Molecules 1a Research Articles

X-ray diffraction analysis of 4- and 4′-substituted CnH2n + 1O–C6H3(OH)–CH=N–C6H4–CmH2m + 1 (n/m = 2/1 and 3/4) salicylideneanilines

X-ray diffraction study of two crystalline modifications of С2Н5O–C6H3(OН)–СН=N–C6H4–CH3 (1a, sp. gr. Р21/n, and 1b, sp. gr. С2/c) and С3H7O–C6H3(OН)–СН=N–C6H4–C4H9 (2, sp. gr. Р212121) has been performed. The 1a crystal structure contains two independent molecules. The molecules are conformationally nonrigid with respect to the mutual rotation of benzene rings; the dihedral angles between their planes are 29.19° and 26.00° in the independent molecules of 1a, 18.72° in the molecule of 1b, and 50.35° in the molecule of 2. The crystal packing of the compounds is discussed.

Radical scavenging potency of 2-(benzofuran-2-yl)-2-oxoethyl 3-(methyl/amino)benzoate: synthesis, crystal structure and Hirshfeld surface analysis

Abstract Two novel 2-(benzofuran-2-yl)-2-oxoethyl 3-(methyl/amino)benzoates 2(a–b), were synthesized under mild conditions and characterized by spectroscopic analysis. The three-dimensional (3D) crystal structures of these compounds were further determined using single crystal X-ray diffraction technique and revealed that both compounds tend to twist away with respect to their attached carbonyl groups at the C(=O)–C–O–C(=O) connecting bridge, exhibiting a nearly perpendicular conformation with torsion angle in a range of 75–94°. In both compounds, each of the benzofuran and substituted phenyl rings are individually planar while almost perpendicular to each other. Their molecular conformation are comparable with related structures from the Cambridge Structural Database (CSD). Furthermore, the intermolecular interactions in these crystal structures were quantified and analyzed using Hirshfeld surfaces computational method. The quantitative data on the percentage contributions of overall interactions on the molecules 2a and 2b (A & B) is calculated by the 2-D fingerprint plots from the HS analysis. These structures were evaluated for their antioxidant properties by diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, ferrous ion chelating (FIC) and hydrogen peroxide radical scavenging assays (H2O2). Noteworthy, compound 2b with an amino substituent attached to the phenyl ring exhibited an IC50 value of 45.37 μg/mL in H2O2 scavenging assay, which showed better scavenging effect than the standard drug, ascorbic acid (IC50=81.02 μg/mL).

Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT2C Modulators.

A series of pyrimidine derivatives 4a–i were synthesized and evaluated for their binding affinities towards 5-HT2C receptors. With regard to designed molecules 4a–i, the influence of the size of alkyl ether and the absolute configuration of a stereogenic center on the 5-HT2C binding affinity and selectivity was studied. The most promising diasteromeric mixtures 4d and 4e were selected in the initial radioligand binding assay and they were further synthesized as optically active forms starting from optically active alcohols 5d and 5e, prepared by an enzymatic kinetic resolution. Pyrimidine analogue (R,R)-4e displayed an excellent 5-HT2C binding affinity with good selectivity values against a broad range of other 5-HT receptor subtypes.

Synthesis of Two Novels-Shaped Dibenzo[c,l] Chrysene Derivatives, Crystal Structure, and the Evaluation of their Photophysical Properties

Two s-shaped polyaromatic dibenzo[c,l]chrysene derivatives have been synthesized by a two-step process, via. The Wittig reaction, followed by iodine, promoted photocyclization. These molecules have been characterized by 1H NMR, FAB-MS, and elemental analysis. Further, the molecular structures of 4a and 4b have been confirmed by single crystal X-ray diffraction analysis. The protons located in the cove-regions of molecules 4a and 4b showed downfield shifts of the protons. Molecule 4a crystallized under the monoclinic system with space group C2/c, and the molecule 4b crystallized under the monoclinic system with space group P21/n. Molecules 4a and 4b showed strong absorption maxima wavelengths at 310 nm and 324 nm, respectively. The molar extinctinction coefficients (ε) of the compounds 4a and 4b indicated that molecule 4b has a better ability to absorb UV light than molecule 4a. The emission spectra of the molecules 4a and 4b displayed peaks in the region 429–456 nm. The shape of the UV-Visible and Fluorescence spectra of the molecules 4a and 4b look almost identical. However, molecule 4b exhibited better fluorescence intensity than molecule 4a. This may be due to the difference in the substituents of molecules 4a and 4b.

