[Show abstract][Hide abstract] ABSTRACT: Bioorthogonal ligation methods are the focus of current research due to their versatile applications in biotechnology and materials science for post-functionalization and immobilization of biomolecules. Recently, inverse electron demand Diels-Alder (iEDDA) reactions employing 1,2,4,5-tetrazines as electron deficient dienes emerged as powerful tools in this field. We adapted iEDDA in microcontact chemistry (μCC) in order to create enhanced surface functions. μCC is a straightforward soft-lithography technique which enables fast and large area patterning with high pattern resolutions. In this work, tetrazine functionalized surfaces were reacted with carbohydrates conjugated with norbornene or cyclooctyne acting as strained electron rich dienophiles employing μCC. It was possible to create monofunctional as well as bifunctional substrates which were specifically addressable by proteins. Furthermore we structured glass supported alkene terminated self-assembled monolayers with a tetrazine conjugated atom transfer radical polymerization (ATRP) initiator enabling surface grafted polymerizations of poly(methylacrylate) brushes. The success of the surface initiated iEDDA via μCC as well as the functionalization with natural and synthetic polymers was verified via fluorescence and optical microscopy, X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS), atomic force microscopy (AFM) and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR).
[Show abstract][Hide abstract] ABSTRACT: In this article, we report a light-responsive supramolecular system based on the host–guest interaction of β-cyclodextrin covered silica nanoparticles and a bifunctional, noncovalent azobenzene linker in dilute aqueous solution. β-Cyclodextrin was immobilized onto silica nanoparticles either by nucleophilic substitution or by thiol–ene click chemistry. Azobenzene has two isomers which can be converted into each other by alternating irradiation with visible light (λ = 465 nm) and UV light (λ = 350 nm). When using visible light, the trans isomer of the azobenzene moieties on the linker bind to the β-cyclodextrin cavities on the nanoparticle surface leading to aggregation of the nanoparticles. The aggregation is reversible, since irradiation with UV light leads to the formation of the cis isomer of the azobenzene linker, dissociation of the azobenzene and the cyclodextrin, and subsequent dispersion of the nanoparticles. The light-responsive supramolecular system is investigated by using optical density measurements (OD600), DLS and TEM measurements.
[Show abstract][Hide abstract] ABSTRACT: Basierend auf der Kombination der einzigartigen Eigenschaften von polyionischen Flüssigkeiten und kugelförmigen, kolloidalen Kristallen wurde eine neue Klasse von Opalkugeln mit einer Reihe besonderer Eigenschaften hergestellt. Diese photonischen Kugeln konnten nicht nur als responsive photonische Mikrogele verwendet werden, sondern auch als multifunktionelle Mikrokugeln, die die Haupteigenschaften herkömmlicher Moleküle wie optische Eigenschaften, spezifische molekulare Erkennung, Reaktivität, Derivatisierung und Anisotropie nachahmen.
[Show abstract][Hide abstract] ABSTRACT: Functionalization of metal, glass, and semiconductor substrates with polymers and nanoparticles is a key challenge for surface-based material science. Such substrates have the potential to find widespread application in optical and electronic devices, microarrays, and materials for information storage. We report site-specific immobilization of nitroxide-mediated polymerization initiators via microcontact chemistry employing thiol–ene click chemistry on glass-supported alkene-terminated self-assembled monolayers. The polymer initiator covered substrates are used for preparation of poly(styrene) and poly(acrylate) brushes with defined and tunable brush thicknesses. Brush thickness dependent site-specific protein adsorption of streptavidin and concanavalin A on structured polystyrene brushes is reported. Poly(styrene) brushes with a thickness of 40 nm or larger showed protein repellence whereas brushes below 15 nm thickness reveal protein adhesive properties. We also disclose the site selective host–guest assisted immobilization of β-cyclodextrin-coated silica nanoparticles and the tethering of liposomes modified with amphiphilic β-cyclodextrin onto adamantane-functionalized poly(acrylate) brushes. Selective immobilization of these supramolecular colloids via the multivalent hydrophobic inclusion complex of β-cyclodextrin and adamantane can be readily verified by fluorescence microscopy imaging, atomic force microscopy, and quartz crystal microbalance with dissipation monitoring.
