Ni-Unsymmetrical Salen Complex-Catalyzed One-Pot Multicomponent Reactions for Efficient Synthesis of Biologically Active 2-Amino-3-cyano-4H-pyrans.

In this report, four new Ni(II)-unsymmetrical salen complexes, [NiL1-4], were prepared by refluxing Ni(Ac)2·4H2O with unsymmetrical salen ligands, H2L1-4. All of the synthesized ligands and complexes were characterized by various physicochemical methods. Also, the solid-state structures of [NiL1], [NiL2], and [NiL4] were defined through single-crystal X-ray diffraction methods. The catalytic potential of [NiL1-4] was investigated by economic and environmentally friendly one-pot-three-component reactions (using reagent: 1,3-dicarbonyls, malononitrile, benzaldehyde, or its derivatives) for the synthesis of biologically active 2-amino-3-cyano-4H-pyran derivatives (total 16 derivatives). After optimization of the reaction conditions, this new synthetic protocol by taking Ni(II)-unsymmetrical salen complexes as catalysts shows excellent conversion with a maximum yield of up to 98% of the effective catalytic products within 1 h of reaction time. In addition, it was observed that the aromatic aldehyde containing an electron-withdrawing group as a ring substituent shows better conversion (up to 98%), and the electron-donating group substituent shows similar or less conversion compared to benzaldehyde under the optimized reaction conditions. From the comparison of results between all these Ni complexes, it was found that the efficiency of the catalytic performance follows the order [NiL1] > [NiL3] > [NiL2] > [NiL4]. A possible reaction pathway was predicted and established through UV-vis spectroscopy. Intermediate II proposed in the reaction pathway was also trapped and characterized through 1H and 13C NMR.

Dimeric ethyl-tin(IV)-dibromide-hydroxide-N,N-di-methyl-formamide.

Di-µ-hydroxido-bis-[di-bromido-(di-methyl-formamide-κO)ethyl-tin(IV)], [Sn2Br4(C2H5)2(OH)2(C3H7NO)2], was prepared from ethyl-tin(IV) bromide and N,N-di-methyl-formamide (DMF) in air. The crystal structure exhibits the typical structural features of dimeric Lewis-base-stabilized monoorganotin(IV)-dihalide-hydroxides, RSnHal2(OH), i.e. two octa-hedrally coordinated Sn atoms are linked together via two bridging hydroxide groups, resulting in a centrosymmetric four-membered rhomboid-like Sn-OH ring with acute angles at the Sn atom, obtuse angles at the O atoms and two different tin-oxygen bond lengths. With the shorter bond trans to the ethyl group, this observation underlines once more the so-called trans-strengthening effect in monoorganotin(IV) com-pounds with octa-hedrally coordinated Sn atoms. Differences and similarities in the bond lengths and angles in the four-membered Sn-OH rings have been worked out for the rings in dimeric diorganotin(IV)-halide-hydroxides, [R 2SnHal(OH)]2, and hydrates of dimeric tin(IV)-trihalide-hydroxide-aqua-hydrates, [SnHal3(OH)(H2O)]2·nH2O.

A Series of Non-Oxido VIV Complexes of Dibasic ONS Donor Ligands: Solution Stability, Chemical Transformations, Protein Interactions, and Antiproliferative Activity.

A series of mononuclear non-oxido vanadium(IV) complexes, [VIV(L1-4)2] (1-4), featuring tridentate bi-negative ONS chelating S-alkyl/aryl-substituted dithiocarbazate ligands H2L1-4, are reported. All the synthesized non-oxido VIV compounds are characterized by elemental analysis, spectroscopy (IR, UV-vis, and EPR), ESI-MS, as well as electrochemical techniques (cyclic voltammetry). Single-crystal X-ray diffraction studies of 1-3 reveal that the mononuclear non-oxido VIV complexes show distorted octahedral (1 and 2) or trigonal prismatic (3) arrangement around the non-oxido VIV center. EPR and DFT data indicate the coexistence of mer and fac isomers in solution, and ESI-MS results suggest a partial oxidation of [VIV(L1-4)2] to [VV(L1-4)2]+ and [VVO2(L1-4)]-; therefore, all these three complexes are plausible active species. Complexes 1-4 interact with bovine serum albumin (BSA) with a moderate binding affinity, and docking calculations reveal non-covalent interactions with different regions of BSA, particularly with Tyr, Lys, Arg, and Thr residues. In vitro cytotoxic activity of all complexes is assayed against the HT-29 (colon cancer) and HeLa (cervical cancer) cells and compared with the NIH-3T3 (mouse embryonic fibroblast) normal cell line by MTT assay and DAPI staining. The results suggest that complexes 1-4 are cytotoxic in nature and induce cell death in the cancer cell lines by apoptosis and that a mixture of VIV, VV, and VVO2 species could be responsible for the biological activity.

