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Background Noscapine is a non-narcotic, antitussive alkaloid isolated from plants of Papaveraceae family. This benzylisoquinoline alkaloid and its synthetic derivatives, called noscapinoids, are being evaluated for their anticancer potential. Methods The structure of a novel analogue, N-(3-bromobenzyl) noscapine (N-BBN) was elucidated by X-ray crystallography. Effect of N-BBN on cancer cell proliferation and cellular microtubules were studied by sulphorhodamine B assay and immunofluorescence, respectively. Binding interactions of the alkaloid with tubulin was studied using spectrofluorimetry. Results N-BBN, synthesized by introducing modification at site B (‘N’ in isoquinoline unit) and a bromo group at the 9th position of the parent compound noscapine, was found to be superior to many of the past-generation noscapinoids in inhibiting cancer cell viability and it showed a strong inhibition of the clonogenic potential of an aggressively metastatic breast tumour cell line, MDA-MB-231. The compound perturbed the tertiary structure of purified tubulin as indicated by an anilinonaphthalene sulfonic acid-binding assay. However, substantiating the common feature of noscapinoids, it did not alter microtubule polymer mass considerably. In cells, the drug-treatment showed a peculiar type of disruption of normal microtubule architecture. Conclusion N-BBN may be considered for further investigations as a potent antiproliferative agent.

A new class of (E)-N-phenyl-3-styrylpyridin-2-amine conjugates were designed and synthesized on the basis of E7010 and resveratrol scaffolds. These conjugates were evaluated for their antiproliferative activity in four human cancer cell lines with GI50 values ranging from 2.1 μM to 20 μM. Two of the conjugates RSV-1 and RSV-11 were found to possess 13-fold higher GI50 values than resveratrol and 1 to 2 fold higher GI50 values than E7010 against the human cervical HepG2 cancer line. They displayed high potency and selectivity in a panel of NCI 60 human cancer cell lines. Based on the GI50 values against the panel of 60 NCI cancer cell lines and dock scores from the molecular modelling studies, we selected RSV-1 and RSV-11 for tubulin polymerization and mechanistic studies. Furthermore, RSV-1 and RSV-11 compounds inhibited the assembly of tubulin by strongly binding to the colchicine-binding site. The G2/M-phase is arrested in HepG2 cells as assessed by flow cytometry. Structure based studies, western blotting and immunofluorescence experiments demonstrated that RSV-1 and RSV-11 depolymerize microtubules in the HepG2 cell line, resulting in an accumulation of G2/M cells.

A palladium catalyzed domino coupling reaction of 1,4-disubstituted triazoles via homocondensation with a second molecule is presented. The domino couplings involve the formation of biaryl and bi(hetero)aryl bonds through a five membered carbopalladacycle intermediate. The approach provides a simple, straight forward and facile route to access triazolo[1,5-f]phenanthridines in high yields. Furthermore, the developed protocol was extended to heterocondensation in the presence of norbornene.

A mild and efficient AgOTf catalyzed alkyne-annulation/Diels–Alder cascade for the construction of tetrahydrospiro[carbazole-4,3′-indoline] derivatives has been established from N-tosyl-2-(but-3-en-1-yn-1-yl) aniline in the presence of methyleneindolinones. This strategy provides access to the one-pot synthesis of a new class of various novel and structurally complex spirooxindole molecules with high diastereoselectivity.

(±)-Asenapine, sold in the market as Saphris/Sycrest for the treatment of bipolar disorders, is synthesized in an optically pure form involving an Ireland–Claisen rearrangement as the key step. This approach allows access to all diastereomers.

The synthesis of oxazolines and oxazines from N-allylamides was accomplished via an unprecedented reaction set. This reaction involved an intramolecular cyclization of N-allylamides resulting from nucleophilic attack of the allylamine on the benzoxazin-4-one. Unlike the previous literature, the isolable N-allylamide could readily be subjected to exo and endo fashion ring-closure under conditions to afford the title compounds.

