The title compound, C34H38ClN5O2, has spiro links connecting the pyrrolidine ring and indole residue, as well as the piperidine and pyrrolidine rings. A half-chair conformation is found for the piperidine ring with the C atom connected to the spiro-C atom lying 0.738 (4) Å out of the plane of the remaining five atoms (r.m.s. deviation = 0.0407 Å). The methyl-ene C atom is the flap in the envelope conformation for the pyrrolidine ring. In the crystal, supra-molecular chains are sustained by alternating eight-membered {⋯HNCO}2 and 14-membered {⋯HC5O}2 synthons. Chains are connected into a three-dimensional network by (pyrrolidine-bound phenyl-meth-yl)C-H⋯π(pyrrolidine-bound phen-yl) edge-to-face inter-actions.
Two spiro links are found in the title compound, C31H28Cl3N3O2, one connecting the piperidine and pyrrolidine rings, and the other connecting the pyrrolidine ring and indole residue. The piperidine ring adopts a half-chair conformation, in which the C atom connected to the spiro-C atom lies 0.741 (3) Å out of the plane of the remaining five atoms (r.m.s. deviation = 0.053 Å). The pyrrolidine ring has an envelope conformation with the flap atom being the methyl-ene C atom. Centrosymmetric eight-membered {⋯HNCO}2 amide dimers are the most significant feature of the crystal packing. These are connected into layers parallel to (-120) by C-H⋯O and π-π inter-actions between pyrrolidine-bound benzene rings [inter-centroid distance = 3.8348 (15) Å]. Slipped face-to-face inter-actions between the edges of pyrrolidine-bound benzene [shortest C⋯C separation = 3.484 (4) Å] connect the layers into a three-dimensional architecture.
The title compound, C30H28ClN3O2, features two spiro links, one connecting the piperidine and pyrrolidine rings, and the other connecting the pyrrolidine ring and indole residue. The configuration about the ethene bond is E. The piperidine ring adopts a half-chair conformation where the C atom connected to the spiro-C atom lies 0.713 (3) Å out of the plane of the remaining five atoms (r.m.s. deviation = 0.086 Å). The pyrrolidine ring has an envelope conformation with the flap atom being the methyl-ene C atom. Centrosymmetric eight-membered {⋯HNCO}2 amide synthons feature in the crystal packing. These are consolidated into a three-dimensional architecture by phen-yl-pyrrolidine C-H⋯N and chloro-benzene-pyrrolidine-bound phenyl C-H⋯π inter-actions.
In the title salt, C11H12ClN2O(+)·Cl(-), the ten non-H atoms comprising the quinolinium residue are coplanar (r.m.s. deviation = 0.041 Å) and the hy-droxy-ethyl group is approximately perpendicular to this plane [Cring-N-Cmethyl-ene-C torsion angle = -74.61 (18)°]. A supra-molecular chain aligned along [101] mediated by charge-assisted O/N-H⋯Cl(-) hydrogen bonds features in the crystal packing. Chains are connected into a three-dimensional architecture by C-H⋯O(hy-droxy) inter-actions.
In the title mol-ecule, C(14)H(9)N(3)O(3), the dihedral angle between the quinoxaline and benzene rings is 77.13 (9)°. The mol-ecule is twisted about the ether-benzene O-C bond, with a C-O-C-C torsion angle of -102.8 (2)°. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, forming layers in the ab plane, with one nitro O atom accepting two such inter-actions. The layers stack along the c-axis direction via weak C-H⋯π inter-actions.
The pyran-oside ring in the title compound, C(21)H(24)O(11), has a chair conformation with the substituted benzene ring occupying an equatorial position. The crystal packing is dominated by C-H⋯O inter-actions that lead to the formation of supra-molecular layers in the ab plane.
The galactose ring in the title compound, C(21)H(24)O(11), has a chair conformation with the substituted benzene ring occupying an equatorial position. The crystal packing features C-H⋯O inter-actions that lead to the formation of supra-molecular layers in the ab plane.
