Helical self-assembly and co-assembly of fluorinated, preorganized discotics

The synthesis and self-assembly properties of a fluorinated C(3)-symmetrical 3,3'-bis(acylamino)-2,2'-bipyridine discotic (1) in the mesophase and in solution are described. First, 3,4,5-tris-(1H,1H,2H,2H,3H,3H-perfluoroundecyl-1-oxy)benzoyl chloride was coupled to mono-t-BOC protected 2,2'-bipyridine-3,3'-diamine to afford after deprotection the corresponding fluorinated aromatic amine on a multigram scale. Then, three-fold reaction of this amine with trimesyl chloride yielded the target C(3)-symmetrical fluorinated disc. The latter displayed columnar liquid crystallinity over a temperature range of more than 350 K in which helical rectangular and hexagonal columnar mesophases were detected by X-ray diffraction measurements. (1)H-NMR spectroscopy showed a preorganized structure due to strong intramolecular hydrogen bonding between the amide N-H's and bipyridine nitrogen atoms, even in the presence of a large excess of hexafluoroisopropanol. This preorganized structure allows the formation of helical self-assemblies in fluorinated solvents, as was established using UV-Vis spectroscopy. The fluorinated disc and two chiral hydrocarbon analogues (a C(3)-symmetrical and a desymmetrized disc) were mixed in a 1:10 v:v mixture of methoxynonafluorobutane (MNFB) and 1,1,2-trichloro-1,2,2-trifluoroethane (Freon 113). Importantly, the C(3)-symmetrical hydrocarbon disc dissolves only in the presence of fluorinated disc in the latter solvent mixture, proving a mutual interaction. CD spectroscopy performed on these mixtures points to a preference for alternating self-assemblies of fluorinated and chiral hydrocarbon discotics.     

Nanostructured organic pn junctions towards 3D photovoltaics

The working principle of so-called organic bulk heterojunction solar cells prepared with blends of poly(2-methoxy-5-(3,7-dimethyl-octyloxy))-p-phenylene vinylene (MDMO-PPV), acting as an electron donor, and (6,6)-phenyl-C₆₁-butyric-acid methyl ester (PCBM) (a soluble C60 derivative), acting as electron acceptor, is based on the presence of three-dimensional nanostructured pn junctions and percolation paths for charge transport. At high PCBM contents, spontaneous phase separation occurs giving rise to PCBM-rich spherical/ellipsoidal regions (electron transport) embedded in a MDMO-PPV-rich matrix (hole transport). With transmission electron microscopy and scanning probe microscopy techniques it has been demonstrated that the size of the PCBM-rich region depends strongly on the preparation conditions such as solvents and drying conditions. The morphology of the active films in high-performance bulk heterojunction solar cells is characterized by a significantly higher number and a smaller size (nanoscale) of the PCBM-rich regions than for the low-performance cells. This morphology yields both an increase of the useful photoactive volume and an increase of the percolation paths for charge transport. Towards mature and high-performance organic-based three-dimensional photovoltaics, it is clear that besides mastering the electro-optical properties of the constituting materials it also of key importance to control the nanomorphology of the solid-state blends in order to obtain efficient interpenetrating pn networks. PACS 68.37.Lp; 72.80.Le; 73.50.Pz     

A concise synthesis of (+)-SCH 351448

[structure: see text] We describe a highly convergent synthetic approach to the natural product (+)-SCH 351448 (1)-a hexane-soluble heptacoordinate monosodium salt of a C(2)-symmetrical macrocyclic dilactone. Our approach implements a photochemical acylation as the key step to combine two nearly identical but orthogonal C1-C29 fragments, followed by a base-induced intramolecular acylation and deprotection to yield the natural product.     

Total synthesis of sparstolonin B via a palladium-catalyzed aldehyde α-arylation

A concise and convergent total synthesis of sparstolonin B was developed. A palladium-catalyzed aldehyde α-arylation was utilized to construct the carbon skeleton of the natural product. A subsequent simple one-pot procedure effected global deprotection and closure of the final two rings via an unusual autoredox mechanism for the conversion of a bis-hydroquinone intermediate to the natural product. The 6 step synthetic sequence was realized in 18% overall yield.     

Solubilization of itraconazole as a function of cyclodextrin structural space

Cyclodextrins are functional pharmaceutical excipients, which can dynamically include poorly water-soluble drugs and drug candidates resulting in improved solubility, stability and oral bioavailability. A number of formulations containing “natural” and chemically modified cyclodextrins have reached the market and are enjoying widespread attention and use. One such example is itraconazole, a broad-spectrum antifungal agent which is available in an aqueous hydroxypropyl-β-cyclodextrin (HPβCD) vehicle for both oral and parenteral use (Sporanox Oral Solution and Sporanox Intravenous Injection^®). While the interaction of itraconazole and HPβCD is well described, its ability to form complexes with other cyclodextrins is less understood. This creates an intriguing opportunity of screening the structural space of available cyclodextrin derivates by assessing their complexation with a single chemical probe, in this case itraconazole. To this end, a number of cyclodextrin derivatives were assess with regard to their ability to improve the water solubility of the test substrate. In some instances, more detail assessments including the effect of pH and the physical form of the drug probe were also completed. The various cyclodextrins solubilized itraconazole to varying extents (micrograms to milligrams) and by varying inclusion mechanisms and stoichiometries.     

