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Owing to the broad applications of quaternary ammonium salts (QAS), we present the synthesis of benzimidazolium-based analogues with variation in the alkyl and alkoxy group at N-1 and N-3 positions. All the compounds were characterized by spectroscopic techniques and found stable to air and moisture both in the solid and solution state. Moreover, molecular structures were established through single-crystal X-ray diffraction studies. The crystal packing of the compounds was stabilized by numerous intermolecular interactions explored by Hirshfeld surface analysis. The enrichment ratio was calculated for the pairs of chemical species to acquire the highest propensity to form contacts. Void analysis was carried out to check the mechanical response of the compounds. Furthermore, theoretical investigations were also performed to explore the optoelectronic properties of compounds. Natural population analysis (NPA) has been conducted to evaluate the distribution of charges on the synthesized compounds, whereas high band gaps of the synthesized compounds by frontier molecular orbital (FMO) analysis indicated their stability. Nonlinear optical (NLO) analysis revealed that the synthesized QAS demonstrates significantly improved NLO behaviour than the standard urea.

Abstract A large number of new synthetic compounds are synthesized in the field of heterocyclic chemistry having a variety of biological potentials. In the present study, some synthetic indole derivatives are used to check anti-inflammatory, analgesic, antipyretic and gastroprotective activity in albino mice. Albino mice of either sex of reproductive age were used for each study (n = 5). In anti-inflammatory activity, the negative control (NC) and positive control group animals were treated with normal saline and 10 mg/kg of indomethacin respectively. The treated groups received the twenty four different synthetic chemicals, after 30 min of sub cutaneous injection of carrageenan. In analgesic activity, hot-plate method is used and for each group the latency period was recorded at zero moment of the provision of required dose and after 30, 60, 90, 120 and 180 min. In anti-pyretic activity, Pyrexia was induced by using Brewer's yeast method. Before any treatment and then after duration of 18 h, the rectal temperatures were recorded. Among all the chemicals, only those chemicals which show any potential related to above mentioned activities were selected for gastroprotective activity. The gastroprotective activity was performed to check the gastric ulcers by using 300 mg/kg of single oral dose of indomethacin to animals of all groups except NC group. This study helped to screen out the most potent indole derivatives 3a-II and 4a-II from the 24 synthetic indole derivatives which demonstrated the best biological potential (anti-inflammatory, analgesic, antipyretic, and gastroprotection) as compared to the remaining ones. The micrometric and biochemical results also support the histological findings. Out of the twenty-four novel indole amines tested, 3a-II and 4a-II have shown the effective pharmacological capacity and additionally have not shown any overt and systemic toxicity. Thus these two indole amines need further in-depth pharmacokinetic and pharmacodynamics studies before they are recommended for any pre-clinical trial.

Peptoids mimic the functions of peptides which have a side chain appended to amidic nitrogen instead of α carbon. This structural change in their backbone gives them increased resistance from proteolysis, improved biostability, greater immunogenicity, and better bioavailability. Therefore, they are specifically designed for various biological activities, including antibacterial, antifungal, antioxidant, antifouling, and anticancer properties. The aim of the research is the one-pot synthesis of quinoline-based peptoids 5(a-b) via Ugi-4CR by the reaction of 1R-(-)-myrtenal 1, benzylamine 2, quinoline-based carboxylic acids 3(a-b), and cyclohexyl isocyanide 4. These peptoids were characterized by FT-IR, 1H NMR, 13C NMR, and HR ESI-MS. In computational studies, the spectral results of 5(a-b) were compared with the calculated spectral values computed at B3LYP/6-311G (d,p) level. TD-DFT method was used to predict electron excitation of 5(a-b) and the contribution of orbitals. The electronic transition of peptoids from charge distribution was computed using natural bond order (NBO) analysis. NPA and MEP analysis was calculated to predict charge distribution in 5(a-b). The FMOs analysis was executed to calculate the global reactivity descriptor to predict the reactivity and stability of peptoids. DFT analysis showed that 5b was slightly more reactive than 5a due to extended conjugation. The biological activities were also predicted using an in silico approach that involved molecular docking and molecular dynamic (MD) simulations. The antiulcer, antibacterial, and antifungal activities were predicted based on ligand–protein binding interactions, binding energy calculations, and dissociation constants. 5(a-b) were evaluated in-vitro for anticholinesterase activity, and they showed 71% inhibition. The umbrella sampling was performed to probe ligand–protein binding.

