O-Acylated Flavones in the Alpine Daisy Celmisia viscosa: Intraspecific Variation.

Flavonoids acylated on their core phenolic groups are rare. The Aotearoa New Zealand endemic alpine daisy Celmisia viscosa is widespread, but its flavonoids have not previously been identified. Leaf extracts yielded a series of 8-O-acylated flavones with combinations of 3-methylbutanoate, 2-methylbutanoate, and 2-methylpropanoate groups and one, two, or three O-methyls, all previously unreported. Regiochemistries of 8-(3″-methylbutanoyl)-5-hydroxy-6,7,4'-trimethoxyflavone (5) and 8-(2″-methylbutanoyl)-5,7,4'-trihydroxy-6-methoxyflavone (10) were defined by X-ray crystallography. LC analyses of leaf extracts from the full geographic range of C. viscosa showed intraspecific variation of these flavones: most had high concentrations of trimethoxy 8-O-acylated flavones, but dimethoxy 8-O-acylated flavones were the most abundant flavonoids in two individuals. Three other viscid (sticky leaved) Celmisa species also contained these rare flavones, but four nonviscid Celmisa had none detectable.

Active compounds from a diverse library of triazolothiadiazole and triazolothiadiazine scaffolds: synthesis, crystal structure determination, cytotoxicity, cholinesterase inhibitory activity, and binding mode analysis.

In an effort to identify novel cholinesterase candidates for the treatment of Alzheimer's disease (AD), a diverse array of potentially bioactive compounds including triazolothiadiazoles (4a-h and 5a-f) and triazolothiadiazines (6a-h) was obtained in good yields through the cyclocondensation reaction of 4-amino-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thiol (3) with various substituted aryl/heteroaryl/aryloxy acids and phenacyl bromides, respectively. The structures of newly prepared compounds were confirmed by IR, (1)H and (13)C NMR spectroscopy and, in case of 4a, by single crystal X-ray diffraction analysis. The purity of the synthesized compounds was ascertained by elemental analysis. The newly synthesized conjugated heterocycles were screened for cholinesterase inhibitory activity against electric eel acetylcholinesterase (EeAChE) and horse serum butyrylcholinesterase (hBChE). Among the evaluated hybrids, several compounds were identified as potent inhibitors. Compounds 5b and 5d were most active with an IC50 value of 3.09 ± 0.154 and 11.3 ± 0.267 µM, respectively, against acetylcholinesterase, whereas 5b, 6a and 6g were most potent against butyrylcholinesterase, with an IC50 of 0.585 ± 0.154, 0.781 ± 0.213, and 1.09 ± 0.156 µM, respectively, compared to neostigmine and donepezil as standard drugs. The synthesized heteroaromatic compounds were also tested for their cytotoxic potential against lung carcinoma (H157) and vero cell lines. Among them, compound 6h exhibited highest antiproliferative activity against H157 cell lines, with IC50 value of 0.96 ± 0.43 µM at 1mM concentration as compared to vincristine (IC50=1.03 ± 0.04 µM), standard drug used in this study.

Synthesis, physiochemical characterization, and biocompatibility of a chitosan/dextran-based hydrogel for postsurgical adhesion prevention.

An amine-functionalized succinyl chitosan and an oxidized dextran were synthesized and mixed in aqueous solution to form an in situ chitosan/dextran injectable, surgical hydrogel for adhesion prevention. Rheological characterization showed that the rate of gelation and moduli were tunable based on amine and aldehyde levels, as well as polymer concentrations. The CD hydrogels have been shown to be effective post-operative aids in prevention of adhesions in ear, nose, and throat surgeries and abdominal surgeries in vivo. In vitro biocompatibility testing was performed on CD hydrogels containing one of two oxidized dextrans, an 80 % oxidized (CD-100) or 25 % (CD-25) oxidized dextran. However, the CD-100 hydrogel showed moderate cytotoxicity in vitro to Vero cells. SC component of the CD hydrogel, however, showed no cytotoxic effect. In order to increase the biocompatibility of the hydrogel, a lower aldehyde level hydrogel was developed. CD-25 was found to be non-cytotoxic to L929 fibroblasts. The in vivo pro-inflammatory response of the CD-25 hydrogel, after intraperitoneal injection in BALB/c mice, was also determined by measuring serum TNF-α levels and by histological analysis of tissues. TNF-α levels were similar in mice injected with CD-25 hydrogel as compared to the negative saline injected control; and were significantly different (P < 0.05) as compared to the positive, lipopolysaccharide, injected control. Histological examination revealed no inflammation seen in CD hydrogel injected mice. The results of these in vitro and in vivo studies demonstrate the biocompatibility of the CD hydrogel as a post-operative aid for adhesion prevention.

