1,297 research outputs found
Exploring transition metal catalysis in water for <i>in vivo </i>applications
Transition metal catalysis proves a powerful tool to achieve otherwise synthetically challenging, or even impossible, transformations with (high) selectivity and is therefore employed in various areas of chemistry. Recently, transition metal-catalysed reactions have been successfully performed in cells (in vitro) and living systems (in vivo). The achievements made thus far reveal the potential of transition metal catalysis and its applications in such biological settings. Interestingly, the scope is limited compared to the breadth of transition metal-catalysed reactions that have been unlocked for synthetic applications. Translating transition metal-catalysed reactions from flasks to cells is non-trivial as the conditions in cells are fairly different compared to the highly controlled and adaptable conditions achieved in a flask. The development of catalytic systems for future applications in vivo therefore proceeds through many steps, starting with evaluating their reactivity, selectivity, and stability in water and under biologically relevant and biomimetic conditions. By exploring transition metal-catalysed reactions in water for in vivo applications, this dissertation has contributed to the subfield of bioorthogonal chemistry devoted to complementing Natureâs repertoire of reactions. Our studies have revealed the challenges associated with the performance of transition metal catalysis in aqueous media and how a detailed understanding of a catalytic system can address them. Apart from these fundamental studies, we have performed explorative studies under biologically relevant and biomimetic conditions in the context of intracellular drug synthesis. Moreover, we have developed a new and compatible protocol that enables detailed kinetic studies in complex reaction media, comparable to the cellular environment, to facilitate the translation of transition metal catalysis from flasks to cells
Antimonene: a tuneable post-graphene material for advanced applications in optoelectronics, catalysis, energy and biomedicine.
The post-graphene era is undoubtedly marked by two-dimensional (2D) materials such as quasi-van der Waals antimonene. This emerging material has a fascinating structure, exhibits a pronounced chemical reactivity (in contrast to graphene), possesses outstanding electronic properties and has been postulated for a plethora of applications. However, chemistry and physics of antimonene remain in their infancy, but fortunately recent discoveries have shed light on its unmatched allotropy and rich chemical reactivity offering a myriad of unprecedented possibilities in terms of fundamental studies and applications. Indeed, antimonene can be considered as one of the most appealing post-graphene 2D materials reported to date, since its structure, properties and applications can be chemically engineered from the ground up (both using top-down and bottom-up approaches), offering an unprecedented level of control in the realm of 2D materials. In this review, we provide an in-depth analysis of the recent advances in the synthesis, characterization and applications of antimonene. First, we start with a general introduction to antimonene, and then we focus on its general chemistry, physical properties, characterization and synthetic strategies. We then perform a comprehensive study on the allotropy, the phase transition mechanisms, the oxidation behaviour and chemical functionalization. From a technological point of view, we further discuss the applications recently reported for antimonene in the fields of optoelectronics, catalysis, energy storage, cancer therapy and sensing. Finally, important aspects such as new scalable methodologies or the promising perspectives in biomedicine are discussed, pinpointing antimonene as a cutting-edge material of broad interest for researchers working in chemistry, physics, materials science and biomedicine
Multifrequency atomic force microscopy for the in-plane and out-of-plane nanomechanical characterization of graphitic surfaces
Graphene is considered as one of the most promising materials for numerous applications such as electronics, photonics, membranes, sensors, heat dissipators, lubricants and many more [1, 2]. In addition to its outstanding electronic properties, in particular, the extraordinary mechanical properties of graphene have become the focus of scientific attention. For example, it has been shown that defect-free graphene has an enormously high Youngâs modulus of about 1 TPa [3]. However, little research has been done on the local influence of defects on the nanomechanical properties of graphene. Several challenges come to mind as possible reasons, such as (i) imaging graphene with atomic resolution, (ii) simultaneous analysis of sample properties parallel and perpendicular to the sample plane, (iii) preparation of adsorbate-free graphene samples, and (iv) targeted introduction of defects.
