Supramolecular architecture of theophylline polymorphs, monohydrate and co-crystals with iodine: study from the energetic viewpoint.

The regularities of crystal structure organization were thoroughly studied in all to date known polymorphic modifications of theophylline (THP) using an energetic approach. The monohydrate and a co-crystal of theophylline with one half equivalent of an iodine molecule were similarly investigated. The calculations of pairwise interaction energies have showed that the crystals studied can be divided into two groups according to their basic structural motifs: columnar-layered or columnar. The energetic approach also allows the role of different interactions in the crystal structure formation to be estimated. It was found that strong N-H⋯N, N-H⋯O hydrogen bonds and stacking interactions play the most important roles in polymorphic modifications of THP and the THP monohydrate. In the case of the co-crystal with iodine, N-H⋯O hydrogen bond participates in the dimeric building unit formation. However, instead of a stacking interaction the π⋯π interaction between carbonyl groups of neighboring molecules plays the highest role in the supramolecular architecture of this crystal. The lattice energies calculations in periodic conditions for polymorphic structures have shown that polymorph with the most anisotropic energetic structure may be considered as stable and all others forms metastable. In the polymorphic modification 1 of THP a zwitter-ionic resonance form is predominant, which affects significantly the solubility and the intermolecular interactions of this modification.

Cyclohexene-Embedded Dicyanomethylene Merocyanines - Consecutive Three-Component Coupling-Addition Synthesis and Chromophore Characteristics.

A concise and efficient consecutive three-component alkynylation-addition synthesis of cyclohexene-embedded dicyanomethylene merocyanines furnishes a small library of dyes in moderate to excellent yield. The dyes possess strong absorption coefficients of the longest wavelength absorption bands. According to the crystal structure, the small bond length alternations account for a highly delocalized electronic ground state. The electronic structure of the absorption bands is qualitatively rationalized by TDDFT calculations, which explain that intense HOMO-LUMO transitions along the merocyanine axis lead to cyanine similar Stokes shifts.

3,9-Disubstituted Bis[1]benzothieno[3,2-b;2',3'-e][1,4]thiazines with Low Oxidation Potentials and Enhanced Emission.

Dibrominated bis[1]benzothieno[3,2-b;2',3'-e][1,4]thiazines (BBTT) are efficiently synthesized and applied in Suzuki and Buchwald-Hartwig cross-coupling reactions to give access to 3,9-disubstituted BBTT derivatives with extended π-conjugation and enhanced electronic properties. For instance, 3,9-di(hetero)aryl substituted BBTT derivatives surpass their parent congeners phenothiazines with lower oxidation potentials and pronounced yellow to orange-red fluorescence (Φf ≈ 30-45%). In addition, 3,9-bis(di(hetero)arylamino substituted BBTT possess very high lying HOMO energy (EHOMO = -4.46 to -4.83 eV), a favorable property of hole transport molecules. A representative X-ray structure analysis reveals that the central BBTT core in these extended π-systems is essentially planarized. Upon protonation of a 3,9-bis(di(hetero)arylamino) substituted BBTT, the absorption color shifts from yellow to deep blue with a concomitant loss of the emission. The optical properties of these novel BBTT derivatives can be plausibly rationalized by time-dependent density functional theory (TD(DFT)) calculations and correlation between experimentally determined oxidation potentials and σp parameters as well as between photophysical data and the specific substituent parameter σp- by establishing electronic structure-property relationships.

Antimicrobial Hexaaquacopper(II) Complexes with Novel Polyiodide Chains.

The non-toxic inorganic antimicrobial agents iodine (I2) and copper (Cu) are interesting alternatives for biocidal applications. Iodine is broad-spectrum antimicrobial agent but its use is overshadowed by compound instability, uncontrolled iodine release and short-term effectiveness. These disadvantages can be reduced by forming complex-stabilized, polymeric polyiodides. In a facile, in-vitro synthesis we prepared the copper-pentaiodide complex [Cu(H2O)6(12-crown-4)5]I6 · 2I2, investigated its structure and antimicrobial properties. The chemical structure of the compound has been verified. We used agar well and disc-diffusion method assays against nine microbial reference strains in comparison to common antibiotics. The stable complex revealed excellent inhibition zones against C. albicans WDCM 00054, and strong antibacterial activities against several pathogens. [Cu(H2O)6(12-crown-4)5]I6 · 2I2 is a strong antimicrobial agent with an interesting crystal structure consisting of complexes located on an inversion center and surrounded by six 12-crown-4 molecules forming a cationic substructure. The six 12-crown-4 molecules form hydrogen bonds with the central Cu(H2O)6. The anionic substructure is a halogen bonded polymer which is formed by formal I5- repetition units. The topology of this chain-type polyiodide is unique. The I5- repetition units can be understood as a triodide anion connected to two iodine molecules.

