Structural characterization of heparins from different commercial sources

Seven commercial heparin active pharmaceutical ingredients and one commercial low molecular weight from different manufacturers were characterized with a view profiling their physicochemical properties. All heparins had similar molecular weight properties as determined by polyacrylamide gel electrophoresis (M _N, 10–11 kDa; M _W, 13–14 kDa; polydispersity (PD), 1.3–1.4) and by size exclusion chromatography (M _N, 14–16 kDa; M _W, 21–25 kDa; PD, 1.4–1.6). one-dimensional ¹H- and ¹³C-nuclear magnetic resonance (NMR) evaluation of the heparin samples was performed, and peaks were fully assigned using two-dimensional NMR. The percentage of glucosamine residues with 3-O-sulfo groups and the percentage of N-sulfo groups and N-acetyl groups ranged from 5.8–7.9%, 78–82%, to 13–14%, respectively. There was substantial variability observed in the disaccharide composition, as determined by high performance liquid chromatography (HPLC)-mass spectral analysis of heparin lyase I–III digested heparins. Heparin oligosaccharide mapping was performed using HPLC following separate treatments with heparin lyase I, II, and III. These maps were useful in qualitatively and quantitatively identifying structural differences between these heparins. The binding affinities of these heparins to antithrombin III and thrombin were evaluated by using a surface plasmon resonance competitive binding assay. This study provides the physicochemical and activity characterization necessary for the appropriate design and synthesis of a generic bioengineered heparin.     

Synthesis of an N-Acetylated Heparin Pentasaccharide and its anticoagulant activity in comparison with the heparin pentasaccharide with high anti-factor-Xa activity

The synthesis of tri-N-acetylated heparin pentasaccharide 2 is described. It was assembled from five suitably blocked monosaccharide units ( 3 – 7 ). Glucuronic-acid building block 4 was prepared from glucose by direct Jones oxidation of the 6-O-trityl derivative 18 . The resulting acid 16 was esterified to 17 in large mounts using methyl chloroformate/base. Trimethylsilyl bromide proved to be an excellent reagent for the hydrolysis of a prop-1-enyl glycoside ( 19 →21 ). The pentasaccharide 29 was obtained by a [2 + 2] + 1 synthesis, the glycosylation reactions furnished good to very good yields. The identity of protected oligosaccharides was confirmed by ¹H-NMR spectroscopy. Sequential deblocking of the pentasaccharide, O-sulfation, and N-acetylation gave 2 which was shown to exhibit ca. 600 times lower anticoagulant activity than pentasaccharide 1 .     

The Unique Antithrombin III Binding Domain of Heparin: A Lead to New Synthetic Antithrombotics

Heparin, a sulfated glycosaminoglycan, is well known for its anticoagulant effect mediated by the serine protease inhibitor antithrombin III (AT III). Heparin has been used clinically for more than half a century for the prophylaxis and treatment of venous thrombosis and thromboembolism. Up until the 1980s it was assumed that the biological activity of heparin was mainly caused by its polyanionic character. However, this paradigm was contradicted when it was discovered that part of the heparin polysaccharides contains a well-defined pentasaccharide domain that specifically binds and activates AT III. The specificity of the interaction between the characteristic pentasaccharide and AT III has become more obvious after the synthesis and biological testing of various heparin analogues. This article reviews the synthesis of the heparin pentasaccharide, some closely related counterparts, and some highly modified analogues. With the aid of molecular modeling and through “tailored” molecular modifications of the pentasaccharide, much knowledge has been gained concerning structure-activity relationships. On this basis not only have more potent and simplified derivatives been developed, but also the recognition between heparin and AT III can now be understood in greater detail at the molecular level.     

Qualitative analysis of enzymatic and chemical depolymerized low molecular weight heparins by UHPLC coupled with electrospray ionization quadrupole time‐of‐flight‐mass spectrometry

Complete heparin digestion with heparin lyase I and II results in a mixture of hexasaccharides and tetrasaccharides with 3‐O‐sulfo group‐containing glucosamine residues at their reducing ends. Because these tetrasaccharides are derived from antithrombin III‐binding sites of heparin, we examined whether this method could be applied to estimate the anticoagulant activity of heparin. Therefore, this paper presents a new low molecular weight heparin sample preparation method–chemical depolymerization. Qualitative analysis of the studied compounds and a comparison of their composition are an important contribution to the structural analysis of low molecular weight heparins, which has not been fully conducted so far. Qualitative on‐line liquid chromatography–mass spectrometric analysis of these resistant oligosaccharides is also described in this paper.     