Crystal structure of 9-(3-bromo-5-chloro-2-hydroxy-phen-yl)-10-(2-hy-droxy-eth-yl)-3,3,6,6-tetra-methyl-3,4,6,7,9,10-hexa-hydro-acridine-1,8(2H,5H)-dione.

The title compound C25H29BrClNO4, comprises a 3,3,6,6-tetra-methyl-tetra-hydro-acridine-1,8-dione ring system that carries a hy-droxy-ethyl substituent on the acridine N atom and a 3-bromo-5-chloro-2-hy-droxy-phenyl ring on the central methine C atom of the di-hydro-pyridine ring. The benzene ring is inclined to the acridine ring system at an angle of 89.84 (6)° and this conformation is stabilized by an intra-molecular O-H⋯O hydrogen bond between the hy-droxy substituent on the benzene ring and one of the carbonyl groups of the acridinedione unit. In the crystal, O-H⋯O, C-H⋯O and C-H⋯Br hydrogen bonds combine to stack mol-ecules in inter-connected columns propagating along the a-axis direction.

Crystal structure of 2-(4-chloro-phen-yl)-2-oxoethyl 3-bromo-benzoate.

2-(4-Chloro-phen-yl)-2-oxoethyl 3-bromo-benzoate, C15H10BrClO3, was synthesized in a single-step reaction by condensation of 3-bromo-benzoic acid with 2-bromo-1-(4-chloro-phen-yl)ethanone in di-methyl-formamide in the presence of tri-ethyl-amine as a catalyst. The structure consists of an aryl ketone moiety linked to an aryl ester unit by a methyl-ene group. Both units are reasonably planar (r.m.s. deviations of 0.119 and 0.010 Šfor the aryl ketone and aryl ester units, respectively) and are almost orthogonal, with an angle of 88.60 (3)° between them. In the crystal, mol-ecules form five separate sets of inversion dimers. Three of these are generated by two C-H⋯O inter-actions and a C-H⋯Br contact, and form chains along c and along the ab cell diagonal. In addition, two inversion-related π-π stacking inter-actions between like aryl rings again form chains of mol-ecules but in this instance along the bc diagonal. These contacts generate infinite layers of mol-ecules parallel to (011) and stack the mol-ecules along the a-axis direction.

Crystal structure of 4-(prop-2-yn-yloxy)-2,2,6,6-tetra-methyl-piperidin-1-ox-yl.

The title compound, C12H20NO2, was synthesized from 4-hy-droxy-2,2,6,6-tetra-methyl-piperidin-1-oxyl (hy-droxy-TEMPO) and propargyl bromide. The six-membered ring adopts a flattened chair conformation and carries a propyn-yloxy substituent in an equatorial orientation at the 4-position. The N-O bond length of the piperidin-1-oxyl unit is 1.289 (3) Å. In the crystal, C-H⋯O hydrogen bonds combine with unusual C-H⋯π inter-actions involving the alkyne unit as acceptor to generate a three-dimensional network.

Crystal structures of (µ2-η(2),η(2)-4-hydroxybut-2-yn-1-yl 2-bromo-2-methylpropanoate-κ(4) C (2),C (3):C (2),C (3))bis[tricarbonylcobalt(II)](Co-Co) and [µ2-η(2),η(2)-but-2-yne-1,4-diyl bis(2-bromo-2-methyl-propanoate)-κ(4) C (2),C (3):C (2),C (3)]bis[tricarbonylcobalt(II)](Co-Co).

The title compounds, [Co2(C8H11BrO3)(CO)6], (1), and [Co2(C12H16Br2O4)(CO)6], (2), result from the replacement of two carbonyl ligands from dicobalt octa-carbonyl by the alkynes 4-hy-droxy-but-2-ynyl 2-bromo-2-methyl-propano-ate and but-2-yne-1,4-diyl bis-(2-bromo-2-methyl-propano-ate), respectively. Both mol-ecules have classic tetra-hedral C2Co2 cluster cores with the Co(II) atoms in a highly distorted octa-hedral coordination geometry. The alkyne ligands both adopt a cis-bent conformation on coordination. In the crystal structure of (1), classical O-H⋯O and non-classical C-H⋯O contacts form inversion dimers. These combine with weak O⋯O and Br⋯O contacts to stack the mol-ecules into inter-connected columns along the b-axis direction. C-H⋯O and C-H⋯Br contacts stabilize the packing for (2), and a weak Br⋯O contact is also observed. Inter-connected columns of mol-ecules again form along the b-axis direction.