One dinuclear Cd(II) complex, [Cd2(μ-L)2(L)2(py)4] (1), and a mononuclear Zn(II) complex, [Zn(L)2(py)2] (2), have been prepared in aqueous methanol–DMF medium at ambient conditions by self-assembly from the metal(II) nitrates, 3,5-dinitrobenzoic acid (HL) and an ancillary pyridine (py) ligand. The complexes have been substantiated by elemental analyses, IR spectroscopy, UV–Vis spectra, fluorescence, PXRD and single-crystal X-ray diffraction studies. Complex 1 is a new triclinic ( P 1 ¯ ) polymorph. The monoclinic (P21/n) form (CSD reference code VESWOG) has previously been reported by Guo et al. (2006). The binuclear core in 1 comprises of two bridging 3,5-dinitrobenzoates, each of the Cd(II) centers is further coordinated to one bidentate 3,5-dinitrobenzoate and two pyridine ligands thereby completing a six-coordinate octahedral geometry. The structural aspects associated with the two polymorphs have been discussed in detail. In 2, the coordination environment around the Zn(II) ion is distorted tetrahedral with two monodentate 3,5-dinitrobenzoate moieties and two pyridine ligands. Density functional theory (DFT) calculations have been employed to calculate the energy difference between the polymorphic pair (1 and VESWOG). Finally, in the crystal packing of 1 and 2, the importance of various non-covalent interactions, such as π–π, lone pair(lp)–π and π–hole, has been highlighted and analyzed computationally.

A highly regio and diastereoselective copper catalyzed three component reaction of tetrahydroisoquinolines (THIQs), aldehydes, and naphthols to furnish naphthoxazine derivatives under mild conditions was developed. The initial generation of iminium ions followed by the nucleophilic attack of naphthol presumed to deliver 15-phenyl-7a,12,13,15-tetrahydronaphtho[1′,2′:5,6][1,3]oxazino[2,3-a]isoquinoline derivatives. The reaction ensured the formation of C–C, C–N and C–O bonds in a one-pot reaction to produce ring fused N,O-acetals in good yields. The three component reaction, the inexpensive copper catalyst in the absence of a co-oxidant/additive and the direct regioselective oxidative sp3 C–H functionalization are the attractive features of this approach. The preliminary photophysical properties obtained for selected compounds were presented.

Palladium catalyzed conversion of 1-(2-aminophenyl)-propargyl alcohols to 3-alkynyl quinolines is realized via a cascade that involves aminopalladation, oxidative coupling with alkynes and dehydration. The method is shown to have a broad substrate scope with respect to propargyl alcohols as well as alkynes. Vinyl ketones as coupling partners in the same reaction afforded 3-alkenyl quinolines with equal ease.

The common house hold pharmaceutical drug, paracetamol (PAR), has been synthesized from 4-chloroaniline as a first ever report. After the synthesis, good quality single crystals were obtained for slow evaporation technique under the room temperature. The crystal and molecular structures were re-determined by the single crystal X-ray diffraction. The vibrational spectral measurements were carried out using FT-IR and FT-Raman spectroscopy in the range of 4000–400 cm−1. The single crystal X-ray studies shows that the drug crystallized in the monoclinic system polymorph (Form-I). The crystal packing is dominated by N H⋯O and O H⋯O classical hydrogen bonds. The ac diagonal of the unit cell features two chain C(7) and C(9) motifs running in the opposite directions. These two chain motifs are cross-linked to each other to form a ring R44(22) motif and a chain C22(6) motif which is running along the a-axis of the unit cell. Along with the classical hydrogen bonds, the methyl group forms a weak C H⋯O interactions in the crystal packing. It offers the support for molecular assembly especially in the hydrophilic regions. Further, the strength of the hydrogen bonds are studied the shifting of vibrational bands. Geometrical optimizations of the drug molecule were done by the Density Functional Theory (DFT) using the B3LYP function and Hartree–Fock (HF) level with 6-311++G(d,p) basis set. The optimized molecular geometry and computed vibrational spectra are compared with experimental results which show significant agreement. The factor group analysis of the molecule was carried out by the various molecular symmetry, site and factor group species using the standard correlation method. The Natural Bond Orbital (NBO) analysis was carried out to interpret hyperconjugative interaction and intramolecular charge transfer (ICT). The chemical softness, chemical hardness, electro-negativity, chemical potential and electrophilicity index of the molecule were found out first time by HOMO–LUMO plot. The frontier orbitals shows lower band gap values signify the possible biological/pharmaceutical activity of the molecule. The thermodynamical properties are also obtained from the calculated frequencies of the optimized structures.

An efficient and mild one-pot, gold-catalyzed intramolecular cyclization of N-propargylic β-enaminones has been achieved for the generation of 1,4-oxazepine derivatives. This synthetic transformation tolerates a range of substituted N-propargylic β-enaminones in moderate to good yields.

