaktivierung von Proteinen durch US. Mit der Verwendung von GFP als Modellsystem zeigen wir modellhaft, wie Proteine mit US-Empfindlichkeit ausgestattet werden können. Der Einbau von langen und hochgeladenen Domänen ermöglicht eine effiziente Kraftübertragung auf die Proteinstruktur. Dieses Prinzip nutzen wir dann, um die katalytische Aktivität von Trypsin zu aktivieren, indem wir die Freisetzung seines Inhibitors auslösen. Wir erwarten, dass das Konzept des Ein- und Ausschaltens der Proteinaktivität durch US als Bauplan für die Fernsteuerung anderer bioaktiver Moleküle dienen wird. 2021 1 18 1 1521-3757 https://doi.org/10.1002/ange.202010324 Angewandte Chemie 133 1515--1519 1 3 Enzyme, Mechanochemie, Fluoreszenz, Protein-Engineering, Ultraschall Yu Zhou Shuaidong Huo Mark Loznik Robert Göstl Arnold J. Boersma Andreas Herrmann article slootman_quantifying_2020 Elastomers are highly valued soft materials finding many applications in the engineering and biomedical fields for their ability to stretch reversibly to large deformations. Yet their maximum extensibility is limited by the occurrence of fracture, which is currently still poorly understood. Because of a lack of experimental evidence, current physical models of elastomer fracture describe the rate and temperature dependence of the fracture energy as being solely due to viscoelastic friction, with chemical bond scission at the crack tip assumed to remain constant. Here, by coupling new fluorogenic mechanochemistry with quantitative confocal microscopy mapping, we are able to quantitatively detect, with high spatial resolution and sensitivity, the scission of covalent bonds as ordinary elastomers fracture at different strain rates and temperatures. Our measurements reveal that, in simple networks, bond scission, far from being restricted to a constant level near the crack plane, can both be delocalized over up to hundreds of micrometers and increase by a factor of 100, depending on the temperature and stretch rate. These observations, permitted by the high fluorescence and stability of the mechanophore, point to an intricate coupling between strain-rate-dependent viscous dissipation and strain-dependent irreversible network scission. These findings paint an entirely novel picture of fracture in soft materials, where energy dissipated by covalent bond scission accounts for a much larger fraction of the total fracture energy than previously believed. Our results pioneer the sensitive, quantitative, and spatially resolved detection of bond scission to assess material damage in a variety of soft materials and their applications. 2020 12 04 1 10.1103/PhysRevX.10.041045 Physical Review X 10 041045 1 4 Juliette Slootman Victoria Waltz C. Joshua Yeh Christoph Baumann Robert Göstl Jean Comtet Costantino Creton article li_dna_2020 The biomedical application of nanoparticles (NPs) for diagnosis and therapy is considerably stalled by their inefficient cellular internalization. Many strategies to overcome this obstacle have been developed but are not generally applicable to different NP systems, consequently underlining the need for a universal method that enhances NP entry into cells. Here we describe a method to increase NP cellular uptake via strand hybridization between DNA-functionalized NPs and cells that bear the respective complementary sequence incorporated into the membrane. By this, the NPs bind efficiently to the cellular surface enhancing internalization of three completely different NP types: DNA tetrahedrons, gold (Au) NPs, and polystyrene (PS) NPs. We show that our approach is a simple and generalizable strategy that can be applied to virtually every functionalizable NP system. 2020 10 29 1 2040-3372 10.1039/D0NR02405H Nanoscale 12 21299--21305 1 41 Hongyan Li Jilin Fan Eva Miriam Buhl Shuaidong Huo Mark Loznik Robert Göstl Andreas Herrmann article shi_toward_2020 Traditional pharmacotherapy suffers from multiple drawbacks that hamper patient treatment, such as the buildup of antibiotic resistances or low drug selectivity and toxicity during systemic application. To overcome these challenges, drug activity can be controlled by employing delivery, targeting, or release solutions that mostly rely on the response to external physicochemical stimuli. Due to various technical limitations, mechanical force as a stimulus in the context of polymer mechanochemistry has so far not been used for this purpose, yet it has been proven to be a convenient and robust method to site-selectively rearrange or cleave bonds with submolecular precision in the realm of materials chemistry. Here, we present an unprecedented mechanochemically responsive system capable of successively releasing small furan-containing molecules, including the furylated fluorophore dansyl and the drugs furosemide as well as furylated doxorubicin, by ultrasound-induced selective scission of disulfide-centered polymers in solution. We show that mechanochemically generated thiol-terminated polymers undergo a Michael-type addition to Diels–Alder (DA) adducts of furylated drugs and acetylenedicarboxylate derivatives, initiating the downstream release of the small molecule drug by a retro DA reaction. We believe that this method can serve as a blueprint for the activation of many other small molecules. 