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A series of phenothiazine analogues were synthesized to study the structure–activity relationship and their potency as TLK1 inhibitors for cancer therapy.

Crystal engineering of gefitinib by forming cocrystals help in modulating its physico-chemical properties while retaining its biological activity.

A series of stimuli-responsive AIEgens of tetraphenylethylene (TPE) fused imidazole derivatives (1–7) were synthesized, and their substituent controlled fluorescence properties in the solid state were explored. The structure of the synthesised compounds was characterized by NMR, mass and single crystal X-ray diffraction spectroscopy techniques. 1–7 exhibited a typical aggregation induced emissive (AIE) behaviour in the THF : water mixture. These compounds exhibited substituent dependent strong solid state fluorescence (Φf = 16.6–55.7%) with a tunable λmax between 458 and 496 nm. Chlorine substituted 6 showed the highest fluorescence efficiency (Φf = 55.7%), whereas acetyl substituted 3 exhibited the lowest fluorescence efficiency (Φf = 16.6%). All the seven compounds showed a mechanical pressure induced reversible fluorescence switching. Crushing 1–7 resulted in red shifted fluorescence, which was reversed to its initial state by heating/solvent vapour exposure. Interestingly, integration of 1–7 into a hydrophobic PMMA polymer resulted in blue shifted fluorescence at 470 nm, whereas that into hydrophilic PVA polymer resulted in red shifted fluorescence at 491 nm. Thus highly solid state emissive TPE fused imidazole compounds were prepared, and their stimuli-induced reversible fluorescence switching and polymer controlled tunable fluorescence were demonstrated.

The emergence of antibiotic-resistant strains of Helicobacter pylori necessitates the development of novel therapeutic strategies to fight against its infection. Recently, the enzyme inosine-5'-monophosphate dehydrogenase (IMPDH) has emerged as a promising target to treat bacterial infections due to its crucial role in the de novo purine biosynthesis pathway. The differences between the prokaryotic and eukaryotic IMPDHs, in the NAD

An anhydrous nature of benzylidene derivatives of nicotin and isonicotinamides crystal structures is determined and studied for their weak intermolecular interactions. The molecular structure is non-planar in general with the pyridine ring twisted with respect to the central hydrazone moiety. The crystal structures depict various intermolecular interactions, including N–H⋯O, C–H⋯O, N–H⋯N, and C–H⋯N hydrogen bonding along with weak C–H … π and π … π contacts. Further, Hirshfeld surface and 2D-fingerprint plot analysis confirm the role of intermolecular interactions in building the crystal packing in these derivatives. The PIXELC energy calculation shows that dispersion energy plays an essential role in stabilizing the crystal packing in all six derivatives.

Pyridyl acrylonitrile without traditional auxiliary groups form stable organogels in ethanol. The addition of a second non-gelating cyanostilbene component results in a more stable two-component gel. Single crystal X-ray data reveal the influence of C-H⋅ ⋅ ⋅N, C-H⋅ ⋅ ⋅π, and π-π interactions in the formation of organogels. The morphology of the xerogels was studied by using SEM, which showed the self-assembly of molecules to fibers and sheet-like structures, and phase differences upon the gel formation and the structural phase characterization was measured using powder XRD. Exposure of the organogels to acidic (TFA) vapors results in distinct color changes and loss of gelation properties, thus highlighting the potential of these gels in sensing. The results represent a rare example of two-component organogels using two different cyanostilbene units and show that functional two-component organogels can be formed by utilizing the synergistic effects of the individual components.

CD151 is an abundantly expressed eukaryotic transmembrane protein on the cell surface. It is involved in cell adhesion, angiogenesis and signal transduction as well in disease conditions such as cancer and viral infections. However, the molecular mechanism of CD151 activation is poorly understood due to the lack of structural information. By considering the difficulties in expressing the membrane protein in E. coli, herein we introduce the strategic design for the effective expression of recombinant CD151 protein in E. coli with high yield, that would aid for the structural studies. CD151 having four transmembrane domain (TMD's) along with small and a large extracellular loop (LEL) is constructed in parts to enhance the soluble expression of the protein attached with fusion tag. This has led to the high yield of the recombinant CD151 protein in the designed constructs. The recombinant CD151 protein is characterized and confirmed by western blot, CD and Mass peptide fingerprint. The molecular dynamics simulations (MDS) for the full-length CD151 shows conformational changes in the LEL of the protein in the presence and absence of cholesterol and indicate the certainty of closed and open conformation of CD151 based on cholesterol binding. The MDS results have led to the understanding of the possible underlying mechanism for the activation of the CD151 protein.

