Boris Schade

Supramolecular assembly of self-labeled amphicalixarenes.

The synthesis and precise supramolecular organization of new amphicalixarene 4 bearing four rodlike aligned fluorescent terephthalic benzamide moieties in the upper rim is reported. The aggregation of 4 was monitored by a combination of fluorescence, conductometry, and cryo-TEM measurements at different pH values and revealed significant structural differences. Most interestingly, we found that exactly 12 molecules of 4 assemble to form a spherical and structurally persistent micelle at pH 7, which coexists with rodlike micelles. In contrast to other examples of structurally defined micelles reported previously, this new type of self-labeled amphiphile serves as a fluorescence reporter with the terephthalic units additionally providing an extended cavity structure in the hydrophilic part, which facilitates the inclusion of guest molecules. In addition to the observed formation of well-defined micelles, the other highly important finding from this study is the fact that guest molecules directly influence the micellar organization because they can interact with both the free amphiphiles below the critical micelle concentration (cmc) or the micellar aggregate itself. These two types of interactions are especially pronounced in the case of the cationic pyrene derivative 10, which binds electrostatically with the amphiphile 4. In addition, a very unique membrane structure exhibiting a regular hexagonal pattern of 5 nm pores is formed by 4 at pH 4.

Electron cryomicroscopy reveals different F1+F2 protein States in intact parainfluenza virions.

ABSTRACT Electron cryomicrographs of intact parainfluenza virus 5 (PIV5) virions revealed two different surface structures, namely, a continuous layer and distinct individual spikes. The structure of these spikes reconstructed from intact virions was compared with known F ectodomain structures and was found to be different from the prefusion PIV5 F0 structure but, surprisingly, very similar to the human PIV3 F postfusion structure. Hence, we conclude that the individual F1+F2 spikes in intact PIV5 virions also correspond to the postfusion state. Since the observed fusion activity of PIV5 virions has to be associated with prefusion F1+F2 proteins, they have necessarily to be localized in the continuous surface structure. The data therefore strongly suggest that the prefusion state of the F1+F2 protein requires stabilization, most probably by the association with hemagglutinin-neuraminidase. The conversion of F1+F2 proteins from the prefusion toward the postfusion state while embedded in the virus membrane is topologically difficult to comprehend on the basis of established models and demands reconsideration of our current understanding.

Non‐ionic Dendronized Multiamphiphilic Polymers as Nanocarriers for Biomedical Applications

A new class of non-ionic dendronized multiamphiphilic polymers is prepared from a biodegradable (AB)n-type diblock polymer synthesized from 2-azido-1,3-propanediol (azido glycerol) and polyethylene glycol (PEG)-600 diethylester using Novozym-435 (Candida antarctica lipase) as a biocatalyst, following a well-established biocatalytic route. These polymers are functionalized with dendritic polyglycerols (G1 and G2) and octadecyl chains in different functionalization levels via click chemistry to generate dendronized multiamphiphilic polymers. Surface tension measurements and dynamic light scattering studies reveal that all of the multiamphiphilic polymers spontaneously self-assemble in aqueous solution. Cryogenic transmission electron microscopy further proves the formation of multiamphiphiles towards monodisperse spherical micelles of about 7-9 nm in diameter. The evidence from UV-vis and fluorescence spectroscopy suggests the effective solubilization of hydrophobic guests like pyrene and 1-anilinonaphthalene-8-sulfonic acid within the hydrophobic core of the micelles. These results demonstrate the potential of these dendronized multiamphiphilic polymers for the development of prospective drug delivery systems for the solubilization of poorly water soluble drugs.

Amphiphilic Perylene–Calix[4]arene Hybrids: Synthesis and Tunable Self-Assembly

The first highly water-soluble perylene-calix[4]arene hybrid with the calixarene scaffold acting as a structure-determining central platform is presented. In this tetrahedrally shaped amphiphilic architecture the hydrophilic and hydrophobic subunits are oriented at the opposite side of the calixarene platform. The hydrophobic part contains the two perylene diimide moieties, which enable strong π-π interactions in self-assembly processes. Two hydrophilic Newkome-type dendrons provide sufficient water solubility at slightly basic conditions. The tetrahedrally shaped amphiphile displays an unprecedented aggregation behavior down to concentrations as low as 10(-7) mol L(-1). The intriguing self-assembly process of the compound in water as well as under changed polarity conditions, achieved by addition of THF, could be monitored by the complemented use of cryogenic transmission electron microscopy (cryo-TEM), UV-vis spectroscopy, and fluorescence spectroscopy. Molecular-dynamics and molecular modeling simulations helped in understanding the interplay of supramolecular and optical behavior.

