Routine patch testing with frullanolide mix: an European Environmental and Contact Dermatitis Research Group multicentre study.

Contact sensitivity to plants containing 1 or more sesquiterpene lactones (SLs) is difficult to diagnose. The mixture of SLs (SL mix) has been shown to detect only about 60% of sensitized individuals. In order to improve the diagnosis of sensitization to plants containing SLs, we have tested a mixture of frullanolides contained in Frullania dilatata and Frullania tamarisci at 3 different concentrations (0.01%, 0.033% and 0.1% in petrolatum). 8605 consecutive eczema patients in 1 North American and 15 European dermatology departments were tested with this mix, and 0.35% of positive cases to the different concentrations were found. Routine use of this mix permitted detection of only a small percentage of extra cases and did not improve the SL mix score. The frullanolide mix should therefore be restricted to investigations in particular geographical zones and/or in particular occupations.

Helical molecular programming: folding of oligopyridine-dicarboxamides into molecular single helices.

Molecular strands composed of alternating 2,6-diaminopyridine and 2,6-pyridinedicarbonyl units have been designed to self-organize into single stranded helical structures upon forming intramolecular hydrogen bonds. Pentameric strands 11, 12, and 14, heptameric strands 1 and 20, and undecameric strand 15 have been synthesized using stepwise convergent strategies. Single helical conformations have been characterized in the solid state by single crystal X-ray diffraction analysis for four of these compounds. Helices from pentameric strands 12 and 14 extend over one turn, and helices from heptameric 20 and undecameric 15 species extend to one and a half and two and a half turns, respectively. Intramolecular hydrogen bonds are responsible for the strong bending of the strands. 1H NMR shifts both in polar and nonpolar organic solvents indicate intramolecular overlap between the peripheral aromatic groups. Thus, helical conformations also predominate in solution. Molecular stochastic dynamic simulations of strand folding starting from a high energy extended linear conformer show a rapid (600 ps at 300 K) conversion into a stable helical conformation.

Helical molecular programming: supramolecular double helices by dimerization of helical oligopyridine-dicarboxamide strands.

Helically preorganized oligopyridine-dicarboxamide strands are found to undergo dimerization into double helical supramolecular architectures. Dimerization of single helical strands with five or seven pyridine rings has been characterized by NMR and mass spectrometry in various solvent/ temperature conditions. Solution studies and stochastic dynamic simulations consistently show an increasing duplex stability with increasing strand length. The double helical structures of three different dimers was characterized in the solid phase by X-ray diffraction analysis. Both aromatic stacking and hydrogen bonding contribute the double helical arrangement of the oligopyridinedicarboxamide strand. Inter-strand interactions involve extensive face-to-face overlap between aromatic rings, which is not possible in the single helical monomers. Most hydrogen bonds occur within each strand of the duplex and stabilize its helical shape. Some inter-strand hydrogen bonds are found in the crystal structures. Dynamic studies by NMR as well as by molecular modeling computations yield structural and kinetic information on the double helices and on monomer-dimer interconversion. In addition, they reveal the presence of a spring-like extension/compression as well as rotational displacement motions.

Interconversion of single and double helices formed from synthetic molecular strands.

Synthetic single-helical conformations are quite common, but the formation of double helices based on recognition between the two constituent strands is relatively rare. Known examples include duplex formation through base-pair-specific hydrogen bonding and stacking, as found in nucleic acids and their analogues, and polypeptides composed of amino acids with alternating L and D configurations. Some synthetic polymers and self-assembled fibres have double-helical winding induced by van der Waals interactions. A third mode of non-covalent interaction, coordination of organic ligands to metal ions, can give rise to double, triple and quadruple helices, although in this case the assembly is driven by the coordination geometry of the metal and the structure of the ligands, rather than by direct inter-strand complementarity. Here we describe a family of oligomeric molecules with bent conformations, which exhibit dynamic exchange between single and double molecular helices in solution, through spiral sliding of the synthetic oligomer strands. The bent conformations leading to the helical shape of the molecules result from intramolecular hydrogen bonding within 2'-pyridyl-2-pyridinecarboxamide units, with extensive intermolecular aromatic stacking stabilizing the double-stranded helices that form through dimerization.

Template-induced and molecular recognition directed hierarchical generation of supramolecular assemblies from molecular strands

The linear oligo-isophthalamide strand 1 undergoes a conformational reorganization upon binding of a cyanuric acid template as effector to afford a helical disklike object possessing radially disposed alkyl residues. Solvophobic and stacking interactions, in turn, drive a "second level" self-assembly of the templated structure, the stacking of the helical disks, to yield fibers as revealed by electron microscopy. These data provide insight into the interplay of the different structural and interactional features of the molecular components towards the formation of supramolecular fibers through sequential hierarchical self-assembly events and suggest design strategies for the effector-controlled generation of related supramolecular assemblies.

Evidence for [2 + 2] photoreaction of alpha-methylene-gamma-butyrolactones with thymine: an explanation for chronic actinic dermatitis to sesquiterpene lactones?

The photoreactivity of isoalantolactone, a natural sesquiterpene lactone, toward thymine was studied. After 313 nm irradiation of a deoxygenated acetone solution of isoalantolactone (2 x 10(-3) M) and thymine (4 x 10(-3) M), two intermolecular [2 + 2] photoadducts, 3 and 4, were isolated with respective yields of 30% and 18%. The structures of these two photoadducts were determined by a combination of NMR experiments. Compound 3 was identified as a cis-syn-exo intermolecular [2 + 2] photoadduct involving the 5,6 double bond of thymine and the exomethylenic double bond of the lactone, while compound 4 was identified as an intermolecular [2 + 2] photoadduct involving the same bonds but with the cis-syn-endo conformation. This high photoreactivity of sesquiterpene lactones toward thymine could be an explanation of the progressive evolution of allergic contact dermatitis toward chronic actinic dermatitis.

Mechanism of allergic contact dermatitis from propacetamol: sensitization to activated N,N-diethylglycine.

In order to confirm the mechanism of skin sensitization to propacetamol, a pro-drug of acetaminophen, 3 patients with allergic contact dermatitis from propacetamol were patch tested with N,N-diethylglycine phenyl ester, an activated form of N,N-diethylglycine. Positive patch tests were observed in all the patients at 10% in pet., while 20 control patients remained negative. This strongly suggests that propacetamol is acting as an activated form of N,N-diethylglycine, transferring this part of the molecule to nucleophilic residues of proteins. This also explains why reactions to acetaminophen have never been observed in patients sensitized to propacetamol.