To overcome the aforementioned challenges, first, an atomic force microscopy-based method was developed within this work that enables imaging of graphene in air under ambient conditions with atomic resolution. In addition, the method was designed to allow quantification of interaction forces, both, perpendicular and parallel to the graphene surface. This is particularly important to access the complete set of elastic constants of graphene. An important finding of this work is that different adsorbate types could be observed on the graphene surface shortly after the preparation of graphene samples. Therefore, a detailed analysis of the adsorbates was performed using the developed multifrequency atomic force microscopy method. Furthermore, the extent to which oxygen-plasma treatment can be used to remove adsorbates from a graphene sample stored under laboratory air conditions was examined. Adsorbate removal is a basic requirement for the targeted introduction of defects, as well as for the investigation of their influence on the local nanomechanical properties. The effect of oxygen-plasma treatment on different graphene-/graphite-samples was additionally investigated by Raman spectroscopy
Rational development of stabilized cyclic disulfide redox probes and bioreductive prodrugs to target dithiol oxidoreductases
Countless biological processes allow cells to develop, survive, and proliferate. Among these, tightly balanced regulatory enzymatic pathways that can respond rapidly to external impacts maintain dynamic physiological homeostasis. More specifically, redox homeostasis broadly affects cellular metabolism and proliferation, with major contributions by thiol/disulfide oxidoreductase systems, in particular, the Thioredoxin Reductase Thioredoxin (TrxR/Trx) and the Glutathione Reductase-Glutathione-Glutaredoxin (GR/GSH/Grx) systems.
These cascades drive vital cellular functions in many ways through signaling, regulating other proteins' activity by redox switches, and by stoichiometric reductant transfers in metabolism and antioxidant systems. Increasing evidence argues that there is a persistent alteration of the redox environment in certain pathological states, such as cancer, that heavily involve the Trx system: upregulation and/or overactivity of the Trx system may support or drive cancer progression, making both TrxR and Trx promising targets for anti-cancer drug development.
Understanding the biochemical mechanisms and connections between certain redox cascades requires research tools that interact with them. The state-of-the-art genetic tools are mostly ratiometric reporters that measure reduced:oxidized ratios of selected redox pairs or the general thiol pool. However, the precise cellular roles of the central oxidoreductase systems, including TrxR and Trx, remain inaccessible due to the lack of probes to selectively measure turnover by either of these proteins. However, such probes would allow measuring their effective reductive activity apart from expression levels in native systems, including in cells, animals, or patient samples. They are also of high interest to identify chemical inhibitors for TrxR/Trx in cells and to validate their potential use as anti-cancer agents (to date, there is no selective cellular Trx inhibitor, and most known TrxR inhibitors were not comprehensively evaluated considering selectivity and potential off-targets). However, small molecule redox imaging tools are underdeveloped: their protein specificity, spectral properties, and applicability remain poorly precedented.
This work aimed to address this opportunity gap and develop novel, small molecule diagnostic and therapeutic tools to selectively target the Trx system based on a modular trigger cargo design: artificial cyclic disulfide substrates (trigger) for oxidoreductases are tethered to molecular agents (cargo) such that the cargoâs activity is masked and is re-established only through reduction by a target protein.
The rational design of these novel reduction sensors to target the cell's strongest disulfide-reducing enzymes was driven by the following principles: (i) cyclic disulfide triggers with stabilized ring systems were used to gain low reduction potentials that should resist reduction except by the strongest cellular reductases, such as Trx; and (ii) the cyclic topology also offers the potential for kinetic reversibility that should select for dithiol-type redox proteins over the cellular monothiol background. Creating imaging agents based on such two-component designs to selectively measure redox protein activity in native cells required to combine the correct trigger reducibility, probe activation kinetics, and imaging modalities and to consider the overall molecular architecture.
The major prior art in this field has applied cyclic 5-membered disulfides (1,2 dithiolanes) as substrates for TrxR in a similar way to create such tools. However, this motif was described elsewhere as thermodynamically instable and was due to widely used for dynamic covalent cascade reactions. By comparing a novel 1,2 dithiolane-based probe to the state-of-the-art probes, including commercial TrxR sensors, by screening a conclusive assay panel of cellular TrxR modulations, I clarified that 1,2 dithiolanes are not selective substrates for TrxR in biological settings (Nat Commun 2022).
Instead, aiming for more stable ring systems and thus more robust redox probes, during this work, I developed bicyclic 6 membered disulfides (piperidine fused 1,2 dithianes) with remarkably low reduction potentials. I showed that molecular probes using them as reduction sensors can be mostly processed by thioredoxins while being stable against reduction by GSH. The thermodynamically stabilized decalin like topology of the cis-annelated 1,2 dithianes requires particularly strong reductants to be cleaved. They also select for dithiol type redox proteins, like Trx, based on kinetic reversibility and offer fast cyclization due to the preorganization by annelation (JACS 2021).
