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Crystalline Compounds (crystalline + compound)
Selected AbstractsA solid-state approach to enable early development compounds: Selection and animal bioavailability studies of an itraconazole amorphous solid dispersionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2010David Engers Abstract A solid-state approach to enable compounds in preclinical development is used by identifying an amorphous solid dispersion in a simple formulation to increase bioavailability. Itraconazole (ITZ) was chosen as a model crystalline compound displaying poor aqueous solubility and low bioavailability. Solid dispersions were prepared with different polymers (PVP K-12, K29/32, K90; PVP VA S-630; HPMC-P 55; and HPMC-AS HG) at varied concentrations (1:5, 1:2, 2:1, 5:1 by weight) using two preparation methods (evaporation and freeze drying). Physical characterization and stability data were collected to examine recommended storage, handling, and manufacturing conditions. Based on generated data, a 1:2 (w/w) ITZ/HPMC-P dispersion was selected for further characterization, testing, and scale-up. Thermal data and computational analysis suggest that it is a possible solid nanosuspension. The dispersion was successfully scaled using spray drying, with the materials exhibiting similar physical properties as the screening samples. A simple formulation of 1:2 (w/w) ITZ/HPMC-P dispersion in a capsule was compared to crystalline ITZ in a capsule in a dog bioavailability study, with the dispersion being significantly more bioavailable. This study demonstrated the utility of using an amorphous solid form with desirable physical properties to significantly improve bioavailability and provides a viable strategy for evaluating early drug candidates. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3901,3922, 2010 [source] The Relationship Between 27Al Quadrupolar Parameters and AlF63, Octahedron Connectivity in Crystalline and Glassy Fluoroaluminates,EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 14 2007Monique Body Abstract 27Al SATRAS and MQ-MAS spectra were recorded for eight crystalline compounds, from the CaF2,AlF3 and BaF2,AlF3 binary and BaF2,CaF2,AlF3 ternary systems, and four glass compositions with different CaF2/BaF2/AlF3 contents. For the crystalline phases, the reconstruction of the spectra leads to the precise determination of the NMR parameters. For the glassy phases, the 27Al SATRAS spectra have been reconstructed using quadrupolar parameter distributions. The main finding of this study is the dependence of the quadrupolar frequency on the type of AlF63, octahedron connectivity. For crystalline phases the experimental ,Q values range between 75 kHz and 510 kHz for structures built up from isolated octahedra, and are between 560 kHz and 1250 kHz for structures built up from isolated chains of cis -connected octahedra, and are between 1530 kHz and 1580 kHz for structures built up from isolated chains of trans -connected octahedra. In the glassy phases the maximum of the quadrupolar frequency distribution shifts toward larger values and its width increases with increasing AlF3 content, and subsequently with the number of connected octahedra. The range of the ,Q values seems to indicate that when the octahedra are connected, cis connections occur most frequently. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Generation and Reactions of Overcrowded Diaryldilithiostannane and DiaryldipotassiostannaneEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 21 2005Tomoyuki Tajima Abstract Exhaustive reduction of an overcrowded dibromostannane bearing two bulky aromatic substituents, Tbt(Dip)SnBr2 {Tbt = 2,4,6-tris[bis(trimethylsilyl)methyl]phenyl; Dip = 2,6-diisopropylphenyl}, with an excess amount of lithium naphthalenide in THF at ,78 °C gave the corresponding dilithiostannane, Tbt(Dip)SnLi2, the generation of which was confirmed by trapping experiments with some electrophiles together with 119Sn and 7Li NMR spectroscopy. The diaryldilithiostannane was found to be stable in solution under an inert gas below ,25 °C. The potassium analogue, Tbt(Dip)SnK2, was also generated by the reduction of the dibromostannane in THF at ,78 °C by the use of KC8 as a reductant. The reactions of dilithiostannane and dipotassiostannane obtained with o -dibromobenzene did not give a stannacyclopropabenzene derivative but an unexpected cyclization product, a stannacyclobutabenzene derivative, in contrast to thereactions of the corresponding dilithiosilane and dilithiogermane, Tbt(Dip)ELi2 (E = Si, Ge), with o -dibromobenzene leading to the formation of the corresponding metallacyclopropabenzenes as stable crystalline compounds. A preliminary result of the synthesis of a tin,tellurium double-bond compound from the dilithiostannane is also presented. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Enantioselective Preparation of 2-Aminomethyl Carboxylic Acid Derivatives: Solving the ,2 -Amino Acid Problem with the Chiral Auxiliary 4-Isopropyl-5,5-diphenyloxazolidin-2-one (DIOZ).HELVETICA CHIMICA ACTA, Issue 6 2003Preliminary Communication Multigram amounts of suitably protected ,2 -amino acids with 17 of the 20 proteinogenic side chains are prepared by diastereoselective reactions of Li, B, or Ti enolates of the corresponding 3-acyl-4-isopropyl-5,5-diphenyloxazolidin-2-ones (acyl-DIOZ; 1) with appropriate electrophiles (amidomethylation, hydroxyalkylation, (benzyloxycarbonyl)methylation) in yields of 55,90% and with diastereoselectivities of 80 to >97% (Scheme). The primary products 2,8 thus obtained are converted to protected ,2 -amino acids by standard procedures (Table,1). Many of the DIOZ derivatives are highly crystalline compounds (31 X-ray crystal structures in Table,2). The chiral auxiliary DIOZ, readily prepared in either enantiomeric form, is recovered with high yield. [source] Chemical bonding in ternary magnesium hydridesINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 3 2003Emilio Orgaz Abstract The electronic structure of various alkali and alkaline,earth magnesium-based hydrides was investigated in detail. These types of crystalline compounds show MgH4 or MgH6 units ordered within a light-metal framework. We investigated the nature of the chemical bonding in these units by means of quantum chemical calculations of several related clusters. The properties of the charge density of the clusters, within the framework of the theory of atoms in molecules, was analyzed. A further set of computations of the band structure of the solid hydrides was conducted using a state-of the-art density functional-based method and the mechanism of stabilization of the MgH units is discussed. It was found that the properties obtained at the molecular level correlate well with those of the solid crystals, indicating the molecular nature of the extended systems in which the units MgHx, x = 4, 6, are stabilized by means of MgH closed-shell interactions. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 150,164, 2003 [source] Human skin permeation of ,8 -tetrahydrocannabinol, cannabidiol and cannabinolJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2004Audra L. Stinchcomb ABSTRACT The purpose of this study was to quantify the in-vitro human skin transdermal flux of ,8 -tetrahydrocannabinol (,8 -THC), cannabidiol (CBD) and cannabinol (CBN). These cannabinoids are of interest because they are likely candidates for transdermal combination therapy. Differential thermal analysis and in-vitro diffusion studies with human tissue were completed for the compounds. Heats of fusion, melting points and relative thermodynamic activities were determined for the crystalline compounds, CBD and CBN. Flux, permeability, tissue concentration and lag times were measured in the diffusion experiments. CBN had a lower heat of fusion and corresponding higher calculated relative thermodynamic activity than CBD. Ethanol concentrations of 30 to 33% significantly increased the transdermal flux of ,8 -THC and CBD. Tissue concentrations of ,8 -THC were significantly higher than for CBN. Lag times for CBD were significantly smaller than for CBN. The permeabilities of CBD and CBN were 10-fold higher than for ,8 -THC. Combinations of these cannabinoids with ethanol will be further studied in transdermal patch formulations in vitro and in vivo, as significant flux levels of all the drugs were obtained. CBD, the most polar of the three drugs, and other more polar cannabinoids will also be the focus of future drug design studies for improved transdermal delivery rates. [source] [5-(p -alkoxy)phenyl-10, 15, 20-tri-phenyl] porphyrin and their rare earth complex liquid crystallineJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 4 2007Miao Yu Abstract Three series of porphyrin liquid crystalline compounds, [5-(p -alkoxy)phenyl-10, 15, 20-tri-phenyl] porphyrin and their rare earth complexes (Tb (III), Dy (III), Er (III), Yb (III)), with a hexagonal columnar discotic columnar(Colh) phase have been synthesized. These compounds were characterized by elemental analysis, molar conductances, UV-visible spectra, infrared spectra, luminescence spectra, and cyclic voltammetry. These compounds exhibit more than one mesophases, which transition points of temperature change from ,33.6 to 16.0,°C, and transition points of temperature for isotropic liquid also increase from 4.9 to 38.2,°C, with increasing chain length. Their surface photovoltage (SPV) response have also been investigated by the means of surface photovoltage spectroscopy (SPS) and field-induced surface photovoltage spectroscopy (EFISPS). It was found that their SPV bands are analogous with the UV-visible absorption spectra and derived from the same transition. Copyright © 2007 John Wiley & Sons, Ltd. [source] Main-Chain Liquid Crystalline Polymers Based on Bis-Etherified 9,9-Dihexyl-2,7-bis(4,-hydroxy-1,1,-biphen-4-yl)fluorenesMACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 13 2007Tanja Sovi Abstract A series of liquid crystalline compounds based on 2,7-bis(biphenyl)fluorenes was synthesised by a Suzuki cross-coupling reaction and subsequent etherification with different bromoalkenes. By simple variations of the chain lengths the temperature range in which the nematic mesophase is present could be tuned. The described approach offers the possibility of covalent incorporation of the mesogens into polymers via olefin metathesis techniques, resulting in enlarged stability of the mesophase. Monomers and polymers could be easily aligned on rubbed polyimide substrates as revealed by polarised absorption spectroscopy. [source] Stereoselective Complex Formation between Polybutadiene and Cyclodextrins in BulkMACROMOLECULAR RAPID COMMUNICATIONS, Issue 11 2008Yukari Kuratomi Abstract Polybutadienes (PBs) are found to form inclusion complexes with cyclodextrins (CDs) stereoselectively to give crystalline compounds in bulk. These complexes have been isolated and characterized by means of 1H NMR and 13C CP/MAS NMR spectroscopy, and X-ray diffraction. Although , -CD did not form inclusion complexes with any kinds of PBs in aqueous solutions, , -CD did form inclusion complexes with PBs having 1,4- cis - and 1,4- trans -butadiene units in bulk by heating at 100,°C. On the other hand, PB having 79% of a 1,2-structure did not form inclusion complexes with , -CD. The yield of the inclusion complexes increases with an increase in the content of the 1,4- cis -structure of PB and decreases with the molecular weights of the PBs. [source] Structural effects on the solid-state photodimerization of 2-pyridone derivatives in inclusion compoundsACTA CRYSTALLOGRAPHICA SECTION C, Issue 7 2009Marina Telzhensky The structures of six crystalline inclusion compounds between various host molecules and three guest molecules based on the 2-pyridone skeleton are described. The six compounds are 1,1,-biphenyl-2,2,-dicarboxylic acid,2-pyridone (1/2), C14H10O4·2C5H5NO, (I,a), 1,1,-biphenyl-2,2,-dicarboxylic acid,4-methyl-2-pyridone (1/2), C14H10O4·2C6H7NO, (I,c), 1,1,-biphenyl-2,2,-dicarboxylic acid,6-methyl-2-pyridone (1/2), C14H10O4·2C6H7NO, (I,d), 1,1,6,6-tetraphenyl-2,4-hexadiyne-1,6-diol,1-methyl-2-pyridone (1/2), C30H22O2·2C6H7NO, (II,b), 1,1,6,6-tetraphenyl-2,4-hexadiyne-1,6-diol,4-methy-2-pyridone (1/2), C30H22O2·2C6H7NO, (II,c), and 4,4,,4,,-(ethane-1,1,1-triyl)triphenol,6-methyl-2-pyridone,water (1/3/1), C20H18O3·3C6H7NO·H2O, (III,d). In two of the compounds, (I,a) and (I,d), the host molecules lie about crystallographic twofold axes. In two other compounds, (II,b) and (II,c), the host molecules lie across inversion centers. In all cases, the guest molecules are hydrogen bonded to the host molecules through O,H...O=C hydrogen bonds [the range of O...O distances is 2.543,(2),2.843,(2),Å. The pyridone moieties form dimers through N,H...O=C hydrogen bonds in five of the compounds [the range of N...O distances is 2.763,(2),2.968,(2),Å]. In four compounds, (I,a), (I,c), (I,d) and (II,c), the molecules are arranged in extended zigzag chains formed via host,guest hydrogen bonding. In five of the compounds, the guest molecules are arranged in parallel pairs on top of each other, related by inversion centers. However, none of these compounds underwent photodimerization in the solid state upon irradiation. In one of the crystalline compounds, (III,d), the guest molecules are arranged in stacks with one disordered molecule. The unsuccessful dimerization is attributed to the large interatomic distances between the potentially reactive atoms [the range of distances is 4.027,(4),4.865,(4),Å] and to the bad overlap, expressed by the lateral shift between the orbitals of these atoms [the range of the shifts from perfect overlap is 1.727,(4),3.324,(4),Å]. The bad overlap and large distances between potentially photoreactive atoms are attributed to the hydrogen-bonding schemes, because the interactions involved in hydrogen bonding are stronger than those in ,,, interactions. [source] Calcite microcrystals in the pineal gland of the human brain: First physical and chemical studiesBIOELECTROMAGNETICS, Issue 7 2002Simon Baconnier Abstract A new form of biomineralization has been studied in the pineal gland of the human brain. It consists of small crystals that are less than 20 ,m in length and that are completely distinct from the often observed mulberry-type hydroxyapatite concretions. A special procedure was