The structure of 2,4,6-tris(1H–pyrazol-1-yl)-1,3,5-triazine in the solid state: on polymorphs, pseudopolymorphs and co-crystals

Three structures of 2,4,6-tris(1H–pyrazol-1-yl)-1,3,5-triazine (TPT) have been determined at 193 K: the isolated molecule (2a), a solvate containing molecules of water and acetonitrile (2b) and a complex of two molecules of TPT and three molecules of water (2c). To discuss the structures, B3LYP/6–311++G(d,p) calculations have been carried out, in particular, in what concerns hydrogen bonds.

3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-1,2-dimethylpyridinium iodide molekülünün geometrik yapısının incelenmesi

In this study, the ground state of 3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-1,2-dimethylpyridinium iodide [ C 9 H 13 IN 2 O 3 ] (1A) molecule of the theoretical molecular structure were performed by using Gaussian 09 program. B3LYP levels of density functional theory with the LanL2DZ basis set have been used to perform above-mentioned calculations. The molecular structure of 1A molecule was determined and the vibrational properties were investigated. In addition, the molecular frontier orbital ( HOMO-LUMO) energies, the electronic properties (total energy, dipole moment, electronegativity, chemical hardness and softness), nonlinear optical (the mean polarizability (<α>) and the anisotropy of the polarizability (Δα)) properties, Mulliken atomic charges and thermodynamic parameters were investigated using DFT quantum chemical calculations.

Its Environment Engraves the Geometry of a Molecular Entity: Allyl Coordination within a Dicationic Ruthenium(IV) Complex

The best molecular arrangements for [Ru(η5-C5(CH5)5)(η3-CH2CHCHC6H5)(CH3CN)2]2+ (1) in various environments are determined. The isolated compound 1a serves as a point of reference. On the basis of crystal structure data, solid-state environments are modeled by first placing the cationic compound into the appropriate anionic environment 2a and then completing the unit cell contents by addition of the solvent molecule 3a. Density functional calculations (BP86) augmented by various dispersion corrections (BP86-D2, BP86-D3, BP86-D3(BJ), BP86-dDsC) establish the computational approach for electronic structure and geometry optimization. According to the models considered, intermolecular electrostatic interactions are to a major part responsible for substantial changes in intramolecular arrangements.

Control of supramolecular nanoassemblies by tuning the interactions of bent-shaped rod-coil molecules.

Rod-coil molecules 1a, 1b and 2a, 2b, consisting of biphenyl and phenyl units connected by an acetylene bond as the rod segment and oligo(ethylene glycol) (OEG) as the coil segment, were synthesized and characterized. Molecules 1a and 1b incorporate a butoxy group at the apex of their bent-shaped rigid building blocks, while both 1b and 2b contain a lateral methyl group between the rod and coil segments. The self-assembling behavior of these molecules was investigated using DSC, SAXS, CD, AFM, and TEM in bulk and aqueous solutions. In the bulk state, 1a self-assembles into oblique columnar structures, whereas 1b, incorporating butoxy and lateral methyl groups, self-assembles into three-dimensional body-centered tetragonal structures. Molecules 2a and 2b with no butoxy groups, and 2b incorporating a lateral methyl group, self-assemble into hexagonal perforated lamellar and oblique columnar structures, respectively. In dilute aqueous solutions, 1a assembles into tubular nanoassemblies, while 1b self-organizes into micelles and nanoparticles. On the other hand, 2a and 2b spontaneously aggregate into nanoribbons and nanofibers. Furthermore, CD experiments together with AFM investigations of 2b indicate the creation of self-organized helical fibers, implying that the lateral methyl group induces the helical stacking of the rod building block. These results reveal that the butoxy and lateral methyl groups between the rod and coil segments dramatically influence the creation of supramolecular nanostructures and morphologies.