2020 8 26 1 0002-7863 10.1021/jacs.0c07077 Journal of the American Chemical Society 142 14725--14732 1 34 Zhiyuan Shi Jingnan Wu Qingchuan Song Robert Göstl Andreas Herrmann article willisfox_going_2020 Mechanical forces can drive chemical transformations in polymers, directing reactions along otherwise inaccessible pathways, providing exciting possibilities for developing smart, responsive materials. The state-of-the-art test for solution-based polymer mechanochemistry development is ultrasonication. However, this does not accurately model the forces that will be applied during device fabrication using processes such as 3D printing or spray coating. Here, a step is taken toward predictably translating mechanochemistry from molecular design to manufacturing by demonstrating a highly controlled nozzle flow setup in which the shear forces being delivered are precisely tuned. The results show that solvent viscosity, fluid strain rate, and the nature of the breaking bond can be individually studied. Importantly, it is shown that the influence of each is different to that suggested by ultrasonication (altered quantity of chain breakage and critical polymer chain length). Significant development is presented in the understanding of polymer bond breakage during manufacturing flows to help guide design of active components that trigger on demand. Using an anthracene-based mechanophore, the triggering of a fluorescence turn-on is demonstrated through careful selection of the flow parameters. This work opens the avenue for programmed chemical transformations during inline manufacturing processes leading to tunable, heterogeneous final products from a single source material. 2020 7 02 1 1616-3028 10.1002/adfm.202002372 Advanced Functional Materials 30 2002372 1 27 mechanophores, polymer mechanochemistry, fluid strain rate, manufacturing flow, nozzle flow Niamh Willis‐Fox Etienne Rognin Christoph Baumann Talal A. Aljohani Robert Göstl Ronan Daly article stratigaki_methods_2020 In recent years, polymer mechanochemistry has evolved as a methodology to provide insights into the action-reaction relationships of polymers and polymer-based materials and composites in terms of macroscopic force application (stress) and subsequent deformation (strain) through a mechanophore-assisted coupling of mechanical and chemical phenomena. The perplexity of the process, however, from the viewpoint of mechanophore activation via a molecular-scaled disruption of the structure that yields a macroscopically detectable optical signal, renders this otherwise rapidly evolving field challenging. Motivated by this, we highlight here recent advancements of polymer mechanochemistry with particular focus on the establishment of methodologies for the efficient activation and quantification of mechanophores and anticipate to aptly pinpoint unresolved matters and limitations of the respective approaches, thus highlighting possible developments. 2020 6 01 1 2192-6506 10.1002/cplu.201900737 ChemPlusChem 85 1095--1103 1 6 mechanical properties, mechanochemistry, mechanophores, fluorescence, polymer chemistry Maria Stratigaki Robert Göstl article li_engineered_2020 Fluorescent proteins are investigated extensively as markers for the imaging of cells and tissues that are treated by gene transfection. However, limited transfection efficiency and lack of targeting restrict the clinical application of this method rooted in the challenging development of robust fluorescent proteins for in vivo bioimaging. To address this, a new type of near-infrared (NIR) fluorescent protein assemblies manufactured by genetic engineering is presented. Due to the formation of well-defined nanoparticles and spectral operation within the phototherapeutic window, the NIR protein aggregates allow stable and specific tumor imaging via simple exogenous injection. Importantly, in vivo tumor metastases are tracked and this overcomes the limitations of in vivo imaging that can only be implemented relying on the gene transfection of fluorescent proteins. Concomitantly, the efficient loading of hydrophobic drugs into the protein nanoparticles is demonstrated facilitating the therapy of tumors in a mouse model. It is believed that these theranostic NIR fluorescent protein assemblies, hence, show great potential for the in vivo detection and therapy of cancer. 2020 4 28 1521-4095 10.1002/adma.202000964 Advanced Materials 32 2000964 1 17 nanoparticles, engineered proteins, NIR fluorescent imaging, tumor therapy Jingjing Li Bo Li Jing Sun Chao Ma Sikang Wan Yuanxin Li Robert Göstl Andreas Herrmann Kai Liu Hongjie Zhang article izak-nau_shear-induced_2020 We here performed an in-depth investigation of the behavior of microgels (μgels) and their associated physicochemical transformations under shear force. Thermo- and mechanoresponsive poly(N-vinylcaprolactam) (PVCL) μgels (d ∼ 400 nm) cross-linked with a force-responsive mechanofluorophore in different cross-linking degrees were synthesized and examined. Fluorescence spectroscopy (FS), confocal laser scanning microscopy (CLSM), dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryoTEM), high-resolution magic-angle sample spinning (HRMAS) nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), and X-ray photoelectron spectroscopy (XPS) are used to characterize the μgels before, during, and after shearing with different shear rates and intensities. The obtained results suggest nonuniform structural features consisting of a softer outer “corona” and a harder particle “core” (cross-linker-rich). Upon shearing, the μgels rapidly lose their corona and the cores agglomerate altering μgel functionality. Surprisingly, μgels degrade promptly, even when subjected to low shear forces, such as the extrusion through a needle. This has potential implications for all applications in which shear forces in solution are expected, including extrusion, injection, and filtration processes involving colloidal μgel solutions as well as circulation within the bloodstream of living organisms. 