6-Mercaptopurine (an anti cancer drug), is coming under the class II Biopharmaceutics Classification System (BCS). In order to enhance the solubility with retained physiochemical/pharmaceutical properties, the present work was attempted with its salt form. The single crystals of 6-mercaptopurinium chloride (6MPCl) were successfully grown by slow evaporation technique under ambient temperature. The X-ray diffraction study shows that the crystal packing is dominated by N–H⋯Cl classical hydrogen bonds leading to corrugated laminar network. The hydrogen bonds present in the lamina can be dismantled as three chain C21(6), C21(7) and C21(8) motifs running along ab-diagonal of the unit cell. These primary chain motifs are interlinked to each other forming ring R63(21) motifs. These chain and ring motifs are aggregated like a dendrimer structure leading to the above said corrugated lamina. This low dimensional molecular architecture differs from the ladder like arrays in pure drug though it possess lattice water molecule in lieu of the chloride anion in the present compound. Geometrical optimizations of 6MPCl were done by Density Functional Theory (DFT) using B3LYP function with two different basis sets. The optimized molecular geometries and computed vibrational spectra are compared with their experimental counterparts. The Natural Bond Orbital (NBO) analysis was carried out to interpret hyperconjugative interaction and Intramolecular Charge Transfer (ICT). The chemical hardness, electronegativity, chemical potential and electrophilicity index of 6MPCl were found along with the HOMO–LUMO plot. The lower band gap value obtained from the Frontier Molecular Orbital (FMO) analysis reiterates the pharmaceutical activity of the compound. The anticancer studies show that 6MPCl retains its activity against human cervical cancer cell line (HeLa). Hence, this anticancer efficacy and improved solubility demands 6MPCl towards the further pharmaceutical applications.

The single crystal of the hydrated anticancer drug, 6-Mercaptopurine (6-MP), has been grown by slow evaporation technique under room temperature. The structure was determined by single crystal X-ray diffraction. The vibrational spectral analysis was carried out using Laser Raman and FT-IR spectroscopy in the range of 3300–100 and 4000–400 cm−1. The single crystal X-ray studies shows that the crystal packing is dominated by N–H⋯O and O–H⋯N classical hydrogen bonds leading to a hydrogen bonded ensemble. This classical hydrogen bonds were further connected through O–H⋯S hydrogen bond to form two primary ring R44(16) and R44(12) motifs. These two primary ring motifs are interlinked with each other to build a ladder like structure. These ladders are connected through N–H⋯N hydrogen bond along c-axis of the unit cell through chain C(5) motifs. Further, the strength of the hydrogen bonds is studied through vibrational spectral measurements. The shifting of bands due to the intermolecular interactions was also analyzed in the solid crystalline state. Geometrical optimizations of the drug molecule were done by Density Functional Theory (DFT) using the B3LYP function and Hartree–Fock (HF) level with 6-311++G(d,p) basis set. The optimized molecular geometry and computed vibrational spectra are compared with experimental results which show significant agreement. The natural bond orbital (NBO) analysis was carried out to interpret hyperconjugative interaction and intramolecular charge transfer (ICT). The chemical hardness, electro-negativity and chemical potential of the molecule are carried out by HOMO–LUMO plot. In which, the frontier orbitals has lower band gap value indicating the possible pharmaceutical activity of the molecule.

Cocrystals are molecular solids composed of at least two types of neutral chemical species held together by noncovalent forces. Crystallization of thymine [systematic name: 5-methylpyrimidine-2,4(1H,3H)-dione] with four phenolic coformers resulted in cocrystal formation,viz.catechol (benzene-1,2-diol) giving thymine–catechol (1/1), C5H6N2O2·C6H6O2, (I), resorcinol (benzene-1,3-diol) giving thymine–resorcinol (2/1), 2C5H6N2O2·C6H6O2, (II), hydroquinone (benzene-1,4-diol) giving thymine–hydroquinone (2/1), 2C5H6N2O2·C6H6O2, (III), and pyrogallol (benzene-1,2,3-triol) giving thymine–pyrogallol (1/2), C5H6N2O2·2C6H6O3, (IV). The resorcinol molecule in (II) occupies a twofold axis, while the hydroquinone molecule in (III) is situated on a centre of inversion. Thymine–thymine base pairing is common across all four structures, albeit with different patterns. In (I)–(III), the base pair is propagated into an infinite one-dimensional ribbon, whereas it exists as a discrete dimeric unit in (IV). In (I)–(III), the two donor N atoms and one carbonyl acceptor O atom of thymine are involved in thymine–thymine base pairing and the remaining carbonyl O atom is hydrogen bonded to the coformer. In contrast, in (IV), just one donor N atom and one acceptor O atom are involved in base pairing, and the remaining donor N atom and acceptor O atom of thymine form hydrogen bonds to the coformer molecules. Thus, the utilization of the donor and acceptor atoms of thymine in the hydrogen bonding is influenced by the coformers.