The pharmacological effectiveness of indoles, benzoxazepines and benzodiazepines initiated our synthesis of indole fused benoxazepine/benzodiazepine heterocycles, along with enhanced biological usefulness of the fused rings. Activated indoles 5, 6 and 7 were synthesized using modified Bischler indole synthesis rearrangement. Indole 5 was substituted with the trichloroacetyl group at the C7 position, yielding 8, exclusively due to the increased nucleophilic character of C7. When trichloroacylated indole 8 was treated with basified ethanol or excess amminia, indole acid 9 and amide 10 were yielded, respectively. Indole amide 10 was expected to give indole fused benoxazepine/benzodiazepine 11a/11b on treatment with alpha halo ester followed by a coupling agent, but when the reaction was tried, an unexpectedly rearranged novel product, 1,3-bezodiazine 12, was obtained. The synthetic compounds were screened for anticholinesterase and antibacterial potential; results showed all products to be very important candidates for both activities, and their potential can be explored further. In addition, 1,3-bezodiazine 12 was explored by DFT studies, Hirshfeld surface charge analysis and structural insight to obrain a good picture of the structure and reactivity of the products for the design of derivatised drugs from the novel compound.

The work here reflects synthesis, DFT studies, Hirshfeld charge analysis and crystal data exploration of pharmacologically important (R)-2-(2-(1,3-dioxoisoindolin-2-yl)propanamido)benzoic acid methyl ester (5) to understand its properties for further chemical transformations. The methyl anthranilate (2) was produced by the esterification of anthranilic acid in an acidic medium. The phthaloyl-protected alanine (4) was rendered by the fusion of alanine with phthalic anhydride at 150 °C, followed by coupling with (2) furnished isoindole (5). The characterization of products was performed using IR, UV-Vis, NMR and MS. Single-crystal XRD also verified the structure of (5) in which N-H⋯O bonding stabilizes the molecular configuration of (5), resulting in the formation of S(6) hydrogen-bonded loop. The molecules of isoindole (5) are connected in the form of dimers, and the π⋯π stacking interaction between aromatic rings further stabilizes the crystal packing. DFT studies suggest that HOMO is over the substituted aromatic ring, the LUMO is present mainly over the indole side, and nucleophilic and electrophilic corners point out the reactivity of the product (5). In vitro and in silico analysis of (5) shows its potential as an antibacterial agent targeting DNA gyrase and Dihydroorotase from E. coli and tyrosyl-tRNA synthetase and DNA gyrase from Staphylococcus aureus.

Peptic ulcer is a common disorder of the gastrointestinal system affecting people of all ages worldwide. Ethanol is one of the most common causative agents for peptic ulcer. The aim of this study was to evaluate the protective effect of two newly synthesized indole imines (389 and 393) against ethanol-induced gastric ulcer in rats. Animals were orally administered different treatments: group I–II (vehicle & ulcer controls, respectively); 0.5% aqueous CMC solution, group III (standard control; omeprazole; 20 mg/kg bw); groups IV–VI, test compound 389 (20, 40 and 60 mg/kg bw) and groups VII–IX, test compound 393 (20, 40 and 60 mg/kg bw). Various parameters including pH, gastric contents, ulcer index and percentage protection were determined and histopathological study of gastric mucosa was performed to evaluate the protective effect of the test compounds. Oral administration of the test compounds, i.e. 389 and 393 (20, 40 and 60 mg/kg bw), significantly (p

The lack of safety and efficacy of existing hepatoprotective agents urge the need to explore novel hepatoprotective agents. The research work was planned to study the therapeutic potential of some newly synthesized chalcones against 4-acetaminophenol induced hepatotoxicity in rats. Male albino rats (N = 30) were divided into 6 groups of 5 animals each i.e. group I; Toxic control (4-acetaminophenol), group II; normal control (Normal saline), group III; Positive control (silymarin; 50 mg/kg bw) and groups IV-VI (test groups) treated with 3 chalcone analogues i-e 3a, 3f & 3 g (100, 150, 150 mg/kg bw, respectively). All the study group animals were administered with 4-acetaminophenol to induce hepatotoxicity except normal control. Following hepatotoxicity induction, test group animals were administered with selected doses of test compounds and toxic group animals left untreated. Liver enzymes including ALT, AST, ALP and serum bilirubin were determined photometrically. Antioxidant activities of test compounds were also determined. Histopathological examination of liver biopsies was also carried out through H & E staining. The test chalcones ( 3a , 3f & 3 g ) significantly decreased the levels of liver enzymes and serum bilirubin toward normal and the pattern of results in the test group animals were comparable to silymarin administered animals indicating the hepatoprotective potential of test compounds. Moreover, the test chalcones ( 3a , 3f & 3 g ) antagonized the effect of 4-acetaminophenol and thus, raised the catalase (CAT) and superoxide dismutase (SOD) while decreased the malondialdehyde (MDA) in experimental animals. The test chalcones ( 3a , 3f & 3 g ) on histological examination of liver showed improvement of tissue morphology. The study concluded that the tested compounds have antioxidant potential and may act as hepatoprotective agent. However, in-depth studies are required to validate their safety and to elucidate the exact mechanism of action.

