Side-chain Units Research Articles

Bioreducible poly(amido amine)s with oligoamine side chains: Synthesis, characterization, and structural effects on gene delivery

A group of bioreducible poly(amido amine)s containing multiple disulfide linkages in main chain and oligoamines in side chain ( SS–PAOAs) were prepared by Michael-type polyaddition of N-tert-butyloxycarbonyl ( N-Boc) protected oligoamine to the disulfide-containing cystaminebisacrylamide, followed by deprotection of the Boc-protective groups. These linear polymers show strong DNA condensation capability at low N/P ratios. The chemical structure of oligoamine side chains ( i.e. amine type and amino spacer length) in the SS–PAOAs has a distinct effect on their buffer capacity, transfection efficiency and toxicity profile. The SS–PAOAs containing secondary amino functions in the side chain show high buffer capacities and are able to transfect COS-7 cells in vitro at low N/P ratios, with transfection efficiencies similar or even higher than those of 25 kDa branched pEI, along with very low cytotoxicity as determined by XTT assay. Increase of the alkyl spacer from ethylene to propylene between the amino units in side chains results in significant lower transfection and increased toxicity. This study presents detailed factors influencing the relationship between structure and gene delivery properties and may provide helpful insights for the further development of safe and efficient non-viral vectors.

Comb macromolecules with attracting functional groups in side chains

The conformational behavior of a single comb-shaped macromolecule with associating groups in side chains was studied by means of Monte Carlo simulation. The side chains contain two types of units, type A representing nonfunctional units (main chain units are likewise classified with type A) and type B representing functional (attracting) units. As a result of an increase in attraction energy between associating groups, the transition of the macromolecule from coil to the globule state takes place. The coil-globule transition is accompanied by segregation of unlike units; as a result, the globule has a complex structure: the core of the globule is formed by attracting groups of side chains, and the envelope is formed from soluble units of both main and side chains. The dependence of the size and shape of the macromolecule on its structural parameters, such as the length of main and side chains and the graft density of side chains, and on the position of the functional groups in side chains was examined. Along with the single globule, conformations in which the attracting units of side chains formed several bead globules were observed.

A high-viscosity glycoglucuronomannan from the gum exudate of Vochysia thyrsoidea: Comparison with those of other Vochysia spp.

The polysaccharide (VTh) extracted with water from the gum exudate of the trunk Vochysia thyrsoidea gave a solution of high viscosity and was homogeneous, with M w 92.5 × 10 3 and d n/d c = 0.212. Partial hydrolysis gave a main chain of →4)-β- d-Glc pA-(1 → 2)-α- d-Man p-(1→ repeating groups. Since VTh contained 24% GlcA, neither its monosaccharide ratio (GC–MS of alditol acetates) nor methylation results were accurate. It was therefore carbodiimide-reduced to CR 3VTh, which contained Ara, Xyl, Man, Gal, and Glc in a molar ratio of 28:4:29:19:25: methylation analysis showed mainly nonreducing end-units of Ara f (25%), Ara p (8%), and Gal p (8%) and side-chain units of 3- O- (6%) and 3,4-di- O-subst. Gal p (12%). Main-chain units of Man p were 2,3-di- O-substituted (17%), showing that they were substituted at O-3 by side chains, but there was less side-chain substitution of Glc p units, which were mainly 4- O-substituted (12%). Most Ara f units in VTh and CR 3VTh were single nonreducing end-units, and were present in groups of α- l-Ara f-(1 → 3)- d-Man p and α- l-Ara f-(1 → 3)-[α- l-Ara f-(1 → 4)]-β- d-Gal p-(1 → 3)-α- d-Man p. Other degradation products derived from VTh agreed with this structure. The degree of side-chain substitution of the same main chain was greatest with the gum exudate polysaccharide of V. tucanorum, and progressively less with those of V. thyrsoidea, and V. lehmannii. High-viscosity aqueous solutions were formed by the gum of V. thyrsoidea, in contrast with those of V. lehmannii and V. tucanorum.