Synthesis of new bioactive aminophosphonates and study of their antioxidant, anti-inflammatory and antibacterial activities as well the assessment of their toxicological activity

Two new categories of α-aminophosphonates molecules were synthesized and characterized by UV-Vis, IR, and NMR. Their spectral properties show a perfect convergence. Their biological activities were evaluated. Molecules 1a, 2a, and 1d present a greater antioxidant potential than BHT and vitamin C. The best anti-inflammatory activity is shown by the 2b molecule and that of 1a, 2a, and 2c molecules are closely comparable to that of diclofenac. The antibacterial activity of the synthesized compounds is significantly higher than the antibiotic amoxicillin. The hemolysis rate HR of compounds 1b, 1c, 2b, and 2c was lower than 5%.

Experimental and molecular docking investigation on DNA interaction of N-substituted phthalimides: antibacterial, antioxidant and hemolytic activities.

A series of Schiff base molecules derived from a phthalimide scaffold was investigated as efficient antibacterial, antioxidant and DNA-interacting agents. The spectroscopic characterization of these derivatives was studied in detail using elemental analysis and spectroscopic techniques. The DNA-binding profile of title molecules against Ct-DNA (calf thymus) was investigated by absorbance, fluorescence, hydrodynamics and thermal denaturation investigations. The bacterial inhibition potential of these molecules was investigated against Escherichia coli and Staphylococcus aureus. Molecule 3c emerged as the most active against S. aureus (IC50 : 14.8 μg/mL), whereas compounds 3a and 3b displayed potential antibacterial activities against E. coli (IC50 : 49.7 and 67.6 μg/mL). Molecular docking studies of these compounds against GlcN-6-P synthase were carried out to rationalize antibacterial efficiency of these molecules. These newly synthesized molecules were screened for their scavenging capacity against 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and H2 O2 free radicals and the results were compared with ascorbic acid as synthetic antioxidant. The title molecules 3a, 3b and 3e showed less than 20% hemolysis, which indicated their significant non-toxic behavior.

Synthesis of new liquid crystals embedded gold nanoparticles for photoswitching properties

A new series of liquid crystals decorated gold nanoparticles is synthesized whose molecular architecture has azobenzenes moieties as the peripheral units connected to gold nanoparticles (Au NPs) via alkyl groups. The morphology and mesomorphic properties were investigated by field emission scanning electron microscope, high-resolution transmission electron microscopy, differential scanning calorimetry and polarizing optical microscopy. The thiolated ligand molecules (3a–c) showed enantiotropic smectic A phase, whereas gold nanoparticles (5a–c) exhibit nematic and smectic A phase with monotropic nature. HR-TEM measurement showed that the functionalized Au NPs are of the average size of 2nm and they are well dispersed without any aggregation. The trans-form of azo compounds showed a strong band in the UV region at ∼378nm for the π-π∗ transition, and a weak band in the visible region at ∼472nm due to the n-π∗ transition. These molecules exhibit attractive photoisomerization behaviour in which trans-cis transition takes about 15s whereas the cis-trans transition requires about 45min for compound 5c. The extent of reversible isomerization did not decay after 10 cycles, which proved that the photo-responsive properties of 5c were stable and repeatable. Therefore, these materials may be suitably exploited in the field of molecular switches and the optical storage devices.

Self-organizing p-quinquephenyl building blocks incorporating lateral hydroxyl and methoxyl groups into supramolecular nano-assemblies.