One-pot synthesis of a white-light emissive bichromophore operated by aggregation-induced dual emission (AIDE) and partial energy transfer.

Merocyanine-triarylamine bichromophores are readily synthesized by sequentially Pd-catalyzed insertion-alkynylation-Michael-Suzuki four-component reactions. White-light emissive systems form upon aggregation in 1 : 99 and 0.1 : 99.9 vol% CH2Cl2-cyclohexane mixtures, ascribed to aggregation-induced dual emission (AIDE) in combination with partial energy transfer between both chromophore units as supported by spectroscopic studies.

One-pot activation-alkynylation-cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion.

A consecutive three-component activation-alkynylation-cyclization reaction of (hetero)aryl glyoxylic acids, oxalyl chloride, arylacetylenes, and hydrazides efficiently forms 1,5-diacyl-5-hydroxypyrazolines in moderate to good yields. The structures were unambiguously corroborated by comprehensive NMR spectroscopy and X-ray structure analyses of selected derivatives.

Game of Isomers: Bifurcation in the Catalytic Formation of Bis[1]benzothieno[1,4]thiazines with Conformation-Dependent Electronic Properties.

Two regioisomers of bis[1]benzothieno[1,4]thiazine are unexpectedly obtained by tuning the catalytic conditions of the intermolecular-intramolecular Buchwald-Hartwig amination. Mechanistic insights and evidence of intermediates support a conclusive mechanistic rationale. Furthermore, a computationally based study on the influence of conformational aspects on the HOMO energy level of anellated 1,4-thiazine paves the way to enhance the electronic properties, thus successfully achieving higher luminescent and easier oxidizable syn- syn bis[1]benzothieno[1,4]thiazines.

Divalent Sialylated Precision Glycooligomers Binding to Polyomaviruses and the Effect of Different Linkers.

Divalent precision glycooligomers terminating in N-acetylneuraminic acid (Neu5Ac) or 3'-sialyllactose (3'-SL) with varying linkers between scaffold and the glycan portions are synthesized via solid phase synthesis for co-crystallization studies with the sialic acid-binding major capsid protein VP1 of human Trichodysplasia spinulosa-associated Polyomavirus. High-resolution crystal structures of complexes demonstrate that the compounds bind to VP1 depending on the favorable combination of carbohydrate ligand and linker. It is found that artificial linkers can replace portions of natural carbohydrate linkers as long as they meet certain requirements such as size or flexibility to optimize contact area between ligand and receptor binding sites. The obtained results will influence the design of future high affinity ligands based on the structures presented here, and they can serve as a blueprint to develop multivalent glycooligomers as inhibitors of viral adhesion.

Bis[1]benzothieno[1,4]thiazines: Planarity, Enhanced Redox Activity and Luminescence by Thieno-Expansion of Phenothiazine.

Twofold Buchwald-Hartwig aminations selectively furnish three regioisomers of bis[1]benzothieno[1,4]thiazines; X-ray structure analyses and DFT calculations were corroborated for correlation of their electronic properties. All regioisomers outscore the parent compound phenothiazine with respect to a low-lying oxidation potential and reversible redox activity. The anti-anti bis[1]benzothieno[3,2-b:2',3'-e][1,4]thiazines possess the lowest oxidation potentials in this series and displayed pronounced green luminescence in solution (ΦF ≈20 %) and in the solid state. Syn-anti regioisomers were only weakly luminescent in solution, but showed aggregation-induced emission enhancement and solid-state luminescence. Most interestingly, X-ray structure analyses revealed that anti-anti derivatives have an amazingly coplanar structure of the pentacyclic anellated 1,4-thiazine system, emphasizing a structural similarity to heteroacenes. The calculated theoretical nucleus-independent chemical shifts additionally suggested that these 8π-electron core systems can be considered as the first electronically unbiased anellated 1,4-thiazines with antiaromatic character.