Twist‐chair conformation of the tetraoxepane ring remains unchanged in tetraoxaspirododecane diamines

A detailed structural analysis has been performed for N,N′‐bis(4‐chlorophenyl)‐7,8,11,12‐tetraoxaspiro[5.6]dodecane‐9,10‐diamine, C₂₀H₂₂Cl₂N₂O₄, (I), N,N′‐bis(2‐fluorophenyl)‐7,8,11,12‐tetraoxaspiro[5.6]dodecane‐9,10‐diamine, C₂₀H₂₂F₂N₂O₄, (II), and N,N′‐bis(4‐fluorophenyl)‐7,8,11,12‐tetraoxaspiro[5.6]dodecane‐9,10‐diamine, C₂₀H₂₂F₂N₂O₄, (III). The seven‐membered ring with two peroxide groups adopts a twist‐chair conformation in all three compounds. The lengths of the C—N and O—O bonds are slightly shorter than the average statistical values found in the literature for azepanes and 1,2,4,5‐tetraoxepanes. The geometry analysis of compounds (I)–(III), the topological analysis of the electron density at the (3, ?1) bond critical points within Bader's quantum theory of `Atoms in molecules' (QTAIM) and NBO (natural bond orbital) analysis at the B3LYP/6‐31G(d,2p) level of theory showed that there are n_O→σ*(C—O), n_N→σ*(C—O) and n_O→σ*(C—N) stereoelectronic effects. The molecules of compounds (I) and (III) are packed in the crystals as zigzag chains due to strong N—H…O and C—H…O hydrogen‐bond interactions, whereas the molecules of compound (II) form chains in the crystals bound by N—H…O, C—H…π and C—H…O contacts. All these data show that halogen atoms and their positions have a minimal effect on the geometric parameters, stereoelectronic effects and crystal packing of compounds (I)–(III), so that the twist‐chair conformation of the tetraoxepane ring remains unchanged.     

(2′‐O‐Methyl‐RNA)‐3′‐PNA Chimeras: A New Class of Mixed Backbone Oligonucleotide Analogues with High Binding Affinity to RNA

The automated on‐line synthesis of DNA‐3′‐PNA chimeras 1 – 4 and (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras 5 – 8 is described, in which the 3′‐terminal part of the oligonucleotide is linked to the N‐terminal part of the PNA via N‐(ω‐hydroxyalkyl)‐N‐[(thymin‐1‐yl)acetyl]glycine units (alkyl=Et, Ph, Bu, and pentyl). By means of UV thermal denaturation, the binding affinities of all chimeras were directly compared by determining their T_m values in the duplex with complementary DNA and RNA. All investigated DNA‐3′‐PNA chimeras and (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras form more‐stable duplexes with complementary DNA and RNA than the corresponding unmodified DNA. Interestingly, a N‐(3‐hydroxypropyl)glycine linker resulted in the highest binding affinity for DNA‐3′‐PNA chimeras, whereas the (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras showed optimal binding with the homologous N‐(4‐hydroxybutyl)glycine linker. The duplexes of (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras and RNA were significantly more stable than those containing the corresponding DNA‐3′‐PNA chimeras. Surprisingly, we found that the charged (2′‐O‐methyl‐RNA)‐3′‐PNA chimera with a N‐(4‐hydroxybutyl)glycine‐based unit at the junction to the PNA part shows the same binding affinity to RNA as uncharged PNA. Potential applications of (2′‐O‐methyl‐RNA)‐3′‐PNA chimeras include their use as antisense agents acting by a RNase‐independent mechanism of action, a prerequisite for antisense‐oligonucleotide‐mediated correction of aberrant splicing of pre‐mRNA.     

