A catalyst-free approach to synthesis of spiroacenaphthylene-pyranopyrazole derivatives in water media.

A simple approach for the synthesis of spiroacenaphthylene-pyranopyrazole derivatives was achieved via the reaction between acenaphthoquinone, pyrazolones, and activated methylene compounds (malononitrile derivatives) in water as a green solvent without using any catalyst in order to avoid the use of transition metal. This method has the advantages of mild reaction condition, short reaction time, easy workup, excellent yields, and avoidance of environmentally hazardous solvents.

An Efficient Synthesis of Acenaphtho[1,2-b]indole Derivatives via Domino Reaction.

A concise and efficient synthesis of acenaphtho[1,2-b]indole derivatives via the domino reactions of enaminones with acenaphthoquinone catalyzed by l-proline has been developed. This protocol has the advantages of good yields, operational convenience and high regioselectivity.

Tridecacyclene: A Cyclic Tetramer of Acenaphthylene.

In this manuscript, we describe the single-step preparation of a cyclic tetramer of acenaphthylene through a Lewis acid-catalyzed aldol cyclization of 1-acenaphthenone. The previously unexplored cyclic tetramer material differs from the better-known cyclic trimer, decacyclene, due to the presence of a central eight-membered ring. This ring not only forces the molecule to distort significantly from planarity, but is also responsible for its unique electronic properties, including a decrease in the reduction potential (by about 0.4 eV) and optical gap (by about 0.73 eV), compared to the more planar decacyclene. The synthesized compound crystallizes into a unique packing structure with significant π-stacking observed between adjacent molecules. Furthermore, due to its saddle-like shape, the cyclic tetramer is able to form shape-complementary interactions between its concave surface and the convex outer surface of buckminsterfullerene to generate cocrystalline supramolecular assemblies.

Synthesis, Fluorescence Spectra, Redox Property and the DNA Binding Studies of 7-phenylacenaphtho[1,2-b]quinoxalin-7-ium chloride: Evidences of the Formation of Neutral Radical Analogue.

Reaction of acenaphthoquinone with N-phenyl-o-phenylenediamine in methanol in presence of HCl yielded 7-phenylacenaphtho[1,2-b]quinoxalin-7-ium chloride, [1][Cl]. [1][Cl] is brightly fluorescencent in dichloromethane (λex = 403 nm and λem = 442, 464, 488 nm) and water (λex = 408 nm and λem = 545 nm). Density functional theory (DFT) and time dependent (TD) DFT calculations on [1](+) at the B3LYP level of the theory elucidated that the origin of the lower energy excitation at around 400 nm is due to π → π(*) transition. [1](+) is redox active and exhibits a reversible cathodic wave at -0.66 V referenced to Fc(+)/Fc couple due to [1](+)/[1](•) redox couple. Electrogenerated neutral radical analogue [1](•) was characterized by electron paramagnetic resonance (EPR), UV-vis spectra and DFT calculations. DNA binding studies using the techniques of UV-vis absorption, fluorescence, circular dichroism (CD) spectra, viscosity, gel electrophoresis, hydrodynamic, isothermal titration calorimetry (ITC) and UV optical melting studies of [1][Cl] revealed that [1](+) is a strong DNA intercalator obeying neighbor exclusion principle. ITC experiment authenticated that the binding of [1](+) to DNA is entropy driven.

Three-component, one-pot sequential synthesis of functionalized cyclazines: 3H-1,2a1,3-triazaacenaphthylenes.

An efficient tandem route to the synthesis of 3H-1,2a(1),3-triazaacenaphthylene derivatives of the cyclazine family has been developed. Target compounds were obtained in moderate to good yields by a Yb(OTf)(3)/Ag(2)CO(3)-catalyzed, three-component domino reaction. This in turn will set the stage for a wide application of this useful reaction for the synthesis of structurally diverse polyheterocyclic skeletons containing the imidazo[1,2-a]pyridine privileged structure.

Multicomponent approaches to 8-carboxylnaphthyl-functionalized pyrazolo[3,4-b]pyridine derivatives.