[Show abstract][Hide abstract] ABSTRACT: Cyclodextrin vesicles (CDVs) consist of a bilayer of amphiphilic cyclodextrins (CDs). CDVs exhibit CD cavities at their surface that are able to recognize and bind hydrophobic guest molecules via size-selective inclusion. In this study, the permeability of α- and β-CDVs is investigated by pulsed field gradient-stimulated echo (PFG-STE) NMR. Diffusion experiments with water and two types of water-soluble polymers, polyethylene glycol (PEG) and polypropylene glycol (PPG), revealed three main factors that influence the exchange rate and permeability of CDVs. First, the length of the hydrophobic chain of the CD amphiphile plays a crucial role. Reasonably, vesicles consisting of amphiphiles with a longer aliphatic chain are less permeable since both membrane thickness and melting temperature Tm increase. Second, the exchange rate through the bilayer membrane depends on the molecular weight of the polymer and decreases with increasing weight of the polymer. Most interestingly, a size-selective distinction of permeation due to the embedded CDs in the bilayer membrane was found. The mechanism of permeation is shown to occur through the CD cavity, such that depending on the size of the cavity, permeation of polymers with different cross-sectional diameter takes place. Whereas PPG permeates through the membrane of β-CD vesicles, it does not permeate α-CD vesicles.
[Show abstract][Hide abstract] ABSTRACT: Chemical, photochemical and electrical stimuli are versatile possibilities to exert external control on self-assembled materials. Here, a trifunctional molecule that switches between an "adhesive" and a "non-adhesive" state in response to metal ions, or light, or oxidation is presented. To this end, an azobenzene-ferrocene conjugate with a flexible N,N'-bis(3-aminopropyl)ethylenediamine spacer was designed as a multistimuli-responsive guest molecule that can form inclusion complexes with β-cyclodextrin. In the absence of any stimulus the guest molecule induces reversible aggregation of host vesicles composed of amphiphilic β-cyclodextrin due to the formation of intervesicular inclusion complexes. In this case, the guest molecule operates as a noncovalent cross-linker for the host vesicles. In response to any of three external stimuli (metal ions, UV irradiation, or oxidation), the conformation of the guest molecule changes and its affinity for the host vesicles is strongly reduced, which results in the dissociation of intervesicular complexes. Upon elimination or reversal of the stimuli (sequestration of metal ion, visible irradiation, or reduction) the affinity of the guest molecules for the host vesicles is restored. The reversible cross-linking and aggregation of the cyclodextrin vesicles in dilute aqueous solution was confirmed by isothermal titration calorimetry (ITC), optical density measurements at 600 nm (OD600 ), dynamic light scattering (DLS), ζ-potential measurements and cyclic voltammetry (CV). To the best of our knowledge, a dynamic supramolecular system based on a molecular switch that responds orthogonally to three different stimuli is unprecedented.
[Show abstract][Hide abstract] ABSTRACT: Based on the combination of the unique features of both polyionic liquids and spherical colloidal crystals, a new class of inverse opaline spheres with a series of distinct properties was fabricated. It was found that such photonic spheres could not only be used as stimuli-responsive photonic microgels, but also serve as multifunctional microspheres that mimic the main characteristics of conventional molecules, including intrinsic optical properties, specific molecular recognition, reactivity and derivatization, and anisotropy.
Angewandte Chemie International Edition 03/2014; · 11.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A broad spectrum of physiological processes is mediated by highly specific noncovalent interactions of carbohydrates and proteins. In a recent communication we identified several cyclic hexapeptides in a dynamic combinatorial library that interact selectively with carbohydrates with high binding constants in water. Herein, we report a detailed investigation of the noncovalent interaction of two cyclic hexapeptides (Cys-His-Cys (which we call HisHis) and Cys-Tyr-Cys (which we call TyrTyr)) with a selection of monosaccharides and disaccharides in aqueous solution. The parallel and antiparallel isomers of HisHis or TyrTyr were synthesized separately, and their interaction with monosaccharides and disaccharides in aqueous solution was studied by isothermal titration calorimetry, NMR spectroscopic titrations, and circular dichroism spectroscopy. From these measurements, we identified particularly stable complexes (Ka >1000 M(-1) ) of the parallel isomer of HisHis with N-acetylneuraminic acid and with methyl-α-D-galactopyranoside as well as of both isomers of TyrTyr with trehalose. To gain further insight into the structure of the peptide-carbohydrate complexes, structure prediction was performed using quantum chemical methods. The calculations confirm the selectivity observed in the experiments and indicate the formation of multiple intermolecular hydrogen bonds in the most stable complexes.
