Pentamethylene Spacer Research Articles

C3-symmetric ferrichrome-mimicking Fe3+-complexes containing the 1-hydroxypyrimidinone Fe3+-binding moieties based on α-cyclodextrin: helicities in solvent environments

Two homologous C3-symmetric ferrichrome mimics, La and Lb, equipped with three 1-hydroxypyrimidinone terminals for receiving an Fe3+ ion have been designed and synthesized; the side chains of La and Lb, which include dimethylene and pentamethylene spacers, respectively, are anchored to the narrower rim of the α-cyclodextrin framework through an amide linkage. The 1∶1 Fe3+-complexes of La and Lb provide strong circular dichroic exciton coupling of negative and positive signs at 480 nm, showing Δ- and Λ-helices, respectively, in polar aprotic solvents such as dimethylformamide and dimethyl sulfoxide. The magnitude of the signals increases with the increasing hydrogen-bond accepting ability of the solvent. It is inferred, therefore, that hydrogen-bonding interactions of the linker amide N–H groups with the solvent play a primary role in inducing a helicity within aprotic solvents. The mechanisms of the helicity inductions are discussed. Meanwhile, the signals for La are still negative, but weak in alcohols and water. However, the signal sign for Lb having the relatively flexible spacers depends on the nature of alcohols, and no CD signal was observed in water. p

Dimesogenic compounds consisting of a cholesteryl moiety and an aromatic mesogen interconnected through a central pentamethylene spacer

New non-symmetric dimesogens consisting of a cholesteryl moiety and an aromatic mesogenic unit interconnected through a pentamethylene spacer have been prepared. The aromatic units consist of two phenyl rings linked by carboxy, oxycarbonyl, ethylene, ethynylene, azo or Schiff's base groups. The mesomorphic and transitional properties have been investigated by using optical microscopy, differential scanning calorimetry, helical pitch measurements, and electric field and miscibility studies. The structures of the mesophases have been studied using X-ray diffraction. Several kinds of smectic packings are observed depending on the nature of the linking group and an attempt to understand the origin of the different phase structures at a molecular level is made.

Ethylene polymerization initiated by anchored CpIndZrCl2 on silica with hexamethyltrisiloxane and pentamethylene spacers

Ethylene polymerization initiated by anchored CpIndZrCl2 on silica with hexamethyltrisiloxane and pentamethylene spacers

Ethylene polymerization initiated by anchored CpIndZrCl2 on silica with hexamethyltrisiloxane and pentamethylene spacers

For ethylene polymerization, the supported metallocene catalyst was prepared by anchoring CpIndZrCl2 on silica with an appropriate spacer. The three procedures were applied for CpIndZrCl2 anchoring on silica with a hexamethyltrisiloxane or pentamethylene spacer. The anchoring procedures exerted a strong influence on the catalyst activity since the different anchoring methods gave the formation of different structures of active sites. With the new anchoring route, it was possible to prepare the “heterogeneous single-site” catalyst which was found to have only one catalyst structure on silica and exhibited a higher catalyst activity than that of the other supported catalysts. At a polymerization temperature of 70°C, the activity of the heterogeneous single-site catalyst was comparable to that of the unsupported homogeneous zirconocene. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 1071–1080, 1999

Design of Lysosomotropic Macromolecular Prodrug of Doxorubicin Using N-Acetyl-α-1,4-Polygalactosamine as a Targeting Carrier to Hepatoma Tissue

α-1,4-Polygalactosamine (PGA) and N-acetylated α-1,4-polygalactosamine (NAPGA) are chitosan- and chitin-like biodegradable α-1,4-linked polysaccharides, respectively. Radioactivity of 14C-50% N-acetylated PGA injected into hepatomized mice, was found to accumulate more in the liver, kidney, ileum and hepatoma tumor tissues, compared with other organs. To provide a lysosomotropic macromolecular prodrug of doxorubicin (DXR) targeted to hepatoma tumor tissue, DXR was immobilized on water-soluble 6-O-carboxymethyl(CM)-NAPGA by Gly-Phe-Leu-Gly spacer groups (CM-NAPGA/Gly-Phe-Leu-Gly/DXR conjugate). The conjugate showed cathepsin B susceptible DXR release behavior and exhibited remarkable survival effects in mice bearing MH134Y hepatoma implanted by subcutaneous (s.c.) implantation/intravenous (i.v.) injection, compared with free DXR and CM-NAPGA-immobilized DXRs with pentamethylene spacer groups (CM-NAPGA/C5/DXR conjugate).