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P® activation of 3-arylpropiolic acids.

In situ activation of 3-arylpropiolic acids with T3P® (n-propylphosphonic acid anhydride) initiates a domino reaction furnishing 4-arylnaphtho[2,3-c]furan-1,3-diones in excellent yields. Upon employing these anhydrides as reactive intermediates blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones are formed by consecutive pseudo three-component syntheses in a one-pot fashion. The Stokes shifts correlate excellently with the Hammett-Taft σR parameter indicating an extended degree of resonance stabilization in the vibrationally relaxed excited singlet state.

Hydrogen bonds and van der Waals forces as tools for the construction of a herringbone pattern in the crystal structure of hexane-1,6-diaminium hexane-1,6-diyl bis-(hydrogen phospho-nate).

The asymmetric unit of the title salt, [H3N(CH2)6NH3][(HO)O2P(CH2)6PO2(OH)], consists of one half of a hexane-1,6-diaminium dication and one half of a hexane-1,6-diyl bis-(hydrogen phospho-nate) dianion. Both are located around different centres of inversion (Wyckoff sites: 2a and 2d) of the space group P21/c. The shape of the hexane-1,6-diaminium cation is best described as a double hook. Both aminium groups as well as the two attached CH2 groups are turned out from the plane of the central four C atoms. In contrast, all six C atoms of the dianion are almost in a plane. The hydrogen phospho-nate (-PO3H) groups of the anions and the aminium groups of the cations form two-dimensional O-H⋯ and O-H⋯N hydrogen-bonded networks parallel to the ac plane, built up from ten-membered and twelve-membered ring motifs with graph-set descriptors R33(10) and R54(12), respectively. These networks are linked by the alkyl-ene chains of the anions and cations. The resulting three-dimensional network shows a herringbone pattern, which resembles the parent structures 1,6-di-amino-hexane and hexane-1,6-di-phospho-nic acid.

Hydrogen bonding, π-π stacking and van der Waals forces-dominated layered regions in the crystal structure of 4-amino-pyridinium hydrogen (9-phosphono-non-yl)phospho-nate.

The asymmetric unit of the title mol-ecular salt, [C5H7N2+][(HO)2OP(CH2)9PO2(OH)-], consists of one 4-amino-pyridinium cation and one hydrogen (9-phos-phono-non-yl)phospho-nate anion, both in general positions. As expected, the 4-amino-pyridinium moieties are protonated exclusively at their endocyclic nitro-gen atom due to a mesomeric stabilization by the imine form which would not be given in the corresponding double-protonated dicationic species. In the crystal, the phosphonyl (-PO3H2) and hydrogen phospho-nate (-PO3H) groups of the anions form two-dimensional O-H⋯O hydrogen-bonded networks in the ab plane built from 24-membered hydrogen-bonded ring motifs with the graph-set descriptor R66(24). These networks are pairwise linked by the anions' alkyl-ene chains. The 4-amino-pyridinium cations are stacked in parallel displaced face-to-face arrangements and connect neighboring anionic substructures via medium-strong charge-supported N-H⋯O hydrogen bonds along the c axis. The resulting three-dimensional hydrogen-bonded network shows clearly separated hydro-philic and hydro-phobic structural domains.

α-Aminoxy Oligopeptides: Synthesis, Secondary Structure, and Cytotoxicity of a New Class of Anticancer Foldamers.

α-Aminoxy peptides are peptidomimetic foldamers with high proteolytic and conformational stability. To gain an improved synthetic access to α-aminoxy oligopeptides we used a straightforward combination of solution- and solid-phase-supported methods and obtained oligomers that showed a remarkable anticancer activity against a panel of cancer cell lines. We solved the first X-ray crystal structure of an α-aminoxy peptide with multiple turns around the helical axis. The crystal structure revealed a right-handed 28 -helical conformation with precisely two residues per turn and a helical pitch of 5.8 Å. By 2D ROESY experiments, molecular dynamics simulations, and CD spectroscopy we were able to identify the 28 -helix as the predominant conformation in organic solvents. In aqueous solution, the α-aminoxy peptides exist in the 28 -helical conformation at acidic pH, but exhibit remarkable changes in the secondary structure with increasing pH. The most cytotoxic α-aminoxy peptides have an increased propensity to take up a 28 -helical conformation in the presence of a model membrane. This indicates a correlation between the 28 -helical conformation and the membranolytic activity observed in mode of action studies, thereby providing novel insights in the folding properties and the biological activity of α-aminoxy peptides.

