Phase structures of a hydrated anionic phospholipid composition containing cationic dendrimers and pegylated lipids

The effect of 4th generation poly(amidoamine) dendrimer (4G PAMAM) present in an anionic phospholipid composition, consisting of hydrogenated soyphosphatidylcholine (HSPC), cholesterol (CH), dicetyl phosphate (DCP), and poly(ethylene glycol) (Mw approximately 2000) derivatized phosphatidylethanolamine (PEG2000-PE), on the hydration and liquid crystalline structure formation was investigated. The optical and polarized light microscopies of the liposomal dispersion obtained from the hydrated lipid composition show two types of birefringent structures (mesophases): plastic, wormlike microstructures and conventional, over-elongated lamellae. Differential scanning calorimetry (DSC) shows an increase in the liquid crystalline phase transition (Tg) of the lipid composition from 60 to 94 degrees C with increasing 4G PAMAM concentrations from 0 to 0.011 mM, respectively. The Tg values of the two microstructures were 68 and 84 degrees C, respectively, indicating that the plastic microstructures were 4G PAMAM/DCP-complexes-rich (alpha mesophases) and the conventional and elongated lamellae were dendrimer-doped HSPC/CH-rich microstructures (beta mesophases). Optical microscopy shows that the alpha mesophases convert into various other types of vesicular structures such as giant unilamellar vesicles and biliquid foams, upon heating above the phase transition temperature of the lipid composition (approximately 60-65 degrees C). The microstructure transformation is a result of an osmotic influx of water and the detergent action of PEG2000-PE present in the lipid composition. The transmission electron microscopy (TEM) images of the liposomal dispersion show particles embedding circular transparent domains that exactly correlate to the theoretical 4G PAMAM/DCP complex sizes, thus, providing evidence of 4G PAMAM interspersed within the two mesophases. Small-angle X-ray scattering (SAXS) measurements indicate that the alpha mesophases are a dendrimer-interlinked, symmetrically undulated lamellar phase and the beta mesophases are dendrimer-doped, occasionally kinked lamellae. An increase in dendrimer concentration in the lipid composition was found to decrease interlamellar spacing. On the basis of optical microscopy, DSC, TEM, and SAXS data, a model of dendrimer-doped mesophase structure and lamellae fusion is proposed. This investigation provides new self-assembled materials for drug/gene delivery and supplements the understanding of mechanisms involved in various biological processes such as membrane fusion, transmembrane permeation, and endocytosis.     

Synthesis of (±) lupinifoun, di-o-methyl xanthohumol and isoxanthohumol and related compounds

Nuclear prenylation of naringenin (7) with 2-methylbut-3-en-2-ol in the presence of boron trifluoride etherate gives a mixture of 6-C-prenyl-(11), 8-C-prenyl-(15) and 6,8-di-C-prenyl-(8) derivatives. On formic acid cyclisation, 11 yielded two monodihydropyrans (12 and 13), but 15 afforded only one viz 16; similarly 8 formed the bisdihydropyran 10. Methylation of 8-C-prenyl naringenin (15) with Me₂SO₄ resulted in the formation of di-O-methyl derivatives of xanthohumol (22) and isoxanthohumol (23).

Cyclodehydrogenation of 6,8-di-C-prenyl-naringenin (8) with DDQ gave a mono-C-prenyl-2,2-dimethylpyran (1) corresponding to (±) lupinifolin. The angular isomer (2) was also formed. The structure of natural flemichin-B therefore needs further consideration. Similarly, cyclodehydrogenation of 6-C-(11)- and 8-C-prenyl-(15) naringenins afforded the corresponding linear (24) and angular (25) derivatives which have been characterized by conversion into known chalcones 26 and 27 by O-methylation.     