Hydrophobic Self-Association of Cholesterol Moieties Covalently Linked to Polyelectrolytes: Effect of Spacer Bond

Polyelectrolytes carrying cholesterol (Chol) pendants were synthesized by free-radical copolymerization of sodium 2-(acrylamido)-2-methylpropanesulfonate with cholesteryl methacrylate (CholMA) or cholesteryl 6-methacryloyloxyhexanoate (Chol-C5-MA), with the contents of CholMA and Chol-C5-MA units in the copolymers ranging from 0.5 to 1.0 and 0.5 to 10 mol %, respectively. In the CholMA copolymer, Chol is directly linked to the polymer main chain by an ester bond, whereas in the Chol-C5-MA copolymer, Chol is linked via a pentamethylene spacer. The association behavior of these Chol-carrying polymers in aqueous solution was investigated by turbidimetry, 1H NMR, fluorescence, size exclusion chromatography (SEC), static light scattering (SLS), quasielastic light scattering (QELS), and viscometry, with a focus on the effect of the spacer bond on the self-association of Chol pendants. For fluorescence studies, Chol-carrying polymers labeled with a pyrene (Py) or naphthalene (Np) moiety were employed. Fluorescen...

Polymerization of ethylene by using zirconocene catalyst anchored on silica with trisiloxane and pentamethylene spacers

AbstractNew supported catalysts on the basis of cyclopentadienylindenylzirconium dichloride (CpIndZrCl2) anchored on silica with a trisiloxane spacer (ZATS) and a pentamethylene spacer (ZAPM) were prepared and used for ethylene polymerization with modified methylaluminoxane (MAO) as cocatalyst. ZATS and ZAPM produce polyethylene with lower molecular weight but show higher activity than silica‐supported CpIndZrCl2 which was prepared by reacting zirconocene directly with silica, i.e., the activity of silica‐supported CpIndZrCl2 is enhanced by introducing a spacer between silica surface and metallocene species.

In Vivo and in Vitro Antitumor Activity of CM-Chitin Immobilized Doxorubicins by Lysosomal Digestible Tetrapeptide Spacer Groups

In vivo and in vitro antitumor activities of macromolecular prodrugs of doxorubicin (DXR) using 6- O-carboxymethylchitin (CM-chitin) as a carrier polymer were investigated. In order to determine the effect of a spacer group between a drug and a carrier polymer on the antitumor activity, we employed two different spacer groups, a lysosomal digestible tetrapeptide (Gly-Phe-Leu-Gly) and a simple hydrophobic pentamethylene to immobilize DXR molecules to CM-chitin. The cytotoxic activity of the conjugates obtained were investigated against four kinds of tumor cell lines, p388D1 lymphocytic leukemia, L1210 leukemia, HLE human hepatoma and Hela utrocervical carcinoma cell in vitra The CM-chitin/Gly-Phe-Leu-Gly/DXR conjugate 1 with lysosomal digestible tetrapeptide spacer groups showed slightly higher in vitro cytotoxic activity against these tumor cells than CM-chitin/C5/DXR conjugate 2 with a simple pentamethylene spacer group. However, the cytotoxic activity of these two conjugates was weaker than that of the free DXR. The survival effects of these conjugates were investigated against p388 lymphocytic leukemia bearing mice in vivo by intraperitoneal (i.p.) implantation and intravenous (i.v.) injection. Although these conjugates did not show very high cytotoxic activities in vitro compared with the free DXR, conjugate 1, with the lysosomal digestible tetrapeptide spacer groups, exhibited survival effects against p388 lymphocytic leukemia in mice i.p./i.v. However, conjugate 2, with the simple pentamethylene spacer group, did not show any survival effects under the same conditions. These conjugates did not display an acute toxicity in the high dose ranges.

Synthesis of 6-O-carboxymethylchitin immobilizing doxorubicins through tetrapeptide spacer groups and its enzymatic release behavior of doxorubicin in vitro

Chitin is a non-toxic biodegradable polysaccharide. 6-O-Carboxymethylchitin (CM-chitin) is a water-soluble chitin derivative. In order to provide a water-soluble macromolecular prodrug of doxorubicin (DXR) reducing the side-effects and exhibiting high antitumor activity, the fixation of DXRs to CM-chitin through covalent bonds was carried out. Especially, a lysosomally digestible tetrapeptide (Gly-Phe-Leu-Gly) was used as spacer groups between CM-chitin and DXRs. In this paper, two kinds of conjugates, CM-chitin/Gly-Phe-Leu-Gly/DXR conjugate 5 having lysosomally digestible tetrapeptide spacer groups and CM-chitin/C5/DXR conjugate 6 having pentamethylene spacer groups, were synthesized. The effect of introduction of the spacer groups on the release behavior of DXR from the conjugate was investigated. The conjugate 5 having tetrapeptide spacer groups showed a distinct increase in the release rate of DXR in the presence of the lysosomal enzyme cathepsin B at 37°C in vitro; however, the conjugate 6 did not show such specific release behavior.