2020 4 10 1 10.1021/acsapm.0c00111 ACS Applied Polymer Materials 2 1682--1691 1 4 Emilia Izak-Nau Dan E. Demco Susanne Braun Christoph Baumann Andrij Pich Robert Göstl article izak-nau_polymer_2020 Over the past decades, it became clear that next to heat and light, pericyclic reactions can be induced mechanochemically when the reacting motifs are embedded as latent force-responsive groups (mechanophores) into polymer architectures. Not only does this enable a variety of functions and applications on a material level, but moreover grants access to symmetry-forbidden reaction products with respect to the Woodward–Hoffmann rules. The latter indicates that polymer mechanochemistry follows its own set of rules that, however, regarding underlying mechanisms and design rationales is far from being holistically understood. Here we review the existing body of literature and identify common structural features and substitution prerequisites to the polymer framework shining light on the differences between polymer mechanochemical pericyclic reactions and their traditional counterparts. By this, we believe to contribute to the major challenge of not only retrospectively describing force-induced reactivity but eventually finding a common molecular design guideline. 2020 3 31 1 1759-9962 10.1039/C9PY01937E Polymer Chemistry 11 2274--2299 1 13 Emilia Izak-Nau Davide Campagna Christoph Baumann Robert Göstl article sun_fabrication_2020 Protein-based structural biomaterials are of great interest for various applications because the sequence flexibility within the proteins may result in their improved mechanical and structural integrity and tunability. As the two representative examples, protein-based adhesives and fibers have attracted tremendous attention. The typical protein adhesives, which are secreted by mussels, sandcastle worms, barnacles, and caddisfly larvae, exhibit robust underwater adhesion performance. In order to mimic the adhesion performance of these marine organisms, two main biological adhesives are presented, including genetically engineered protein-based adhesives and biomimetic chemically synthetized adhesives. Moreover, various protein-based fibers inspired by spider and silkworm proteins, collagen, elastin, and resilin are studied extensively. The achievements in synthesis and fabrication of structural biomaterials by DNA recombinant technology and chemical regeneration certainly will accelerate the explorations and applications of protein-based adhesives and fibers in wound healing, tissue regeneration, drug delivery, biosensors, and other high-tech applications. However, the mechanical properties of the biological structural materials still do not match those of natural systems. More efforts need to be devoted to the study of the interplay of the protein structure, cohesion and adhesion effects, fiber processing, and mechanical performance. 2020 2 13 1 1521-4095 10.1002/adma.201906360 Advanced Materials 32 1906360 1 6 fibers, proteins, adhesives, genetic engineering Jing Sun Juanjuan Su Chao Ma Robert Göstl Andreas Herrmann Kai Liu Hongjie Zhang article stratigaki_fractography_2020 Due to their soft and brittle nature, the mechanical characterization of polymer hydrogels is a difficult task employing traditional testing equipment. Here, we endowed poly(N-isopropyl acrylamide) (PNIPAAm) hydrogel networks with Diels–Alder adducts of π-extended anthracenes as mechanofluorophore crosslinkers. After swelling the networks with varying amounts of water and subjecting them to force, we visualized the subsequent fluorescence caused by covalent bond scission with confocal laser scanning microscopy (CLSM) and related the intensities to the macroscopic fracture mechanics and the elastic moduli recorded with traditional uniaxial compression. The sensitivity of the mechanofluorophores allowed the analysis of low levels of mechanical stress produced via a hand-induced needle-puncturing process and, thus, is an alternative to conventional force application methods. The detection and precise localization of covalent bond scission via CLSM helps elucidating the interrelationship between molecular structure and the macroscopic properties of chemically crosslinked polymeric hydrogels. We believe that this micro-scale mechanophore-assisted fractography can establish a new paradigm for the mechanical analysis of soft matter in fields covering traditional polymer and life sciences. 2020 1 02 1 1759-9962 10.1039/C9PY00819E Polymer Chemistry 11 358--366 1 2 Maria Stratigaki Christoph Baumann Lambert C. A. van Breemen Johan P. A. Heuts Rint P. Sijbesma Robert Göstl article yildiz_anti-stokes_2019 The development of methods to detect damage in macromolecular materials is of paramount importance to understand their mechanical failure and the structure–property relationships of polymers. Mechanofluorophores are useful and sensitive molecular motifs for this purpose. However, to date, tailoring of their optical properties remains challenging and correlating emission intensity to force induced material damage and the respective events on the molecular level is complicated by intrinsic limitations of fluorescence and its detection techniques. Now, this is tackled by developing the first stress-sensing motif that relies on photon upconversion. By combining the Diels–Alder adduct of a π-extended anthracene with the porphyrin-based triplet sensitizer PtOEP in polymers, triplet–triplet annihilation photon upconversion of green to blue light is mechanochemically activated in solution as well as in the solid state. 2019 9 09 1 1521-3773 10.1002/anie.201907436 Angewandte Chemie International Edition 58 12919-12923 1 37 mechanochemistry, pericyclic reactions, polymers, triplet–triplet annihilation, photon upconversion Deniz Yildiz Christoph Baumann Annabel Mikosch Alexander J. C. Kuehne Andreas Herrmann Robert Göstl article yildiz_anti-stokes-belastungsanzeige:_2019 Die Entwicklung von Methoden zum Nachweis von Schäden in makromolekularen Materialien ist von großer Bedeutung, um deren mechanisches Versagen und die Struktur-Eigenschafts-Beziehungen von Polymeren zu verstehen. Mechanofluorophore haben sich als nützliche und empfindliche molekulare Motive für diesen Zweck erwiesen. Die Anpassung ihrer optischen Eigenschaften bleibt jedoch bis heute eine Herausforderung, und die Korrelation der Emissionsintensität zur kraftinduzierten Materialschädigung sowie den Ereignissen auf molekularer Ebene wird durch intrinsische Beschränkungen der Fluoreszenzdetektionstechniken erschwert. Hier begegnen wir dieser Herausforderung, indem wir das erste Belastungssonden-Motiv entwickeln, das auf der Hochkonversion von Photonen beruht. Durch die Kombination des Diels-Alder-Adduktes eines π-ausgedehnten Anthracens mit dem Porphyrin-basierten Triplett-Sensibilisator {PtOEP} in Polymeren können wir die Hochkonversion durch Triplett-Triplett-Annihilierung von grünem zu blauem Licht sowohl in Lösung als auch im festen Zustand mechanisch aktivieren. Wir sind zuversichtlich, dass dieser Ansatz den Weg zur quantitativen Anti-Stokes-Belastungsanzeige für {UV}-intransparente Materialien ebnet. 