Carba-closo-dodecaborate anions with two functional groups: [1-R-12-HC≡C-closo-1-CB11H10]⁻ (R = CN, NC, CO2H, C(O)NH2, NHC(O)H).

Disubstituted carba-closo-dodecaborate anions with one functional group bonded to the cluster carbon atom and one ethynyl group bonded to the antipodal boron atom were synthesized from easily accessible {closo-1-CB11} clusters. [Et4N][1-NC-12-HC≡C-closo-1-CB11H10] ([Et4N]4b) was prepared starting from Cs[12-Et3SiC≡C-closo-1-CB11H11] (Cs1c) via salts of the anions [1-HO(O)C-12-HC≡C-closo-1-CB11H10](-) (2b) and [1-H2N(O)C-12-HC≡C-closo-1-CB11H10](-) (3b). In a similar reaction sequence [Et4N][1-CN-12-HC≡C-closo-1-CB11H10] ([Et4N]7b) was obtained from Cs[1-H2N-12-HC≡C-closo-1-CB11H10] (Cs5b) by formamidation to yield [Et4N][1-H(O)CHN-12-HC≡C-closo-1-CB11H10] ([Et4N]6b) and successive dehydration. In addition, the synthesis of the isonitrile [Et4N][1-CN-closo-1-CB11H11] ([Et4N]7a) is presented. The {closo-1-CB11} derivatives were characterized by multinuclear NMR as well as vibrational spectroscopy, mass spectrometry, and elemental analysis. The crystal structures of [Et4N][1-HO(O)C-12-HC≡C-closo-1-CB11H10] ([Et4N]2b), [Et4N][1-H2N(O)C-12-HC≡C-closo-1-CB11H10] ([Et4N]3b), [Et4N][1-NC-12-HC≡C-closo-1-CB11H10] ([Et4N]4b), [Et4N][1-H(O)CHN-12-HC≡C-closo-1-CB11H10] ([Et4N]6b), [Et4N][1-CN-12-HC≡C-closo-1-CB11H10] ([Et4N]7b), and K[1-H(O)CHN-closo-1-CB11H11] ([Et4N]6a) were determined. The transmission of electronic effects through the carba-closo-dodecaboron cage was studied based on (13)C NMR spectroscopic data, by results derived from density functional theory calculations, and by a comparison to the data of related benzene and bicyclo[2.2.2]octane derivatives.

(Di-methyl-phosphor-yl)methanaminium hydrogen oxalate-oxalic acid (2/1).

The reaction of (di-methyl-phosphor-yl)methanamine (dpma) with oxalic acid in ethanol yielded the title solvated salt, C3H11NOP(+)·C2HO4 (-)·0.5C2H2O4. Its asymmetric unit consists of one dpmaH(+) cation, one hydrogen oxalate anion and a half-mol-ecule of oxalic acid located around a twofold rotation axis. The H atom of the hydrogen oxalate anion is statistically disordered over two positions that are trans to each other. The hydrogen oxalate monoanion is not planar (bend angle ∼16°) whereas the oxalic acid molecule shows a significantly smaller bend angle (∼7°). In the crystal, the components are connected by strong O-H⋯O and much weaker N-H⋯O hydrogen bonds, leading to the formation of layers extending parallel to (001). The structure was refined from a racemically twinned crystal with twin components in an approximate 1:1 ratio.

(Di-methyl-phosphor-yl)methanaminium iodide-(di-methyl-phosphor-yl)methan-amine (1/1).

The asymmetric unit of the title structure, C3H11NOP(+)·I(-)·C3H10NOP, consists of one (di-methyl-phosphor-yl)methanamine (dpma) mol-ecule, one (di-methyl-phosphor-yl)methanaminium (dpmaH) ion and one iodide counter-anion. In the crystal, medium-strong to weak N-H⋯O and N-H⋯N hydrogen bonds connect dpmaH cations and dpma mol-ecules into strands along [001]. The iodide counter-anions form only very weak hydrogen bonds. The crystal used for the diffraction study was found to be an inversion twin with a ratio of 0.83 (2):0.17 (2). The title structure is isotypic to that of dpmaH[ClO4]·dpma [Buhl et al. (2013 ▶). Crystals 3, 350-362].