A simple and novel protocol for the efficient synthesis of a series of 8-carboxylnaphthyl functionalized pyrazolo[3,4-b]pyridine derivatives was developed through a one-pot, three-component reaction involving acenaphthylene-1,2-dione and 1H-pyrazol-5-amine in acetic acid medium. The reaction represents the first facile conversion of acenaphthenequinone to naphthoic acid via C-C bond cleavage without need for multi-step transformation.

CaCl(2) as a bifunctional reusable catalyst: diversity-oriented synthesis of 4H-pyran library under ultrasonic irradiation.

CaCl(2) is applied as an efficient reusable and eco-friendly bifunctional catalyst for the one-pot three-component synthesis of 4H-pyrans under ultrasonic irradiation. A broad range of substrates including the aromatic and heteroaromatic aldehydes, indoline-2,3-dione (isatin) derivatives, acenaphthylene-1,2-dione (acenaphthenequinone) and 2, 2-dihydroxy-2H-indene-1,3-dione (ninhydrin) were condensed with carbonyl compounds possessing a reactive α-methylene group and alkylmalonates. All reactions are completed in short times, and the products are obtained in good to excellent yields. The catalyst could be recycled and reused several times without any loss of efficiency.

Synthesis and biological evaluation of novel acenaphthene derivatives as potential antitumor agents.

Twelve novel acenaphthene derivatives have been synthesized. The structures of all compounds were confirmed by ¹H-NMR, MS and elemental analysis. Their antitumor activities were evaluated in six human solid tumor cell lines, namely non-small cell lung cancer (H460), human colon adenocarcinoma (SW480), human breast cancer cell (MDA-MB-468 and SKRB-3), human melanoma cell (A375) and human pancreatic cancer (BxPC-3). Among them, compound 3c shows the best antitumor activity against SKRB-3 cell line, as high as the positive control adriamycin.

Syntheses, structures and antimicrobial activities of bis(imino)acenaphthene (BIAN) imidazolium salts.

The syntheses of four new bis(imino)acenaphthene (BIAN) imidazolium chlorides are reported, three of which have been structurally characterized. The synthesis of a new, structurally authenticated BIAN ligand is also described. We report the results of the use of these BIAN imidazolium salts as antimicrobials against the pathogens S. aureus, B. subtilis, E. coli and P. aeruginosa. The antimicrobial efficacies were particularly high for the N-(2,6-diisopropylphenyl)- and N-(mesityl)-substituted BIAN imidazolium salts (MIC values < 0.6 µg/mL).

Novel acenaphtho[1,2-b]pyrrole-carboxylic acid family: synthesis, cytotoxicity, DNA-binding and cell cycle evaluation.

A family of 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid derivatives were synthesized as a result of our efforts to modify a series of acenaphthopyrrole aromatic-heterocycle compounds that proved to be potent anticancer drugs. Among the derivatives, 3d (3-(dimethylamino-propylamino)-8-oxo-8H-acenaphtho-[1,2-b]pyrrole-9-carboxylic acid) and 3g (3-piperidine-8-oxo-8H-acenaphtho-[1,2-b]pyrrole-9-carboxylic acid) showed potential anticancer activity and different action mechanism from our previously reported compounds. UV-vis absorption, circular dichroism and viscosity measurement indicated that effect of both compounds on the advanced DNA conformation was different, although they could bind to DNA in the same way. Cell cycle analysis showed that 3d could induce S-phase arrest followed by apoptosis, while 3g induced apoptosis. The results seem to imply that different action mechanism could contribute to the dissimilitude of biological activities toward 3d and 3g.

A new bis(1-naphthylimino)acenaphthene compound and its Pd(II) and Zn(II) complexes: synthesis, characterization, solid-state structures and density functional theory studies on the syn and anti isomers.