2019 9 9 1 1521-3757 10.1002/ange.201907436 Angewandte Chemie 131 13051-13055 1 37 Mechanochemie, Pericyclische Reaktionen, Photonen-Hochkonversion, Polymere, Triplett-Triplett-Annihilierung Deniz Yildiz Christoph Baumann Annabel Mikosch Alexander J. C. Kuehne Andreas Herrmann Robert Göstl article li_fast_2019 Abstract Safety and efficacy, two significant parameters in drug administration, can be improved by site-specific delivery approaches. Here a fast, efficient, and targeted liposome delivery system steered by a DNA hybridization recognition mechanism is presented. For this purpose, lipid-terminated DNA is inserted in both liposome and cell membranes by simple mixing of the components. Cellular accumulation of cargo encapsulated in the liposomal core is substantially enhanced when the DNA sequence on the cell is complementary to that on the liposome. Additionally, in mixed cell populations, liposomes discriminate targets by their complementary DNA sequences. Exposure of cells to low temperature and endocytosis inhibitors suggests a caveolae-dependent endocytosis uptake pathway. Mechanistically, hybridization between DNA strands spatially traps liposomes and cell membranes in close proximity, consequently increases the local liposome concentration, and thereby enhances cellular uptake of liposomes and their payload. This programmable delivery system might contribute to new applications in molecular biology and drug delivery. 2019 7 1 1 2192-2640 10.1002/adhm.201900389 Advanced Healthcare Materials 8 1900389 1 14 liposomes, drug delivery systems, DNA hybridization, endocytosis Hongyan Li Qing Liu Bart J. Crielaard Jan W. Vries Mark Loznik Zhuojun Meng Xintong Yang Robert Göstl Andreas Herrmann article steppert_reversible_2019 Tuning the resonator quality is a long established technique for inorganic lasers giving access to extremely short or temporally precise laser pulses. However, this so-called q-switching, where the resonator can be “on” and sustain lasing or be switched “off” and inhibit lasing is widely unknown for conjugated polymer lasers. Here, we admix thermally stable photochromic dithienylethenes with conjugated polymer laser gain materials on 1D and 2D diffractive feedback gratings, which are generated by two-photon laser writing. By irradiation with differently colored light, the thermally bistable dithienylethenes reversibly modulate the refractive index of and exhibit competing absorption with the gain medium, effectively suppressing laser emission in the one state and allowing low threshold (2.15 mJ/cm2) laser emission in the other state. 2019 2 20 1 10.1021/acsphotonics.8b01641 ACS Photonics 6 558--564 1 2 Ann-Kathrin Steppert Annabel Mikosch Tamás Haraszti Robert Göstl Alexander J. C. Kuehne article fernandez-castano_romera_mimicking_2019 Stiffening due to internal stress generation is of paramount importance in living systems and is the foundation for many biomechanical processes. For example, cells stiffen their surrounding matrix by pulling on collagen and fibrin fibers. At the subcellular level, molecular motors prompt fluidization and actively stiffen the cytoskeleton by sliding polar actin filaments in opposite directions. Here, we demonstrate that chemical cross-linking of a fibrous matrix of synthetic semiflexible polymers with thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) produces internal stress by induction of a coil-to-globule transition upon crossing the lower critical solution temperature of PNIPAM, resulting in a macroscopic stiffening response that spans more than 3 orders of magnitude in modulus. The forces generated through collapsing PNIPAM are sufficient to drive a fluid material into a stiff gel within a few seconds. Moreover, rigidified networks dramatically stiffen in response to applied shear stress featuring power law rheology with exponents that match those of reconstituted collagen and actomyosin networks prestressed by molecular motors. This concept holds potential for the rational design of synthetic materials that are fluid at room temperature and rapidly rigidify at body temperature to form hydrogels mechanically and structurally akin to cells and tissues. 2019 2 06 1 0002-7863 10.1021/jacs.8b10659 Journal of the American Chemical Society 141 1989--1997 1 5 Marcos Fernández-Castaño Romera Robert Göstl Huda Shaikh Gijs Huurne Jurgen Schill Ilja K. Voets Cornelis Storm Rint P. Sijbesma article sharma_fluorescent_2018 In-line electrolyte monitoring during hemodialysis treatment is an important step towards personalized treatment, for optimization of clinical blood pressure management and minimization of cardiovascular complications and bone-mineral disease. But how to achieve such in-line measurement? We propose a real-time electrolyte measurement system based on a molecular fluorescence “on-off” switching mechanism. We have fabricated a disposable polymeric micro-optofluidic device in polydimethylsiloxane (PDMS) with integrated optical fibers to enable in-line electrolyte monitoring. The sensing principle is based on photoinduced electron transfer (PET) that ion-selectively quenches the fluorescence of a molecular optical probe. The PET molecules are covalently immobilized onto the PDMS microchannel walls. As a proof-of-concept, we determine sodium concentration in a flowing medium. A clear relation between fluorescence intensity and sodium concentration is observed. The PET principle can also be applied to many other ion types. 