This work further expanded the systemâs modularity with structural cores based on piperazine-fused 1,2 dithianes with the two amines allowing independent derivatization. Diagnostic tools using them as reduction sensors proved equally robust but with highly improved activation kinetics and were thus cellularly activated. Cellular studies evolved that they are substrates for both Trxs and their protein cousins Grxs, so measuring the cellular dithiol protein pool rather than solely Trx activity (preprint 2023).
Finally, a trigger based on a slightly adapted reduction sensor, a desymmetrized 1,2 thiaselenane, was designed for selective reduction by TrxRâs selenol/thiol active site, then combined with a precipitating large Stokesâ shift fluorophore and a solubilizing group, to evolve the first selective probe RX1 to measure cellular TrxR activity, which even allowed high throughput inhibitor screening (Chem 2022).
The central principle of this work was further advanced to therapeutic prodrugs based on the duocarmycin cargo (CBI) with tunable potency (JACS Au 2022) that can be used to create off-to-on therapeutic prodrugs. Such CBI prodrugs employing stabilized 1,2 dichalcogenide triggers proved to be cytotoxins that depend on Trx system activity in cells. They could further be exploited for cell-line dependent reductase activity profiling by screening their redox activation indices, the reduction-dependent part of total prodrug activation, in 177 cell lines. Beyond that, these prodrugs were well-tolerated in animals and showed anti-cancer efficacy in vivo in two distinct mouse tumor models (preprint 2022).
Taken together, I introduced unique monothiol-resistant reducible motifs to target the cellular Trx system with chemocompatible units for each for TrxR and Trx/Grx, where the cyclic nature of the dichalcogenides avoids activation by GSH. By using them with distinct molecular cargos, I developed novel selective fluorescent reporter probes; and introduced a new class of bioreductive therapeutic constructs based on a common modular design. These were either applied to selectively measure cellular reductase activity or to deliver cytotoxic anti cancer agents in vivo. Ongoing work aims to differentiate between the two major redox effector proteins Trx and Grx, requiring additional layers of selectivity that may be addressed by tuned molecular recognition. The flexible use of various molecular cargos allows harnessing the same cellular redox machinery by either probes or prodrugs. This allows predictive conclusions from diagnostics to be directly translated into therapy and offers great potential for future adaptation to other enzyme classes and therapeutic venues.Die zellulĂ€re Redox-Homöostase hĂ€ngt von Thiol/Disulfid-Oxidoreduktasen ab, die den Stoffwechsel, die Proliferation und die antioxidative Antwort von Zellen beeinflussen. Die wichtigsten Netzwerke sind die Thioredoxin Reduktase-Thioredoxin (TrxR/Trx) und Glutathion Reduktase-Glutathion-Glutaredoxin (GR/GSH/Grx) Systeme, die ĂŒber Redox-Schalter in Substratproteinen lebenswichtige zellulĂ€re Funktionen steuern und so an der Redox-Regulation und -SignalĂŒbertragung beteiligt sind. Persistente VerĂ€nderungen des Redoxmilieus in pathologischen ZustĂ€nden, wie z. B. bei Krebs, sind in hohem MaĂe mit dem Trx-System verbunden. Eine Hochregulierung und/oder ĂberaktivitĂ€t des Trx-Systems, die bei vielen Krebsarten auftreten, unterstĂŒtzt zudem das Fortschreiten des Krebswachstums, was TrxR/Trx zu vielversprechenden Zielproteinen fĂŒr die Entwicklung neuer Krebsmedikamente macht.
Um die biochemischen Prozesse dahinter zu erforschen, sind spezielle Techniken zur Visualisierung und Messung enzymatischer AktivitĂ€t nötig. Die hierzu geeigneten, meist genetischen Sensoren messen ratiometrisch das VerhĂ€ltnis reduzierter/oxidierter Spezies in zellulĂ€rem Umfeld oder spezifisch ausgewĂ€hlte Redoxpaare. Die weitere Erforschung der exakten Funktion von TrxR/Trx und deren Substrate ist jedoch durch mangelnde Nachweismethoden limitiert. Diese sind auĂerdem zur Validierung chemischer Hemmstoffe fĂŒr TrxR/Trx in Zellen und deren potenziellen Verwendung als Krebsmittel von groĂem Interesse. Bislang gibt es keinen selektiven zellulĂ€ren Trx-Inhibitor und potenzielle Off-Target-Effekte der bekannten TrxR-Inhibitoren wurden nicht abschlieĂend bewertet.