The quinoxaline system in the title hydrate, C(15)H(13)N(3)·H(2)O, is roughly planar, the r.m.s. deviation for the 18 non-H atoms being 0.188 Å; this conformation features a short intra-molecular C-H⋯N(pyrazine) inter-action. In the crystal, the amine H atom forms an N-H⋯O hydrogen bond to the water mol-ecule, which in turn forms two O-H⋯N hydrogen bonds to the pyrazine N atoms of different organic mol-ecules. These inter-actions lead to supra-molecular arrays in the bc plane that are two mol-ecules thick; additional π-π inter-actions stabilize the layers [ring centroid-centroid distance = 3.5923 (7) Å]. The layers stack along the a-axis direction via C-H⋯π contacts.
In the title compound, C(10)H(9)N(3)O(3), there is a small twist between the benzene and triazole rings [dihedral angle = 6.32 (7)°]; the carb-oxy-lic acid residue is almost coplanar with the benzene ring to which it is attached [O-C-C-C torsion angle = 1.49 (19)°]. The main deviation from coplanarity of the non-H atoms is found for the hy-droxy group which is almost perpendicular to the remaining atoms [N-C-C-O torsion angle = -75.46 (16)°]. In the crystal, the presence of O-H⋯O (between carboxyl groups) and O-H⋯N (between the hy-droxy group and the triazole ring) hydrogen bonds leads to supra-molecular chains along [03[Formula: see text]]. The chains are connected into sheets via C-H⋯O(hy-droxy) inter-actions.
The compound with R=CH2CH3 in Bi(S2CNR2)3 (1) is highly cytotoxic against a range of human carcinoma, whereas that with R=CH2CH2OH (2) is considerably less so. Both 1 and 2 induce apoptosis in HepG2 cells with some evidence for necrosis induced by 2. Based on DNA fragmentation, caspase activities and human apoptosis PCR-array analysis, both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. While both compounds activate mitochondrial and FAS apoptotic pathways, compound 1 was also found to induce another death receptor-dependent pathway by induction of CD40, CD40L and TNF-R1 (p55). Further, 1 highly expressed DAPK1, a tumour suppressor, with concomitant down-regulation of XIAP and NF-κB. Cell cycle arrest at the S and G2/M phases correlates with the inhibition of the growth of HepG2 cells. The cell invasion rate of 2 is 10-fold higher than that of 1, a finding correlated with the down-regulation of survivin and XIAP expression by 1. Compounds 1 and 2 interact with DNA through different binding motifs with 1 interacting with AT- or TA-specific sites followed by inhibition of restriction enzyme digestion; 2 did not interfere with any of the studied restriction enzymes.
The synthesis and characterisation of R3PAu[S2CN((i)Pr)CH2CH2OH], for R = Ph (1), Cy (2) and Et (3)4, is reported. Compounds 1-3 are cytotoxic against the doxorubicin-resistant breast cancer cell line, MCF-7R, with 1 exhibiting greater potency and cytotoxicity than either of doxorubicin and cisplatin. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis by 1, and necrosis by 2 and 3, are demonstrated, by both extrinsic and intrinsic pathways. Compound 1 activates the p53 gene, 2 activates only the p73 gene, whereas 3 activates both the p53 and p73 genes. Compounds 1 and 3 activate NF-κB, and each inhibits topoisomerase I.
In the organic mol-ecule of the title hydrate, C11H15N3OS·H2O, {systematic name: 3-ethyl-1-{(E)-[1-(2-hy-droxy-phen-yl)ethyl-idene]amino}-thio-urea monohydrate}, a dihedral angle of 5.39 (2)° is formed between the hy-droxy-benzene ring and the non-H atoms comprising the side chain (r.m.s. deviation = 0.0625 Å), with the major deviation from planarity noted for the terminal ethyl group [the C-N-C-C torsion angle = -172.17 (13)°]. The N-H H atoms are syn and an intra-molecular hy-droxy-imine O-H⋯N hydrogen bond is noted. In the crystal, the N-bonded H atoms form hydrogen bonds to symmetry-related water mol-ecules, and the latter form donor inter-actions with the hy-droxy O atom and with a hy-droxy-benzene ring, forming a O-H⋯π inter-action. The hydrogen bonding leads to supra-molecular tubes aligned along the b axis. The tubes are connected into layers via C-H⋯O inter-actions, and these stack along the c axis with no directional inter-actions between them.