2018 5 15 1 1530-437X 10.1109/JSEN.2018.2816986 IEEE Sensors Journal 18 3946--3951 1 10 Fluorescence, Monitoring, Electrolytes, Microchannels, Microfluidics, Optical sensors, Sodium, dialysis, in-line monitoring, optical sensor, photoinduced electron transfer M. K. Sharma Robert Göstl A. J. H. Frijns F. P. Wieringa J. P. Kooman R. P. Sijbesma D. M. J. Smeulders inbook gostl_optical_2017 This chapter discusses recent approaches towards the optical detection of stress and deformation in polymeric materials, an important tool in monitoring material integrity and in the study of failure mechanisms of polymeric materials. Optical sensing has specific advantages based on the ease of detection, high sensitivity and spectral resolution of light. In this chapter, a classification of sensing mechanisms is used that distinguishes between the molecular phenomena of isomerization, bond scission, change in conjugation and collective phenomena such as changes in chromophore aggregation and photonic band gap tuning. Molecular mechanisms are discussed that have been used to obtain stress-induced changes in absorption and fluorescence properties and recent work is presented in which the chain scission of dioxetanes is used to produce a luminescent signal with high detectability. Pi-conjugated systems play an important role in optical detection of stress and damage in polymers because their optical properties are very sensitive to changes in conformation and aggregation state. Finally, photonic band gap polymers and cholesteric liquid crystals are discussed, in which the periodic organization of structural features at the scale of the wavelength of light leads to strain-dependent reflection and absorption bands. 2017 10 24 1 10.1039/9781782623885-00053 Mechanochemistry in Materials Royal Society of Chemistry 53--75 1 Robert Göstl J. M. Clough R. P. Sijbesma article zhang_nematic_2017 Over the last decades, water-based lyotropic liquid crystals of nucleic acids have been extensively investigated because of their important role in biology. Alongside, solvent-free thermotropic liquid crystals (TLCs) from DNA are gaining great interest, owing to their relevance to DNA-inspired optoelectronic applications. Up to now, however, only the smectic phase of DNA TLCs has been reported. The development of new mesophases including nematic, hexagonal, and cubic structures for DNA TLCs remains a significant challenge, which thus limits their technological applications considerably. In this work, a new type of DNA TLC that is formed by electrostatic complexation of anionic oligonucleotides and cationic surfactants containing an azobenzene (AZO) moiety is demonstrated. DNA–AZO complexes form a stable nematic mesophase over a temperature range from −7 to 110 °C and retain double-stranded DNA structure at ambient temperature. Photoisomerization of the AZO moieties from the E- to the Z-form alters the stiffness of the DNA–AZO hybrid materials opening a pathway toward the development of DNA TLCs as stimuli-responsive biomaterials. 2017 9 01 1 1613-6829 10.1002/smll.201701207 Small 13 1701207 1 34 photomechanics, {DNA}, thermotropic liquid crystals, stimuli-responsive Lei Zhang Sourav Maity Kai Liu Qing Liu Robert Göstl Giuseppe Portale Wouter H. Roos Andreas Herrmann article liu_dnasurfactant_2017 Over the last few years, {DNA}–surfactant complexes have gained traction as unique and powerful materials for potential applications ranging from optoelectronics to biomedicine because they self-assemble with outstanding flexibility spanning packing modes from ordered lamellar, hexagonal and cubic structures to disordered isotropic phases. These materials consist of a {DNA} backbone from which the surfactants protrude as non-covalently bound side chains. Their formation is electrostatically driven and they form bulk films, lyotropic as well as thermotropic liquid crystals and hydrogels. This structural versatility and their easy-to-tune properties render them ideal candidates for assembly in bulk films, for example granting directional conductivity along the {DNA} backbone, for dye dispersion minimizing fluorescence quenching allowing applications in lasing and nonlinear optics or as electron blocking and hole transporting layers, such as in {LEDs} or photovoltaic cells, owing to their extraordinary dielectric properties. However, they do not only act as host materials but also function as a chromophore itself. They can be employed within electrochromic {DNA}–surfactant liquid crystal displays exhibiting remarkable absorptivity in the visible range whose volatility can be controlled by the external temperature. Concomitantly, applications in the biological field based on {DNA}–surfactant bulk films, liquid crystals and hydrogels are rendered possible by their excellent gene and drug delivery capabilities. Beyond the mere exploitation of their material properties, {DNA}–surfactant complexes proved outstandingly useful for synthetic chemistry purposes when employed as scaffolds for {DNA}-templated reactions, nucleic acid modifications or polymerizations. These promising examples are by far not exhaustive but foreshadow their potential applications in yet unexplored fields. Here, we will give an insight into the peculiarities and perspectives of each material and are confident to inspire future developments and applications employing this emerging substance class. 