Ziel dieser Arbeit ist die Entwicklung niedermolekularer, diagnostischer und therapeutischer Werkzeuge, die selektiv auf das Trx-System abzielen und auf einem modularen Trigger-Cargo Design basieren. Hierzu werden zyklische Disulfid-Substrate (Trigger) fĂŒr Oxidoreduktasen so mit molekularen Wirkstoffen (Cargo) verknĂŒpft, dass dabei die WirkstoffaktivitĂ€t maskiert, und erst nach Reduktion durch ein Zielprotein wiederhergestellt wird. Diese neuartigen, synthetischen Reduktionssensoren basieren auf den folgenden Grundprinzipien: (i) Zyklische Disulfide sind thermodynamisch stabilisiert und können nur durch die stĂ€rksten Reduktasen gespalten werden; und (ii) die zyklische Topologie ermöglicht die kinetische ReversibilitĂ€t der zwei Thiol-Disulfid-Austauschreaktionen, die eine erste Reaktion mit Monothiolen, wie z. B. GSH, sofort umkehrt und so eine vollstĂ€ndige Reduktion verhindert.
Die meisten frĂŒheren Arbeiten auf diesem Gebiet verwendeten ein zyklisches, fĂŒnfgliedriges Disulfid (1,2 Dithiolan) als Substrat fĂŒr TrxR. Das gleiche Strukturmotiv wurde jedoch an anderer Stelle als thermodynamisch instabil beschrieben und aufgrund dieser Eigenschaft explizit fĂŒr dynamische Kaskadenreaktionen verwendet. Deshalb vergleicht diese Arbeit zu Beginn einen neuen 1,2 Dithiolan basierten fluorogenen Indikator mit bestehenden, z. T. kommerziellen, Redox Sonden fĂŒr TrxR in einer Reihe von Zellkultur-Experimenten unter Modulation der zellulĂ€ren TrxR AktivitĂ€t und stellt so einen Widerspruch in der Literatur klar: 1,2 Dithiolane eignen sich nicht als selektive Substrate fĂŒr TrxR, da sie labil sowohl gegen die Reduktion durch andere Redoxproteine, als auch gegen den Monothiol Hintergrund in Zellen sind (Nat. Commun. 2022).
Als alternatives Strukturmotiv wird in dieser Arbeit ein bizyklisches sechsgliedriges Disulfid (anneliertes 1,2 Dithian) etabliert. Durch sein niedriges Reduktionspotenzial, also seine hohe Resistenz gegen Reduktion, werden molekulare Sonden basierend auf diesem 1,2 Dithian als Reduktionssensor fast ausschlieĂlich von Trx aktiviert, nicht aber von TrxR oder GSH (JACS 2021). Dieses Kernmotiv bestimmt dabei die Reduzierbarkeit, und damit die EnzymspezifitĂ€t, durch seine zyklische Natur und die Annelierung, auch unter Verwendung unterschiedlicher Farb-/Wirkstoffe. Auf dieser Grundlage konnte die molekulare Struktur durch einen weiteren Modifikationspunkt fĂŒr die flexible Verwendung weiterer funktioneller Einheiten ergĂ€nzt werden. Obwohl zellulĂ€re Studien ergaben, dass diese neuartigen 1,2 Dithian Einheiten in Zellen sowohl Trx als auch das strukturell verwandte Grx adressieren, sind die daraus resultierenden diagnostischen MolekĂŒle wertvoll, um den katalytischen Umsatz zellulĂ€rer Dithiol-Reduktasen, der sogenannten Trx Superfamilie, selektiv anzuzeigen (Preprint 2023).
BegĂŒnstigt durch das modulare MolekĂŒldesign stellt diese Arbeit zudem das erste Reportersystem RX1 zum selektiven Nachweis der TrxR-AktivitĂ€t in Zellen vor. Es basiert auf der Verwendung eines zyklischen, unsymmetrischen Selenenylsulfid-Sensors (1,2 Thiaselenan), der selektiv von dem einzigartigen Selenolat der TrxR angegriffen wird, und dadurch letztlich nur von TrxR reduziert werden kann. RX1 eignete sich zudem fĂŒr eine Hochdurchsatz-Validierung bestehender TrxR Inhibitoren und unterstreicht dadurch den kommerziellen Nutzen derartiger Diagnostika (Chem 2022).