Electric field gradient at the Hf site and the phase transition in HfV2

The electric quadrupole interaction at the Hf site in the cubic HfV₂ compound, which shows lattice instability when cooled below 120 K, has been studied using the 482 keV (5/2⁺) state in¹⁸¹Ta. The time differential perturbed angular correlation (TDPAC) studies involving (133+136)-482 keV - cascade at room temperature show that only a fraction of¹⁸¹Ta nuclei see a cubic symmetry while the remaining experience a weak, randomly oriented, electric quadrupole interaction described by a Gaussian frequency distribution with _Q=6.1±1.0 Mrad/sec and the relative width =0.5. There is a dramatic change in TDPAC pattern indicating a phase transition when the compound is cooled down to 77 K. At this temperature the quadrupole interaction frequency is found to be _Q=40.6±3.0 Mrad/sec with =0.35. The experimentally observed EFG both at the Hf and the V sites are compared to the theoretical estimates based on point charge model.     

Ionic discotic liquid crystals: synthesis and characterization of pyridinium bromides containing a triphenylene core

Five novel pyridinium salts tethered with hexaalkoxytriphenylene molecules were synthesized by the quaternization of pyridine with ω-bromo-substituted triphenylene derivatives. Their chemical structures were determined by ¹H NMR, ¹³C NMR, IR, UV spectroscopy and elemental analysis. The thermotropic liquid crystalline properties of these salts were investigated by polarizing optical microscopy and differential scanning calorimetry. These triphenylene-based pyridinium salts with bromide as counterion were found to be mesomorphic over a wide temperature range.     

Mössbauer study on thermal decomposition of ammonium tris (malonato) ferrate (III) tetrahydrate

Thermal decomposition of ammonium tris (malonato) ferrate (III) tetrahydrate, i. e. (NH₄)₃[Fe(CH₂C₂O₄)₃]·4H₂O has been studied up to 973 K in static air atmosphere employing Mössbauer and infrared spectroscopies, and non-isothermal techniques (TG, DTG, DTA). The anhydrous complex decomposes into an iron (II) intermediate at 453 K. The iron (II) species on further heating is reoxidized to -Fe₂O₃ as the final thermolysis product. An increase in particle size of -Fe₂O₃ with increasing decomposition temperature has been observed. The results are compared with the analogous oxalate complex.     

New pyridine carboxamide ligands and their complexation to copper(II). X-Ray crystal structures of mono-, di, tri- and tetranuclear copper complexes

Seven new pyridine dicarboxamide ligands H2L(1-7) have been synthesised from condensation reactions involving pyridine-2,6-dicarboxylic acid (H2dipic), pyridine-2,6-dicarbonyl dichloride or 2,6-diaminopyridine with heterocyclic amine or carboxylic acid precursors. Crystallographic analyses of N,N'-bis(2-pyridyl)pyridine-2,6-dicarboxamide monohydrate (H2L8 x H2O), N,N'-bis[2-(2-pyridyl)methyl]pyridine-2,6-dicarboxamide and N,N'-bis[2-(2-pyridyl)ethyl]pyridine-2,6-dicarboxamide monohydrate revealed extensive intramolecular hydrogen bonding interactions. 2,6-Bis(pyrazine-2-carboxamido)pyridine (H2L6) and 2,6-bis(pyridine-2-carboxamido)pyridine (H2L7) reacted with copper(II) acetate monohydrate to give tricopper(II) complexes [Cu3(L)2(mu2-OAc)2]. X-Ray crystallography confirmed deprotonation of the amidic nitrogen atoms and that the (L6,7)2- ligands and acetate anions hold three copper(II) ions in approximately linear fashion. H2L8. Reacted with copper(II) tetrakis(pyridine) perchlorate to give [Cu(L8)(OH2)]2 x 2H2O, in which (L8)2- was tridentate through the nitrogen atoms of the central pyridine ring and the deprotonated carboxamide groups at one copper centre, with one of the terminal pyridyl rings coordinating to the other copper atom in the dimer. The corresponding reaction using H2L7 gave [Cu3(L7)2(py)2][ClO4]2, which transformed during an attempted recrystallisation from ethanol under aerobic conditions to a tetracopper(II) complex [Cu4(L7)2(L7-O)2].     

