A Torquospecific 1,5-Electrocyclization

Saponification of homodiazepine 1a and 1b , in the absence of any proton donors, led to the formation of the 6π electron anionic species A which, by virtue of a 1,5-electrocyclization, is in equilibrium with the allylic anion B . This latter tricyclic species is thermodynamically less favoured than its bicyclic isomer A . Nevertheless, B could be trapped by acylation and led tupe- 2 compounds which are the major reaction products. This is due to the fact that B is more nucleophilic and, therefore, much more reactive than A . The transoid topology of the tricyclic products 2 was demonstrated by ¹H-NMR and by an X-ray diagram of 2d . The transoid geometry of 2 is a consequence of a torquospecific 1,5-electrocyclization (of A ), which is due to a steric, and possibly even to an electronic factor.     

Unexpected formation of rearrangement and fragmentation products during the thermal activation of pyrazolino diazepines

Ionic and radical mechanistic steps are postulated in order to explain the formation of the rearrangement-, the isomerization- and the fragmentation-products isolated during the thermal treatment of pyrazolo-diazepines.     

Helical nanofibers of self-assembled bipolar phospholipids as template for gold nanoparticles

Bipolar phospholipids (bolalipids) represent an exciting class of amphiphilic molecules as they self-assemble in water to distinct structures of nanoscopic dimensions. Reported here are structural details of helical nanofibers, composed of achiral, symmetrical single-chain bolalipids with phosphocholine headgroups. These nanofibers are used as template for the fixation of gold nanoparticles (AuNPs) without prior functionalization. This realization of a metal array on bolalipid nanofibers is one of the rare examples of one-dimensional AuNP arrangements in solution. The loading and the heat of binding of AuNPs are determined applying transmission electron microscopy and isothermal titration calorimetry.     

Temperature-dependent self-assembly and mixing behavior of symmetrical single-chain bolaamphiphiles

The temperature-dependent self-assembly and the mixing behavior of symmetrical single-chain bolaamphiphiles with different polymethylene chain lengths and different headgroup structures were investigated in water by differential scanning calorimetry (DSC), cryo transmission electron microscopy (cryo-TEM), and small angle neutron scattering (SANS). The even-numbered polymethylene-1,omega-bis(phosphocholines) (PC-C n-PC) are known to form nanofibers composed of stretched molecules with an all- trans alkyl chain conformation (Drescher, S.; Meister, A.; Blume, A.; Karlsson, G.; Almgren, M.; Dobner, B. Chem.Eur. J. 2007, 13, 5300-5307). The odd-numbered analogues were synthesized to study a possible even-odd effect of these bolaamphiphiles during their aggregation in water. In addition to these bolaamphiphiles with phosphocholine headgroups, a new series of polymethylene-1,omega-bis(phosphodimethylethanolamines) (Me2PE-Cn-Me2PE) with smaller headgroup sizes was synthesized. These bolaamphiphiles show an additional fiber-fiber transition when the alkyl chain length exceeds 26 carbon atoms. The mixing behavior of both types of bolaamphiphiles indicates that differences in the alkyl chain length up to six carbon atoms are tolerated within the fiber structure. The mixing of two Me2PE-Cn-Me2PE or PC-Cn-PC type bolaamphiphiles with different alkyl chain lengths offers the possibility to adjust the temperature, where the cross-linking of the fibers is disrupted and where the fibers break apart. As a consequence, temperature switchable hydrogels are obtained that can be fine-tuned for drug delivery applications. The comparison with dotriacontane-1,32-diyl-bis[2-(methylammonio)-ethylphosphate] (MePE-C32-MePE), a new bolaamphiphile with even smaller phosphomonomethylammonio headgroups, illustrates the importance of the headgroup size for the aggregation behavior. This bolaamphiphile self-assembles exclusively into lamellar structures, and this aggregate type persists in mixtures with the fiber forming Me2PE-C32-Me2PE.     

General synthesis and aggregation behaviour of new single-chain bolaphospholipids: variations in chain and headgroup structures

The chemical structures of polymethylene-1,omega-bis(phosphocholines) that self-assemble into nanofibres was modified on the one hand in the hydrophobic chain region, by introduction of sulfur and oxygen atoms, and on the other hand by variation of the polar headgroup structure with functionalised tertiary amines. The temperature-dependent self-assembly of these novel bolaphospholipids into nanofibres and spherical micelles was investigated by differential scanning calorimetry (DSC) and transmission electron microscopy (TEM). The thermal stabilities of the nanofibres strongly depend on the chemical compositions of the headgroups and of the hydrophobic chains. The insertion of new functionalities in the headgroup region by click chemistry makes these substances interesting for potential applications in bioscience and materials science.     

Self-assembly of different single-chain bolaphospholipids and their miscibility with phospholipids or classical amphiphiles

A variety of bolalipids with a single long alkyl chain and two identical headgroups self-assemble in aqueous solutions into helical entangled nanofibers leading to the formation of a hydrogel. An increase in temperature usually leads to the break-up of the fiber structure into micellar aggregates. In this paper the question is addressed whether bolalipids of different lengths or different headgroup structures can form mixed fibers. Also, the stability of the fiber aggregation of bolalipids in mixtures with phospholipids forming lamellar bilayers is discussed. Here, the question whether single-chain bolalipids can be incorporated into phospholipid bilayers to stabilize bilayer membranes is important, as possibly lipid vesicles used for drug delivery can be improved. Finally, the stability of the fiber aggregate against solubilisation by common surfactants was studied. The paper addresses the question which type of aggregate structure dominates the self-assembly of bipolar and monopolar amphiphiles in aqueous suspension.     

A Dehydratase Domain in Ambruticin Biosynthesis Displays Additional Activity as a Pyran‐Forming Cyclase

Hydropyran rings are a common structural motif in reduced polyketides. Information on their biosynthetic formation and particularly the biochemical characterization of the responsible enzymes has only been reported in few cases. The dehydratase domain AmbDH3 from the ambruticin polyketide synthase was investigated. Through in vitro assay of the recombinant domain with synthetically‐derived substrate surrogates, it was shown that it has a second catalytic activity as a cyclase that performs oxa‐conjugate addition. Probing AmbDH3 with synthetic substrate analogues revealed stereoselectivity and substrate tolerance in both substeps. This is the first characterization of a pyran‐forming cyclase from a cis‐AT PKS system and the first report of a polyketide synthase domain with this kind of dual activity. Finally, it was revealed that this domain shows potential for application in chemoenzymatic synthesis.