Synthesis of Highly Functionalized Anthraquinones and Evaluation of Their Antitumor Activity

AbstractHighly functionalized anthraquinones which derive from the natural products mensacarcin, islandicin, and chrysophanol have been efficiently synthesized using a Diels–Alder reaction as key step. The introduction of the proposed pharmacophoric side chain unit has been achieved by an addition of an aryllithium species onto different aldehydes. Furthermore, the antitumor activity of these novel compounds has been studied by the in vitro growth inhibition of human lung carcinoma cells of line A549.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Synthesis and biological activity of saccharide based lipophilic siderophore mimetics as potential growth promoters for mycobacteria

Siderophores based on sugar backbones substituted at the 2,3,4- or 2,3,6 positions with hydroxamic or retro-hydroxamic acid chelating units were synthesized and characterized. The alkyl terminus of the iron-coordinating side chain units facilitate lipophilic interactions. Iron coordination properties and complex stability were investigated by ESI-MS and the CAS-Test. The results were correlated to structure activity relationships determined by microbial growth promotion studies under iron limited conditions using wild type strains and iron transport mutants of Mycobacterium smegmatis.

1P314 4-ジメチルアミノアゾベンゼンを側鎖として組み込んだ合成DNAの可視光応答性(バイオエンジニアリング,ポスター発表,第45回日本生物物理学会年会)

1P314 4-ジメチルアミノアゾベンゼンを側鎖として組み込んだ合成DNAの可視光応答性(バイオエンジニアリング,ポスター発表,第45回日本生物物理学会年会)

Side-chain pseudopolyrotaxanes by threading cucurbituril[6] onto quaternized poly-4-vinylpyridine derivative: Synthesis and properties

A novel side-chain pseudopolyrotaxanes 4 is synthesized from cucurbituril (CB[6]) and quaternized poly-4-vinylpyridine derivative 3 in water by simple stirring at room temperature. CB[6] beads are localized on hexamethylene units in side chains of 3 as found by NMR studies, and the hydrophobic and charge-dipole interactions are the driving force. The degree of threading (q/n, the average number of CB[6] beads per repeat recognition unit of 3) can be controlled from 0.2 to 1.0 by controlling the amount of CB[6] added. The reduced viscosity of pseudopolyrotaxanes in aqueous solution has smaller change with the change of the concentration or temperature, which is consistent with the hydrodynamic radius and more rigid chain conformation because of the threaded CB[6]. DLS results show the average hydrodynamic diameter (Dh) of the pseudopolyrotaxanes in solution increases with the increasing of CB[6] threaded. The pseudopolyrotaxanes have higher thermal stability and intensity of absorption band than the parent polymer 3 as found by TGA and UV–vis studies. The decomposition temperature and intensity of absorption increase with increasing amount of CB[6] threaded. The effect of NaI to pseudopolyrotaxanes is studied by the transmittance with UV–vis, and the result shows that NaI is the satisfied precipitant to the pseudopolyrotaxanes.

Side chain length dependence on supra-molecular structures in a series of aromatic polyimides having terminal 4-cyanobiphenyl liquid crystalline side chains

A series of newly designed polyimides, composed of aromatic polyimide backbones and methylene side chains with terminal 4-cyanobiphenyl groups, were synthesized based on the polycondensation of 3,3′,4,4′-biphenyl tetracarboxylic dianhydride (BPDA) with 2,2′-bis{ω-[4-(4-cyanophenyl)phenyoxy- n-alkoxycarbonyl]}-4,4′-biphenyl diamine ( nCBBP, where n is the number of methylene units in the side chains). We report our structural and morphological studies on this series of BPDA– nCBBP, which possesses n=7, 9, and 11 methylene units in the side chains. For these three polyimides, a nematic (N) phase was first formed at high-temperatures during cooling from the isotropic melt. The transition temperatures and enthalpies were cooling-rate independent as observed in differential scanning calorimetry. This N phase was further confirmed by the results of wide angle X-ray diffraction (WAXD) and polarized light microscopic experiments. At lower temperatures, ordered structures were formed. It was surprising that in the cases of BPDA– nCBBP ( n=7 and 9), triclinic lattices were observed; while in the case of BPDA-11CBBP, a hexagonal lattice was evident, as determined by 2D WAXD experiments. This indicated that by increasing the number of methylene units in the LC side chains, the individual chains (base unit) used in constructing these supra-molecular structures changed their packing symmetry. Namely, when the number of methylene units in the side chains was relatively low (i.e. the length is short), the individual chains were packed into a ribbon-like structure. However, when the side chain length is long enough, the individual chains exhibit cylindrical symmetry. Regardless of the lattice formed by the supra-molecular structures, they are all on the nanometer length scale.

