GaCl(3)-catalyzed ortho-ethynylation of phenols

Phenols are ethynylated at the ortho position with silylated chloroethyne in the presence of a catalytic amount of GaCl3 and lithium phenoxide. The lithium salt is essential for the catalysis, and addition of 2,6-di(tert-butyl)-4-methylpyridine inhibits desilylation and hydration of the products. The reaction can be applied to various substituted phenols giving the ortho-ethynylated products in high yields, and the turnover numbers based on GaCl3 are between 8 and 10. The reaction mechanism involves addition of in situ formed phenoxygallium to the haloethyne followed by the elimination of GaCl3.     

Cu-catalyzed regio- and stereoselective sulfonylation of multi-substituted allenes

Regio- and stereoselective sulfonylation of allenes under Cu catalysis is described. Allenyl sp carbons exclusively react with TsCN to give the corresponding alkenyl sulfones. The reaction is initiated by addition of tosyl radical to form benzyl radical intermediates, which determines the reaction pathway. The structure of the products is highly dependent on the substituents on allenes.     

Induction of a remarkable conformational change in a human telomeric sequence by the binding of naphthyridine dimer: inhibition of the elongation of a telomeric repeat by telomerase

The binding of a dimeric form of the 2-amino-1,8-naphthyridine derivative (naphthyridine dimer) to a human telomeric sequence, TTAGGG, was investigated by UV melting, CD spectra, and CSI-MS measurements. Both the 9-mer d(TTAGGGTTA) and the 15-mer d(TTAGGGTTAGGGTTA) showed apparent melting temperatures (T(m)) of 45.6 and 63.6 degrees C, respectively, in the presence of naphthyridine dimer (30 microM) in sodium cacodylate buffer (50 mM, pH 7.0) containing 100 mM NaCl. The CD spectra at 235 and 255 nm of the 9-mer increased in intensity accompanied with strong induced CDs at 285 and 340 nm upon complex formation with naphthyridine dimer. UV titration of the binding of naphthyridine dimer to the 9-mer at 320 nm showed a hypochromism of the spectra. A Scatchard plot of the data showed the presence of multiple binding sites with different association constants. Cold spray ionization mass spectrometry of the complex between naphthyridine dimer and the 9-mer clearly showed that one to three molecules of the ligand bound to the dimer duplex of the 9-mer. Telomeric repeat elongation assay showed that the binding of naphthyridine dimer to the telomeric sequence inhibits the elongation of the sequence by telomerase.     

Secondary hypervalent I(III)...O interactions: synthesis and structure of hypervalent complexes of diphenyl-lambda3-iodanes with 18-crown-6

Reported here for the first time are the synthesis and characterization of supramolecular complexes between diaryl-lambda(3)-iodanes and 18-crown-6 (18C6). Slow evaporation of solvents afforded 1:1 and 2:1 complexes between Ph(2)IBF(4) and 18C6 as stable crystals, depending on the conditions. X-ray crystal structures of these complexes indicated that each iodine atom contacts with the three adjacent oxygen atoms of 18C6 through two hypervalent secondary bonding and a weak interaction. (1)H NMR analyses and CSI-MS spectra showed that, in dichloromethane solution, Ph(2)IBF(4) exclusively forms the 1:1 complex with 18C6 (binding constant K(a), 1.02 x 10(3) M(-)(1)). The binding constants decrease with the increased solvent donor ability (Gutmann's DN). Changing the heteroatom ligand from BF(4) to the less nucleophilic PF(6) and AsF(6) increased the binding constant by about six times. Substitution of an electron-withdrawing group onto the para position of Ph(2)IBF(4) tends to increase in the complex stability. A linear Hammett relationship (rho = 0.59) between log K(a) and sigma(p)(+) values of substituents indicates that the diaryl-lambda(3)-iodanes with electropositive iodine(III) interact more efficiently with 18C6. Decreased binding magnitude was measured with 15C5, dibenzo-18C6, dibenzo-21C7, and dibenzo-30C10.     