Redetermination of the crystal structure of di-µ2-hydroxido-bis-[di-tert-butyl-chlorido-tin(IV)] at 100†K.

The structure of the dimeric title compound, [Sn2(C4H9)4Cl2(OH)2], was redetermined at 100 K by use of an area detector to provide new data to improve the structural parameters for detailed analysis. Noteworthy is the folding of the central, non-symmetric, four-membered [SnO]2 ring [dihedral angle about the O⋯O axis = 1.09 (3)°], as well as the elongation of the Sn-Cl bonds [mean value = 2.5096 (4) Å], as a result of inter-molecular O-H⋯Cl hydrogen bonds; the latter lead to a chain-like arrangement of dimeric mol-ecules along [101].

Temperature-Controlled Chemoselective Synthesis of Multisubstituted 4-Alkynyl/trans 4-Alkenyl Coumarins.

A temperature-controlled facile synthesis of multisubstituted 4-alkynyl/trans 4-alkenyl coumarins with a metal salt cascade approach is reported. H2O serves both as a nucleophile and hydrogen source. The presence of metal salt facilitates the reduction of alkyne. The present protocol bypasses the structural shortcomings of the existing Sonogashira and Heck coupling reactions. In addition, the obtained 2,3-disubstituted coumarins are readily transformed into 2,3-disubstituted dihydrocoumarins, which serve as important building blocks in organic transformations.

Di-tert-butyl-tin(IV)-hydroxide-iodide, t Bu2Sn(OH)I, the last missing member in the series of pure di-tert-butyl-tin(IV)-hydroxide-halides.

The crystal structure of di-tert-butyl-hydroxido-iodido-tin(IV), [Sn(C4H9)2I(OH)] or t Bu2Sn(OH)I, consists of dimeric, centrosymmetric mol-ecules exhibiting the typical structural features of diorganotin(IV)-hydroxide-halides, R 2Sn(OH)Hal. Two trigonal-bipyramidally coordinated tin(IV) atoms are bridged via two hydroxyl groups, resulting in a planar, four-membered {Sn-O}2 ring of rhombic shape, with acute angles at tin, obtuse angles at oxygen and two different Sn-O distances depending whether the oxygen atom adopts an axial or equatorial position at the tin(IV) atom. In contrast to its fluorine, chlorine and bromine homologues, no hydrogen bonds between the OH group and the halide atom exist, confining the inter-molecular inter-actions to van der Waals forces.

Ba3[Sn(OH)6][SeO4]2·3H2O, a hydrated 1:2 double salt of barium hexa-hydroxidostannate(IV) and barium selenate(VI).

Single crystals of tribarium hexa-hydroxidostannate(IV) bis-[selenate(VI)] trihydrate, Ba3H12O17Se2Sn or Ba3[Sn(OH)6][SeO4]2·3H2O, prepared from solid BaSnO3 and aqueous Na2[SeO4] solutions have hexa-gonal (P63) symmetry. The structure consists of four different primary building units: a hexa-hydroxidostannate(IV) ion, two different selenate(VI) ions, all three of point group symmetry C 3, and a mono-capped {BaO9}-square anti-prism of point group symmetry C 1. The secondary building units result from three of the barium coordination polyhedra linked together via common edges. While one of the two tetra-hedral voids formed from these trimeric units is filled by one bidentate, chelating µ2-selenate ion, the other one remains unoccupied as the corresponding second selenate ion only acts as a monodentate, µ1-ligand. SBUs are completed by hexa-hydroxidostannate(IV) ions sharing adjacent edges on the uncapped faces of the three, mono-capped square anti-prisms. These SBUs are arranged into layers via common edges on the uncapped, square faces of the {BaO9} coordination polyhedra in a way that the hexa-hydroxidostannate(IV) ions act as linkage between two neighboring layers.