In the title compound, C8H3N3O2 (systematic name: 4-nitro-benzene-1,2-dicarbo-nitrile), the nitro group is twisted out of the plane of the benzene ring to which it is attached [O-N-Cring-Cring torsion angle = 9.80 (13)°]. In the crystal packing, supra-molecular layers with a zigzag topology in the ac plane are sustained by C-H⋯N inter-actions.
In the title compound, C8H7N3O4 (systematic name: 4-nitro-benzene-1,2-dicarboxamide), each of the substituents is twisted out of the plane of the benzene ring to which it is attached [dihedral angles of 11.36 (2)° for the nitro group, and 60.89 (6) and 34.39 (6)° for the amide groups]. The amide groups are orientated to either side of the least-squares plane through the benzene ring with the amine groups being directed furthest apart. In the crystal, a three-dimensional architecture is established by a network of N-H⋯O hydrogen bonds.
The title compound, C17H15N3O2, is a monoclinic polymorph (P21/c with Z' = 1) of the previously reported triclinic (P-1 with Z' = 2) form [Gajera et al. (2013 ▸). Acta Cryst. E69, o736-o737]. The mol-ecule in the monoclinic polymorph features a central pyrazolyl ring with an N-bound p-tolyl group and a C-bound 1,3-benzodioxolyl fused-ring system on either side of the C atom bearing the amino group. The dihedral angles between the central ring and the N- and C-bound rings are 50.06 (5) and 27.27 (5)°, respectively. The angle between the pendent rings is 77.31 (4)°, indicating the mol-ecule has a twisted conformation. The five-membered dioxolyl ring has an envelope conformation with the methyl-ene C atom being the flap. The relative disposition of the amino and dioxolyl substituents is syn. One of the independent mol-ecules in the triclinic form has a similar syn disposition but the other has an anti arrangement of these substituents. In the crystal structure of the monoclinic form, mol-ecules assemble into supra-molecular helical chains via amino-pyrazolyl N-H⋯N hydrogen bonds. These are linked into layers via C-H⋯π inter-actions, and layers stack along the a axis with no specific inter-actions between them.
In the title compound, C26H24O5, the pyran ring has a flattened-boat con-formation, with the 1,4-related ether O and methine C atoms lying 0.1205 (18) and 0.271 (2) Å, respectively, above the least-squares plane involving the doubly bonded C atoms (r.m.s deviation = 0.0208 Å). An envelope conformation is found for the cyclo-hexene ring, with the flap atom being the middle methyl-ene C atom, lying 0.616 (2) Å out of the plane defined by the remaining atoms (r.m.s. deviation = 0.0173 Å). The fused four-ring system is approximately planar, with the dihedral angle between the least-squares planes through the cyclo-hexene and naphthyl rings being 10.78 (7)°. The tris-ubstituted benzene ring occupies a position almost perpendicular to the pyran ring [dihedral angle = 83.97 (4)°]. The most prominent feature of the packing is the formation of zigzag supra-molecular chains mediated by aryl-C-H⋯O(meth-oxy) inter-actions; chains are connected into a three-dimensional architecture by methyl-ene- and methyl-C-H⋯π inter-actions. The prevalence of C-H⋯O and C-H⋯π inter-actions is confirmed by an analysis of the Hirshfeld surface. A comparison with related structures suggests that the mol-ecular conformation of the title compound is relatively robust with respect to varying substitution patterns at the methine C atom of the pyran ring.