The crystal structures of four derivatives of diethyl 2-(((aryl)amino)methylene)malonate (DAM) have been studied by single crystal X-ray diffraction. The molecular structures of all the four derivatives were found to be in co-planar conformation. The detailed analysis of molecular conformation in four derivatives reveals the presence of a common strong intramolecular N–H⋯O hydrogen bonding, forming a ring of graph-set motif S11 (6). The effect of chloro and nitro substitution on their relative strengths of hydrogen bonding are analyzed here. Particularly, in compound 1, additional intramolecular hydrogen bonding between –NO2 and N–H was observed that results in the formation of another six-membered chelate ring. On the other hand in case of compound 3, we have observed type-I Cl⋯Cl interaction for the first time in this class of compounds. Further, Hirshfeld surface has been generated that is mapped with dnorm shape index and curvedness to summarize the weak interactions and examine the molecular shapes in all four derivatives. Effect of nitro (1 and 2) and chloro (3 and 4) substitution on the C⋯H, N⋯O and C⋯O interaction is highlighted in molecular contour and 2D fingerprint plots.

Helicobacter pylori (H. pylori), the major cause of several gastric disorders has been recognied as a type I carcinogen. By virtue of resistance developed by H. pylori strains, currently used antibiotic based treatments rather demonstrate high failure rates. Hence, there is an emerging need for identification of new targets to treat H. pylori infection. Inosine-5′-monophosphate dehydrogenase (IMPDH) has been studied as a potential target to treat H. pylori infection. Here, a detailed enzyme kinetic study of recombinant expressed H. pylori inosine-5′-monophosphate dehydrogenase (HpIMPDH) is presented. A new in-house synthesized indole-based scaffold is identified as an inhibitor for HpIMPDH. These indole-based compounds showed non-competitive inhibition against IMP and NAD+ whereas the benzimidazole compounds were found be uncompetitive inhibitors. The new indole scaffold ensures specificity due to its high selectivity for bacterial IMPDH over human IMPDH II. Our work aims to overcome the drawback of existing inhibitors by introducing new indole scaffold for targeting bacterial IMPDH.

Oximes are building block of organic synthesis and they have wide range applications in laboratories, industries, and pharmaceutical as antidotes. Herein we report the crystal structures of oxime derivative Beta-p-Dimethylaminodeoxybenzionoxime (I) and o-Chloro-p-dimethylaminodeoxybenzion (II) the precursor molecule of o-Chloro-p-dimethylaminodeoxybenzionoxime and their intermolecular interactions studies through Hirshfeld surface & 2D-fingerprint plot analysis along with PIXELC and DFT calculations. The packing arrangements in I and II are driven by O H⋯N and O H⋯C interactions respectively. The O H⋯N hydrogen bonding in I facilitates the formation of the dimer with the motif of R (22(6)), whereas in II absence of oxime moiety ( NOH) restricts the dimer formation. The 2D-fingerprint plot shows the close contacts for the intermolecular interactions in I & II. The PIXELC calculation of II suggests O H⋯C contributes for intermolecular interaction that stabilizes the crystal packing with the total energy value of 60.4 kcal/mol. The DFT calculation using B3LYP with 6-311G (d, p) functional set for both the derivatives shows a small deviation in the benzene ring (I) and chlorobenzene ring (II) with the RMSD value of 0.5095 A and 0.8472 A respectively.

In the title isoxazole derivative, the phenyl and isoxazole rings are in the same plane, as indicated by the C—C—C—O torsion angle of 0.1 (3)°. The ester group has an extended conformation and is almost in the same plane with respect to the isoxazole ring, as indicated by the O—C—C—N torsion angle of −172.86 (18)°., The title compound, C12H11NO3, is an inter­mediate used in the synthesis of many drug-like mol­ecules. The mol­ecule is almost planar, with the phenyl ring inclined to the isoxazole ring by 0.5 (1)°. The ester moiety has an extended conformation and is almost in the same plane with respect to the isoxazole ring, as indicated by the O—C—C—N torsion angle of −172.86 (18)°. In the crystal, mol­ecules are linked via pairs of C—H⋯O hydrogen bonds with the same acceptor atom, forming inversion dimers with two R 2 1(7) ring motifs. The mol­ecules stack in layers lying parallel to (10-3). Analysis using Hirshfeld surface generation and two-dimensional fingerprint plots explores the distribution of weak inter­molecular inter­actions in the crystal structure.