A five‐coordinate iron(III) porphyrin complex including a neutral axial pyridine N‐oxide ligand

While six‐coordinate iron(III) porphyrin complexes with pyridine N‐oxides as axial ligands have been studied as they exhibit rare spin‐crossover behavior, studies of five‐coordinate iron(III) porphyrin complexes including neutral axial ligands are rare. A five‐coordinate pyridine N‐oxide–5,10,15,20‐tetraphenylporphyrinate–iron(III) complex, namely (pyridine N‐oxide‐κO)(5,10,15,20‐tetraphenylporphinato‐κ⁴N,N′,N′′,N′′′)iron(III) hexafluoroantimonate(V) dichloromethane disolvate, [Fe(C₄₄H₂₈N₄)(C₅H₅NO)][SbF₆]·2CH₂Cl₂, was isolated and its crystal structure determined in the space group P. The porphyrin core is moderately saddled and the Fe—O—N bond angle is 122.08 (13)°. The average Fe—N bond length is 2.03 Å and the Fe—ONC₅H₅ bond length is 1.9500 (14) Å. This complex provides a rare example of a five‐coordinate iron(III) porphyrin complex that is coordinated to a neutral organic ligand through an O‐monodentate binding mode.     

Site-specific control of N7-metal coordination in DNA by a fluorescent purine derivative

A synthetic strategy that utilizes O6‐protected 8‐bromoguanosine gives broad access to C8‐guanine derivatives with phenyl, pyridine, thiophene, and furan substituents. The resulting 8‐substituted 2′‐deoxyguanosines are push–pull fluorophores that can exhibit environmentally sensitive quantum yields (Φ=0.001–0.72) due to excited‐state proton‐transfer reactions with bulk solvent. Changes in nucleoside fluorescence were used to characterize metal‐binding affinity and specificity of 8‐substituted 2′‐deoxyguanosines. One derivative, 8‐(2‐pyridyl)‐2′‐deoxyguanosine (2PyG), exhibits selective binding of Cu^II, Ni^II, Cd^II, and Zn^II through a bidentate effect provided by the N7 position of guanine and the 2‐pyridyl nitrogen atom. Upon incorporation into DNA, 2‐pyridine‐modified guanine residues selectively bind to Cu^II and Ni^II with equilibrium dissociation constants (K_d) that range from 25 to 850 nM ; the affinities depend on the folded state of the oligonucleotide (duplex>G‐quadruplex) as well as the identity of the metal ion (Cu>Ni?Cd). These binding affinities are approximately 10 to 1 000 times higher than for unmodified metal binding sites in DNA, thereby providing site‐specific control of metal localization in alternatively folded nucleic acids. Temperature‐dependent circular‐dichroism studies reveal metal‐dependent stabilization of duplexes, but destabilization of G‐quadruplex structures upon adding Cu^II to 2PyG‐modified oligonucleotides. These results demonstrate how the addition of a single pyridine group to the C8 position of guanine provides a powerful new tool for studying the effects of N7 metalation on the structure, stability, and electronic properties of nucleic acids.     

Three isomorphous Ln complexes: {[Ln2(bt)6(bno)(H2O)4]·bno}n (bt is but‐2‐enoate and bno is 4,4′‐bipyridyl N,N′‐dioxide), with Ln = Nd,Er and Y

The polymeric title compounds, namely catena‐poly[[[di‐μ‐but‐2‐enoato‐κ³O:O,O′;κ³O,O′:O′‐bis[diaquadibut‐2‐enoato‐κO;κ²O,O′‐neodymium(III)]]‐μ‐4,4′‐bipyridyl N,N′‐dioxide‐κ²O:O′] 4,4′‐bipyridyl N,N′‐dioxide solvate] and the erbium(III) and yttrium(III) analogues, {[Ln₂(C₄H₅O₂)₆(C₁₀H₈N₂O₂)(H₂O)₄]·C₁₀H₈N₂O₂}_n (Ln = Nd, Er and Y), form from [Ln₂(bt)₆(H₂O)₄] dimers (bt is but‐2‐enoate) bridged by 4,4′‐bipyridyl dioxide (bno) spacers into sets of parallel chains; these linear arrays are interconnected by aqua‐mediated hydrogen bonds into broad two‐dimensional structures, which in turn interact with each other though the hydrogen‐bonded bridged bno solvent units. Both independent bno units in the structures are bisected by symmetry centres.     