The 2'-deoxyribofuranoside of 3-phenyltetrahydropyrimido[4,5-c]pyridazin-7-one: a bicyclic nucleoside with sugar residues in N and S conformations, and its molecular recognition.

The title compound 3-phenyltetrahydropyrimido[4,5-c]pyridazine 2'-deoxyribonucleoside [systematic name: 6-(2-deoxy-ß-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-3-phenylpyrimido[4,5-c]pyridazin-7-one monohydrate, C17H18N4O4·H2O, 1] shows two conformations in the crystalline state and the two conformers (1a and 1b) adopt different sugar puckers. The sugar residue of 1a shows a C2'-endo S-type conformation, while 1b displays a C3'-endo N-type sugar pucker. Both conformers adopt similar anti conformations around the N-glycosylic bonds, with χ = -97.5 (3)° for conformer 1a and χ = -103.8 (3)° for conformer 1b. The extended crystalline network is stabilized by several intermolecular hydrogen bonds involving nucleoside and water molecules. The nucleobases and phenyl substituents of the two conformers (1a and 1b) are stacked and display a reverse alignment. A Hirshfeld surface analysis supports the hydrogen-bonding pattern, while curvedness surfaces visualize the stacking interactions of neighbouring molecules. The recognition face of nucleoside 1 for base-pair formation mimics that of 2'-deoxythymidine. Nucleoside 1 shows two pKa values: 1.8 for protonation and 11.2 for deprotonation. DNA oligonucleotides containing nucleoside 1 were synthesized and hybridized with complementary DNA strands. Nucleoside 1 forms a stable base pair with dA which is as stable as the canonical dA-dT pair. The bidentate 1-dA base pair is strengthened by a third hydrogen bond provided by the dA analogue 3-bromopyrazolo[3,4-d]pyrimidine-4,6-diamine 2'-deoxyribofuranoside (4). By this, duplex stability is increased and the suggested base-pairing patterns are supported.

Protein binding and cytotoxic activities of monomeric and dimeric oxido-vanadium(V) salan complexes: Exploring the solution behavior of monoalkoxido-bound oxido-vanadium(V) complex.

Three ONNO donor tetradentate diamino bis(phenolato) "salan" ligands, N, N'-dimethyl-N, N'-bis-(5-chloro-2-hydroxy-3-methyl-benzyl)-1,2-diaminoethane (H2L1), N, N'-dimethyl-N, N'-bis-(5-chloro-2-hydroxy-3-isopropyl-6-methyl-benzyl)-1,2-diamino-ethane (H2L2) and N, N'-bis-(5-chloro-2-hydroxy-3-isopropyl-6-methyl-benzyl)-1,2-diaminocyclohexane (H2L3) have been synthesized by following Mannich condensation reaction. Reaction of these ligands with their corresponding vanadium metal precursors gave one oxidomethoxidovanadium(V) [VVOL1(OCH3)] (1) and two monooxido-bridged divanadium (V, V) complexes [VVOL2-3]2(µ-O) (2-3). The complexes were characterized by IR, UV-vis, NMR and ESI mass spectrometry. Also, the structure of all the complexes (1-3) was confirmed by the Single-Crystal X-ray diffraction analysis, which revealed a distorted octahedral geometry around the metal centres. The solution behavior of the [VVOL1(OCH3)] (1) reveals the formation of two different types of V(V) species in solution, the structurally characterized compound 1 and its corresponding monooxido-bridged divanadium (V, V) complex [VVOL1]2(µ-O), which was further studied by IR, and NMR spectroscopy. The electrochemical behavior of all the complexes was evaluated through cyclic voltammetry. Interaction of the salan-V(V) complexes with human serum albumin (HSA) and bovine serum albumin (BSA) were analysed through fluorescence quenching, UV-vis absorption titration, synchronous fluorescence, circular dichroism studies, and förster resonance energy transfer (FRET). Finally, the in vitro cytotoxicity of the complexes was investigated against MCF-7 and HT-29 and NIH-3T3 cell lines. Cytotoxicity value of complexes in both MCF-7 and HT-29 follows the same trend that is 3 > 1 > 2 which is in line with protein binding affinity of the complexes.