A series of new tricyclic heterocyclic xanthene-1,8-diones tethered with chromophoric dibenzo [b, d]furan, dibenzo[b, d]thiophene and 9-methyl-9H-carbazoles were synthesized through one-pot condensation of dibenzo[b, d]furan-2-carbaldehyde, dibenzo[b, d] thiophene-2-carbaldehyde and 9-methyl-9H-carbazole-3-carbaldehyde with cyclic 1,3-dicarbonyls in the presence of recyclable PPA-SiO2 catalyst under solvent-free conditions. Further, UV-Visible absorption properties of all the synthesized compounds were investigated in CHCl3, THF and acetonitrile.

We report here a simple one-pot synthesis, characterization and cation recognition properties of two benzothiazole based ferrocenyl pyrazoline derivatives (4 and 5). These compounds behave as highly selective multichannel sensors towards Hg2+ and Cu2+ ions in acetonitrile solution. An anodic shift of the ferrocene/ferrocenium couple, with a progressive perturbation in the lower energy band, was observed upon interaction of the cations with these receptors. A colour change, from yellow to brown and red, for Hg2+ and Cu2+ ions respectively enabled facile “naked eye” detection using the ‘test strips’ prepared from these receptors. The competitive metal-ion binding experiments indicated high selectivity towards Hg2+ as compared to Cu2+ ions. A 45–59 fold chelation enhancement of fluorescence (CHEF) towards Hg2+ ion was observed in the emission spectrum of 4 and 5. 1H NMR studies and DFT calculations were used to determine the binding sites of receptor 4 involved in the complexation process.

The three-component coupling (3CC) of α-diazoamide, aldehyde and 3-arylideneoxindole using 5 mol-% of Rh2(OAc)4 is described to afford a novel class of dispirooxindole derivatives with complete regio- and stereoselectivity. It is a first report on the synthesis of natural product inspired libraries of dispirooxindoles through a carbonyl ylide cycloaddition.

A new polymorph of cytosine, C4H5N3O, is reported half a century after the report of its first known crystal structure [Barker & Marsh (1964).Acta Cryst.17, 1581–1587]. Cytosine thus provides the first polymorphic example in the category of parent nucleobases. The new form, denoted (Ib), was observed unexpectedly during an attempt to cocrystallize cytosine with catechol. Form (Ib) crystallizes in the orthorhombic centrosymmetric space groupPccnwith two molecules in the asymmetric unit. The previously known form, denoted (Ia), crystallizes in the orthorhombic noncentrosymmetric space groupP212121. The cytosine molecule is planar in both forms. Hydrogen-bonding interactions are also similar for both forms. Infinite one-dimensional ribbons composed of cytosine base-pair dimers inR22(8) arrangements are observed in both (Ia) and (Ib). However, the way that the ribbons are packed differs in (Ia) and (Ib). This appears to guide the centrosymmetricversusnoncentrosymmetric space-group selection through the formation of an inversion-related motif in polymorph (Ib) and a helical propagation in polymorph (Ia). A few selected polymorphic systems have been gathered from the Cambridge Structural Database to understand possible structural features responsible for achiral molecules adopting centro- and noncentrosymmetric space groups.

A series of 3-(allyloxy)-propylidene acetals 1a to 6a of some natural terpenoids like andrographolides 1, 2, forskolins 3–5 and arjunolic acid 6 were developed by a novel one pot synthetic strategy using ceric ammonium nitrate as a catalyst. The method is both chemo and regioselective towards 1,3-acetal formation without affecting other poly functional groups of terpenoids. O-Allylation is an important functional group transformation for alcohols and the resulting end allylic double bond may participate in a number of synthetically useful transformations like olefin metathesis. Acetal of andrographolide 1a was further converted into 1b, 1c and 1d by dimerization, acetylation and epoxidation respectively. All the synthesized compounds were screened for in vitro antiproliferative activity against four cancer cell lines B16F10, THP-1, PC-3 and SKOV3. Derivatives of andrographolide 1a, 1b, 1c and 2a, forskolin 4a and arjunolic acid 6a have shown promising cytotoxicity (IC50 < 10 μg ml−1) in most of the tested cell lines. Also compounds 1b (IC50 0.83 μg ml−1) and 5a (IC50 3.43 μg ml−1) showed significant α-glucosidase inhibition in an in vitro assay. Structures of all the synthesized compounds were confirmed by NMR, mass and IR spectral data. A single crystal X-ray analysis of 5a also confirmed the 3-(allyloxy)-propylidene acetal formation.