Structural consequences of weak interactions in dispirooxindole derivatives

Spiro scaffolds are being increasingly utilized in drug discovery due to their inherent three‐dimensionality and structural variations, resulting in new synthetic routes to introduce spiro building blocks into more pharmaceutically active molecules. Multicomponent cascade reactions, involving the in situ generation of carbonyl ylides from α‐diazocarbonyl compounds and aldehydes, and 1,3‐dipolar cycloadditon with 3‐arylideneoxindoles gave a novel class of dispirooxindole derivatives, namely 1,1′′‐dibenzyl‐5′‐(4‐chlorophenyl)‐4′‐phenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐2,2′′‐dione, C₄₄H₃₃ClN₂O₃, (I), 1′′‐acetyl‐1‐benzyl‐5′‐(4‐chlorophenyl)‐4′‐phenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐2,2′′‐dione, C₃₉H₂₉ClN₂O₄, (II), 1′′‐acetyl‐1‐benzyl‐4′,5′‐diphenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐2,2′′‐dione, C₃₉H₃₀N₂O₄, (III), and 1′′‐acetyl‐1‐benzyl‐4′,5′‐diphenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐2,2′′‐dione acetonitrile hemisolvate, C₃₉H₃₀N₂O₄·0.5C₂H₃N, (IV). All four compounds exist as racemic mixtures of the SSSR and RRRS stereoisomers. In these structures, the two H atoms of the dihydrofuran ring and the two substituted oxindole rings are in a trans orientation, facilitating intramolecular C—H...O and π–π interactions. These weak interactions play a prominent role in the structural stability and aid the highly regio‐ and diastereoselective synthesis. In each of the four structures, the molecular assembly in the crystal is also governed by weak noncovalent interactions. Compound (IV) is the solvated analogue of (III) and the two compounds show similar structural features.     

A cyanide‐bridged bimetallic complex, [CrPr(CN)6(C3H7NO)4(H2O)3]·H2O

The crystal structure of the bimetallic cyanide‐bridged title complex, tri­aqua‐1κ³O‐μ‐cyano‐1:2κ²N:C‐penta­cyano‐2κ⁵C‐tetrakis(N,N‐di­methyl­form­amide)‐1κ⁴O‐chromium(III)­prase­odymium(III) monohydrate, was obtained by single‐crystal X‐ray diffraction. The central praseodymium(III) ion is eight‐coordinate, arranged in a square antiprism, while the chromium(III) ion is six‐coordinate, oriented octahedrally. Molecules in the crystal lattice are held together by a network of hydrogen bonds.     

Synthesis and Biological Evaluation of the Forssman Antigen Pentasaccharide and Derivatives by a One‐Pot Glycosylation Procedure

The synthesis and biological evaluation of the Forssman antigen pentasaccharide and derivatives thereof by using a one‐pot glycosylation and polymer‐assisted deprotection is described. The Forssman antigen pentasaccharide, composed of GalNAcα(1,3)GalNAcβ(1,3)Galα(1,4)Galβ(1,4)Glc, was recently identified as a ligand of the lectin SLL‐2 isolated from an octocoral Sinularia lochmodes. The chemo‐ and α‐selective glycosylation of a thiogalactoside with a hemiacetal donor by using a mixture of Tf₂O, TTBP and Ph₂SO, followed by activation of the remaining thioglycoside, provided the trisaccharide at the reducing end in a one‐pot procedure. The pentasaccharide was prepared by the α‐selective glycosylation of the N‐Troc‐protected (Troc=2,2,2‐trichloroethoxycarbonyl) thioglycoside with a 2‐azide‐1‐hydroxyl glycosyl donor, followed by glycosidation of the resulting disaccharide at the C3 hydroxyl group of the trisaccharide acceptor in a one‐pot process. We next applied the one‐pot glycosylation method to the synthesis of pentasaccharides in which the galactosamine units were partially and fully replaced by galactose units. Among the three possible pentasaccharides, Galα(1,3)GalNAc and Galα(1,3)Gal derivatives were successfully prepared by the established method. An assay of the binding of the synthetic oligosaccharides to a fluorescent‐labeled SLL‐2 revealed that the NHAc substituents and the length of the oligosaccharide chain were both important for the binding of the oligosaccharide to SLL‐2. The inhibition effect of the oligosaccharide relative to the morphological changes of Symbiodinium by SLL‐2, was comparable to their binding affinity to SLL‐2. In addition, we fortuitously found that the synthetic Forssman antigen pentasaccharide directly promotes a morphological change in Symbiodinium. These results strongly indicate that the Forssman antigen also functions as a chemical mediator of Symbiodinium.     