The self-assembling behavior of coil-rod-coil molecules 1a, 1b, and 2a, 2b was investigated using DSC, POM, SAXS, and AFM in bulk and aqueous solutions. These molecules contain p-quinquephenyl groups as rod segments incorporating lateral hydroxyl or methoxyl groups in the center positions and oligo(ethylene oxide)s as the coil segments. Molecules 1a and 1b, with lateral methoxyl groups in the rod segments, self-assemble into oblique columnar structures in the crystalline phase and transform into nematic phases. On the other hand, molecules 2a and 2b, with hydroxyl groups in the center of their rod segments, self-organize into hexagonal perforated lamellar and oblique columnar nano-structures in the crystalline and liquid crystalline phase, respectively. In aqueous solutions, these molecules aggregate into nano-ribbons and vesicles, depending on their lateral groups and oligo(ethylene oxide) chain lengths. These results imply that the lateral methoxyl or hydroxyl groups, present in the center of the rod segments, significantly influence the formation of various supramolecular nano-structures in the bulk state and in aqueous solution. This is achieved via tuning of the non-covalent interactions of the rod building blocks.

Syntheses, Characterization and DFT Analysis of Two Novel Thiaheterohelicene Derivatives

Two novel thiaheterohelicene derivatives were synthesized from the corresponding 2,2'-(2,6-naphthalenediyl-di-2,1-ethenediyl) bis-thiophene and its dimethyl substituted analogue 2,2'-(2,6-naphthalenediyldi-2,1-ethenediyl) bis-2’’-methylthiophene using oxidative photo cyclization reaction. The compounds were characterized by 1H NMR, electron impact-mass spectrometry, elemental analyses, and the absolute molecular structures were determined by single crystal X-ray diffraction analysis. They crystallized under monoclinic system with space group P21/n for the unsubstituted compound and P21/c for the methyl substituted compound, respectively. The dihedral angle between the terminal thiophene ring and the molecular center was observed to be 20.82? for the unsubstituted compound and 14.27? for the methyl substituted compound, respectively. Furthermore, molecules oriented as herringbone structures by intermolecular π-π stacking in the crystals. The relative study of the actual arrangement of these molecules has been carried out using X-ray diffraction analysis. The two molecules have different crystal packing. The molecule 3b has herring bone like arrangement due to the substituent bulkiness and weak CH-π interaction. On the other hand, the molecular packing of molecule 3a is not herringbone probably due to the multiple weak intermolecular CH-S short contacts between columns consisting of stacked molecules.

Supramolecular nano-assemblies from self-assembly of ABC coil-rod-coil triblock oligomers: Construction of tetragonal perforated lamellar and columnar nano-structures

In this article, we report the self-assembling behavior of ABC coil-rod-coil triblock molecules 1a-1c and 2a-2c, containing biphenyl and phenyl units connected with ether and ester bonds as a rod segment and poly(propylene oxide)s (PPO) with a degree of polymerization (DP) of 7, 12 and 17 as a A block and octyl or hexadecyl alkyl chains as a C block of the coil segments. The supramolecular nanostructures of these molecules were characterized by a combination of techniques consisting of differential scanning calorimetry (DSC), thermal polarized optical microscopy (POM), and small-angle X-ray scattering (SAXS) measurement in the bulk state. Molecule 1a composed of PPO with a DP of 7 and a octyl alkyl chain as coil segment, self organize into unusal tetragonal perforated lamellar (TPL) and bicontinuous cubic (BCC) structures in the solid state and the liquid crystalline phase, respectively. While, molecule 2a consisting of same PPO coil as 1a and a hexadecyl alkyl chain, self assemble into TPL and BCC nano-structures in the crystalline phase. Meanwhile, molecules 1b-2b and 1c-2c incorporating longer PPO coil chains than 1a and 2a, self assemble into the columnar nano-structures in the solid state and liquid crystalline phase. These results clearly implied that self-organizing behavior of such molecules was dramatically influenced by the length of the PPO and alkyl coil chains connected with the rigid rod building block.