Gamma secretase activating protein (GSAP) present in β-amyloid pathway orchestrates the formation of β-amyloid plaques by γ-secretase activation and is an emerging therapeutic target for the treatment of Alzheimer's disease. It forms a ternary complex with γ-secretase and APP C-99. However, there are limited reports for the interaction of APP C-99 with GSAP. Here, we report the characterization of purified maltose binding protein (MBP) tagged human GSAP and its interaction with synthetic APP C-99 peptide fragments (712IATVIVITLVMLKKQ727 (712IQ727), 719TLVMLKKKQYTSIHHGVVEVDAAVT743 (719TT743) 734GVVEVDAAVTPEERHLSKMQQNGY757 (734GY757), and 746ERHLSKMQQNGYENPTYKFFEQMQN770 (746EN770)). The results emphasize the selective interaction of peptide (719TT743) with MBP-GSAP with a dissociation constant of 0.136 μM. Further, computational modeling of the GSAP-719TT743 complex finds an optimal bound pose of 719TT743 within an extended groove on the surface of GSAP. The preliminary results highlight the interaction between the two major proteins in the plausible ternary complex: APP C-99-GSAP-γ-secretase. It paves a futuristic path to investigate the GSAP-APP C-99 binding in detail and accentuates the role of GSAP in the β-amyloid pathway.

The syntheses of newmyo-inositol derivatives have received much attention due to their important biological activities. 1,2-O-Cyclohexylidene-myo-inositol is an important intermediate formed during the syntheses of certainmyo-inositol derivatives. We report herein the crystal structure of 1,2-O-cyclohexylidene-myo-inositol dihydrate, C12H20O6·2H2O, which is an intermediate formed during the syntheses ofmyo-inositol phosphate derivatives, to demonstrate the participation of water molecules and hydroxy groups in the formation of several intermolecular O—H...O interactions, and to determine a low-energy conformation. The titlemyo-inositol derivative crystallizes with two water molecules in the asymmetric unit in the space groupC2/c, withZ= 8. The water molecules facilitate the formation of an extensive O—H...O hydrogen-bonding network that assists in the formation of a dense crystal packing. Furthermore, geometrical optimization and frequency analysis was carried out using density functional theory (DFT) calculations with B3LYP hybrid functionals and 6-31G(d), 6-31G(d,p) and 6-311G(d,p) basis sets. The theoretical and experimental structures were found to be very similar, with only slight deviations. The intermolecular interactions were quantitatively analysed using Hirshfeld surface analysis and 2D (two-dimensional) fingerplot plots, and the total lattice energy was calculated.

Two derivatives of pyrazole have been synthesized with one of the systematic substitutions made on the ortho position of the phenyl ring attached to the pyrazole moiety and characterised via single crystal X-ray diffraction. The nature of the molecules appear as planar with the hydrogen bonding features analysed quantitatively. The derivatives are geometrically optimized and studied for its molecular confirmation at the B3LYP/6-311G (d,p). The structure overlay, molecular packing and intermolecular hydrogen bonding are studied quantitatively using Hirshfeld surface and 2D fingerprint plots. In both the compounds, packing of the molecules is derived via strong O–H···N and weak C–H···O, C–H···π interactions stabilizing the packing. Further, the structure overlay between the experimental structures and the geometrically optimized structures along with frequency analysis at the quantum chemical level shows the deviation in the central pyrazole moiety and the substituted phenyl ring with the RMSD value of 0.5051 and 0.6305 A respectively. The lattice energy is calculated for both the compounds using PIXELC module in Coulomb–London–Pauli (CLP) package and is partitioned into corresponding coulombic, polarization, dispersion and repulsion contributions.

Gefitinib or Iressa is an orally administered anilinoquinazoline used in cancer chemotherapy for the treatment of lung and breast cancer. It is reported to exist in two polymorphic forms, a stable form I and a metastable form II. Both of the forms belong to the triclinic P\overline{1} space group. In this work, we report the crystallization of Gefitinib to form a methanol solvate [systematic name: N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine methanol hemisolvate, C22H24ClFN4O3·0.5CH3OH] that was theoretically and experimentally investigated. The unit cell is composed of two independent Gefitinib molecules (A and B) that form a stable molecular complex with methanol in the crystal lattice. To understand the crystal lattice stabilization, a combination of techniques, namely X-ray diffraction, IR spectroscopy, thermogravimetric/differential scanning calorimetry (TG-DSC), Hirshfeld surface analysis and CLP-PIXEL methods were used. The analysis of the crystal structure of this dimer revealed a three-dimensional isostructurality with the already reported form II. The A and B molecules are connected via trifurcated C—H...O and N—H...O hydrogen bonding. In addition, the presence of the methanol molecule stabilizes the crystal structure via C—H...O, N—H...O and C—H...Cl interactions between the two monomers. The IR analysis of the dimer has shown characteristic fingerprint values when compared to the commercial form. The TG-DSC analysis of the solvated dimer is in good agreement with the patent reporting cocrystals of Gefitinib. Finally, theoretical calculations by the CLP-PIXEL method and Hirshfeld surface and two-dimensional (2D) fingerprint plot analysis were carried out in order to quantify the different intermolecular interactions and their energies in the crystal packing.