The asymmetric unit of the title compound, [Cd2(C12H10N2)3(C6H12NOS2)4]·4C2H3N, comprises a Cd(II) atom, two di-thio-carbamate (dtc) anions, one and a half trans-1,2-dipyridin-4-yl-ethyl-ene (bpe) mol-ecules and two aceto-nitrile solvent mol-ecules. The full binuclear complex is generated by the application of a centre of inversion. The dtc ligands are chelating, one bpe mol-ecule coordinates in a monodentate mode while the other is bidentate bridging. The resulting cis-N2S4 coordination geometry is based on an octa-hedron. Supra-molecular layers, sustained by hy-droxy-O-H⋯O(hy-droxy) and hy-droxy-O-H⋯N(bpe) hydrogen bonding, inter-penetrate to form a three-dimensional architecture; voids in this arrangement are occupied by the aceto-nitrile solvent mol-ecules. Additional inter-molecular inter-actions falling within the specified framework have been analysed by Hirshfeld surface analysis, including π-π inter-actions.
The common feature of the mol-ecular structures of the title compounds, [Zn(C5H10NS2)2(C5H5NO)], (I), and [Zn(C4H8NOS2)2(C5H5NO)], (II), are NS4 donor sets derived from N-bound hy-droxy-pyridyl ligands and asymmetrically chelating di-thio-carbamate ligands. The resulting coordination geometries are highly distorted, being inter-mediate between square pyramidal and trigonal bipyramidal for both independent mol-ecules comprising the asymmetric unit of (I), and significantly closer towards square pyramidal in (II). The key feature of the mol-ecular packing in (I) is the formation of centrosymmetric, dimeric aggregates sustained by pairs of hy-droxy-O-H⋯S(di-thio-carbamate) hydrogen bonds. The aggregates are connected into a three-dimensional architecture by methyl-ene-C-H⋯O(hy-droxy) and methyl-C-H⋯π(chelate) inter-actions. With greater hydrogen-bonding potential, supra-molecular chains along the c axis are formed in the crystal of (II), sustained by hy-droxy-O-H⋯O(hy-droxy) hydrogen bonds, with ethyl-hydroxy and pyridyl-hydroxy groups as the donors, along with ethyl-hydroxy-O-H⋯S(di-thio-carbamate) hydrogen bonds. Chains are connected into layers in the ac plane by methyl-ene-C-H⋯π(chelate) inter-actions and these stack along the b axis, with no directional inter-actions between them. An analysis of the Hirshfeld surfaces clearly distinguished the independent mol-ecules of (I) and reveals the importance of the C-H⋯π(chelate) inter-actions in the packing of both (I) and (II).
The asymmetric unit of the title salt, C14H16N4O2 (2+)·2C9H5O6 (-), comprises half a dication, being located about a centre of inversion, and one anion, in a general position. The central C4N2O2 group of atoms in the dication are almost planar (r.m.s. deviation = 0.009 Å), and the carbonyl groups lie in an anti disposition to enable the formation of intra-molecular amide-N-H⋯O(carbon-yl) hydrogen bonds. To a first approximation, the pyridinium and amide N atoms lie to the same side of the mol-ecule [Npy-C-C-Namide torsion angle = 34.8 (2)°], and the anti pyridinium rings are approximately perpendicular to the central part of the mol-ecule [dihedral angle = 68.21 (8)°]. In the anion, one carboxyl-ate group is almost coplanar with the ring to which it is connected [Cben-Cben-Cq-O torsion angle = 2.0 (3)°], whereas the other carboxyl-ate and carb-oxy-lic acid groups are twisted out of the plane [torsion angles = 16.4 (3) and 15.3 (3)°, respectively]. In the crystal, anions assemble into layers parallel to (10-4) via hy-droxy-O-H⋯O(carbon-yl) and charge-assisted hy-droxy-O-H⋯O(carboxyl-ate) hydrogen bonds. The dications are linked into supra-molecular tapes by amide-N-H⋯O(amide) hydrogen bonds, and thread through the voids in the anionic layers, being connected by charge-assisted pyridinium-N-O(carboxyl-ate) hydrogen bonds, so that a three-dimensional architecture ensues. An analysis of the Hirshfeld surface points to the importance of O-H⋯O hydrogen bonding in the crystal structure.