Three‐dimensional crystalline supramolecular nanostructures from self‐assembly of rod–coil molecules incorporating lateral carboxyl group in the middle of the rod segment

AbstractWe report the synthesis and self‐assembling behaviour of coil–rod–coil molecules 1a–1c and 2a–2c, which incorporate lateral carboxyl or ester groups in the middle of the rod segment. The self‐assembling behaviour of these molecules was investigated in the bulk using differential scanning calorimetry, polarised optical microscopy and small‐angle X‐ray scattering. Our results reveal that hydrogen bonds strongly influence the self‐assembling behaviour of rod‐like building blocks. Molecules 1a–1c, which incorporate carboxyl groups in the middle of rod segments, self‐assemble into two‐dimensional (2‐D) columnar, three‐dimensional (3‐D) body‐centred tetragonal and 3‐D hexagonal close‐packed assemblies in the crystalline state. However, molecules 2a–2c, which contain ester groups in the centre of rod segments, self‐assemble into unexpected lamellar, hexagonal perforated lamellar and 2‐D columnar nanostructures in the bulk, indicating that hydrogen bonds impede intermolecular stacking in this rod–coil system. © 2015 Society of Chemical Industry

Synthesis, characterization and comparative study of a series of fluorinated Schiff bases containing different orientation [sbnd]CH[dbnd]N[sbnd] spacers

Investigation of the crystal structures of three pairs of multi-fluorinated compounds with bridge-flipped isomeric character, which on the molecular level differ only in the orientation of the bridging bond CHN connecting two larger parts of the molecule, offers a useful context for the examination and evaluation of supramolecular assembly in the case. The results show that the orientation of the bridging bond CHN determines the conformation of six organic molecules 1a–b, 2a–b and 3a–b, thus further influencing intermolecular weak interactions and final supramolecular arrangements. Accordingly, each molecule of six multi-fluorinated compounds as supramolecular building block unit, via strong intermolecular interactions, including interactions between fluorine atoms and aromatic ring hydrogen atoms, between fluorine atoms, and between hydroxyl groups and fluorine atoms, as well as interaromatic π⋯π stacking interactions etc., constructs a series of different and attractive crystal packings. These results demonstrate that by changing CHN orientation, we can obtain different hydrogen-bonded supramolecular structures through different interactions.

Coronin 1A depletion protects endothelial cells from TNFα-induced apoptosis by modulating p38β expression and activation

Coronins are conserved actin-binding proteins that regulate various cellular processes such as migration and endocytosis. Among coronin family members, coronin 1A is highly expressed in hematopoietic lineage cells where it regulates cell homeostasis. However, the expression and function of coronin 1A in endothelial cells have not yet been elucidated. We found that coronin 1A is expressed in the human umbilical vein endothelial cell (HUVEC) and human brain microvascular endothelial cell (HBMVEC). In HUVEC depleted of coronin 1A by siRNA transfection, tumor necrosis factor α (TNFα)+cyclohexamide (CHX) treatment resulted in a decrease in the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive apoptotic cells. Coronin 1A depletion also resulted in the suppression of caspase 3 and poly(ADP-ribose) polymerase cleavage and a reduction in caspase 3 activity. Next, we examined TNFα-induced activation of several pro- and anti-apoptotic signaling molecules to find the target molecule of coronin 1A and found that p38 phosphorylation was enhanced by TNFα stimulation in coronin 1A-depleted HUVEC. Among the p38 isoforms, the expression of p38β was significantly upregulated after coronin 1A depletion, suggesting that the expression and phosphorylation of anti-apoptotic p38β were significantly induced in coronin 1A-depleted HUVEC. Inhibition of p38β upregulation in coronin 1A-depleted HUVEC restored the cleavage of caspase 8 and caspase 3 and induced more apoptosis than in coronin 1A-depleted HUVEC in response to TNFα+CHX. These findings suggest that coronin 1A modulates endothelial cell apoptosis by regulating p38β expression and activation.