The float formulation is a strategy to improve the bioavailability of drugs by gastroretentive drug delivery system (GRDDS). A drug delivery model based on swellable and reswellable low density biopolymers has been designed to evaluate its drug release profile using ranitidine (RNT) as a model drug and formulations have been prepared utilizing 32 factorial designs. The drug release (DR) data has been subjected to various kinetic models to investigate the DR mechanism. A reduction in rate has been observed by expanding the amounts of PSG and LSG parts, while an expansion has been noted by increasing the concentration of tragacanth (TG) and citric acid (CA) with an increment in floating time. The stearic acid (SA) has been used to decrease the lag time because a decrease in density of system was observed. The kinetic analysis showed that the optimized formulation (S4F3) followed zero-order kinetics and power law was found to be best fitted due to its minimum lag time and maximum floating ability. The resemblance of observed and predicted values indicated the validity of derived equations for evaluating the effect of independent variables while kinetic study demonstrated that the applied models are feasible for evaluating and developing float for RNT.

Novel chiral 4,1-benzoxazepine-2,5-diones have been unusually synthesized in a single step by exploiting the chiral pool methodology. Substituted anthranilic acids afford N-acylanthranilic acids and (3R)-3-alkyl-4,1-benzoxazepines-2,5-dione upon coupling with α-chloroacids or α-bromoacids, respectively.

We report an efficient silica-H2SO4 mediated synthesis of a variety of chalcones that afforded the targeted compounds in very good yield compared to base catalyzed solvent free conditions as well as acid or base catalyzed refluxing conditions.

In the title compound, C14H12ClNO2, the dihedral angle between the aromatic rings is 14.87 (11)° and an intramolecular N—H...O hydrogen bond generates an S(6) ring. In the crystal, molecules are linked by O—H...O hydrogen bonds, generating C(6) chains propagating along the c-axis direction.

In the title compound, C13H13NO4, the dihedral angle between the nine-membered phthalimino ring system and the carboxylic acid group is 67.15 (9)°. An intramolecular C—H...O close contact, which forms an S(6) ring, may help to establish the molecular conformation. In the crystal, molecules are linked by O—H...O hydrogen bonds, thereby forming C(7) chains propagating in [010].

In the crystal structure of the title compound, C14H13NO2, the molecules are approximately planar, the r.m.s. deviation for all non-H atoms being 0.0435 Å; the dihedral angle between the two rings is 3.45 (12)°. The planarity is accounted for in terms of the presence of intramolecular N—H...O and C—H...O hydrogen bonding, each of which completes an S(6) ring motif. The molecules are stabilized in the form of supramolecular chains extending along the crystallographic c axis due to intermolecular O—H...O and C—H...O hydrogen bonding; each type leads to an R21(6) ring motif.

In the essentially planar (r.m.s. deviation = 0.023 Å) title compound, C10H6Br2O, an intramolecular O—H...Br hydrogen bond generates an S(5) ring. In the crystal, molecules are linked by an ...O—H...O—H...O— C(2) chain extending along [100], which involves the same H atom that participates in the intramolecular hydrogen bond. Aromatic π–π interactions [centroid–centroid separation = 3.737 (4) Å] help to consolidate the packing.

In the title compound, C10H6N2O5, the two fused rings are almost co-planar, with an r.m.s. deviation of 0.0163 Å. The nitro groups are oriented at dihedral angles of 2.62 (11) and 44.69 (11)° with respect to the plane of the parent fused rings. Intramolecular O—H...O and C—H...O hydrogen bonds complete S(6) ring motifs. In the crystal, molecules are linked into chains along [101] by intermolecular O—H...O hydrogen bonds. π–π interactions [centroid–centroid distances = 3.6296 (15), 3.8104 (15) and 3.6513 (14) Å] might play a role in stabilizing the structure.

