A simple and efficient concept has been developed for the synthesis of pH‐responsive molecular nanocarriers based on commercially available hyperbranched polymers. These dendritic core‐shell architectures can encapsulate, transport, and selectively release polar guest molecules in an acidic environment (pH 3–6, see scheme). The observed release properties render these molecular nanocarriers promising candidates for controlled drug and gene delivery.

Due to several limitations of heparin, a widely used antithrombotic drug, there is large interest to develop alternatives. The aim of the presented study was to produce fully synthetic highly branched heparin mimetics. For this purpose, a new type of 'treelike' polysulfated polymers based on dendritic polyglycerol was synthesized. An efficient synthetic approach has been chosen to prepare several polyglycerol sulfates with different molecular weights as well as a polyglycerol carboxylate analogue and to evaluate them for their anticoagulant and anticomplementary activities. In contrast to the nonderivatized and the carboxylated polyglycerols, the polyglycerol sulfates prolong the activated partial thromboplastin time (APTT) and thrombin time (TT) and inhibit both the classical (CCA) and alternative complement activation (ACA). Whereas their anticoagulant activity in the APTT and in the TT amounts to 5.7-8.1% and 15.7-33.6%, respectively, of that of unfractionated heparin (UFH), their CCA and ACA inhibitory activity is 13.4-23.9 and 2.7-3.7 times, respectively, higher. In contrast to sulfated polysaccharides, the activities are not clearly dependent on the molecular weight, which might be due to the globular 3D-structure of the dendritic molecules. Due to the coherence between coagulation, complement activation and inflammation in the pathophysiology of numerous diseases, polyglycerol sulfates with both anticoagulant and anticomplementary activities represent promising candidates for the development of potential drugs.

Glycidol as latent branching AB2 monomer was used in combination with glycidyl ethers as linear AB comonomers for the preparation of hyperbranched random copolymers with controlled degree of polymerization (DPn ) 42-72) and relatively low polydispersity (Mw/Mn < 1.7). Extending previous theoretical considerations, equations that permit to calculate the DB for AB2/AB copolymerizations under slow monomer addition conditions were derived. The degree of branching (DB) for the random copolymers of glycidol and allyl glycidyl ether (AGE) as well as phenyl glycidyl ether (PGE) was controlled by the comonomer ratio (DB ) 9%-58%). Furthermore, comparable block copolymers of glycidol and AGE, i.e., multiarm star polymers, have been prepared by sequential addition of the monomers. Thermal behavior of all materials has been investigated with respect to copolymer composition. Furthermore, reactions of the random glycidol/AGE copolymers have been developed: (i) cleavage of the allyl groups, leading to linear 1,3-glycerol units bearing primary hydroxy groups; (ii) dihydroxylation of the double bond, leading to hyperbranched polyglycerols with enhanced DB; and (iii) hydroformylation with subsequent reductive amination, making use of the orthogonality of the OH and allyl functionalities.

Since many potential drugs are poorly water soluble, there is a high demand for solubilization agents. Here, we describe the synthesis of dendritic core-shell-type architectures based on hyperbranched polyglycerol for the solubilization of hydrophobic drugs. Amphiphilic macromolecules containing hydrophobic biphenyl groups in the core were synthesized in an efficient three- or four-step procedure by employing Suzuki-coupling reactions. These species were then used to solubilize the commercial drug nimodipine, a calcium antagonist used for the treatment of heart diseases and neurological deficits. Pyrene was also used as a hydrophobic model compound. It turned out that the transport properties of the dendritic polyglycerol derivatives, which are based on hydrophobic host-guest interactions, depend strongly on the degree and type of core functionalization. In the case of the multifunctional nimodipine, additional specific polymer-drug interactions could be tailored by this flexible core design, as detected by UV spectroscopy. The enhancement of solubilization increased 300-fold for nimodipine and 6000-fold for pyrene at a polymer concentration of 10 wt%. The sizes of the polymer-drug complexes were determined by both dynamic light scattering (DLS) experiments and transmission electron microscopy (TEM), and extremely well-defined aggregates with diameters of approximately 10 nm in the presence of a drug were observed. These findings together with a low critical aggregate concentration of 4x10(-6) mol L-1 indicate the controlled self-assembly of the presented amphiphilic dendritic core-shell-type architectures rather than a unimolecular transport behavior.