Br···O contacts and π-π stacking dominate the packing in methyl 4-bromo-3,5-dimethoxybenzoate.

The title compound, C10H11BrO4, a useful precursor to pharmaceutically active isocoumarin and isochroman derivatives, crystallizes with two unique molecules in the asymmetric unit. A π-π stacking interaction links the planar molecules in the asymmetric unit. Additional π-π contacts stack pairs of molecules along the c axis. A feature of the crystal packing is the presence of a number of short Br···O contacts. A particularly unusual arrangement involves the formation of dimers, with pairs of Br···O contacts imposing a close Br···Br interaction and generating five-membered rings within an eight-membered ring formed by two Br···O contacts. Only two comparable arrangements have been reported previously. The Br···O contacts combine with weak C-H···O hydrogen bonds to form corrugated sheets of molecules approximately parallel to (001). These sheets are stacked along the c axis by π-π interactions to generate a three-dimensional network.

Similarities and differences in the structures of 5-bromo-6-hydroxy-7,8-dimethylchroman-2-one and 6-hydroxy-7,8-dimethyl-5-nitrochroman-2-one.

The title compounds, C11H11BrO3, (I), and C11H11NO5, (II), respectively, are derivatives of 6-hydroxy-5,7,8-trimethylchroman-2-one substituted at the 5-position by a Br atom in (I) and by a nitro group in (II). The pyranone rings in both molecules adopt half-chair conformations, and intramolecular O-H···Br [in (I)] and O-H···O(nitro) [in (II)] hydrogen bonds affect the dispositions of the hydroxy groups. Classical intermolecular O-H···O hydrogen bonds are found in both molecules but play quite dissimilar roles in the crystal structures. In (I), O-H···O hydrogen bonds form zigzag C(9) chains of molecules along the a axis. Because of the tetragonal symmetry, similar chains also form along b. In (II), however, similar contacts involving an O atom of the nitro group form inversion dimers and generate R2(2)(12) rings. These also result in a close intermolecular O···O contact of 2.686 (4) Å. For (I), four additional C-H···O hydrogen bonds combine with π-π stacking interactions between the benzene rings to build an extensive three-dimensional network with molecules stacked along the c axis. The packing in (II) is much simpler and centres on the inversion dimers formed through O-H···O contacts. These dimers are stacked through additional C-H···O hydrogen bonds, and further weak C-H···O interactions generate a three-dimensional network of dimer stacks.

2-(4-Meth-oxy-phen-yl)-1-pentyl-4,5-di-phenyl-1H-imidazole.

The title compound, C27H28N2O, is a lophine (2,4,5-triphenyl-1H-imidazole) derivative with an n-pentyl chain on the amine N atom and a 4-meth-oxy substituent on the benzene ring. The two phenyl and meth-oxy-benzene rings are inclined to the imidazole ring at angles of 25.32 (7), 76.79 (5) and 35.42 (7)°, respectively, while the meth-oxy substituent lies close to the plane of its benzene ring, with a maximum deviation of 0.126 (3) Šfor the meth-oxy C atom. In the crystal, inversion dimers linked by pairs of C-H⋯O hydrogen bonds generate R2(2)(22) loops. These dimers are stacked along the a-axis direction.

2-(1H-Indol-3-yl)acetohydrazide.

In the title compound C(10)H(11)N(3)O, the mean plane of the indole ring system (r.m.s. deviation 0.0131 Å) subtends a dihedral angle of 87.27 (5)° to the almost planar acetohydrazide substituent (r.m.s. deviation 0.0291 Å). In the crystal, bifurcated N-H⋯(O,N) and N-H⋯N hydrogen bonds involving the pyrrole N-H grouping combine to form zigzag chains along a. Additional N-H⋯O contacts from the hydrazide N-H group augmented by C-H⋯π inter-actions link the mol-ecules into chains along the a axis. The overall effect of these contacts is a three-dimensional network structure with mol-ecules stacked along the b-axis direction.