New rac‐XP(O)(OC6H5)(NHC6H4‐p‐CH3) [X = N(CH3)(cyclo‐C6H11) and NH(C3H5)] and rac‐(C6H5CH2NH)P(O)(OC6H5)(NH‐cyclo‐C6H11) mixed‐amide phosphinates

The mixed‐amide phosphinates, rac‐phenyl (N‐methylcyclohexylamido)(p‐tolylamido)phosphinate, C₂₀H₂₇N₂O₂P, (I), and rac‐phenyl (allylamido)(p‐tolylamido)phosphinate, C₁₆H₁₉N₂O₂P, (II), were synthesized from the racemic phosphorus–chlorine compound (R,S)‐(Cl)P(O)(OC₆H₅)(NHC₆H₄‐p‐CH₃). Furthermore, the phosphorus–chlorine compound ClP(O)(OC₆H₅)(NH‐cyclo‐C₆H₁₁) was synthesized for the first time and used for the synthesis of rac‐phenyl (benzylamido)(cyclohexylamido)phosphinate, C₁₉H₂₅N₂O₂P, (III). The strategies for the synthesis of racemic mixed‐amide phosphinates are discussed. The P atom in each compound is in a distorted tetrahedral (N¹)P(=O)(O)(N²) environment. In (I) and (II), the p‐tolylamido substituent makes a longer P—N bond than those involving the N‐methylcyclohexylamido and allylamido substituents. In (III), the differences between the P—N bond lengths involving the cyclohexylamido and benzylamido substituents are not significant. In all three structures, the phosphoryl O atom takes part with the N—H unit in hydrogen‐bonding interactions, viz. an N—H...O=P hydrogen bond for (I) and (N—H)(N—H)...O=P hydrogen bonds for (II) and (III), building linear arrangements along [001] for (I) and along [010] for (III), and a ladder arrangement along [100] for (II).     

脱铁伴清蛋白两结合位点不同酪氨酸氢键的特性

The interaction of gallium（Ⅲ） with the ligands containing phenolic group（s）, such as salicylic acid, 8-hydroxyquinoline, N,N＇-bis（2-hydroxybenzyl）ethylenediamine-N,N＇diacetic acid （HBED）, N,N＇-ethylenebis[2-（o- hydroxyphenyl）glycine （EHPG）, and ovotransferrin, was studied, respectively, by means of fluorescence in 0.01 mol/L Hepes at pH 7.4 and room temperature. Fluorescence intensity showed an increase when gallium（Ⅲ） was bound to 8-hydroxyquinoline and HBED. In contrast, it was decreased with the interaction of gallium（Ⅲ） with salicylic acid and EHPG. At pH 7.4, there was N…H-O type intramolecular hydrogen bond in the former, and the latter existed O…H-O type intramolecular hydrogen bond. Fluorescence titration of apoovotransferrin with gallium（Ⅲ） displayed that the fluorescence intensity was decreased at the N-terminal binding site, while enhanced at the C-terminal binding site. It can account for the O…H-O type intramolecular hydrogen bonds for the phenolic groups of Tyr92 and Tyr191 residues at the N-terminal binding site. And there are N…H-O type intramolecular hydrogen bonds for Tyr431 and Tyr524 residues at the C-terminal binding site. In addition, under the same conditions, the conditional binding constant of gallium（Ⅲ） with EHPG or HBED determined by fluorescence method is lg KGa-EHPG=19.18 or lg KGa-HBED= 19.08.     

Hydrogen‐bonded assemblies of 5,10,15,20‐tetrakis(4‐hydroxyphenyl)porphyrin with dimethylformamide,dimethylacetamide and water

