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Daphenylline, a novel daphniphyllum alkaloid, boasts a fused and bridging ring system coupled with six stereogenic centers. Here we present a direct and short construction of the ACDE ring system of daphenylline from the known 3-(2-bromophenyl)propanal in 10 steps and 17 % overall yield. The synthesis features an iron(III)-catalyzed aza-Cope-Mannich reaction, a self-terminating 6-exo-trig aryl radical-alkene cyclization and an intramolecular Friedel-Crafts acylation., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Half-sandwich rhodium(III) polypyridyl (pp) complexes with the metal atom capped by the facial crown thiaether 1,4,7-trithiacyclononane [9]aneS(3) represent a promising class of apoptosis-inducing potent cytostatic agents. The necrotic damage caused by the complexes is negligible. In vitro cytotoxicity assays with the human cancer cell lines MCF-7 and HT-29 and immortalized HEK-293 cells indicate that the dicationic kappa(2)N(imino) complexes [([9]aneS(3))RhCl(pp)](2+) are much more active than monocationic complexes [([9]aneS(3))RhCl(2)(L)](+) (L=imidazole, CH(3)CN). Whereas the kappa(2)N(amino) complex [([9]aneS(3))RhCl(piperazine)](2+) is inactive, replacing piperazine with the structurally analogous kappa(2)S (thiaether) ligand 1,4-dithiane restores cytotoxicity as evidenced by IC(50) values in the range 8.1-11.6 microM. Spectroscopic (CD, UV/Vis, NOESY) and viscosity measurements indicate that the active dppz complex 8 (IC(50) values: 4.7-8.9 microM) exhibits strong intercalative binding towards DNA whereas the even more potent bipyrimidine complex 9 (IC(50) values: 0.6-1.9 microM) causes no alteration of the duplex B conformation. Weaker intercalative binding is observed for the dpq complex 7. A comparative annexin V-propidium iodide binding assay with lymphoma (BJAB) cells and healthy leukocytes demonstrates that the cytotoxic activity of complex 8 and particularly complex 9 is highly selective towards the malignant cells.

Paraquat bis(hexafluorophosphate) undergoes stepwise dissociation in acetone. All three species-the neutral molecule, and the mono- and dications-are represented significantly under the experimental conditions typically used in host-guest binding studies. Paraquat forms at least four host-guest complexes with dibenzo[24]crown-8. They are characterized by both 1:1 and 1:2 stoichiometries, and an overall charge of either zero (neutral molecule) or one (monocation). The monocationic 1:1 host-guest complex is the most abundant species under typical (0.5-20 mM) experimental conditions. The presence of the dicationic 1:1 host-guest complex cannot be excluded on the basis of our experimental data, but neither is it unambiguously confirmed to be present. The two confirmed forms of paraquat that do undergo complexation-the neutral molecule and the monocation-exhibit approximately identical binding affinities toward dibenzo[24]crown-8. Thus, the relative abundance of neutral, singly, and doubly charged pseudorotaxanes is identical to the relative abundance of neutral, singly, and doubly charged paraquat unbound with respect to the crown ether in acetone. In the specific case of paraquat/dibenzo[24]crown-8, ion-pairing does not contribute to host-guest complex formation, as has been suggested previously in the literature.