Das zentrale Trigger-Cargo Konzept dieser Arbeit wurde fĂŒr therapeutische Zwecke weiterentwickelt und nutzt dabei den einzigartigen Wirkmechanismus der Duocarmycin-Naturstoffklasse (CBI) (JACS Au 2022) zur Entwicklung reduktiv aktivierbarer Therapeutika. CBI Prodrugs basierend auf stabilisierten Redox-Schaltern (1,2 Dithiane fĂŒr Trx; 1,2 Thiaselenan fĂŒr TrxR) reagierten signifikant auf TrxR-Modulation in Zellen. Sie wurden darĂŒber hinaus durch das Referenzieren ihrer AktivitĂ€t gegenĂŒber nicht-reduzierbaren KontrollmolekĂŒle fĂŒr die Erstellung zelllinienabhĂ€ngiger Profile der ReduktaseaktivitĂ€t in 177 Zelllinien genutzt. SchlieĂlich waren diese neuen Krebsmittel im Tiermodell gut vertrĂ€glich und zeigten in zwei verschiedenen Mausmodellen eine krebshemmende Wirkung (Preprint 2022b).
Zusammenfassend prĂ€sentiert diese Dissertation monothiol-resistente reduzierbare Trigger-Einheiten fĂŒr das zellulĂ€re Trx-System zur Entwicklung neuartiger, selektiver Reporter-Sonden, sowie eine neue Klasse reduktiv aktivierbarer Krebsmittel auf Basis eines adaptierbaren Trigger-Cargo Designs. Diese fanden entweder zur selektiven Messung zellulĂ€rer ProteinaktivitĂ€t oder zum Einsatz als Antikrebsmittel Verwendung. Es wurden chemokompatible Motive sowohl fĂŒr TrxR als auch fĂŒr Trx/Grx identifiziert, wobei deren zyklische Natur eine Aktivierung durch GSH verhindert. Eine weitere Differenzierung zwischen den beiden Redox-Proteinen Trx und Grx und anderen Proteinen der Trx-Superfamilie erfordert eine zusĂ€tzliche Ebene der Selektierung, z. B. durch molekulare Erkennung, und ist Gegenstand laufender Arbeiten.
Die flexible Verwendung verschiedener molekularer Wirkstoffe ermöglicht dabei die âPipeline-Entwicklungâ von Diagnostika und Therapeutika, die von der zellulĂ€ren Redox-Maschinerie analog umgesetzt werden, und dadurch Schlussfolgerungen aus der Diagnostik direkt auf eine Therapie ĂŒbertragbar machen. Dies birgt groĂes Potenzial fĂŒr kĂŒnftige Entwicklungen bei einer potenziellen Ăbertragung des modularen Konzepts auf andere Enzymklassen und therapeutische Einsatzgebiete
Insilico generation of novel ligands for the inhibition of SARS-CoV-2 main protease (3CLpro) using deep learning
The recent emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease (COVID-19) has become a global public health crisis, and a crucial need exists for rapid identification and development of novel therapeutic interventions. In this study, a recurrent neural network (RNN) is trained and optimized to produce novel ligands that could serve as potential inhibitors to the SARS-CoV-2 viral protease: 3 chymotrypsin-like protease (3CLpro). Structure-based virtual screening was performed through molecular docking, ADMET profiling, and predictions of various molecular properties were done to evaluate the toxicity and drug-likeness of the generated novel ligands. The properties of the generated ligands were also compared with current drugs under various phases of clinical trials to assess the efficacy of the novel ligands. Twenty novel ligands were selected that exhibited good drug-likeness properties, with most ligands conforming to Lipinskiâs rule of 5, high binding affinity (highest binding affinity: â9.4 kcal/mol), and promising ADMET profile. Additionally, the generated ligands complexed with 3CLpro were found to be stable based on the results of molecular dynamics simulation studies conducted over a 100 ns period. Overall, the findings offer a promising avenue for the rapid identification and development of effective therapeutic interventions to treat COVID-19
The Center of Excellence in Atmospheric Science (2002â2019) â from molecular and biological processes to the global climate
The study of atmospheric processes related to climate requires a multidisciplinary approach, encompassing physics, chemistry, meteorology, forest science, and environmental science. The Academy of Finland Centre of Excellence in atmospheric sciences (CoE ATM) responded to that need for 18 years and produced extensive research and eloquent results, which are summarized in this review. The work in the CoE ATM enhanced our understanding in biogeochemical cycles, ecosystem processes, dynamics of aerosols, ions and neutral clusters in the lower atmosphere, and cloud formation and their interactions and feedbacks. The CoE ATM combined continuous and comprehensive long-term in-situ observations in various environments, ecosystems and platforms, ground- and satellitebased remote sensing, targeted laboratory and field experiments, and advanced multi-scale modeling. This has enabled improved conceptual understanding and quantifications across relevant spatial and temporal scales. Overall, the CoE ATM served as a platform for the multidisciplinary research community to explore the interactions between the biosphere and atmosphere under a common and adaptive framework