In the title compound, C13H10ClNO2, the dihedral angle between the aromatic rings is 5.57 (9)° and intramolecular N—H...O and C—H...O hydrogen bonds both generate S(6) rings. In the crystal, molecules are linked by O—H...O hydrogen bonds into C(6) chains propagating along [010]. Molecules from neighbouring chains along the z axis are involved in C—H...π and π–π stacking interactions [centroid–centroid distance = 3.9340 (10) Å].

The asymmetric unit of the title compound, C7H5ClO3, contains two molecules; both feature an intramolecular O—H...O hydrogen bond, which generates an S(6) ring. In the crystal, both molecules form inversion dimers linked by pairs of O—H...O hydrogen bonds with R22(8) ring motifs. The dimers are interlinked by C—H...O interactions.

In the title compound, C12H9NO3S, the isoindoline-1,3-dione group is almost planar, with an r.m.s. deviation of 0.020 Å, whereas the heterocyclic ring approximates to an envelope with the methylene group not adjacent to the S atom in the flap position. A short intramolecular C—H...O contact generates an S(6) ring motif. In the crystal structure, weak aromatic π–π stacking interactions occur between the centroids of the benzene rings at a distance of 3.558 (2) Å.

In the title compound, C13H10ClNO2, the dihedral angle between the aromatic rings is 20.02 (6)° and intramolecular N—H...O and C—H...O hydrogen bonds both generate S(6) rings. In the crystal, molecules are linked by O—H...O hydrogen bonds into C(6) chains propagating in [010].

In the crystal structure of title compound, C13H10N2O4, as expected, the nitro- and hydroxy-substituted benzene rings are planar with r. m. s. deviations of 0.0037 and 0.0014 Å, respectively, but are twisted slightly relative to each other, making a dihedral angle of 12.23 (7)°. The nitro group is only slightly twisted [by 2.71 (16)°] with respect to its parent ring. An intramolecular N—H...O hydrogen bond forms an S(6) ring motif. Intermolecular N—H...O and O—H...O hydrogen bonds build up sheets parallel to the ab plane. Futhermore, weak π–π interactions [centroid–centroid distances = 3.7150 (8) 3.7342 (6) and 3.9421 (8) Å] between the rings yield a three-dimensional network.

The molecule of the title compound, C13H10N2O4, is almost planar with a dihedral angle between the benzene rings of 1.99 (13)°. The nitro group and its parent benzene ring are oriented at a dihedral angle of 7.6 (3)°. Intramolecular C—H...O and N—H...O hydrogen bonds form two planar S(6) motifs. Intermolecular O—H...O=C hydrogen bonds join molecules into chains extending along the c axis.

The title compound, C8H8N2O4, is almost planar (r.m.s. deviation = 0.037 Å) and an intramolecular N—H...O hydrogen bond generates an S(6) ring. In the crystal, inversion dimers linked by pairs of O—H...O hydrogen bonds generate R22(8) loops. Intermolecular N—H...O hydrogen bonds (involving the same H atom that forms the intramolecular hydrogen bond) link the dimers into infinite sheets lying parallel to (102).

The asymmetric unit of title compound, C18H16O2, contains two molecules with slightly different conformations. In the first molecule, the two phenyl rings make dihedral angles of 84.98 (11)° and the five-membered ring makes dihedral angles of 84.80 (12) and 73.00 (12)° with the phenyl rings; the corresponding angles for the second molecule are 86.74 (11), 81.20 (13) and 71.36 (12)°. O—H...O hydrogen bonds between the hydroxy and carbonyl groups are a feature of the crystal packing, which results in chains extending parallel to [100]. Weak C—H...O and C—H...π interactions are also observed.

In the title coordination polymer, [Na(C8H7O2)(H2O)2]n, the cation is chelated by the carboxylate O atoms of the anion in a bidentate mode and is surrounded by the O atoms of four water molecules. The coordination of the Na+ cation is distorted octahedral. The water molecules bridge adjacent metal cations, forming polymeric layers parallel to (100). The structure is stabilized by an extensive network of O—H...O hydrogen bonds.

In the crystal of the title coordination polymer, [Na(C8H5N2O6)]n, the Na(I) ion is linked to five nearby anions. Their bonding modes are three monodentate carboxylate O atoms, one O,O′-bidentate carboxylate group and one O,O′-bidentate nitro group. This results in an irregular NaO7 coordination geometry for the metal ion. This connectivity leads to a layered network propagating in (100).