N,N-Bis(2-hy-droxy-eth-yl)-4-methyl-benzene-sulfonamide.

In the title compound C(11)H(17)NO(4)S, an intra-molecular O-H⋯O hydrogen bond forms an S(8) ring and determines the conformation of the bis-(2-hy-droxy-eth-yl) segment of the mol-ecule, holding the two CH(2)CH(2)OH groups close to coplanar (r.m.s. deviation = 0.185 Å). In the crystal, O-H⋯O hydrogen bonds link the mol-ecules into zigzag chains along the b axis. Weaker additional C-H⋯O and C-H⋯π contacts generate a three dimensional network, with mol-ecules stacked along the b-axis direction.

4,5-Dihydro-cyclo-penta-[b]thio-phen-6-one.

The title compound, C(7)H(6)OS, crystallizes with two similar mol-ecules, 1 and 2, in the asymmetric unit. Both mol-ecules are essentially planar with r.m.s. deviations of 0.0193 and 0.0107 Šfor the planes through the nine non-H atoms of mol-ecules 1 and 2, respectively. The thio-phene and 4,5-dihydro-cyclo-penta-dienone rings are inclined at 2.40 (13)° in 1 and 0.64 (13)° in 2. In the crystal structure π-π [3.6542 (17) Å] and C-H⋯π contacts stack the mol-ecules into columns in an inverse fashion along the b axis. An extensive series of C-H⋯O hydrogen bonds links the columns, generating an extended network structure.

6-Hy-droxy-7,8-dimethyl-chroman-2-one.

The title compound, C(11)H(12)O(3), is essentially planar, with an r.m.s. deviation of 0.179 Šfrom the mean plane through the 14 non-H atoms in the mol-ecule. The benzene ring and the pyranone mean plane are inclined at 13.12 (6)° to one another and the pyran-one ring adopts a flattened chair conformation. In the crystal, O-H⋯O hydrogen bonds and C-H⋯O contacts form R(1) (2)(6) rings and link mol-ecules into chains along b. Additional C-H⋯O contacts generate inversion dimers, with R(2) (2)(8) ring motifs, and form sheets parallel to (-102) which are linked by C-H⋯π interactions.

(Z)-3-(2-Hy-droxy-eth-yl)-2-(phenyl-imino)-1,3-thia-zolidin-4-one.

In the title compound, C(11)H(12)N(2)O(2)S, the thia-zole and phenyl rings are inclined at 56.99 (6)° to one another. The thia-zole ring is planar with an r.m.s. deviation for the five ring atoms of 0.0274 Å. The presence of the phenyl-imine substituent is confirmed with the C=N distance to the thia-zole ring of 1.2638 (19) Å. The mol-ecule adopts a Z conformation with respect to this bond. The -OH group of the hy-droxy-ethyl substituent is disordered over two positions with relative occupancies 0.517 (4) and 0.483 (4). In the crystal, O-H⋯O hydrogen bonds, augmented by C-H⋯N contacts, form dimers with R(2) (2)(11) rings and generate chains along the b axis. Parallel chains are linked in an obverse fashion by weak C-H⋯S hydrogen bonds. C-H⋯O hydrogen bonds together with C-H⋯π contacts further consolidate the structure, stacking mol-ecules along the b axis.

5,6-Dimethyl-1,2,9,10-tetra-hydro-pyrano[3,2-f]chromene-3,8-dione.

The title mol-ecule, C(14)H(14)O(4), lies on a twofold rotation axis that bis-ects the central benzene ring, with only one half-mol-ecule in the asymmetric unit. The pyran-one systems adopt distorted twist- boat conformations, with the two methyl-ene C atoms displaced by 0.537 (1) and 0.163 (2) Šfrom the best-fit plane through the remaining five C and O atoms (r.m.s. deviation = 0.073 Å). In the crystal, bifurcated C-H⋯(O,O) hydrogen bonds link pairs of adjacent mol-ecules in an obverse fashion, stacking mol-ecules along c. These contacts are further stabilized by very weak π-π inter-actions between adjacent benzene rings with centroid-centroid distances of 4.1951 (4) Å. Additional C-H⋯O contacts link these stacks, giving a three-dimensional network.

Synthesis, crystal structure and Hirshfeld surface analysis of 1-ferrocenylundecane-1,11-diol.