Mass spectrometric fragmentation of cyclic peptides belonging to the polymyxin and colistin antibiotics studied by ion trap and quadrupole/orthogonal-acceleration time-of-flight technology

Electrospray ionization linked to quadrupole/orthogonal-acceleration time-of-flight (Q/oaTOF) and ion trap equipment was used to study the fragmentation behavior of the linear side-chain cyclized peptides of the polymyxin B and E antibiotics. This study exemplifies both the benefits and the drawbacks of mass spectrometric techniques for the determination of the sequence of such complex linear side-chain cyclized peptides. Q/oaTOF accurate mass measurements did not help sufficiently to assign the product ions observed in the product ion spectra. An ion trap mass spectrometer providing MS(n) capability was used to eliminate ambiguities encountered with a single MS/MS approach. The complex fragmentation behavior of these compounds of well-established structure is described which could be useful for structural characterization of unknown substances related to polymyxin B and E in the future.     

Synthesis of the C1-C21 (C1'-C21') fragment of the dimeric polyketide natural product SCH 351448

[structure: see text] A convergent, stereoselective assembly of the C1-C21 (C1'-C21') fragment of SCH 351448, a 28-membered bis-lactone natural product, has been developed. A highly efficient approach to this fragment assembles 75% of the carbon skeleton and all the stereochemical elements present in the natural product. In addition, an interesting boron ligand effect on the diastereoselectivity of a key aldol reaction with methyl ketone-derived enolborinates is reported.     

Synthesis and Properties of O‐β‐D‐ribofuranosyl‐(1″→2′)‐guanosine‐5″‐ O‐phosphate and Its Derivatives

The efficient synthesis of O‐β‐D ‐ribofuranosyl‐(1″→2′)‐guanosine‐5″‐O‐phosphate and O‐β‐D ‐ribofuranosyl‐(1″→2′)‐adenosine‐5″‐O‐phosphate, minor tRNA components, have been developed, and their conformational properties were examined by NMR spectroscopy.     

C3-symmetrical supramolecular architectures: fibers and organic gels from discotic trisamides and trisureas

Hydrogen bonded C(3)-symmetrical molecules that associate into supramolecular stacks are described. Structural mutation on these molecules has been performed to elucidate the contribution of the different secondary interactions (hydrogen bonding, pi-pi stacking) to the self-assembly of the disks into chiral stacks. Twelve C(3)-symmetrical molecules have been investigated, six of which contain three central amide functionalities (1a-f) and six of which contain three central urea groups (2a-f). Peripheral groups of the disks are "small", "medium", or "large", half of them being achiral and the other half being chiral, to enable investigation of the supramolecular architectures with CD spectroscopy. In all of the cases, elongated, helical stacks are formed in apolar solution, except for the "medium" amide disks 1c/d. The elongated stacks of the C(3)-symmetrical disks form gels, which are visualized by AFM and SANS, and this confirms the directionality of the interactions. For the "large" urea disk, 2f, fibers with a length of up to 2 microm are observed. Temperature dependent and "sergeants-and-soldiers" CD measurements reveal that the urea stacks are much more rigid than the corresponding amide ones. In case of the "medium" urea disks, 2c/d, a true rigid rod, is formed. Where amide disks immediately reach their thermodynamic equilibrium, kinetic factors seem to govern urea aggregation. In a number of experiments aimed at reversibility with the urea stacks, hysteresis is observed, implying that these urea disks initially form a poorly defined stack, which subsequently transforms slowly into a well-defined, chiral architecture.     

Hydrogen-Bonded Complexes of Diaminopyridines and Diaminotriazines: Opposite Effect of Acylation on Complex Stabilities

The association behavior of several 2,4-diamino-s-triazines, 2,6-diaminopyridines, and their acylated derivatives with uracil derivatives was studied. In solution (1)H-NMR and IR spectroscopy were used, and in the solid state as (co)crystals X-ray diffraction was used. Acylation of 2,6-diaminopyridine leads to an increase of the association constant in CDCl(3) of the complexes with N-propylthymine from 84 to 440-920 M(-)(1), whereas acylation of diamino-s-triazines leads to a dramatic fall in the association constant of the complexes with N-propylthymine from 890 to ca. 6 M(-)(1). This phenomenon is related to different conformational preferences of these compounds. The amide groups in bis(acylamino)pyridines prefer a trans conformation, with the carbonyl group anti with respect to the ring nitrogen and coplanar with the aromatic ring. The amides of bis(acylamino)triazines, however, reside predominantly in a cis conformation. Repulsive secondary electrostatic interactions between the cis-amide and uracil carbonyl groups are thought to be responsible for the low association constant of complexes of bis(acylamino)triazines with uracils. The relatively high dimerization constants of bis(acylamino)triazines have been rationalized by the strong tendency to dimerize via quadruple hydrogen bonding.