Na9 Bi5 Os3 O24 : A Diamagnetic Oxide Featuring a Pronouncedly Jahn-Teller-Compressed Octahedral Coordination of Osmium(VI).

The Jahn-Teller (JT) theorem constitutes one of the most fundamental concepts in chemistry. In transition-element chemistry, the 3d4 and 3d9 configurations in octahedral complexes are particularly illustrative, where a distortion in local geometry is associated with a reduction of the electronic energy. However, there has been a lasting debate about the fact that the octahedra are found to exclusively elongate. In contrast, for Na9 Bi5 Os3 O24 , the octahedron around Os6+ (5d2 ) is heavily compressed, lifting the degeneracy of the t2g set of 5d orbitals such that in the sense of a JT compression a diamagnetic ground state results. This effect is not forced by structural constraints, the structure offers sufficient space for osmium to shift the apical oxygen atoms to a standard distance. The relevance of these findings is far reaching, since they provide new insights in the hierarchy of perturbations defining ground states of open shell electronic systems.

Two coordination compounds of SnCl2 with 4-methyl-pyridine N-oxide.

In the solid-state structures of catena-poly[[di-chlorido-tin(II)]-µ2-(4-methyl-pyridine N-oxide)-κ2 O:O], [SnCl2(C6H7NO)] n , 1, and di-chlorido-bis-(4-methyl-pyridine N-oxide-κO)tin(II), [SnCl2(C6H7NO)2], 2, the bivalent tin atoms reveal a seesaw coordination with both chlorine atoms in equatorial and the Lewis base mol-ecules in axial positions. While the Sn-Cl distances are almost identical, the Sn-O distances vary significantly as a result of the different bonding modes (µ2 for 1, µ1 for 2) of the 4-methyl-pyridin-N-oxide mol-ecules, giving rise to a one-dimensional coordination polymer for the 1:1 adduct, 1, and a mol-ecular structure for the 1:2 adduct, 2. The different coordination modes also influence the bonding parameters within the almost planar ligand mol-ecules, mostly expressed in N-O-bond lengthening and endocyclic bond-angle widening at the nitro-gen atoms. Additional supra-molecular features are found in the crystal structure of 2 as two adjacent mol-ecules form dimers via additional, weak O⋯Sn inter-actions.

Copper(i) catalyzed synthesis of selanyl methylene 4-chromanol and aurone derivatives.

An efficient copper-catalyzed cyclization cascade approach towards highly functionalized methylene 4-chromanol and aurone derivatives has been developed from reactions of ynols via 6-exo-dig and 5-exo-dig cyclization respectively. The catalysis involves alkyne activation via diorgano-diselenides and also their regioselective incorporation into the methylene 4-chromanol and aurone derivative core and is an open-air transformation.

Copper(I)-Catalyzed Synthesis of Functionalized Indolizinones from Substituted Pyridine Homologated Ynones.

An efficient two-component copper-catalyzed cyclization cascade approach toward highly functionalized indolizinone heterocycles has been developed from reactions of pyridine-, isoquinoline-, and quinoline ynones, via 5-exo-dig cyclization. The catalysis involves the activation by diorgano diselenide and diorgano disulfide and also their incorporation into the indolizinone core. In addition, the obtained substituted indolizinones were readily transformed into 1-(organochalcogenyl)indolizin-2-ols, which are important building blocks in organic synthesis.

Polynuclear zinc(II) complexes of thiosemicarbazone: Synthesis, X-ray structure and biological evaluation.