The racemic title compound, [Fe(C5H5)(C16H27O2)], comprises an α,ω-diol-substituted undecyl chain with a ferrocenyl substituent at at one terminus. The alkane chain is inclined to the substituted ring of the ferrocene grouping by 84.22 (13)°. The ferrocene rings are almost eclipsed and parallel. The crystal structure features O-H⋯O and C-H⋯O hydrogen bonds and C-H⋯π contacts that stack the mol-ecules along the c-axis direction. A Hirshfeld surface analysis reveals that H⋯H inter-actions (83.2%) dominate the surface contacts.

Identification of two novel thiazolidin-2-imines as tyrosinase inhibitors: synthesis, crystal structure, molecular docking and DFT studies.

Various N- and S-containing 5-membered heterocycles such as imidazole-2-thiones, thiazolidinones and thiazolidin-2-imines are among the most eminent biologically active organic heterocycles and are present in many marketed drugs. In view of their synthetic and biological significance, an efficient synthesis of two novel thiazolidine-2-imines (4a-b) utilizing a three-component one-pot approach starting from an aldimine, an alkyne and isothiocyanates has been developed. The reaction proceeded via a 5-exo digonal (5-exo dig) cyclization of a propargyl thiourea, formed in situ in the presence of Zn(II)-catalyst. The structures of the resulting products are elucidated by spectroscopic methods and X-ray crystallography. A DFT study explored the structural, thermodynamic and molecular electrostatic potential parameters for the compounds. The newly synthesized compounds (4a & 4b) were evaluated for the inhibition of tyrosinase both in vitro and in silico. The in vitro results revealed that the synthesized thiazolidine-2-imines (4a-b) showed good inhibition activity towards mushroom tyrosinase (IC50 = 1.151 ± 1.25 and 2.079 ± 0.87 µM respectively) in comparison to the kojic acid standard (IC50 = 16.031 ± 1.27 µM) a commonly used anti-pigment agent in plant and animal tissues. The experimental inhibition was further assessed by molecular docking studies between synthesized ligands and the human tyrosinase protein complex to investigate the intermolecular interactions responsible for tyrosinase inhibition activity.

[η-(Phenyl-ethyn-yl)cyclo-penta-dien-yl](η-tetra-phenyl-cyclo-butadiene)cobalt(I).

In the title compound, [Co(C(13)H(9))(C(28)H(20))], the Co atom is sandwiched between cyclo-penta-dienyl and cyclo-butadienyl rings that are inclined at a dihedral angle of 2.6 (3)°. The four phenyl rings are tilted with respect to the cyclo-butadienyl plane so that the C(4)Ph(4) unit constitutes a four-bladed propeller. The phenyl ring of the phenyl-alkyne substituent is inclined to the cyclo-penta-dienyl ring at an angle of 34.92 (18)°. The crystal structure is stabilized solely by C-H⋯π inter-actions which generate a three-dimensional network.

(E)-2-[1-(1-Benzothio-phen-2-yl)ethyl-idene]-N-phenyl-hydrazinecarboxamide.

The title compound, C(17)H(15)N(3)OS, crystallizes with two unique mol-ecules, denoted 1 and 2, in the asymmetric unit. The two mol-ecules are closely similar and overlay with an r.m.s. deviation of 0.053 Å. Both mol-ecules adopt E configurations with respect to the C=N bonds. The dihedral angles between the benzothio-phene groups and N-bound phenyl rings are 36.36 (9)° for mol-ecule 1 and 29.71 (9)° for mol-ecule 2. The C=N-NH-C(O)NH ethyl-idene-hydrazinecarboxamide units are also reasonably planar, with r.m.s. deviations of 0.061 and 0.056 Å, respectively, for the two mol-ecules. The methyl substituents lie 0.338 (3) and 0.396 (3) Å, respectively, from these planes. The C=N-NH-C(O)NH planes are inclined to the phenyl rings at 13.65 (11) and 15.56 (11)°, respectively, in mol-ecules 1 and 2. This conformation is enhanced by weak intra-molecular C-H⋯O hydrogen bonds between ortho-H atoms of the two phenyl rings and the carbonyl O atoms, which generate S(6) rings in each mol-ecule. In the crystal, pairs of mol-ecules are linked by pairs of inter-molecular N-H⋯O hydrogen bonds into dimers. Alternating dimers are further inter-connected by weak C-H⋯O contacts into zigzag rows along b. The rows are stacked along a by C-H⋯π contacts involving the benzene ring from molecule 2 and the thiophene ring from molecule 1 of adjacent benzothio-phene units.