A new rigid bidentate ligand, bis(1-naphthylimino)acenaphthene, L1, and its Zn(II) and Pd(II) complexes [ZnCl 2( L1)], 1, and [PdCl 2( L1)], 2, were synthesized. L1 was prepared by the "template method", reacting 1-naphthyl amine and acenaphthenequinone in the presence of ZnCl 2, giving 1, which was further demetallated. Reaction of 1-naphthyl amine with acenaphthenequinone and PdCl 2 afforded dichloride bis(1-naphthyl)acenaphthenequinonediimine palladium, 2. L1, 1, and 2 were obtained as a mixture of syn and anti isomers. Compound 2 was also obtained by the reaction of PdCl 2 activated by refluxing it in acetonitrile followed by the addition of L1; by this route also a mixture of syn and anti isomers was obtained, but at a different rate. The solid-state structures of L1 and the anti isomer of compound 2 have been determined by single-crystal X-ray diffraction. All compounds have been characterized by elemental analyses; matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry; IR; UV-vis; (1)H, (13)C, and (1)H- (1)H correlation spectroscopy; (1)H- (13)C heteronuclear single quantum coherence; (1)H- (13)C heteronuclear single quantum coherence-total correlation spectroscopy; and (1)H- (1)H nuclear Overhauser effect spectrometry NMR spectroscopies when applied. Density functional theory studies showed that both conformers for [PdCl 2(BIAN)] are isoenergetic, and they can both be obtained experimentally. However, we can predict that the isomerization process is not available in a square-planar complex, but it is possible for the free ligand. The molecular geometry is very similar in both isomers, and only different orientations for naphthyl groups can be expected.

Metal-Catalyzed C-H Bond Activation of 5-Membered Carbocyclic Rings: A Powerful Access to Azulene, Acenaphthylene and Fulvene Derivatives.

Azulene, acenaphthylene and fulvene derivatives exhibit important physical properties useful in materials chemistry as well as valuable biological properties. Since about two decades ago, the metal-catalyzed functionalization of such compounds, via C-H bond activation of their 5-membered carbocyclic ring, proved to be a very convenient method for the synthesis of a wide variety of azulene, acenaphthylene and fulvene derivatives. For such reactions, there is no need to prefunctionalize the 5-membered carbocyclic rings. In this review, the progress in the synthesis of azulene, acenaphthylene and fulvene derivatives via metal-catalyzed C-H bond activation of their 5-membered carbocyclic ring are summarized.

Design, synthesis and antiviral activity of novel 4,5-disubstituted 7-(beta-D-ribofuranosyl)pyrrolo[2,3-d][1,2,3]triazines and the novel 3-amino-5-methyl-1-(beta-D-ribofuranosyl)- and 3-amino-5-methyl-1-(2-deoxy-beta-D-ribofuranosyl)-1,5-dihydro-1,4,5,6,7,8-hexaazaacenaphthylene as analogues of triciribine.

The synthesis of several heterocyclic analogues of the biologically important nucleoside antibiotic toyocamycin and the tricyclic nucleoside triciribine (TCN) were prepared along with their 2'-deoxy counterparts. Coupling of 2-nitropyrrole-3,4-dicarboxamide (15) under a variety of conditions with alpha-chloro-2-deoxy-3,4-di-O-toluoyl-D-ribofuranose (16a) gave mixtures of the alpha and beta anomers. A coupling of 15 with 1-chloro-2,3,5-tri-O-benzoyl-D-ribofuranose (18) gave exclusively the beta anomer. Individually, the two pyrrole nucleosides were treated with Pd/C, H2 to reduce the nitro groups and cyclized with nitrous acid, and the corresponding 4-position was functionalized as a triazoyl derivative. Nucleophillic displacement was carried out with ammonia to give a mixture of 4-amino-1-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyrrolo[2,3-d][1,2,3]triazine-5-carbonitrile (26) and 2-amino-1-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyrrole-3,4-dicarbonitrile (27), the latter being formed via a retro-Diels-Alder reaction. The subsequent addition of hydrogen sulfide, water, methanol, hydroxylamine, cyanamide, hydrazine and methylhydrazine to the 5-cyano group was carried out to give the corresponding analogues. In the case of methyl hydrazine, subsequent treatment with NaOMe in methanol gave the title hexaazaacenaphthylenes. Biological evaluation of the compounds established that the pyrrole (17beta, 19-21) and most of the pyrrolotriazine (22, 24, 28, 32-34) nucleosides were inactive or weakly active against human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1). In contrast 29 and 31 were active against one or both of these viruses but activity was poorly separated from cytotoxicity. In contrast, the 2-aza analogue of sangivamycin (30) was active against HCMV and HSV-1 but this apparent activity was most likely due to its high cytotoxicity. The tricyclic nucleoside 12, was active against its target virus, human immunodeficiency virus type 1 (HIV-1), but this activity was not well separated from cytotoxicity.