2017 8 14 1 1460-4744 10.1039/C7CS00165G Chemical Society Reviews 46 5147--5172 1 16 Kai Liu Lifei Zheng Chao Ma Robert Göstl Andreas Herrmann article liu_liquefaction_2017 Biomacromolecules, such as nucleic acids, proteins, and virus particles, are persistent molecular entities with dimensions that exceed the range of their intermolecular forces hence undergoing degradation by thermally induced bond-scission upon heating. Consequently, for this type of molecule, the absence of a liquid phase can be regarded as a general phenomenon. However, certain advantageous properties usually associated with the liquid state of matter, such as processability, flowability, or molecular mobility, are highly sought-after features for biomacromolecules in a solvent-free environment. Here, we provide an overview over the design principles and synthetic pathways to obtain solvent-free liquids of biomacromolecular architectures approaching the topic from our own perspective of research. We will highlight the milestones in synthesis, including a recently developed general surfactant complexation method applicable to a large variety of biomacromolecules as well as other synthetic principles granting access to electrostatically complexed proteins and DNA.These synthetic pathways retain the function and structure of the biomacromolecules even under extreme, nonphysiological conditions at high temperatures in water-free melts challenging the existing paradigm on the role of hydration in structural biology. Under these conditions, the resulting complexes reveal their true potential for previously unthinkable applications. Moreover, these protocols open a pathway toward the assembly of anisotropic architectures, enabling the formation of solvent-free biomacromolecular thermotropic liquid crystals. These ordered biomaterials exhibit vastly different mechanical properties when compared to the individual building blocks. Beyond the preparative aspects, we will shine light on the unique potential applications and technologies resulting from solvent-free biomacromolecular fluids: From charge transport in dehydrated liquids to DNA electrochromism to biocatalysis in the absence of a protein hydration shell. Moreover, solvent-free biological liquids containing viruses can be used as novel storage and process media serving as a formulation technology for the delivery of highly concentrated bioactive compounds. We are confident that this new class of hybrid biomaterials will fuel further studies and applications of biomacromolecules beyond water and other solvents and in a much broader context than just the traditional physiological conditions. 2017 5 16 1 0001-4842 10.1021/acs.accounts.7b00030 Accounts of Chemical Research 50 1212--1221 1 5 Kai Liu Chao Ma Robert Göstl Lei Zhang Andreas Herrmann article fuhrmann_mit_2017 Moleküle, die ihre Eigenschaften bei Lichtbestrahlung ändern, stehen zunehmend im Blickpunkt der Materialforscher. Denn Ort und Dauer der Lichteinwirkung sind präzise kontrollierbar, und die Schalt-prozesse sind reversibel. 2017 5 01 1868-0054 10.1002/nadc.20174055287 Nachrichten aus der Chemie 65 525--529 1 5 Anne Fuhrmann Michael Kathan Robert Göstl Stefan Hecht article fuhrmann_conditional_2016 Healable materials are typically repaired by heat, which can affect the properties of the substance. Here the authors report a dynamic covalent polymer network in which light can switch the healing abilities on or off, allowing healing at defined locations without affecting the polymer as a whole. 2016 12 12 1 2041-1723 10.1038/ncomms13623 Nature Communications 7 13623 1 Anne Fuhrmann Robert Göstl Robert Wendt Julia Kötteritzsch Martin D. Hager Ulrich S. Schubert Kerstin Brademann-Jock Andreas F. Thünemann Ulrich Nöchel Marc Behl Stefan Hecht article li_promoting_2016 Optical reporting of covalent bond scission in self-assembled structures in water is an important step toward the detection of forces in biological systems. Here we show that micelles of a diblock copolymer comprising hydrophobic poly(butyl acrylate) and hydrophilic poly(acrylic acid) blocks connected by an off-center mechanoresponsive moiety are mechanochemically active when sonicated in aqueous solution. Facile optical read-out of the force-activation is warranted by formation of a blue-fluorescent anthracene cleavage from the mechanophore, an anthracene-maleimide Diels–Alder adduct. In contrast to the efficient bond scission when the block copolymers are noncovalently anchored in liquid-like micellar cores, isolated unimers in solution are not activated by ultrasonication because the dimensions and viscous drag are drastically lower. These results demonstrate that covalent mechanochemistry can be enabled by noncovalent interactions. 2016 9 20 1 10.1021/acsmacrolett.6b00579 ACS Macro Letters 5 995--998 1 9 Hui Li Robert Göstl Marie Delgove Joren Sweeck Qiuyu Zhang Rint P. Sijbesma Johan P. A. Heuts article verstraeten_stress-induced_2016 Under mechanical stress, the hexaarylbiimidazole (HABI) motif can cleave to triphenylimidazolyl radicals when incorporated into a polymer matrix. The mechanically produced coloured radicals can initiate secondary radical reactions yielding polymer networks. Thus, the HABI mechanophore combines optical reporting of bond scission and reinforcement of polymers in a single molecular moiety. 2016 6 30 1 1364-548X 10.1039/C6CC04312G Chemical Communications 52 8608--8611 1 55 F. Verstraeten Robert Göstl R. P. Sijbesma inbook gostl_light-gated_2016 Combining photochromism with stoichiometric and catalytic organic transformations by incorporating photoswitchable molecules into substrates, products, and catalysts provides the unique opportunity to control chemical bond formation with light. This book chapter provides a summary of the approaches described thus far in the literature and covers the current state of the art in this burgeoning field of research. The highlighted remote-controlled synthesis tools allow to carry out chemical reactions with unprecedented spatial and temporal resolution and will play a key role to externally modulate a variety a processes ranging from materials and devices all the way to biology. 