Two new dimeric Zn(II) ([{ZnL1(DMSO2)}2]·DMSO (1), [{ZnL2Cl}2] (2)) and a novel tetrameric Zn(II) complex ([(Zn2L3)2(µ-OAc)2(µ3-O)2] (3)), where H2L1 = 4-(p-methoxyphenyl) thiosemicarbazone of o-hydroxynapthaldehyde, HL2 = 4-(p-methoxyphenyl)thiosemicarbazone of benzoyl pyridine and H2L3 = 4-(p-chlorophenyl)thiosemicarbazone of o-vanillin are reported. Ligands and their complexes were characterized by spectroscopic and single crystal X-ray diffraction techniques. In addition, the complexes exhibited good binding affinity towards HSA (1012 M-1), which is supported by their ability to quench the tryptophan fluorescence emission spectra of HSA. The complexes were also screened for their DNA binding propensity through UV-vis absorption titration, circular dichroism and fluorescence spectral studies. Results show that they effectively interact with CT-DNA through an intercalative mode of binding, with binding constants ranging from 103 to 104 M-1. Among the three complexes 1 has the highest binding affinity towards CT-DNA. Further, the phosphatase activity was evaluated using bis(2,4-dinitrophenyl)phosphate (BDNPP) as substrate, however, the complexes did not yield any measurable catalytic activity. Nevertheless the complexes showed significant cytotoxic potential against HeLa and HT-29 cancer cell lines that was assessed through MTT assay and DAPI staining. Remarkably, complex 1 showed better activity than cisplatin against HT-29 cell line.

Chemistry of mixed-ligand oxidovanadium(IV) complexes of aroylhydrazones incorporating quinoline derivatives: Study of solution behavior, theoretical evaluation and protein/DNA interaction.

A series of eight hexacoordinated mixed-ligand oxidovanadium(IV) complexes [VO(Lx)(LN-N)] (1-8), where Lx = L1 - L4 are four differently substituted ONO donor aroylhydrazone ligands and LN-N are N,N-donor bases like 2,2'-bipyridine (bipy) (1, 3, 5 and 7) and 1,10-phenanthroline (phen) (2, 4, 6 and 8), have been reported. All synthesized complexes have been characterized by various physicochemical techniques and molecular structures of 1 and 6 were determined by X-ray crystallography. With a view to evaluate the biological activity of the VIVO species, the behavior of the systems VIVO2+/Lx, VIVO2+/Lx/bipy and VIVO2+/Lx/phen was studied as a function of pH in a mixture of H2O/DMSO 50/50 (v/v). DFT calculations allowed finding out the relative stability of the tautomeric forms of the ligands, and predicting the structure of vanadium complexes and their EPR parameters. To study their interaction with proteins, firstly the ternary systems VIVO2+/L1,2 with 1-methylimidazole, which is a good model for histidine binding, were examined. Subsequently the interaction of the complexes with lysozyme (Lyz), cytochrome c (Cyt) and bovine serum albumin (BSA) was studied. The results indicate that the complexes showed moderate binding affinity towards BSA, while no interaction takes place with lysozyme and cytochrome c. This could be explained with the higher number of accessible coordinating and polar residues for BSA than for Lyz and Cyt. Further, the complexes were also evaluated for their DNA binding propensity through UV-vis absorption titration and fluorescence spectral studies. These results were consistent with BSA binding affinity and showed moderate binding affinity towards CT-DNA.

New Ag8PtO6: synthesis, crystal structure, physical properties and theoretical analyses.

We report the synthesis, crystal structure, and basic physical properties of Ag8PtO6, which represents the first silver platinum ternary oxide. The crystalline compound was obtained from appropriate mixtures of the binary constituents under alkaline conditions at high oxygen pressure, while applying relatively mild thermal conditions (573 K). Ag8PtO6 crystallizes in a new crystal structure in the triclinic system (P1[combining macron]). The structure consists of slightly distorted, discrete PtO6 octahedra, which are linked via O-Ag-O dumbbells to form a three dimensional framework. It is a diamagnetic semiconductor with a band gap of 0.9 eV. DFT based calculations confirm an electronic ground state that corresponds to a 5d6 6s0 configuration of the Pt atoms, in accordance with the observed diamagnetism.

Guanosine Nucleolipids: Synthesis, Characterization, Aggregation and X-Ray Crystallographic Identification of Electricity-Conducting G-Ribbons.