Identification of a Ubiquinone-binding Site That Affects Autophosphorylation of the Sensor Kinase RegB

Rhodobacter capsulatus regulates many metabolic processes in response to the level of environmental oxygen and the energy state of the cell. One of the key global redox regulators of the cell's metabolic physiology is the sensor kinase RegB that controls the synthesis of numerous energy generation and utilization processes. In this study, we have succeeded in purifying full-length RegB containing six transmembrane-spanning elements. Exogenous addition of excess oxidized coenzyme Q1 is capable of inhibiting RegB autophosphorylation approximately 6-fold. However, the addition of reduced coenzyme Q1 exhibits no inhibitory effect on kinase activity. A ubiquinone-binding site, as defined by azidoquinone photo affinity cross-linking, was determined to lie within a periplasmic loop between transmembrane helices 3 and 4 that contains a fully conserved heptapeptide sequence of GGXXNPF. Mutation of the phenylalanine in this heptapeptide renders RegB constitutively active in vivo, indicating that this domain is responsible for sensing the redox state of the ubiquinone pool and subsequently controlling RegB autophosphorylation.

Variations of the P2 group in HIV-1 protease inhibitors containing a tertiary alcohol in the transition-state mimicking scaffold

A short synthetic protocol leading to HIV-1 protease inhibitors with a tertiary alcohol based transition-state mimicking unit and different P2 side chains has been developed.

Synthesis, characterization and properties of side-chain pseudopolyrotaxanes consisting of cucurbituril[6] and poly- N1-(4-vinylbenzyl)-1,4-diaminobutane dihydrochloride

Pseudopolyrotaxanes 3 is synthesized from cucurbituril[6] (CB[6]) and polymer 2 (poly- N 1-(4-vinylbenzyl)-1,4-diaminobutane dihydrochloride) in water by simple stirring at room temperature. The monomer 1, polymer 2 and pseudopolyrotaxanes 3 are characterized by 1H NMR, 13C NMR, FT-IR and elemental analysis. In 3, the CB[6] beads are localized on tetramethylene units in side chains of 2, and combine N + by noncovalent bonds. The degree of threading (number of CB[6] beads per repeat unit) can be controlled from 0 to 1.0 by controlling the amount of CB[6] added. The properties of polymer 2 and pseudopolyrotaxanes 3 are researched by TGA, X-ray powder diffraction (XRD), environment scanning electron microscope (ESEM) and potentiometric titrations. The pseudopolyrotaxanes have higher thermal stability and chain regularity than the parent polymer which are attributed to the bulkiness and the rigidity of the CB[6] threaded. The decomposition temperature and chain regularity of the pseudopolyrotaxanes increase with increasing amount of CB[6] threaded. The effects of salts (NaCl, NaBr or NaI) to pseudopolyrotaxanes are studied by the transmittance with UV–vis, and the results show that NaI is the satisfied precipitant to the pseudopolyrotaxanes. The surface morphologies of pseudopolyrotaxanes 3 observed by ESEM shows a series of spherical particle with different diameter. The results of potentiometric titrations show that the pseudopolyrotaxanes 3 have larger p K av and smaller n than polymer 2.

INORGANIC–ORGANIC HYBRID PHOTOREFRACTIVE MATERIALS BEARING THE BIFUNCTIONAL CHROMOPHORE

We prepared the photorefractive composite based on organic–inorganic hybrid materials containing charge-transporting molecules, second-order nonlinear optical chromophore, photosensitizer, and plasticizer either as a side chain unit or a guest molecule. New chromophore was synthesized to contain nonlinear optical chromophore and carbazole in one molecule. The functional chromophores were reacted to isocyanatotriethoxysilane to provide the functional precursor molecules. 2,4,7-Trinitrofluorenone (TNF) was added into the sol-gel materials to induce a charge-transfer complex. We also compared the gain coefficient of the photorefractive samples with the change of the concentration of the plasticizer, determined by two-beam coupling technique.