The title free base porphyrin compound forms hydrogen‐bonded adducts with N,N‐dimethylformamide, C₄₄H₃₀N₄O₄·4C₃H₇NO, (I), a mixture of N,N‐dimethylformamide and water, C₄₄H₃₀N₄O₄·4C₃H₇NO·H₂O, (II), and a mixture of N,N‐dimethylacetamide and water, C₄₄H₃₀N₄O₄·6C₃H₇NO·2H₂O, (III). Total solvation of the four hydroxy functions of the porphyrin molecules characterizes all three compounds, thus preventing its supramolecular association into extended network architectures. In (I), the asymmetric unit consist of two five‐component adduct species, while in (III), the nine‐component entities reside on centres of inversion. This report provides the first structural characterizations of the free base tetra(hydroxyphenyl)porphyrin. It also demonstrates that the presence of strong Lewis bases, such as dimethylformamide or dimethylacetamide, in the crystallization mixture prevents direct supramolecular networking of the porphyrin ligands via O—H...O—H hydrogen bonds, due to their competing O—H...N(base) interaction with the hydroxy functions. The crystal packing of compounds (I)–(III) resembles that of other hydrogen‐bonding‐assisted tetraarylporphyrin clathrates.     

Three new phosphoric triamides with a [C(O)NH]P(O)[N(C)(C)]2 skeleton: a database analysis of C—N—C and P—N—C bond angles

In N,N,N′,N′‐tetraethyl‐N′′‐(4‐fluorobenzoyl)phosphoric triamide, C₁₅H₂₅FN₃O₂P, (I), and N‐(2,6‐difluorobenzoyl)‐N′,N′′‐bis(4‐methylpiperidin‐1‐yl)phosphoric triamide, C₁₉H₂₈F₂N₃O₂P, (II), the C—N—C angle at each tertiary N atom is significantly smaller than the two P—N—C angles. For the other new structure, N,N′‐dicyclohexyl‐N′′‐(2‐fluorobenzoyl)‐N,N′‐dimethylphosphoric triamide, C₂₁H₃₃FN₃O₂P, (III), one C—N—C angle [117.08 (12)°] has a greater value than the related P—N—C angle [115.59 (9)°] at the same N atom. Furthermore, for most of the analogous structures with a [C(=O)NH]P(=O)[N(C)(C)]₂ skeleton deposited in the Cambridge Structural Database [CSD; Allen (2002). Acta Cryst. B 58 , 380–388], the C—N—C angle is significantly smaller than the two P—N—C angles; exceptions were found for four structures with the N‐methylcyclohexylamide substituent, similar to (III), one structure with the seven‐membered cyclic amide azepan‐1‐yl substituent and one structure with an N‐methylbenzylamide substituent. The asymmetric units of (I), (II) and (III) contain one molecule, and in the crystal structures, adjacent molecules are linked via pairs of N—H...O=P hydrogen bonds to form dimers.     

Frovatriptan salts of aliphatic carboxylic acids

The interaction of the antimigraine pharmaceutical agent frovatriptan with acetic acid and succinic acid yields the salts (±)‐6‐carbamoyl‐N‐methyl‐2,3,4,9‐tetrahydro‐1H‐carbazol‐3‐aminium acetate, C₁₄H₁₈N₃O⁺·C₂H₃O₂⁻, (I), (R)‐(+)‐6‐carbamoyl‐N‐methyl‐2,3,4,9‐tetrahydro‐1H‐carbazol‐3‐aminium 3‐carboxypropanoate monohydrate, C₁₄H₁₈N₃O⁺·C₄H₅O₄⁻·H₂O, (II), and bis[(R)‐(+)‐6‐carbamoyl‐N‐methyl‐2,3,4,9‐tetrahydro‐1H‐carbazol‐3‐aminium] succinate trihydrate, 2C₁₄H₁₈N₃O⁺·C₄H₄O₄²⁻·3H₂O, (III). The methylazaniumyl substitutent is oriented differently in all three structures. Additionally, the amide group in (I) is in a different orientation. All the salts form three‐dimensional hydrogen‐bonded structures. In (I), the cations form head‐to‐head hydrogen‐bonded amide–amide catemers through N—H...O interactions, while in (II) and (III) the cations form head‐to‐head amide–amide dimers. The cation catemers in (I) are extended into a three‐dimensional network through further interactions with acetate anion acceptors. The presence of succinate anions and water molecules in (II) and (III) primarily governs the three‐dimensional network through water‐bridged cation–anion associations via O—H...O and N—H...O hydrogen bonds. The structures reported here shed some light on the possible mode of noncovalent interactions in the aggregation and interaction patterns of drug molecule adducts.     