Synthesis, Characterization, and Evaluation for Antibacterial and Antifungal Activities of N-Heteroaryl Substituted Benzene Sulphonamides

The synthesis and biological activity of N-heteroaryl substituted benzene sulphonamides (3a–h) were successful. Simple condensation reaction of benzene sulphonyl chloride (1) with substituted heteroaromatic compounds (2a–h) under dry pyridine and acetone gave the target molecules (3a–h) in good to excellent yield. The compounds were characterized using FTIR, 1HNMR, and 13CNMR. The compounds were screened for antibacterial activity against E. coli, Salmonella typhi, P. aeruginosa, B. cereus, K. pneumonia, and Sarcina lutea and antifungal activity against C. albicans and A. niger. The results of the antimicrobial activity showed improved biological activity against some tested organisms.

Molecular modeling design, synthesis, and anti-hyprglycemic evaluation of certain 5-(aryl-alkoxy-benzylidine)-imidazolidine-2,4-dione derivatives as potential PPARγ agonists

A series of novel substituted 5-(aryl-alkoxy-benzylidine)-imidazolidine-2,4-diones (4a–f, 5a) were designed and evaluated as selective PPARγ agonists analogous to the reference lead, rosiglitazone (II). The molecular modeling compare/Fit study of these molecules with the PPARγ agonists’ pharmacophore constructed from known PPARγ agonists and the docking scores of the same designed molecules using the 3D protein crystal structure of the PPARγ receptors were determined. The fit scores of these molecules were more or less similar to the reference drug (II), while the reduced molecule 5a gave highest fit value. The docking scores of molecules 4c–f and 5a were higher than the lead II. These hit molecules were subsequently synthesized and evaluated for their in vivo anti-hyperglycemic activity in hyperglycemic animal model. Compounds 4a–e showed similar or slightly higher activity than the lead drug II. In contrast, the activities of compounds 4f and 5a were 1.2- and 1.3-folds higher than the same lead.

Insights into the Stability and Structures of Phosphine-Boranes and Their α-Metalated Derivatives

The reaction between iPr2PCl and Ph2P(BH3)CH2Li gives the mixed phosphine/phosphine-borane Ph2P(BH3)CH2PiPr2 (1a) in good yield. Thermolysis of 1a leads to borane migration and the formation of Ph2PCH2P(BH3)iPr2 (2a) along with small amounts of Ph2P(BH3)CH2P(BH3)iPr2 (3a) and Ph2PCH2PiPr2 (4a). Compound 3a may be synthesized directly from the reaction of 1a with BH3·SMe2, while 4a can be prepared cleanly by heating 1a in methanol under reflux. Kinetic studies on the conversion of 1a to 2a reveal the reaction to be apparently first order in 1a, suggesting a dissociative process, and yield the activation parameters ΔH⧧ = 63 ± 8 kJ mol–1, ΔS⧧ = −145 ± 24 J K–1 mol–1, and ΔG⧧ = 106 ± 8 kJ mol–1, the negative entropy of activation conversely suggesting an associative process. DFT studies suggest that concerted migration of borane within a molecule of 1a is disfavored, but that both the dissociative and associative mechanisms for borane migration operate simultaneously. Metalation of 1a–4a with nBuLi in the presence of tmeda gives the complexes [{Ph2P(BH3)}CHPiPr2]Li(tmeda) (1b), [Ph2PCH{P(BH3)iPr2}]Li(tmeda) (2b), [{Ph2P(BH3)}CH{P(BH3)iPr2}]Li(tmeda) (3b), and [Ph2PCHPiPr2]Li(tmeda) (4b), respectively, which adopt similar structures in the solid state. Analysis of the crystal structures suggests that the phosphine-borane groups stabilize the adjacent charge to a greater extent than the phosphine groups. This is supported by DFT calculations, which show that the greatest delocalization of negative charge from the carbanion is into the P–C(Ph) or P–C(Pr) σ*-orbitals of the phosphine-borane substituents.