The lipophilization of ß-d-riboguanosine (1) with various symmetric as well as asymmetric ketones is described (→3a-3f). The formation of the corresponding O-2',3'-ketals is accompanied by the appearance of various fluorescent by-products which were isolated chromatographically as mixtures and tentatively analyzed by ESI-MS spectrometry. The mainly formed guanosine nucleolipids were isolated and characterized by elemental analyses, 1 H-, 13 C-NMR and UV spectroscopy. For a drug profiling, static topological polar surface areas as well as 10 logPOW values were calculated by an increment-based method as well as experimentally for the systems 1-octanol-H2 O and cyclohexane-H2 O. The guanosine-O-2',3'-ketal derivatives 3b and 3a could be crystallized in (D6 )DMSO - the latter after one year of standing at ambient temperature. X-ray analysis revealed the formation of self-assembled ribbons consisting of two structurally similar 3b nucleolipid conformers as well as integrated (D6 )DMSO molecules. In the case of 3a ⋅ DMSO, the ribbon is formed by a single type of guanosine nucleolipid molecules. The crystalline material 3b ⋅ DMSO was further analyzed by differential scanning calorimetry (DSC) and temperature-dependent polarization microscopy. Crystallization was also performed on interdigitated electrodes (Au, distance, 5 µm) and visualized by scanning electron microscopy. Resistance and amperage measurements clearly demonstrate that the electrode-bridging 3b crystals are electrically conducting. All O-2',3'-guanosine ketals were tested on their cytostatic/cytotoxic activity towards phorbol 12-myristate 13-acetate (PMA)-differentiated human THP-1 macrophages as well as against human astrocytoma/oligodendroglioma GOS-3 cells and against rat malignant neuroectodermal BT4Ca cells.

Redetermination of Sr2PdO3 from single-crystal X-ray data.

The crystal structure redetermination of Sr2PdO3 (distrontium palladium trioxide) was carried out using high-quality single-crystal X-ray data. The Sr2PdO3 structure has been described previously in at least three reports [Wasel-Nielen & Hoppe (1970 ▸). Z. Anorg. Allg. Chem. 375, 209-213; Muller & Roy (1971 ▸). Adv. Chem. Ser. 98, 28-38; Nagata et al. (2002 ▸). J. Alloys Compd. 346, 50-56], all based on powder X-ray diffraction data. The current structure refinement of Sr2PdO3, as compared to previous powder data refinements, leads to more precise cell parameters and fractional coordinates, together with anisotropic displacement parameters for all sites. The compound is confirmed to have the ortho-rhom-bic Sr2CuO3 structure type (space group Immm) as reported previously. The structure consists of infinite chains of corner-sharing PdO4 plaquettes inter-spersed by SrII atoms. A brief comparison of Sr2PdO3 with the related K2NiF4 structure type is given.

Synthesis of New Potential Lipophilic Co-Drugs of 2-Chloro-2'-deoxyadenosine (Cladribine, 2-CdA, Mavenclad®, Leustatin®) and 6-Azauridine (z6 U) with Valproic Acid.

2-Chloro-2'-deoxyadenosine (cladribine, 1) was acylated with valproic acid (2) under various reaction conditions yielding 2-chloro-2'-deoxy-3',5'-O-divalproyladenosine (3) as well as the 3'-O- and 5'-O-monovalproylated derivatives, 2-chloro-2'-deoxy-3'-O-valproyladenosine (4) and 2-chloro-2'-deoxy-5'-O-valproyladenosine (5), as new co-drugs. In addition, 6-azauridine-2',3'-O-(ethyl levulinate) (8) was valproylated at the 5'-OH group (→9). All products were characterized by 1 H- and 13 C-NMR spectroscopy and ESI mass spectrometry. The structure of the by-product 6 (N-cyclohexyl-N-(cyclohexylcarbamoyl)-2-propylpentanamide), formed upon valproylation of cladribine in the presence of N,N-dimethylaminopyridine and dicyclohexylcarbodiimide, was analyzed by X-ray crystallography. Cladribine as well as its valproylated co-drugs were tested upon their cancerostatic/cancerotoxic activity in human astrocytoma/oligodendroglioma GOS-3 cells, in rat malignant neuro ectodermal BT4Ca cells, as well as in phorbol-12-myristate 13-acetate (PMA)-differentiated human THP-1 macrophages. The most important result of these experiments is the finding that only the 3'-O-valproylated derivative 4 exhibits a significant antitumor activity while the 5'-O- as well as the 3',5'-O-divalproylated cladribine derivatives 3 and 5 proved to be inactive.