Diphenic acid as a selective reagent for the amperometric determination of thorium(IV)

Th(IV) has been titrated amperometrically at an applied e.m.f of −1.0 V (dropping mercury electrode vs. SCE) with diphenic acid (neutralized with sodium hydroxide). Th(IV) in the range 8.0–60.0 mg/100ml can be determined with an error of ±0.5%. A number of foreign ions including Ce(IV), Zr(IV), La(III), U(IV), U(VI) do not interfere even if present in excess but traces of Ti(IV) do. The method is rapid and selective and has been used for the determination of Th(IV) in monazite sand.     

ENERGETICS OF DNA REPAIR IN UV-IRRADIATED PERIPHERAL BLOOD LEUKOCYTES FROM CHRONIC MYELOID LEUKAEMIA PATIENTS

Abstract— The relationship between energy metabolism and UV-induced (251 nm) DNA repair has been investigated in leukocytes obtained from peripheral blood of chronic myeloid leukaemia patients. Energy supply was modulated by using inhibitors of respiratory (antimvcin-A) and glycolytic (2-deoxy-o-glucose and other glucose analogues) pathways for adenosine-triphosphatc (ATP) production. DNA repair was measured by the unscheduled DNA synthesis technique. Parameters of energy metabolism like glucose utilization. lactate production and ATP content of cells. were measured under similar experimental conditions. The observations made indicate the following results: (1) ATP for DNA repair can be supplied by the respiratory and/or by the glycolytic pathway. (2) In the absence of respiration, the rate of glycolysis bears a linear correlation with DNA repair. (3) A minimum threshold rate of ATP-production is necessary for DNA repair.     

Total synthesis of rutamycin B and oligomycin C

The asymmetric synthesis of the macrolide antibiotics (+)-rutamycin B (1) and (+)-oligomycin C (2) is described. The approach relied on the synthesis and coupling of the individual spiroketal fragments 3a and 3b with the C1-C17 polyproprionate fragment 4. The preparation of the spiroketal fragments was achieved using chiral (E)-crotylsilane bond construction methodology, which allowed the introduction of the stereogenic centers prior to spiroketalization. The present work details the synthesis of the C19-C28 and C29-C34 subunits as well as their convergent assembly through an alkylation reaction of the lithiated N,N-dimethylhydrazones 6 and 8 to afford the individual linear spiroketal intermediates 5a and 5b, respectively. After functional group adjustment, these advanced intermediates were cyclized to their respective spiroketal-coupling partners 40 and 41. The requisite polypropionate fragment was assembled in a convergent manner using asymmetric crotylation methodology for the introduction of six of the nine-stereogenic centers. The use of three consecutive crotylation reactions was used for the construction of the C3-C12 subunit 32. A Mukaiyama-type aldol reaction of 35 with the chiral alpha-methyl aldehyde 39 was used for the introduction of the C12-C13 stereocenters. This anti aldol finished the construction of the C3-C17 advanced intermediate 36. A two-carbon homologation completed the construction of the polypropionate fragment 38. The completion of the synthesis of the two macrolide antibiotics was accomplished by the union of two principal fragments that was achieved with an intermolecular palladium-(0) catalyzed cross-coupling reaction between the terminal vinylstannanes of the individual spiroketals 3a and 3b and the polypropionate fragment 4. The individual carboxylic acids 46 and 47 were cyclized to their respective macrocyclic lactones 48 and 49 under Yamaguchi reaction conditions. Deprotection of these macrolides completed the synthesis of the rutamycin B and oligomycin C.     

High-order one-step P-stable methods for the numerical integration of periodic initial value problems

Using Lobatto nodes, one-step methods of order six and eight have been obtained for the second-order differential equation y″ = f(x, y), y(x₀) = y₀, y′(x₀) = y′₀. The methods are shown to be P-stable. If

, then at each integration step a system of dimension 3s, 4s, respectively, has to be solved. The numerical results, for two problems, obtained by using these methods are given in the end.