2016 6 15 978-3-527-68373-4 Photochromic Materials: Preparation, Properties and Applications Wiley-VCH Verlag GmbH & Co. KGaA Tian, He and Zhang, Junji 167--193 1 Photochromism, diarylethenes, organic synthesis, azobenzenes, Photochemistry, light-gated catalysis, photo-controlled equilibia Robert Göstl Antti Senf Stefan Hecht article fredrich_switching_2016 A diarylethene photoswitch was covalently connected to two small triplet sensitizer moieties in a conjugated and nonconjugated fashion and the photochromic performance of the resulting compounds was investigated. In comparison with the parent diarylethene (without sensitizers) and one featuring saturated linkages, the conjugated photoswitch offers superior fatigue resistance upon visible-light excitation due to effective triplet energy transfer from the biacetyl termini to the diarylethene core. Our design makes it possible to switch diarylethenes with visible light in both directions in a highly efficient and robust fashion based on extending π-conjugation and by-product-free ring-closure via the triplet manifold. 2016 1 18 1 1521-3773 10.1002/anie.201509875 Angewandte Chemie International Edition 55 1208--1212 1 3 Photochromism, diarylethenes, singlet oxygen, sensitizers Sebastian Fredrich Robert Göstl Martin Herder Lutz Grubert Stefan Hecht article fredrich_zuverlassiges_2016 Ein Diarylethen-Photoschalter wurde kovalent einmal konjugiert und einmal nichtkonjugiert mit zwei Triplett-Sensibilisatoreinheiten verknüpft, und die resultierenden Verbindungen wurden auf ihre photochromen Eigenschaften untersucht. Im Unterschied zum ursprünglichen Diarylethen (ohne Sensibilisator) und dem Derivat mit gesättigter Bindung zeigt der konjugierte Photoschalter eine ausgezeichnete Ermüdungsresistenz bedingt durch die Anregung mit sichtbarem Licht und den effektiven Triplettenergietransfer vom Biacetylterminus zum Diarylethenkern. Aufgrund der ausgedehnten π-Konjugation und des Ringschlusses über den Triplettzustand lassen sich unsere Diarylethene mit sichtbarem Licht in beide Richtungen effektiv und robust schalten. 2016 1 18 1 1521-3757 10.1002/ange.201509875 Angewandte Chemie 128 1226--1230 1 3 Diarylethene, Photochromie, Sensibilisatoren, Singulettsauerstoff Sebastian Fredrich Robert Göstl Martin Herder Lutz Grubert Stefan Hecht article gostl_-extended_2016 Smart molecular systems having the ability to report on mechanical strain or failure in polymers via alteration of their optical properties are of great interest in materials science. However, only limited attention has been devoted to targeted chromophore engineering to fine-tune their physicochemical properties. Here, we describe the synthesis of π-extended anthracenes that can be released from their respective maleimide Diels–Alder adducts through the application of mechanical stress in solution and in the solid state. We demonstrate the improvement of fluorescence quantum yield as well as the tuning of excitation and emission wavelengths while retaining their excellent mechanochemical properties laying the foundation for a new series of mechanophores whose spectral characteristics can be modularly adjusted. 2016 1 01 1 2041-6539 10.1039/C5SC03297K Chemical Science 7 370--375 1 1 Robert Göstl R. P. Sijbesma inbook gostl_autonomous_2015 Autonomously self-repairing and -healing processes will play a key role in the development of future ‘smart’ materials and devices. Here we present the development of a novel second generation Grubb's catalyst that can be activated through the application of mechanical force in solution as well as in the solid state. We show thorough kinetic analyses as well as extensive optimization for the improvement of the catalyst's activity and lifetime and have eventually translated the concept to the solid state. It could be successfully proven that mechanical activation initiates the ROMP to linear as well as cross-linked polymers in the solid state and by this we present for the first time the autonomous repair of a material that relies on the mechanochemical activation of catalysts on the molecular level. We are certain that this tailor-made prototypical catalyst-system establishes an important step for the implementation of self-healing materials in an everyday environment and are confident that this novel motif will stimulate future research on this field. 2015 11 01 978-1-61499-514-2 978-1-61499-513-5 Self Healing Materials 1 Delft University Press 3--9 Robert Göstl Rint. P. Sijbesma article fredersdorf_exploring_2015 Stimuli responsive compounds and materials are of high interest in synthetic chemistry and materials science, with light being the most intriguing stimulus due to the possibility to remote control the physicochemical properties of a molecule or a material. There is a constant quest to design photoswitches with improved switching efficiency and especially diarylethene-type switches promise photo cyclization quantum yields up to unity. However, only limited attention has been paid towards the influence of the solution conformation on the switching efficiency. Here, we describe a detailed NMR spectroscopic investigation on the conformational distribution of bridge-substituted dithienylcyclopentenes in solution. We could discriminate between several photoactive and photoinactive as well as two diastereomorphous conformations and show that the trends observed in the switching efficiency match the conformer populations obtained from state of the art NMR parameters in solution. 