2-Amino-pyridin-1-ium triiodide.

The asymmetric unit of the title compound, C5H7N2 (+.)I3 (-), consists of one 2-amino-pyridin-1-ium cation (apyH(+)) and one triiodide anion, both located in general postions. The apyH(+) cation is planar within the experimental uncertainties. The short N-C distance [1.328 (5) Å] of the exocyclic NH2 group is typical for the imino-form of protonated 2-amino-pyridines. Consequently, the bond lengths within the six-membered ring vary significantly. The geometric parameters of the triiodide anion are in the typical range, with bond lengths of 2.8966 (3) and 2.9389 (3) Šand a bond angle of 176.02 (1)°. In the crystal, N-H ⋯ I hydrogen bonds connect adjacent ions into screwed chains along the b-axis direction. These chains are twisted pairwise into rectangular rods. The pyridinium moieties of neighbouring rods are arranged parallel to each other with a plane-to-plane distance of 3.423 (5) Å.

trans-Dichlorido-tetra-kis-[(di-methyl-phosphor-yl)methanaminium-κO]cobalt(II) tetra-chloridocobaltate(II).

The asymmetric unit of the title structure, [CoCl2(C3H11NOP)4][CoCl4]2, consists of one half of the trans-dichlorido-tetra-kis-[(di-methyl-phosphor-yl)methanaminium]cobalt(II) tetra-cation lying on an inversion center and one tetra-chloridocobaltate(II) dianion on a general position. Four O-coordinated cationic (di-methyl-phosphor-yl)methanaminium (dpmaH(+)) ligands occupy the equatorial coordination sites, whereas the chloride ligands occupy axial positions of the roughly o-cta-hedral coordination polyhedron of the cobalt metal center. Intra-molecular hydrogen bonds between the aminium groups and the O atom of the phosphoryl groups and additional hydrogen bonds between the aminium groups and the chloride ligands are present. Furthermore, four of the six H atoms not involved in intra-molecular bonding of each cobalt(II) tetra-cation form weak hydrogen bonds to four adjacent tetra-chloridocobaltate(II) counter-anions. By these inter-molecular hydrogen bonds, one-dimensional polymeric strands are formed along the b-axis direction. The hydrogen bonding is analyzed using the graph-set method and the structural similarity with dpmaHCl is discussed.

Pseudosymmetric fac-di-aqua-trichlorido[(di-methyl-phosphor-yl)methanaminium-κO]manganese(II).

In the title compound, [Mn(C3H11NOP)Cl3(H2O)2], the Mn(II) metal center has a distorted o-cta-hedral geometry, coordinated by the three chloride ligands showing a facial arrangement. Two water mol-ecules and the O-coordinated dpmaH cation [dpmaH = (di-methyl-phosphor-yl)methanaminium] complete the coordination sphere. Each complex mol-ecule is connected to its neighbours by O-H⋯Cl and N-H⋯Cl hydrogen bonds. Two of the chloride ligands and the two water ligands form a hydrogen-bonded polymeric sheet in the ab plane. Furthermore, these planes are connected to adjacent planes by hydrogen bonds from the aminium function of cationic dpmaH ligand. A pseudo-mirror plane perpendicular to the b axis in the chiral space group P21 is observed together with inversion twinning [ratio = 0.864 (5):0.136 (5)].

Poly[[(µ4-1,3,5-triamino-1,3,5-tride-oxy-cis-inositol)sodium] bromide].

In the structure of the title compound, {[Na(C6H15N3O3)]Br} n , the sodium cation and the bromide anion are both located on threefold rotation axes. The sodium cation is bonded to the three hy-droxy groups of one 1,3,5-triamino-1,3,5-tride-oxy-cis-inositol (taci) ligand, with the taci ligand residing around the same threefold rotation axis as the sodium ion. The coordination sphere of the sodium ion is completed by three amino groups of three neighbouring taci mol-ecules. Hence, this type of coordination constitutes a three-dimensional open framework with channels along the c axis which are filled with the bromide counter-anions. Each bromide ion forms three symmetry-related hydrogen bonds to both the hy-droxy and the amino groups of neighbouring taci ligands.