Self-assembly of structurally persistent micelles is controlled by specific-ion effects and hydrophobic guests

A combined study using cryo-TEM experiments and molecular dynamics simulations reveals remarkable details of the factors that affect the self-organization of specifically designed T-shaped amphiphilic dendrimers upon treatment of an aqueous solution with ultrasound under a layer of hexane. This treatment leads to dodecameric, structured micelles rather than the heptameric ones observed without hexane. Three-dimensional reconstruction of the cryo-TEM images provides very detailed structures of the micelles, and molecular dynamics simulations suggest that approximately 36 hexane molecules are needed to stabilize the dodecameric micelles. Sodium counterions are found to exert a significant stabilizing effect that results in an apparent attraction between the highly negatively charged polycarboxylate headgroups. DFT calculations support the observation that the formation of ion multiplets is especially crucial for this stabilizing counterion effect, which reduces headgroup repulsion. This and the increased hydrophobic stabilization that results from the hexane-enlarged core of the micelle lead to stable dodecameric micelles. The specific effects found for sodium counterions are largely absent for potassium.

Sodium Effect on Self‐Organization of Amphiphilic Carboxylates: Formation of Structured Micelles and Superlattices

Not only the self-aggregation of dendritic polycarboxylates into structurally persistent micelles, but also that of the micelles themselves into superlattices is controlled by alkali-metal counterions and shows a pronounced sodium effect. Our combined experimental and computational work has revealed the formation of superlattices for the first time. The behavior of a variety of amphiphilic carboxylates and the different effects of the alkali cations Li(+), Na(+), and K(+) have been investigated by conductivity measurements, cryogenic transmission electron microscopy (cryo-TEM), and molecular-dynamics (MD) simulations. Together, these show that sodium salts of the amphiphiles give the most stable micelles, followed by lithium and potassium. Our results suggest that ion multiplets in bridging positions, rather than contact ion pairs, are responsible for the enhanced stability and the formation of hexagonally ordered superlattices with sodium counterions. Potassium ions do not form such ion multiplets and cannot therefore induce aggregation of the micelles. This sodium effect has far-reaching consequences for a large number of biological and technical systems and sheds new light on the origin of specific-ion effects.

Counterions Control the Self‐Assembly of Structurally Persistent Micelles: Theoretical Prediction and Experimental Observation of Stabilization by Sodium Ions

We show by molecular-dynamics (MD) simulations and cryo-transmission electron microscopy (cryo-TEM) experiments that the size and form of structurally persistent micelles formed by the T-shaped amphiphile 1 are controlled by the counterions. The two techniques reveal that the micelles are specifically stabilized by sodium counterions relative to potassium ions. Both the simulations and the cryo-TEM experiments suggest that the micelles are stabilized by strongly conserved hydrated contact ion pairs with sodium counterions but not with potassium ions. We suggest that the TEM is observing local high density due to hydrated carboxylate/sodium ion pairs at the surface of the micelle. A high concentration of such structures is found in MD simulations with sodium counterions, but not with potassium.

Hierarchically Ordered Self‐Assembly of Amphiphilic Bifullerenes

Abstract A series of novel functionalised dumbbell‐shaped bifullerenes in which two [5.0] pentakis‐adducts of C60 are covalently connected by cyclic bismalonates were synthesised. These dimeric compounds, carrying various combinations of hydrophilic and hydrophobic addends, self‐assemble in aqueous solution towards supramolecular architectures of different structural complexity as observed by cryogenic transmission electron microscopy (cryo‐TEM). The detailed analysis of the image data revealed an unprecedented hierarchical aggregation behaviour. Whereas completely hydrophilic substituted bifullerenes formed profoundly monodisperse populations of small oligomeric elementary micelles consisting of only three or four bifullerene molecules in a supposedly bent conformation, their amphiphilic equivalents underwent a hierarchical two‐step assembly process towards larger spherical and even rod‐like structures. The data suggest that the hierarchical assembly process is driven by hydrophobic interactions of preformed tetrameric elementary micelles.

Amino acid networks

The large range of hydrophobicities and water solubilities of α-amino acids, together with the general accessibility of the L (natural) and D (synthetic) enantiomers, makes them ideal candidates for the development of supramolecular networks in crystals, in bulk water and on solid surfaces. In crystal and co-crystal structures of L- and DL- amino acids, amino acid co-crystals and dipeptides, one already finds many useful combinations and obtains definite clues to useful intermolecular interactions. In amphiphilic bilayers and bolaamphiphilic monolayers of amino acid derivatives, crystalline α-networks can also be realized in noncovalent fibers and fiber assemblies. β-Networks presumably depend on some ordering of the fibers on solid subphases or can be made by a stepwise assembly of appropriate amino acids on solid subphases.

Progress in the direct structural characterization of fibrous amphiphilic supramolecular assemblies in solution by transmission electron microscopic techniques

The self-assembly of amphiphilic molecules into fibrous structures has been the subject of numerous studies over past decades due to various current and promising technical applications. Although very different in their head group chemistry many natural as well as synthetic amphiphilic compounds derived from carbohydrates, carbocyanine dyes, or amino acids tend to form fibrous structures by molecular self-assembly in water predominantly twisted ribbons or tubes. Often a transition between these assembly structures is observed, which is a phenomenon already theoretically approached by Wolfgang Helfrich and still focus point in current research. With the development of suitable sample preparation and electron optical imaging techniques, cryogenic transmission electron microscopy (cryo-TEM) in combination with three-dimensional (3D) reconstruction techniques has become a particular popular direct characterization technique for supramolecular assemblies in general. Here we review the recent progress in deriving precise structural information from cryo-TEM data of particularly fibrous structures preferably in three dimensions.