α-Cyanostilbene substituted with dimethylaniline and hydroxyl groups exhibits profound intensity enhanced bathochromic shifts in an aqueous medium as compared to organic solvents. These conspicuous emission changes are attributed to aggregation as a consequence of restricted intramolecular rotation. This observation is commonly termed as aggregation induced enhanced emission (AIEE). Single crystal X-ray crystallographic data suggest a zigzag molecular packing arrangement with intermolecular hydrogen bonding between –CN and –OH moieties. This unique observation is exploited as a diagnostic tool to probe amphiphilic compounds in aqueous media. Fluorescence investigations reveal that at lower surfactant concentrations emission due to aggregation is preserved, while at higher surfactant concentrations the aggregated emission is lost with concomitant changes to the micelle structure. Dynamic light scattering (DLS) and Scanning Electron Microscopy (SEM) experiments were used to examine the effect of surfactants on the particle size and morphology, respectively. This sensitive AIEE fluorescence response can also be visually observed by using a hand-held UV lamp.

Crystals of a new salt in 2:1 ratio of 2-aminopyridine and malonic acid are grown by slow evaporation. These crystals of bis(2-aminopyridinium) malonate are orthorhombic and belong to the non-centrosymmetric space group, Fdd2 with parameters a = 22.0786(6), b = 23.0218(6), c = 5.5595(1)angstrom and Z=8 at 300 K. The crystals are isostructural to those of bis(2-aminopyridinium) maleate, which is a NLO material. The isostructurality index between bis(2-aminopyridinium) maleate and bis(2-aminopyridinium) malonate was also calculated. The hyperpolarizability calculated using semi empirical method MOPAC2009 showed that bis(2-aminopyridinium) malonate has slightly higher beta value compared to that of bis(2-aminopyridinium) maleate. (C) 2011 Elsevier B.V. All rights reserved.

Novel chromogenic thiourea based sensors 4,4'-bis-[3-(4-nitrophenyl) thiourea] diphenyl ether 1 and 4,4'-bis-[3-(4-nitrophenyl) thiourea] diphenyl methane 2 having nitrophenyl group as signaling unit have been synthesized and characterized by spectroscopic techniques and X-ray crystallography. The both sensors show visual detection, UV-vis and NMR spectral changes in presence of fluoride and cyanide anions in organic solvent as well as in aqueous medium. The absorption spectra indicated the formation of complex between host and guest is in 1:2 stoichiometric ratios. (C) 2010 Elsevier B.V. All rights reserved.

Crystal and molecular structures of four low melting halogenated trifluoroacetophenones along with the corresponding nitro derivative have been determined to understand the nature of short halogen−halogen and halogen−oxygen intermolecular contacts. The first four compounds, which are liquids at room temperature, have been analyzed using the technique of in situ cryocrystallography. The basic building block in the crystal lattice is invariant because of an intramolecular C−H···F contact, which locks the molecular conformation. The supramolecular assembly in all these structures is stabilized with additional C−H···O, C−H···F, and aromatic π···π intermolecular interactions. The nitro derivative is further stabilized by intramolecular C−H···O contacts.

The low-temperature crystal structures of 4-fluoroaniline and 2-fluoroaniline, determined following in situ crystal growth from the liquid, reveal the importance of both strong hydrogen bonds and weak intermolecular interactions involving fluorine generating different packing motifs in the crystalline solid in the isomeric molecules.

The title compound, $C_{{21}H_{24}O_{6}}$, is the reduced form of curcumin, and exhibits important cosmoceutical properties. The molecule is non-planar and the benzene rings positioned at the ends of the heptane chain are orthogonally placed, with a dihedral angle of 84.09$(7)^{\mathrm{0}}$ between them. The molecular geometry and H-atom locations reveal that the 'heptane-3,5-dione' moiety exists in the keto-enol form, with the hydroxy H atom disordered over two adjacent sites. The packing of the molecules in the lattice is directed by strong O-H...O intermolecular hydrogen bonds, which generate two-dimensional sheets. These sheets arelinked by C-H...O hydrogen bonds and weak C-H... interactions to develop a three-dimensional network.

In 2,4-diamino-5-(p-chlorophenyl)-6-ethylpyrimidinium hydrogen adipate, $C_{12}H_{14}ClN_4^+.C_6H_9O_4_^-$, the protonated pyrimethamine cation interacts with the carboxylate group of the adipate ion through $N-H^{...}O$ hydrogen bonds, forming a cyclic hydrogen-bonded $R_2^2(8)$ motif. The carboxyl and carboxylate groups of the adipate ions are linked through $O-H^{...}O$ hydrogen bonds in a head-to-tail fashion, forming a chain. Anions and cations are further connected by an extensive network of $N-H^{...}O$ hydrogen bonds.