2015 10 5 1 1521-3765 10.1002/chem.201501842 Chemistry – A European Journal 21 14545--14554 1 41 Photochromism, NMR spectroscopy, Residual dipolar couplings, conformational analysis, NOE Maic Fredersdorf Robert Göstl Andreas Kolmer Volker Schmidts Peter Monecke Stefan Hecht Christina M. Thiele article gostl_photoreversible_2015 A water-soluble furyl-substituted diarylethene derivative has been prepared that can undergo reversible Diels–Alder reactions with maleimides to yield photoswitchable Diels–Alder adducts. Employing bioorthogonal visible light, the release of therapeutically effective concentrations of maleimide-based reactive inhibitors or labels from these “prodrugs” or “protags” could be photoreversibly triggered in buffered, aqueous solution at body temperature. It is shown how the release properties can be fine-tuned and a thorough investigation of the release dynamics is presented. Our system should allow for spatiotemporal control over the inhibition and labeling of specific protein targets and is ready to be surveyed in living organisms. 2015 3 09 1 1521-3765 10.1002/chem.201405767 Chemistry – A European Journal 21 4422--4427 1 11 Drug delivery, inhibitors, pericyclic reactions, prodrugs, Photochemistry Robert Göstl Stefan Hecht article gostl_controlling_2014 The on-going need for feature miniaturization and the growing complexity of structures for use in nanotechnology demand the precise and controlled formation of covalent bonds at the molecular level. Such control requires the use of external stimuli that offer outstanding spatial, temporal, as well as energetic resolution. Thus, photoaddressable switches are excellent candidates for creating a system that allows reversible photocontrol over covalent chemical connection and disconnection. Here we show that the formation of covalent bonds between two reagents and their scission in the resulting product can be controlled exclusively by illumination with differently colored light. A furyl-substituted photoswitchable diarylethene was shown to undergo a reversible Diels–Alder reaction with maleimide to afford the corresponding Diels–Alder adduct. Our system is potentially applicable in any field already relying on the benefits of reversible Diels–Alder reactions. 2014 8 11 1 1521-3773 10.1002/anie.201310626 Angewandte Chemie International Edition 53 8784--8787 1 33 Photochromism, diarylethenes, Diels–Alder reaction, Dynamic covalent chemistry Robert Göstl Stefan Hecht article gostl_kontrolle_2014 Der Wunsch nach Bauteilverkleinerung und die wachsende Komplexität von Strukturen auf dem Gebiet der Nanotechnologie verlangen nach der präzisen und kontrollierten Bildung kovalenter Bindungen auf molekularer Ebene. Eine solche Kontrolle erfordert jedoch den Einsatz externer Stimuli mit herausragender räumlicher, zeitlicher und energetischer Auflösung. Mit Licht adressierbare Schalter sind deshalb exzellente Kandidaten für Systeme, die eine reversible Photokontrolle über kovalente chemische Ver- und Entknüpfungen ermöglichen. Hier stellen wir ein solches System vor, das ausschließlich durch die Bestrahlung mit Licht unterschiedlicher Farbe kontrolliert werden kann. Zu diesem Zweck wurde ein Furyl-substituiertes photoschaltbares Diarylethen konstruiert, das eine reversible Diels-Alder-Reaktion mit Maleinimid eingehen kann. Unser System verspricht Anwendungsmöglichkeiten in allen Gebieten, die schon jetzt die Vorteile von reversiblen Diels-Alder-Reaktionen nutzen. 2014 8 11 1 1521-3757 10.1002/ange.201310626 Angewandte Chemie 126 8929--8932 1 33 Diarylethene, Photochromie, Diels-Alder-Reaktion, Dynamisch kovalente Chemie Robert Göstl Stefan Hecht article gostl_remote-controlling_2014 The foundation of the chemical enterprise has always been the creation of new molecular entities, such as pharmaceuticals or polymeric materials. Over the past decades, this continuing effort of designing compounds with improved properties has been complemented by a strong effort to render their preparation (more) sustainable by implementing atom as well as energy economic strategies. Therefore, synthetic chemistry is typically concerned with making specific bonds and connections in a highly selective and efficient manner. However, to increase the degree of sophistication and expand the scope of our work, we argue that the modern aspiring chemist should in addition be concerned with attaining (better) control over when and where chemical bonds are being made or broken. For this purpose, photoswitchable molecular systems, which allow for external modulation of chemical reactions by light, are being developed and in this review we are covering the current state of the art of this exciting new field. These “remote-controlled synthetic tools” provide a remarkable opportunity to perform chemical transformations with high spatial and temporal resolution and should therefore allow regulating biological processes as well as material and device performance. 2014 2 24 1 1460-4744 10.1039/C3CS60383K Chemical Society Reviews 43 1982-1996 1 6 Robert Göstl Antti Senf Stefan Hecht article gostl_sterically_2012 2012 11 05 1 1521-3765 10.1002/chem.201203111 Chemistry – A European Journal 18 14282--14285 1 45 Quantum yield, Photochromism, diarylethenes, aldol reaction, steric hindrance Robert Göstl Björn Kobin Lutz Grubert Michael Pätzel Stefan Hecht article kuhlich_transformations_2011 2011 3 21 1 1618-2642 10.1007/s00216-011-4674-3 Analytical and Bioanalytical Chemistry 399 3579--3588 1 10 13 citations (Crossref) [2022-05-19] Paul Kuhlich Robert Göstl Philip Teichert Christian Piechotta Irene Nehls article kuhlich_355688-hexamethyl-5678-tetrahydro-2-naphthoic_2010 The title compound, C17H24O2, is the product of a haloform reaction of 6-acetyl-1,1,2,4,4,7-hexamethyltetraline (AHTN). The compound is a racemic mixture with a disorder in its aliphatic ring [occupany ratio 0.683 (4):0.317 (4)] due to two possible half-chair forms. The carboxylic acid unit is slightly twisted out of coplanarity with the aromatic system [dihedral angle = 29.26 (6)degrees]. In the crystal, pairs of short classical intermolecular O-H...O hydrogen bonds link pairs of molecules around a center of symmetry. 2010 9 30 1 10.1107/S1600536810038572 Acta Crystallographica Section E 66 o2687 1 10 Paul Kuhlich Robert Göstl Ramona Metzinger Christian Piechotta Irene Nehls