One-pot synthesis of highly functionalized tetrahydrothiophene (thiolane) derivatives conjugated with biologically useful isooxazole are reported via the Knoevenagel condensation followed by domino sulfa-1,6-Michael/intramolecular vinylogous Henry reactions of aldehydes, 1,4-dithiane-2,5-diol and 3,5-dimethyl-4-nitroisoxazole. From the base and solvent screening, it was found that piperidine (30 mol%) and ethanol are the most suitable conditions giving the desired products with >95% yields in 2–2.5 h overall reaction time.

A series of 3,19-O-acetal derivatives of andrographolide (1) have been synthesized by protecting the hydroxyls at C-3 and C-19 through a novel route. All the derivatives were evaluated for in vitro anticancer activity. Among the synthesized derivatives, compounds 3, 3a, 3d, 3e, 7 and 8 showed potential cytotoxicity against human cancer cell lines A549 (lung), HeLa (cervical), ACHN (renal), B-16 (melanoma) and IEC-6 (small intestine). The binding mode conformation was evaluated through docking simulations, while bioavailability/drug-likeness was evaluated through predictive ADME screening studies. All the derivatives were characterized by spectroscopy and the stereochemistry of compounds 3a and 3e was also confirmed by X-ray analysis.

Some of our group recently demonstrated combining theory and a statistical survey of the Cambridge Structural Database (CSD) that the interaction between the π-holes of nitro groups and electron-rich atoms is somewhat directional (Chem. Commun., 2015, 51, 1491–1493). In this communication, we present a joint experimental and theoretical study on a novel cadmium(II) complex, [Cd(C7H3N2O6)2(C12H8N2)2]·H2O·DMF (1) [where C7H4N2O6 = 3,5-dinitrobenzoic acid and C12H8N2 = 1,10-phenanthroline] to unravel the important role of this π-hole interaction.

Correction for ‘Tandem Prins cyclization for the synthesis of indole fused spiro-1,4-diazocane scaffolds’ by Chandrashekhar Rapelli et al., Org. Biomol. Chem., 2020, 18, 6710–6715, DOI: 10.1039/D0OB01384F.

We report the single crystal diffraction study of a dimorphic 7-benzoyl-1,3-dihydroindol-2-one system and evaluate its stability relationships through thermal, grinding and slurry methods. Computational methods are invoked to understand the stability relationships. The form I crystallizes in the triclinic space group P 1 ¯ with two molecules in the asymmetric unit ( Z ′ = 2), whereas, form II crystallizes in the monoclinic space group P 2 1 / c with a single molecule in the asymmetric unit ( Z ′ = 1). The molecules exhibit subtle conformational variations along the bond connecting the phenyl and indole rings and adopt different crystal packing. While both polymorphs show similar amide dimer of N H⋯O interactions, they do differ significantly in the way the amide dimers are packed. The Differential Scanning Calorimetry (DSC), phase transformation studies and lattice energy calculations clearly established the greater stability of high Z ′ form over low Z ′ form, which contradicts the widely accepted notion that Z ′ > 1 structures are usually kinetic (or metastable). The choice of two different orientations of phenyl rings in form I enforces shorter π⋯π interactions and additional C H⋯π contacts to result in the extra stabilization energy over form II crystal packing with a single conformer. The Z ′ and stability correlation is established in 83 reported polymorphic systems which indicate that the number of stable crystal structures decrease as the Z ′ value increases. However, the polymorphic systems with Z ′ = 1 and 2 combinations are more frequently observed than any other combinations.