Synthesis and NMR-based network structure analysis of cationic hydrogels for seawater applications
Superabsorbent polymers (SAPs) are hydrophilic polymer networks (i. e., hydrogels) that contain charged monomer units along the polymer backbone. Poly(sodium acrylate) (PSA), which has negatively charged carboxylate groups, is the most prominent chemical structure of SAPs. Recent studies have shown that PSA can be used as a separation medium for the desalination of salt water. This approach, however, is limited to NaCl solutions because the divalent Mg and Ca cations in seawater interact electrostatically with the anionic polymer backbone of PSA, inducing thereby a network collapse. To overcome this limitation, this dissertation explores the swelling and desalination capacity of cationic SAPs in seawater. Two cationic SAP model systems with distinct functional groups were synthesized. The first one is based on a poly(acrylamide) (PAM) derivative with a trimethyl quaternary ammonium group as the positively charged monomer unit. The second model system is based on poly(vinyl amine) (PVAm) bearing positively charged ammonium groups. Swelling capacity measurements reveal that divalent SO anions in seawater induce a network collapse of PVAm similar to the PSA analogue. In contrast, the swelling behavior of PAM hydrogels is fully unaffected by seawater, suggesting that the quaternary ammonium moiety is essential to provide seawater resistant swelling properties of SAPs. In addition to swelling capacity studies, this dissertation aims to advance our understanding of the intriguing interplay between macroscopic, mechanical properties and molecular dynamics of the hydrogel network. Due to the inherent multi-length scale structural complexity of hydrogels, the quantitative correlation of mechanical properties with molecular dynamics remains a longstanding challenge. An advanced rheometer setup consisting of a portable low-field NMR unit that is integrated into a rheometer was used to study the gelation kinetics of acrylic acid (AAc) hydrogels. The elastic modulus GâČ was studied by small amplitude oscillatory time sweeps whereas the local molecular mobility of polymer network chains was probed by T relaxation measurements. From the in-situ GâČ and T correlation plots, it can be concluded that the elastic plateau modulus is inversely proportional to the T relaxation time of the hydrogel. Consequently, the mechanical strength of hydrogels can be predicted based on the segmental mobility of polymer network chains, which has important implications for the further development of non-invasive and forceless mechanical characterization techniques
Stable polymer glasses
This thesis presents investigations on stable polymer glasses prepared through physical vapour deposition from different perspectives. This is the first time that polymers have been used in simple vapour deposition and made into stable glass. The ability of our lab to create stable polymer glasses with exceptional stability and extremely long lifetimes is demonstrated through the preparation and characterization of ultrastable PS as well as PMMA glasses. Attempts at preparing stable polymer glass with higher molecular weight are reported, including two different methodsâusing higher molecular weight sources and crosslinking as-deposited glasses with ultraviolet radiation. The surface properties of stable polymer glasses including their surface morphology and surface relaxation are studied. With a slower bulk dynamics in stable glasses as expected, the surface evolution of the as-deposited films and the rejuvenated films are both enhanced compared to the bulk and are not easily distinguishable from each other. Investigations on stable polymer glasses confined to thin films are reported. The results support the existence of a surface mobile layer, and it is found that glass stability decreases with decreasing film thickness, as determined by different measures of stability. By studying stable polymer glasses from different perspectives in this thesis, we hope to provide valuable insights into many fundamental questions about the surface dynamics in thin films, the limit of packing in amorphous materials, and the nature of the complex and fascinating phenomenonâthe glass transition
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