Injectable Polypeptide Hydrogel Depot System for Assessment of the Immune Response–Inducing Efficacy of Sustained Antigen Release Alone

Vaccines typically contain an antigen, delivery system (vehicle), and adjuvant, all of which contribute to inducing a potent immune response. Consequently, design of new vaccines is difficult, because the contributions and interactions of these components are difficult to distinguish. Here, it is aimed to develop an easy‐to‐use, non‐immunogenic, injectable depot system for sustained antigen release that will be suitable for assessing the efficacy of prolonged antigen exposure per se for inducing an immune response. This should mimic real‐life infections. Recombinant elastin‐like polypeptides with periodic cysteine residues (cELPs) are selected, which reportedly show little or no immunogenicity, as carriers and tetanus toxoid (Ttd) as an antigen. After subcutaneous injection of the mixture, cELP rapidly forms a disulfide cross‐linked hydrogel in situ, within which Ttd is physically incorporated, affording a biodegradable antigen depot. A series of Ttd‐containing hydrogels is examined. A single injection induces high levels of tetanus antibody with high avidity for at least 20 weeks in mice. The chain length of cELP proves critical, whereas differences in hydrophobicity has little effect, although hydrophilic cELPs are more rapidly biodegraded. This system's ability to distinguish the contribution of sustained antigen release to antibody induction should be helpful for rational design of next‐generation vaccines.     

Analysis of membrane transport mechanisms of endogenous substrates using chromatographic techniques

Membrane transporters are expressed in various bodily tissues and play essential roles in the homeostasis of endogenous substances and the absortion, distribution and/or excretion of xenobiotics. For transporter assays, radioisotope‐labeled compounds have been mainly used. However, commercially available radioisotope‐labeled compounds are limited in number and relatively expensive. Chromatographic analyses such as high‐performance liquid chromatography with ultraviolet absorptiometry and liquid chromatography with tandem mass spectrometry have also been applied for transport assays. To elucidate the transport properties of endogenous substrates, although there is no difficulty in performing assays using radioisotope‐labeled probes, the endogenous background and the metabolism of the compound after its translocation across cell membranes must be considered when the intact compound is assayed. In this review, the current state of knowledge about the transport of endogenous substrates via membrane transporters as determined by chromatographic techniques is summarized. Chromatographic techniques have contributed to our understanding of the transport of endogenous substances including amino acids, catecholamines, bile acids, prostanoids and uremic toxins via membrane transporters.     

Seeded Polymerization of an Amide-Functionalized Diketopyrrolopyrrole Dye in Aqueous Media

The self-assembly of an amide-functionalized dithienyldiketopyrrolopyrrole (DPP) dye in aqueous media was achieved through seed-initiated supramolecular polymerization. Temperature- and time-dependent studies showed that the spontaneous polymerization of the DPP derivative was temporally delayed upon cooling the monomer solution in a methanol/water mixture. Theoretical calculations revealed that an amide-functionalized DPP derivative adopts an energetically favorable folded conformation in the presence of water molecules due to hydration. This conformational change is most likely responsible for the trapping of monomers in the initial stage of the cooperative supramolecular polymerization in aqueous media. However, the monomeric species can selectively interact with externally added fragmented aggregates as seeds through concerted π-stacking and hydrogen-bonding interactions. Consequently, the time course of the supramolecular polymerization and the morphology of the aggregated state can be controlled, and one-dimensional fibers that exhibit a J-aggregate-like bathochromically shifted absorption band can be obtained.     

Synthesis of bis(N-heterocyclic carbene) palladium complexes derived from (S,S)-1,2-bis(1-hydroxypropyl)benzene

New o-xylylene-linked bis(benzimidazolium) salts were synthesized in six-steps from C₂-symmetric chiral 1,4-diol, 1,2-bis(1-hydroxypropyl)benzene, as a starting material. The silver complex of bis(benzimidazol-2-ylidene) was obtained on treatment of bis(benzimidazolium) salt with silver oxide. The reaction of the silver bis-NHC with [PdCl₂(PhCN)₂] afforded the bis-NHC complex of palladium. The X-ray diffraction studies on Pd complexes revealed that these complexes have distorted square planar geometry around the Pd center coordinating the NHC ligand in mutually cis-position. The arene ring of o-xylylene unit hanged over the Pd center and thus these complexes showed C₁-symmetric structures. The variable temperature NMR spectroscopy revealed that these Pd complexes showed fluxional behavior between C₁- and C₂-symmetric structures in solution state.