A two point N H⋯O dimer or an infinite catemer are the most preferred motifs/synthons for sulfonamide structures. Such synthons are known to be so robust that they are only disrupted in the presence of highly activated O acceptors such as pyridine-N-oxide and sulfoxide. We demonstrate in this article that a multi-point synthon offered by much weaker ethoxy O and amine N acceptors can however strongly compete and disrupt the robust sulfonamide homosynthons. This has been illustrated with the synthon analysis in three polymorphic crystal structures of R-tamsulosin, an active drug used in the treatment of Benign Prostatic Hyperplasia (BPH) and its hydrochloride salt. These crystalline solids are characterized by Single crystal X-ray diffraction (SC-XRD), powder X-ray diffraction (PXRD), Fourier Transform Infrared (FT-IR) and Raman spectroscopy. Forms I, II of the free base and hydrochloride salt crystallize in the monoclinic P 2 1 , C 2, and P 2 1 space groups respectively with two molecules in the asymmetric unit ( Z ′ = 2), whereas, form III of freebase crystallize in the orthorhombic P 2 1 2 1 2 1 space group with Z ′ = 1. Remarkably, all four crystal structures contain a totally unexpected sulfonamide⋯ o -diethoxybenzene heterosynthon. The multi-point motifs observed in polymorphs are relatively stronger than those in the hydrochloride salt because of the gauche conformation of the tamsulosin linker chain which renders an additional hydrogen bond interaction with amine N acceptor, and resemble the crown ether sulfonamide recognition pattern. Observation of this new heterosynthon offers potential scope in the design of pharmaceutical cocrystals for sulfonamide bearing drug molecules. The present study also presents a detailed hydrogen bond motif analysis in 310 primary sulfonamide structures culled from the latest version of Cambridge Structural Database (CSD). The role of various competing groups is discussed in the context of understanding the most recurring sulfonamide homo and heterosynthons.

We report here the design and synthesis of porphyrin-metallocene dyads consisting of a metallocene [either ferrocene or mixed sandwich η(5)-[C5H4(COOH)]Co(η(4)-C4Ph4) connected via an ester linkage at meso phenyl position of either free-base or zinc porphyrin. All these dyad systems were characterized by various spectroscopic and electrochemical methods. A dimeric form of this molecule was observed in the X-ray crystal structure of Zn-TTPCo. The absorption spectra of all four dyads indicated the absence of electronic interactions between porphyrin macrocycle and metallocene in the ground state. However, interestingly, in all four dyads, fluorescence emission of the porphyrin was quenched (19-55%) as compared to their monomeric units. The quenching was more pronounced in ferrocene derivatives rather than cobaltocenyl derivatives. The emission quenching can be attributed to the excited-state intramolecular photoinduced electron transfer from metallocene to singlet excited state of porphyrin and the electron-transfer rates (k(ET)) were established in the range 1.51 × 10(8) to 1.11 × 10(9) s(-1). They were found to be solvent dependent.

A C–O bond-formation reaction that proceeds through C–H functionalization of N,N-dialkylanilines at the ortho-position is presented. The iron-catalyzed selective ortho-benzoyloxylation follows a polar Friedel–Crafts-like mechanism and is sensitive to the nucleophilicity of the anilines. The benzoyloxylation of a variety of N,N-disubstituted anilines and N-phenyl heterocycles is carried out under extremely mild conditions. Furthermore, the methodology has been successfully employed for the generation of 1,4-benzoxazepines and o-aminophenols.

The anticonvulsant and antiepileptic drug lamotrigine was crystallized with three aromatic acids viz., 2,5-dihydroxybenzoic acid (I), para-toluenesulfonic acid (II) and 4-bromobenzoic acid (III), with the objective of understanding the formation of a salt or co-crystal in the solid state. Single crystal X-ray diffraction and FT-infrared spectroscopic measurements were carried out for all of them. The asymmetric units of I and II contain two lamotriginium cations and two anions (2,5-dihydroxybenzoate in I and para-toluenesulfonate in II), respectively, and additionally II contains one water molecule. The asymmetric unit of III comprises one lamotriginium cation, one 4-bromobenzoate anion and one dimethylformamide (DMF) solvate. In all three complexes the protonation occurs at the N2 atom of the triazine ring. In I and II, the complete proton transfer is observed. However in III, only partial proton transfer is inferred from O to N because of the acidic H atom disorder. The protonation of lamotrigine is also confirmed by the unambiguous location of H atom from the difference Fourier map and as well as from the geometrical bond analysis. Further, various lamotrigine-acid complexes from the CSD were analyzed to establish a correlation between different ionization states (neutral, intermediate and ionic) and changes in the geometrical parameters. The bond angles of triazine ring in lamotrigine and bond distances of carboxylic acid are found to be the best descriptors for distinguishing all three ionization states, whereas, the bond angles of carboxylic acid have to failed to distinguish intermediate state from ionic. From hydrogen bonding point of view, only the lamotrigine-acid heterosynthon is observed in I and II, whereas in III, both lamotrigine-lamotrigine homosynthon and lamotrigine-acid heterosynthon are observed. In I, the cation–anion and anion–anion interactions form a supramolecular two-dimension hydrogen-bonded square grid network, while the water molecule of II cross-link the two-dimensional cation–anion hydrogen-bonded layers. In III, a pseudo-quadruple hydrogen bonding is formed with aid of DMF solvate.