developed for isolation of the crystals from the organic matter in the pineal gland. Cubic, hexagonal, and cylindrical morphologies have been identified using scanning electron microscopy. The crystal edges were sharp whereas their surfaces were very rough. Energy dispersive spectroscopy showed that the crystals contained only the elements calcium, carbon, and oxygen. Selected area electron diffraction and near infrared Raman spectroscopy established that the crystals were calcite. With the exception of the otoconia structure of the inner ear, this is the only known nonpathological occurrence of calcite in the human body. The calcite microcrystals are probably responsible for the previously observed second harmonic generation in pineal tissue sections. The complex texture structure of the microcrystals may lead to crystallographic symmetry breaking and possible piezoelectricity, as is the case with otoconia. It is believed that the presence of two different crystalline compounds in the pineal gland is biologically significant, suggesting two entirely different mechanisms of formation and biological functions. Studies directed toward the elucidation of the formation and functions, and possible nonthermal interaction with external electromagnetic fields are currently in progress. Bioelectromagnetics 23:488,495, 2002. © 2002 Wiley-Liss, Inc. [source] Dynamic Supramolecular Polymers Based on Benzene-1,3,5-tricarboxamides: The Influence of Amide Connectivity on Aggregate Stability and Amplification of ChiralityCHEMISTRY - A EUROPEAN JOURNAL, Issue 3 2010Patrick Abstract N-Centred benzene-1,3,5-tricarboxamides (N-BTAs) composed of chiral and achiral alkyl substituents were synthesised and their solid-state behaviour and self-assembly in dilute alkane solutions were investigated. A combination of differential scanning calorimetry (DSC), polarisation optical microscopy (POM) and X-ray diffraction revealed that the chiral N-BTA derivatives with branched 3,7-dimethyloctanoyl chains were liquid crystalline and the mesophase was assigned as Colho. In contrast, N-BTA derivatives with linear tetradecanoyl or octanoyl chains lacked a mesophase and were obtained as crystalline compounds. Variable-temperature infrared spectroscopy showed the presence of threefold, intermolecular hydrogen bonding between neighbouring molecules in the mesophase of the chiral N-BTAs. In the crystalline state at room temperature a more complicated packing between the molecules was observed. Ultraviolet and circular dichroism spectroscopy on dilute solutions of N-BTAs revealed a cooperative self-assembly behaviour of the N-BTA molecules into supramolecular polymers with preferred helicity when chiral alkyl chains were present. Both the sergeants-and-soldiers as well as the majority-rules principles were operative in stacks of N-BTAs. In fact, the self-assembly of N-BTAs resembles closely that of their carbonyl (CO)-centred counterparts, with the exception that aggregation is weaker and amplification of chirality is less pronounced. The differences in the self-assembly of N- and CO-BTAs were analysed by density functional theory (DFT) calculations. These reveal a substantially lower interaction energy between the monomeric units in the supramolecular polymers of N-BTAs. The lower interaction energy is due to the higher energy penalty for rotation around the PhNH bond compared to the PhCO bond and the diminished magnitude of dipole,dipole interactions. Finally, we observed that mixed stacks are formed in dilute solution when mixing N-BTAs and CO BTAs. [source] Bis-Chelated Imine-Alkoxytitanium Complexes: Novel Chiral Dopants with High Helical Twisting Power in Liquid CrystalsCHEMISTRY - A EUROPEAN JOURNAL, Issue 11 2005Manfred Braun Prof. Dr. Abstract Enantiomerically and diastereomerically pure bis-chelated imine-alkoxytitanium complexes 6 and 7 have been synthesized and used as chiral dopants for converting nematic into cholesteric phases. The dopants were tested in mainly commercially available nematic liquid crystalline compounds or mixtures: LC1 (BASF), ZLI-1695 and ZLI-1840 (Merck), as well as N -(4-methoxybenzylidene)-4,-butylaniline (MBBA). The values of the helical twisting power (HTP) were determined by the Grandjean,Cano method. Exceptionally high helical twisting powers were obtained. Thus, the titanium complex 6,h displayed a HTP value of 740 ,m,1 in MBBA, the highest HTP value reported. The helical twisting power has been found to depend strongly on the structure of the nematic phase and the substitution pattern of the chiral ligand in the titanium complexes 6 and 7. Crystal structure analysis of 6,f confirmed the A,R,R configuration of the metal complex. The chiral imine ligands 4 and 5 were derived from the regioisomeric amino alcohols 1 and 2. [source] | |||||||||||||