Accelerated Arene Ligand Exchange in the (Arene)Cr(CO)2L Series

Arene ligand exchange in the (eta(6)-arene)Cr(CO)(2)L series can be accelerated if the ligand L is an electronically unsymmetrical bidentate ligand. The system evaluated here employs derivatives of tris(pyrrolyl)phosphine as L. A series of 2-L'-substituted pyrroles was prepared, where the substituents include: L' = -SMe, -CH(2)SMe, -SPh, -CH(2)SPh, -SCF(3), -S-tBu, -CO(2)Me, -CONMe(2), -2-pyridinyl, and -PPh(2). Reaction with ClP(pyrrolyl)(2) gave a new series of phosphines, (2-L'-pyrrolyl)(pyrrolyl)(2)P. Each of these phosphines was converted to (arene)Cr(CO)(2)[P(2-L'-pyrrolyl)(pyrrolyl)(2)P) complexes. The substituents L'are proposed to provide temporary coordination to the Cr and to lower the barrier to arene exchange. The series was evaluated where the arene in the complex (departing) is benzene, fluorobenzene, toluene, o-xylene, m-xylene, or p-xylene and the incoming arene is C(6)D(6), chlorobenzene-d(5), anisole-d(8), fluorobenzene-d(5), toluene-d(8), o-xylene-d(10), m-xylene-d(10), p-xylene-d(10), or mesitylene-d(12). Most of the new complexes showed a significant increase in the rate of arene exchange due to the side chain unit L'. The strongest effects were seen with the examples where X = -CO(2)Me, -CONMe(2), and -(2-pyridinyl), allowing exchange with a half lifetime as low as 8 h/22 degrees C.

Relationships between Structures and Liquid Crystalline and Optical Properties in Combined-type Copolyisophthalates Having Nitro- and Methoxyazobenzene Units and Aliphatic Spacers in the Side Chain

Combined-type thermotropic liquid crystalline (LC) homo- and copolyisophthalates having nitro- and methoxyazobenzene units and three aliphatic spacers (hexamethylene, octamethylene and decamethylene) in the side chain and biphenyl unit in the main chain were prepared by melt polycondensation and relationships between polymer structures and LC and optical properties were discussed. Differential scanning calorimetry (DSC) measurements, optical texture observations using polarizing microscopy and powder X-Ray analyses indicated that the homopolyisophtalates with the nitroazobenzene unit form highly ordered smectic E phase and the other homo- and copolymers show less ordered smectic B or smectic C phase. The temperature ranges of smectic LC phases in the polymers decreased with increasing the methoxyazobenzene content. In these polymers, specific interaction such as electron donor–acceptor interaction between the nitro- and the methoxyazobenzene units plays no role in the formation and the stabilization of smectic LC phases. All the polymers displayed UV–vis absorption peak maxima on the basis of the azobenzenes or the biphenyl in solutions and in films, but no fluorescent properties were found, probably due to intra- and intermolecular quenching.

Preparation of Comb-like Organoboron Polymer Electrolyte without Generation of Salt

Abstract Comb-like organoboron polymer electrolytes bearing oligo(ethylene oxide) units both in main chain and side chain were prepared without genaration of salt, by means of dehydrocoupling polymerization of triethyleneglycol with hydroborane monomer having oligo(ethylene oxide) tail.

Synthesis and Characterization of Network Type Single Ion Conductors

New single ion conductors were synthesized by grafting the allyl group-containing lithium salt, lithium bis(allylmalonato)borate (LiBAMB), onto allyl group-containing comb-branch polyacrylate or polymethacrylate ethers by means of hydrosilylation. The highest ambient temperature conductivity of 3.5 × 10-7 S cm-1 was obtained for a polyacrylate ether-based single ion conductor containing eight EO units in the side chain and five EO units in the cross-linking side chain, to which the anion was fixed with a salt concentration of EO/Li = 20. For polyacrylate ether-based single ion conductors, an increase of chain length in both side chains and cross-linking anion chains favors an increase of ionic conductivity. The addition of 50 wt % EC/DMC (1/1, wt/wt) increased the ionic conductivity by more than 2 orders of magnitude due to both the increase in ionic mobility from the liquid phase and the increase in the concentration of free ions from the high dielectric constant of the solvent. The preliminary Li/Li cycling profiles of dry polyacrylate- and polymethacrylate ether-based single ion conductors are encouraging as almost no concentration polarization or relaxation was observed. The observed increase in cell potential with cycling is apparently due to an increase in the interfacial impedance associated with the SEI layer, and the cell failure is accompanied by the decomposition of the ester bond of the polyacrylate backbone.