The preparation of a dendritic graft polymer by a very efficient synthesis of polyglycerol directly on a polystyrene resin is presented. This one-step process can be performed on a multigram scale to provide a chemically stable polymeric support. The resulting hybrid polymers were fully characterized by diverse analytical methods (NMR, IR, ESEM, UV detection of cleaved protecting groups, and mass-spectrometric methods). They combine a high loading capacity (up to 4.3 mmol g(-1)) with good swelling properties in a wide range of solvents (including water), which is the major drawback for many existing solid phase supports. In comparison to the widely employed PEGylated resins, these hybrid materials offer a 10-fold higher loading capacity. Their suitability as supports for organic synthesis and for the immobilization of reagents has been demonstrated. These materials also swell in water, and consequently, it should be possible to use these new hybrid materials for synthesis in protic solvents.

Physikalische Aggregate von amphiphilen Molek¸len, z. B. micellare Strukturen, werden h‰ufig f¸r den Wirkstofftransport vorgeschlagen. [1] Diese Aggregate kˆnnen jedoch aufgrund ihrer schwachen Wechselwirkungskr‰fte bei Scherkr‰ften oder anderen ‰u˚eren Einfl¸ssen zerfallen. Auch sind sie weniger f¸r die aktive Freisetzung verkapselter Molek¸le geeignet, die durch externe Signale wie pH-aenderungen ausgelˆst wird. Besonders f¸r den Wirkstofftransport in biologischen Systemen muss sich die Freisetzung von verkapselten Molek¸len auf der Basis schwacher externer Signale ereignen, z. B. einer pH-Erniedrigung in Tumor-oder infiziertem Gewebe bei pH 5±6. [2, 3] Ferner wurde gezeigt, dass Nanopartikel grˆ˚er als 5 nm, z. B. Liposomen und polymere Tr‰ger, biologische Membranen im Vergleich zu kleinen Molek¸len¸ber andere Mechanismen passieren und damit die Spezifit‰t von Wirkstoffen f¸r bestimmtes Gewebe [4±6] (z. B. Tumor) verbessern kˆnnen.Im Unterschied zu physikalischen Aggregaten amphiphiler Molek¸le kˆnnen durch die kovalente Modifizierung dendritischer Makromolek¸le [7] mit entsprechender Schale stabile micellartige Strukturen erhalten werden, welche f¸r die nichtkovalente Verkapselung von Gastmolek¸len geeignet sind. [8] W‰hrend die Verkapselung und der Transport der Gastmolek¸le in solchen dendritischen Architekturen von mehreren Arbeitsgruppen untersucht wird, [9±16] ist relativ wenig¸ber die aktive Freisetzung der verkapselten Gast-molek¸le ± ausgelˆst durch pH-abh‰ngige Spaltung der Schale ± unter physiologischen Bedingungen bekannt. Bisher wurde von einer pH-abh‰ngigen Freisetzung aus dendritischen Architekturen nur unter relativ drastischen Bedingungen [17] oder durch Protonierung von Polypropylenimin-Dendrimeren [18] und deren Derivaten berichtet. [19, 20] ZUSCHRIFTEN 4426

We describe the information technological challenges in the project ArcheoInf which aims at providing a unified access to heterogeneous archaeological databases. We consider the difficulties caused by legacy databases not designed for structured data retrieval and propose an ontology-based solution to this problem. In particular we present a process that migrates the data into an ontologybased triple store system, which can be queried with SPARQL. The problem of heterogeneous vocabularies is solved by a mapping of the respective datafields into an archaeology-specific thesaurus which is also kept in the triple store. Our approach is expanded by the possibility to integrate further SQL-databases into the ArcheoInf-system without migrating them into the triple store, provided they are based on a datamodel which is suitably compatible to the ontology we use.