[Show abstract][Hide abstract] ABSTRACT: N-heterocyclic carbenes (NHCs) represent a leading class of ligands in organometallic chemistry, but have been rarely exploited as stabilizers for metal nanoparticles (NPs). We report the first example of NHC stabilized Pd-NPs that demonstrate long term stability. These NHC Pd-NPs were synthesized by a facile ligand exchange protocol using rationally designed long chained NHCs (LC-NHCs). Furthermore, we demonstrate that the surface modification of Pd-NPs results in significant chemoselectivity in a model reaction.
Chemical Communications 02/2014; · 6.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The molecular recognition of carbohydrates and proteins mediates a wide range of physiological processes and the development of synthetic carbohydrate receptors ("synthetic lectins") constitutes a key advance in biomedical technology. In this article we report a synthetic lectin that selectively binds to carbohydrates immobilized in a molecular monolayer. Inspired by our previous work, we prepared a fluorescently labeled synthetic lectin consisting of a cyclic dimer of the tripeptide Cys-His-Cys, which forms spontaneously by air oxidation of the monomer. Amine-tethered derivatives of N-acetylneuraminic acid (NANA), β-D-galactose, β-D-glucose and α-D-mannose were microcontact printed on epoxide-terminated self-assembled monolayers. Successive prints resulted in simple microarrays of two carbohydrates. The selectivity of the synthetic lectin was investigated by incubation on the immobilized carbohydrates. Selective binding of the synthetic lectin to immobilized NANA and β-D-galactose was observed by fluorescence microscopy. The selectivity and affinity of the synthetic lectin was screened in competition experiments. In addition, the carbohydrate binding of the synthetic lectin was compared with the carbohydrate binding of the lectins concanavalin A and peanut agglutinin. It was found that the printed carbohydrates retain their characteristic selectivity towards the synthetic and natural lectins and that the recognition of synthetic and natural lectins is strictly orthogonal.
[Show abstract][Hide abstract] ABSTRACT: This article describes light-responsive vesicles that can release their contents in response to a light-sensitive molecular trigger. To this end, liposomes were equipped with amphiphilic β-cyclodextrin that was covalently labeled with azobenzene. Using dye encapsulation and confocal laser scanning microscopy, we show that the permeability of these vesicles strongly increases upon UV irradiation (λ = 350 nm) with concomitant isomerization of apolar trans-azobenzene to polar cis-azobenzene on the liposome surface.
[Show abstract][Hide abstract] ABSTRACT: Dynamic chemical reactions at the surface of liposomes are of fundamental interest to the understanding of physiological processes at biological membranes and can be exploited to prepare responsive soft materials. In this paper we describe a covalent yet reversible reaction between liposomes. To this end we explored the reversible thioester exchange reaction of membrane embedded amphiphilic thioesters with dithiols from solution. It was found that thioester exchange leads to the formation of covalent inter-liposomal cross-links and aggregation of liposomes. Liposome aggregation has a characteristic lag phase and the rate of aggregation depends on the concentration of dithiols as well as on the concentration of liposomes in solution. The reversibility of the aggregation could be demonstrated by dissociation of the liposome clusters by the addition of a monothiol. Furthermore we developed a fluorescence anisotropy assay to monitor the thioester exchange reaction on the membrane surface. To the best of our knowledge, the formation of a dynamic covalent network of liposomes is unprecedented.
[Show abstract][Hide abstract] ABSTRACT: Dual-responsive soft matter: A soft hybrid material composed of superparamagnetic nanoparticles and cyclodextrin vesicles self-assembles in microscale linear aggregates in water in response to magnetic field as well as light.
[Show abstract][Hide abstract] ABSTRACT: Cyclodextrins are among the most popular host compounds in supramolecular chemistry. In this paper we describe a versatile approach to the multivalent functionalization of cyclodextrins by using photochemical thiol-alkene addition reactions (“thiol-ene click chemistry”). Starting from cyclodextrins allylated at the 2-OH, 3-OH and/or 6-OH positions, a range of thiols could be introduced in good to excellent yields. By using alkanethiols substituted with hydroxy, carboxylic acid, ester, protected amine, and tetraethyleneglycol groups, a broad variety of functionalized cyclodextrins was obtained. By using fluorinated alkanethiols, highly fluorinated cyclodextrins (up to 56 wt.-% of fluorine) were obtained in excellent yield.