In the title compound, C9H8N2O6, the methyl ester group is almost planar (r.m.s. deviation = 0.002 Å) and is oriented at a dihedral angle of 24.27 (16)° with respect to the benzene ring. The nitro groups make dihedral angles of 4.2 (5)° and 60.21 (11)° with the benzene ring. In the crystal, molecules are linked by C—H...O interactions, resulting in zigzag chains.

In the title compound, C7H6N2O4, an intramolecular O—H...O hydrogen bond generates an S(6) ring. In the crystal, inversion dimers linked by pairs of N—H...O hydrogen bonds occur. Weak C—H...O links consolidate the packing, leading to R21(7) and R22(10) loops within (100) polymeric sheets.

In the title compound, C10H9IO, the asymmetric unit contains two molecules, in which the iodo-bearing six-membered rings adopt envelope conformations [displacements of the flap atoms = 0.419 (3) and 0.431 (3) Å]. In both molecules, the I atoms are disordered over two set of sites in 0.54 (4):0.46 (4) and 0.71 (3):0.29 (3) ratios. In the crystal, the packing features a weak C—H...π interaction.

In the title compound, C8H6N2O6, the O atoms of the nitro groups, the methyl H atoms and the carboxyl C=O and C—OH groups are disordered over two sets of sites with an occupancy ratio of 0.595 (16):0.405 (16). In the crystal, inversion dimers linked by pairs of O—H...O hydrogen bonds arise for both carboxyl disorder components and C—H...O bonds and weak C—H...π interactions consolidate the packing.

The crystal structure of the title compound, C11H9NO4, consists of infinite one-dimensional polymeric chains due to intermolecular O—H...O hydrogen bonds between the carboxylate and carbonyl groups. The phthalimide ring system and the C—COO group are planar, with r.m.s. deviations of 0.0253 and 0.0067 Å, respectively, from their mean square planes and the dihedral angle between them is 66.41 (7)°. The molecules are stabilized by C=O...π interactions and weak intramolecular C—H...O hydrogen bonds.

The title compound, C13H13NO4S, the 1,3-dioxoisoindolin-2-yl unit is planar (r.m.s. deviation 0.0192 Å) and is oriented at a dihedral angle of 79.14 (18)° to the carboxylate group. An intramolecular C—H...O hydrogen bond leads to the formation of a planar (r.m.s. deviation 0.0419 Å)R(5) ring motif. In the crystal, molecules are connected through O—H...O and C—H...O hydrogen bonds with R22(9) ring motifs into chains extending along the b axis.

The asymmetric unit of title compound, C7H6N2O4, contains two molecules, one of which has a disordered nitro group with an occupancy ratio of 0.517 (9):0.483 (9) for the O atoms. Both molecules contain an intramolecular O—H...O hydrogen bond. In the crystal, both molecules form inversion dimers linked by pairs of N—H...O hydrogen bonds, resulting in R22(8) ring motifs. The dimers are connected by further N—H...O links and weak C—H...O interactions, resulting in a layered motif.

The asymmetric unit of the title compound, C13H10N2O4, contains two crystallographically independent molecules. The aromatic rings are oriented at dihedral angles of 24.39 (3) and 7.47 (3)° in the two molecules and intramolecular N—H...O and O—H...O hydrogen bonds result in the formation of two planar six-membered rings. In the crystal structure, intermolecular O—H...O and C—H...O hydrogen bonds link the molecules into chains, forming R22(10) ring motifs. Weak π–π contacts between the benzene and phenyl rings [centroid–centroid distance = 3.955 (3) Å] may further stabilize the structure.

In the centrosymmetric title compound, [Sn4(CH3)8(C6H5O2S)4O2], the central four-membered planar ring (Sn2O2) makes dihedral angles of 66.28 (12) and 77.43 (11)° with the heterocyclic rings of the bridging and monodentate ligands, respectively. One SnIV atom adopts a distorted SnO3C2 trigonal-bipyramidal geometry, with both C atoms in equatorial sites and the other a grossly distorted SnO4C2 octahedral or irregular arrangement. In the crystal, the molecules are connected into pillar-like polymeric units making R22(12) ring motifs due to intermolecular C—H...O interactions. C–H...π interactions are also present. The O atoms of the chelating ligands and the S atom of the monodentate ligand are disordered over two sets of sites in a 0.65 (6):0.35 (6) ratio