A proton transfer complex of 2-aminopyrimidine with phosphoric acid was synthesized and crystallized. Single crystal X-ray studies, the vibrational spectral analysis using Laser Raman and FT-IR spectroscopy in the range of 4000–400 cm−1, UV–Vis-NIR studies and thermogravimetric analyses were carried out in the solid crystalline form. The single crystal X-ray studies shows that the crystal packing is dominated by N H⋯O and O H⋯O hydrogen bonds leading to a hydrogen bonded ensemble. The two dimensional cationic layers, connected through the centrosymmetric anionic dimer of R 2 2 ( 8 ) motif, is extending along ab plane of the crystal leading to zig-zag infinite chain C 2 1 ( 6 ) and C 2 2 ( 6 ) motifs. To investigate the strength of the hydrogen bonds, vibrational spectral studies were adopted and the shifting of bands due to the intermolecular interactions were analyzed. Density Functional Theory (DFT) using the B3LYP function with the 6-311++G(d,p) basis set was applied to the solid state molecular geometry obtained from single crystal X-ray studies. The optimized molecular geometry and computed vibrational spectra are compared with experimental results which shows appreciable agreement. NBO analysis has been carried out by DFT level. In this study explains charge delocalization of the present molecule which shows the possible biological/pharmaceutical activity of the molecule. The number of normal modes were also attempted by the factor group analysis method. It is evident that the influence of extensive intermolecular hydrogen bonds reduces the Td symmetry of the phosphate anion to the lower C2v symmetry. The existence of exothermic peaks in DTA iterate the breaking of intermolecular hydrogen bonds and the phase change of the crystal. The presence of water molecule is also confirmed in the thermal analyses.

A series of 3-indolyl-3-hydroxy oxindole derivatives (n = 41) were synthesized by the green aminocatalytic method with excellent yields under mild reaction conditions. All the newly synthesized derivatives were subjected to evaluate their cytotoxic properties against different human cancer cell lines. Results indicated that about 73% of the derivatives exhibited significant anti-proliferative activities against leukemia (U937, THP-1), lung (A549) and breast cancer (MCF7) cell lines. Among them a few of the derivatives exhibited the most potent and effective cytotoxic activities on U937 (34, 36, 38 and 41) and MCF7 (12, 35, 40 and 41) cell lines, and their anti-proliferation activities are better than the positive control, Etoposide.

Series of new benzoxepinoisoxazolones 4a – d and pyrazolones 6a – t were prepared by the cyclocondensation of substituted ( E )-ethyl 3-oxo-2,3-dihydrobenzo[ b ]oxepine-4-carboxylates 3a – d with hydroxylamine hydrochloride and phenylhydrazine hydrochlorides 5a – k . Synthesized compounds were screened for their in vitro anti-mycobacterial activity and anticancer activity. Ten compounds displayed good anti-mycobacterial activity, among these; compound 4d and 6b found to be potent when compared to standard drug isoniazid. Eleven compounds displayed good anticancer activity and compounds 4b – d displayed equipotent activity on HeLa cell lines when compared to standard drug doxorubicin. Activation of caspase-3 and caspase-9 has been measured for compounds 4b – d on HeLa cell lines (apoptosis). This is the first report assigning in vitro anti-mycobacterial, anticancer and structure–activity relationship for this new class of benzoxepinoisoxazolones and pyrazolones.

A practical and efficient protocol has been developed for the synthesis of 2-imino-4-thiazolidinone through a unique one pot three-component reaction of variety of amines, isothiocyanate and ethylbromoacetate in water. The method is free of catalyst and other toxic solvents, has shorter reaction times, high-yielding, effortlessness in isolation of product, making it more eco-friendly process, and suitable for large scale operation.