Annalen der Chemie und Pharmacie 10/2013; 2013(30). · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vesicles are dynamic supramolecular structures with a bilayer membrane consisting of lipids or synthetic amphiphiles enclosing an aqueous compartment. Lipid vesicles have often been considered as mimics for biological cells. In this paper, we present a novel strategy for the preparation of three-dimensional multilayered structures in which vesicles containing amphiphilic β-cyclodextrin are interconnected by proteins using cyclodextrin guests as bifunctional linker molecules. We compared two pairs of adhesion molecules for the immobilization of vesicles: mannose-concanavalin A and biotin-streptavidin. Microcontact printing and thiol-ene click chemistry were used to prepare suitable substrates for the vesicles. Successful immobilization of intact vesicles through the mannose-concanavalin A and biotin-streptavidin motifs was verified by fluorescence microscopy imaging and dynamic light scattering, while the vesicle adlayer was characterized by quartz crystal microbalance with dissipation monitoring. In the case of the biotin-streptavidin motif, up to six layers of intact vesicles could be immobilized in a layer-by-layer fashion using supramolecular interactions. The construction of vesicle multilayers guided by noncovalent vesicle-vesicle junctions can be taken as a minimal model for artificial biological tissue.
[Show abstract][Hide abstract] ABSTRACT: We have synthesized a series of new fluorescent boron systems 1a-c and 2a-d based on nitrogen (NNN) or nitrogen and oxygen (ONO)-containing tridentate ligands. These novel dyes are characterized by high thermal and chemical stability. They show large Stokes shifts (mostly above 3200 cm(-1)) and quantum yields in solution and in the solid state up to 40%. The easy, modular synthesis facilitates the convenient variation of the axial substituent on the central boron atom, allowing the functionalization of this dye for biochemical use. Introducing a long alkyl chain with a phenyl spacer at this axial position enables the self-assembly of the boron compound 2d to form a fluorescent vesicle, which is able to encapsulate small molecules such as sulforhodamine. Additionally, boron compound 2d was found to serve as a dye for cell imaging since it has the capability of binding to the nuclear membranes of HeLa cells. With phospholipids such as DOPC, giant unilamelar vesicles (GUV) are formed. These results demonstrate the wide applicability of this new boron system in supramolecular and medicinal chemistry.
The Journal of Organic Chemistry 04/2013; · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe a microarray format that selectively detects double-stranded DNA sequences. Cyclooctyne derivatised pyrrole-imidazole polyamides were immobilised to azide-modified glass substrates by exploiting a strain-promoted azide-alkyne cycloaddition (SPAAC) reaction. These polyamide-immobilised substrates selectively detected a seven base-pair binding site incorporated within a double-stranded oligodeoxyribonucleotide (ODN) sequence relative to one, two and three base-pair mismatch ODN sequences. Matched ODN duplex sequences could be detected by fluorescence emission down to one nanomolar concentration. A key aspect of the observed selectivity is the application of a washing step at elevated temperature (50˚C).
Journal of the American Chemical Society 02/2013; · 10.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The preparation of well defined molecular monolayers as well as their patterning at the microscale and nanoscale are key aspects of surface science and chemical nanotechnology. In this article we describe the modification of amine-functionalized surfaces using a new type of contact printing based on chemically patterned, flat PDMS stamps. The developed stamps have discrete areas with surface-bond tetrafluorophenol (TFP) groups, which allow the attachment of carboxylic acids in the presence of coupling agents as diisopropylcarbodiimide (DIC). The generated active esters can be reacted by contacting the stamps with amine-functionalized surfaces. The process leads to the transfer of acyl residues from the stamp to the substrate and therefore to a covalent attachment. Patterning occurs due to the fact that reaction and transfer only takes place in areas with TFP groups present on the stamp surface. Different types of amine decorated surfaces were successfully modified and the transfer was visualized by fluorescence microscopy. To the best of our knowledge, the covalent transfer printing (CTP) of an immobilized molecular monolayer from one surface to another surface is unprecedented.