Synthesis, antimicrobial activity and molecular modeling of cobalt and nickel complexes containing the bulky ligand: bis[N-(2,6-diisopropylphenyl)imino] acenaphthene.

Two cobalt and two Nickel complexes of bis[N-(2,6-diisopropylphenyl)imino]acenaphthene (Pr-BIAN) ligand, have been synthesized. These complexes, namely [Co(Pr-BIAN)Cl2] 1, [Co(OAc)2 (Pr-BIAN)2](ClO4) 2, [Ni(Pr-BIAN)(NO3)2] 3 and [Ni(Pr-BIAN)2](ClO4)2 4, were characterized by elemental analyses, molar conductance, spectral (IR, UV-Visible and NMR) and magnetic moment measurements. In these complexes the geometries about the metal center are significantly different. While for complexes 2 and 3 an octahedral structure is proposed, in complex 4, square-planar coordination with an almost perfect planar arrangement of two Pr-BIAN ligands around the nickel center is suggested. In 1, two imine nitrogen atoms of Pr-BIAN and two chloride atoms are coordinating in a tetrahedral fashion around the cobalt center. Molecular mechanics (MM+) and semiempirical molecular orbital calculations have been performed for the most biologically active complex 1 and its free ligand Pr-BIAN and compared with inactive ligand bis[N-(p-tolylphenyl)imino]acenaphthene 6, to get insight into their molecular structures and to learn more about their stable molecular conformations.

Potential antiinflammatory compounds. 3. Compounds derived from acenaphthene and indan.

Compounds having acenaphthene and indan as their parent nuclei were synthesized for antiinflammatory testing. Compounds which showed activity were 1-phenyl-5-acenaphthenylacetic acid and its alpha-methyl derivative (carrageenan rat paw edema) and the same alpha-methylacenaphthenylacetic acid and 2-(4-chlorobenzylidene)-3-oxo-5-indanacetic acid and its alpha-methyl derivative (rat adjuvant arthritis). None of the compounds was more active than the control compounds phenylbutazone and indomethacin.

Synthesis of phenalene and acenaphthene derivatives as new conformationally restricted ligands for melatonin receptors.

Conformationally restricted phenalene and acenaphthene derivatives 5 were synthesized from phenalen-1-one and acenaphthen-1-one derivatives using the Horner-Emmons reaction. The amines were prepared through the corresponding isocyanates by the Curtius reaction on the acids or by the reduction of the nitriles. Amido derivatives (R(3) = Me, Et, n-Pr, c-Pr) were prepared by acylation of the amines with the appropriate anhydrides or acid chlorides or by the reductive acylation of the nitriles. The affinities of the compounds for melatonin binding sites were evaluated in vitro in binding assays using chicken brain melatonin and the human mt(1) and MT(2) receptors expressed in HEK-293 cells. The functionality of the compounds was determined by the potency to lighten the skin of Xenopus laevis tadpoles. Highly potent compounds were obtained. The data highlighted the role of the methoxy group located in the ortho position to the ethylamido chain as compounds with picomolar affinities such as 14c were obtained (chicken brain, hmt(1), hMT(2) K(i) values = 0.02, 0.008, 0.069 nM, respectively). Compound 14c was equipotent to the corresponding dimethoxy derivative 15c (chicken brain, hmt(1), hMT(2) K(i) values = 0.07, 0.016, 0.1 nM, respectively). On the other hand, the restricted conformation of the amido chain did not influence selectivity for the cloned hmt(1) and hMT(2) receptors. These compounds were also potent agonists of melanophore aggregation in X. laevis. 15a,c were several hundred fold more potent than melatonin (EC(50) = 0.025, 0.004 nM, respectively). Conformational studies indicated that the minimum energy folded conformation of the ethylamido chain could constitute the putative active form in the receptor site in agreement with previous results.