Anion‐directed assemblies of europium(III) coordination polymers based on 1H‐benzimidazole‐5,6‐dicarboxylate: structures and luminescence properties

Two europium(III) coordination polymers (CPs), namely, poly[[diaquabis(μ₄‐1H‐benzimidazole‐5,6‐dicarboxylato‐κ⁶N³:O⁵,O^5′:O⁵,O⁶:O^6′)(μ₂‐oxalato‐κ⁴O¹,O²:O^1′,O^2′)dieuropium(III)] dihydrate], {[Eu₂(C₉H₄N₂O₄)₂(C₂O₄)(H₂O)₂]·2H₂O}_n ( 1 ), and poly[(μ₃‐1H‐benzimidazol‐3‐ium‐5,6‐dicarboxylato‐κ⁵O⁵:O^5′,O⁶:O⁶,O^6′)(μ₃‐sulfato‐κ³O:O′:O′′)europium(III)], [Eu(C₉H₅N₂O₄)(SO₄)]_n ( 2 ), have been synthesized via the hydrothermal method and structurally characterized. CP 1 shows a three‐dimensional network, in which the oxalate ligand acts as a pillar, while CP 2 has a two‐dimensional network based on a europium(III)–sulfate skeleton, further extended into a three‐dimensional framework by hydrogen‐bonding interactions. The structural diversity in the two compounds can be attributed to the different acidification abilities and geometries of the anionic ligands. The luminescence properties of 1 display the characteristic europium red emission with CIE chromaticity coordinates (2/3, 0.34). Interestingly, CP 2 shows the characteristic red emission with CIE chromaticity coordinates (0.60, 0.34) when excited at 280 nm and a near‐white emission with CIE chromaticity coordinates (0.38, 0.29) when excited at 340 nm.     

Multicomponent crystals of erlotinib

Erlotinib [systematic name: N‐(3‐ethynylphenyl)‐6,7‐bis(2‐methoxyethoxy)quinazolin‐4‐amine], a small‐molecule epidermal growth factor receptor inhibitor, useful for the treatment of non‐small‐cell lung cancer, has been crystallized as erlotinib monohydrate, C₂₂H₂₃N₃O₄·H₂O, (I), the erlotinib hemioxalate salt [systematic name: 4‐amino‐N‐(3‐ethynylphenyl)‐6,7‐bis(2‐methoxyethoxy)quinazolin‐1‐ium hemioxalate], C₂₂H₂₄N₃O₄⁺·0.5C₂O₄²⁻, (II), and the cocrystal erlotinib fumaric acid hemisolvate dihydrate, C₂₂H₂₃N₃O₄·0.5C₄H₄O₄·2H₂O, (III). In (II) and (III), the oxalate anion and the fumaric acid molecule are located across inversion centres. The water molecules in (I) and (III) play an active role in hydrogen‐bonding interactions which lead to the formation of tetrameric and hexameric hydrogen‐bonded networks, while in (II) the cations and anions form a tetrameric hydrogen‐bonded network in the crystal packing. The title multicomponent crystals of erlotinib have been elucidated to study the assembly of molecules through intermolecular interactions, such as hydrogen bonds and aromatic π–π stacking.     

Synthesis and Kinetic Study on the Chromium(III) Complex [Cr(ASA)(en)2]Cl·2H2O

In order to explore the transfer mechanism of chromium(III) in mammals, a novel complex [Cr(ASA)(en)₂]Cl· 2H₂O, bis(ethylenediamine‐ κ ² N,N′)(4‐aminosalicylic acid‐ κ ² O,O′) chromium(III) monochloride dihydrate was synthesized (4‐aminosalicylic acid=H₂ASA, ethylenediamine=en). The crystal structure belongs to orthorhombic system with the space group P2₁2₁2₁ by means of X‐ray diffraction. The characteristic for transfer of Cr³⁺ from the compound to the low‐molecular‐mass chelator EDTA and the iron‐binding protein apoovotransferrin (apoOTf) was followed by UV‐visible (UV‐Vis) and fluorescence spectra in 0.01 mol·L^?1 Hepes at pH 7.4. The second order rate constants were calculated. Those spectra in conjunction were used to obtain more accurate information about the interaction of chromium complex with apoOTf. The experimental results indicate that Cr³⁺ can be transferred from the complex to apoOTf with the retention of the 4‐aminosalicylic acid acting as a synergistic anion.