Donor–acceptor polythiophene copolymers with tunable acceptor content for photoelectric conversion devices

The synthesis and characterization of a new series of substituted polythiophenes containing an electron acceptor anthraquinone moiety in the side chain are reported. The acceptor molar content was varied by the co-polymerization of both alkylthiophene and thiophene bearing anthraquinone monomers in different ratios. NMR analysis shows a good correlation between the monomer feed composition at the beginning of the polymerization and the actual unit composition of the backbone. The conjugation length and the chemical composition of the copolymers as a function of the molecular weight have been studied by size exclusion chromatography. Small angle X-ray scattering and UV-Vis absorption spectra have been used to monitor the degree of order and chain organization in the solid state. The materials exhibit a lamellar organization, in which the anthraquinone units of neighboring side chains are also organized to some degree in layered structures parallel to the polythiophene main chains. The photoluminescence measurements in solution suggest that, upon photoexcitation of the polythiophene backbone, the anthraquinone moieties act as electron acceptors and the conjugated backbone as electron donor. The tunability of the donor–acceptor ratio and the morphology in the solid state make these photoactive copolymers interesting candidates for organic photoelectric conversion devices.

Enantioseparation of dansyl amino acids on terguride‐based chiral selectors. Part I: Capillary electrophoretic separation

AbstractA method of separation of dansyl amino acid (Dns‐AA) enantiomers by capillary electrophoresis (CE) using terguride‐based chiral selectors (CSs) was developed using linear polyacrylamide coated capillaries. Due to the high UV absorption of all studied CSs, only the capillary was filled with CS, while the inlet and outlet vials contained buffer solution only. Conditions were found for baseline separation of all Dns‐AA under study. L‐Dns‐AAs were eluted prior to D‐Dns‐AAs on all studied CSs. Use of the optical antipode of allyl‐terguride resulted in reversal of elution order of all Dns‐AAs (the D‐form was eluted prior to the L‐form). The best enantioselectivity was achieved for hydroxyl group‐containing AAs, i. e. serine and threonine. This finding is in good agreement with the proposed mechanism of chiral recognition of these AAs determined by X‐ray studies. Seven CSs with different N(1)‐side chain units, five of them designed for the preparation of silica based HPLC chiral stationary phases, were tested for their ability to resolve enantiomers of Dns‐AAs. Different polarity and hydrophobicity of N(1)‐side chains of the CSs resulted in different CS mobilities, thus influencing the effective separation time in the capillary. 1‐(5‐Aminopentyl)‐terguride showed the best enantioseparation and resolution for the Dns‐AAs studied.

Molecular dynamics of chiral semi-crystalline poly( R)-(3-hydroxyalkanoates)

The inversion-recovery cross-polarization (IRCP) sequence used for measuring cross-relaxation time ( T CH) is modified to obtain signals that show exponential or spin-lock (SL) decay to zero. The new sequence may, therefore, be analogously abbreviated as SLCP. Poly( R)-(3-hydroxybutyrate- co-3-hydroxyhexanoate) {P(HB-HHx) (85:15)} is found to be more mobile than poly( R)-(3-hydroxybutyrate) {PHB} in the crystalline regions. The molecular-level evidence by solid state nuclear magnetic resonance (NMR) that the P(HB-HHx) chain is more flexible than PHB is echoed by the dynamic frequency sweep measurements of the biopolymer melts, which show that the PHB melt has an unusual rheological response with the dynamic loss moduli dominating the storage moduli at all frequencies. This is most likely to be caused by the local anisotropic melt structures due to the long persistence length of PHB in the melt. Upon cooling the PHB melt to the solid state, such high levels of anisotropy may be frozen into the solid causing lower chain mobility, and hence giving rise to lower toughness. The incorporation of longer side chain unit to the main chain gives rise to a dynamic rheological response in P(HB-HHx) similar to that of an isotropic melt. This is believed to be due to the enhanced chain flexibility, and hence reduced persistence length. This further allows P(HB-HHx) to be processed into a more uniform isotropic morphology, and hence with improved mechanical toughness.

Toward a Total Synthesis of Keramamide B

Important building blocks, the 2-bromo-5-hydroxytryptophan-oxazole unit, the α-keto-β-amino acid unit, and the side chain units, for the preparation of keramamide B were efficiently synthesized.