Synthesis, characterization and DNA binding of ruthenium(II) complexes containing the atatp ligand.

Acenaphtheno[1,2-b]-1,4,8,9-tetraazatriphenylene (atatp) and its complexes [Ru(L)2atatp](ClO4)2 x nH2O (L = 2,2'-bipyridine (bpy), n=2 (1); 1,10-phenanthroline (phen), n=2 (2); and 2,9-dimethyl-1,10-phenanthroline (dmp), n=1 (3)) have been synthesized and characterized by elemental analyses and 1H NMR. The spectral and electrochemical properties of these complexes are also examined. Complexes 1 and 2 display bright luminescence in acetonitrile but very weak luminescence in water solution. However, complex 3 is not luminescent in either solvent. The interaction of the complexes with calf thymus DNA (CT-DNA) has been studied by absorption, emission and viscosity measurements. The intrinsic binding constants of complexes 1 and 2 are 7.6 x 10(4) and 8.8 x 10(4) M(-1) respectively. The relatively low affinities of complexes 1 and 2 with DNA may arise from the atatp ligand, indicating that the size and shape of the intercalated ligand have a marked effect on the strength of interaction. Complexes 1 and 2 bind with CT-DNA in an intercalative mode but complex 3 in a non-intercalative one, showing that changing the ancillary ligand affects not only the binding magnitude, but also the binding mode of the interaction.

DNA interactions of cobalt(III) mixed-polypyridyl complexes containing asymmetric ligands.

Three novel asymmetric ligands, 3-(pyridine-2-yl)-5,6-diphenyl-as-triazine (pdtb), 3-(pyridine-2-yl)-as-triazino[5,6-f]acenaphthylene (pdta) and 3-(pyridine-2-yl)-as-triazino[5,6-f]phenanthroline (pdtp) and their cobalt(III) complexes have been synthesized and characterized. Binding of the three complexes with calf thymus DNA (CT-DNA) has been investigated by spectroscopic methods, viscosity, cyclic voltammetry, and electrophoresis measurements. The experimental results indicate that the size and shape of the intercalated ligand have a marked effect on the binding affinity of complexes to CT-DNA. Complexes 2 and 3 have also been found to promote cleavage of plasmid pBR322 DNA from the supercoiled form I to the open circular form II upon irradiation.

Acenaphthenequinone thiosemicarbazone and its transition metal complexes: synthesis, structure, and biological activity.

The reaction of iron, nickel, copper, and zinc chlorides or acetates with acenaphthenequinone thiosemicarbazone, Haqtsc leads to the formation of novel complexes that have been characterized by spectroscopic studies (NMR, IR) and biological properties. The crystal structures of the free ligand Haqtsc 1 and of the compound [Ni(aqtsc)2].DMF 2, have also been determined by X-ray methods from diffractometer data. In 1, the conformation of the two nonequivalent molecules is governed by intramolecular hydrogen bonds, while an intermolecular hydrogen bond is responsible for dimer-like groups formation. In 2, the coordination geometry about nickel is distorted octahedral, and the two ligand molecules are terdentate monodeprotonated. Biological studies have shown that, for the first time at least up the used doses, a free ligand is active both in the inhibition of cell proliferation and in the induced differentiation on Friend erythroleukemia cells (FLC).

Synthesis of 1-amino-6,7,8,8a-tetrahydroacenaphthene and its effect on the inhibition of the MAO-enzyme at the brain cortex and liver level.

(+/-)-1-Amino-6,7,8,8a-tetrahydroacenaphthene was synthesized and evaluated as a novel drug acting on the dopaminergic system. It was shown that the new compound displays activity as MAO inhibitor.