Isomeric form and proton localization in (9<Emphasis Type="Italic">E</Emphasis>)-phenanthrene-9,10-dione[(1<Emphasis Type="Italic">Z</Emphasis>)-3,3-dimethyl-3,4-dihydroisoquinolin-1(2<Emphasis Type="Italic">H</Emphasis>)-ylidene]hydrazonium bromide

(9E)-Phenanthrene-9,10-dione[(1Z)-3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene]hydrazonium bromide (LH)Br (I) was synthesized. The models of protonated forms of the LH⁺ cation were calculated by quantum-chemical methods, and their relative stability was estimated. The crystal structure of compound I was determined by X-ray diffraction analysis. Compound I is built according to the cation-anion type (the mobile protons are located at the nitrogen atoms). The cation exists in the s-cis,cis-isomeric form stabilized by two cyclic hydrogen bonds. The π-electron density is localized on the multiple bonds N(1)-C(1) (1.292(4) Å) and N(3)-C(12) (1.294(4) Å). the spectroscopic characteristics (IR and electronic absorption spectra) of compound I are obtained.     

Regioselective synthesis of polyfluoroalkyl-substituted 7-(1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-1-yl)-6,7-dihydro-1<Emphasis Type="Italic">H</Emphasis>-indazol-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

3-Polyfluoroalkyl-6,6-dimethyl-7-(1H-1,2,3-triazol-1-yl)-6,7-dihydro-1H-indazol-4(5H)-ones were synthesized with high regioselectivity by 1,3-dipolar cycloaddition of terminal alkynes (phenylacetylene, hex- 1-yne, hept-1-yne, and but-3-yn-1-ol) to 7-azido-6,6-dimethyl-3-polyfluoroalkyl-6,7-dihydro-1H-indazol-4(5H)-ones which were prepared by bromination of 6,6-dimethyl-3-polyfluoroalkyl-6,7-dihydro-1H-indazol- 4(5H)-ones with N-bromosuccinimide in anhydrous carbon tetrachloride, followed by treatment of the corresponding 7-bromo derivatives with sodium azide.     

Complexes of cobalt(II) halides with 2-(1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-yl)-4(3<Emphasis Type="Italic">H</Emphasis>)-pyrimidinone

The electronic structures of complexes of cobalt(II) halides with 2-(1H-pyrazol-1-yl)-4(3H)-pyrimidinone have been studied by X-ray photoelectron spectroscopy. The Co2p _3/2 lines of cobalt atoms, N1s lines of nitrogen atoms, and O1s lines of oxygen atoms in the X-ray photoelectron spectra have been analyzed. Based on these data for the free and coordinated ligands, the atoms of the ligand coordinated to the central metal atom are determined. The coordinated organic compound serves as an electron-donating ligand. The results obtained are consistent with IR and UV-Vis spectroscopic data.     

Reaction 5-(Arylmethylidene)pyrimidine-2,4,6(1<Emphasis Type="Italic">H</Emphasis>,3<Emphasis Type="Italic">H</Emphasis>,5<Emphasis Type="Italic">H</Emphasis>)-triones with L-Proline and Aldehydes

Boiling in toluene of 5-(arylmethylidene)pyrimidine-2,4,6(1H,3H,5H)-triones with L-proline and aldehyde led to the formation of previously unknown substituted 1′-arylhexahydro-1H-spiro[pyrimidine-5,2′-pyrrolysine]-2,4,6(1H,3Н,5Н)-triones.     

Cyclofunctionalization of 6-alkenylsulfanylpyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]-pyrimidin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones with arenesulfenyl chlorides

Reactions of 6-allylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-one with arenesulfenyl chlorides in chloroform gave products of addition of the latter at the exocyclic double bond, while analogous reactions in acetic acid in the presence of LiClO₄ were accompanied by intramolecular electrophilic cyclization involving the N⁷ atom. 6-Cinnamylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-one reacted with arenesulfenyl chlorides in acetic acid in the absence of electrolyte to produce fused pyrazolo[4′,3′: 5,6]pyrimido[2,1-b][1,3]thiazine derivatives. Introduction of a bulky phenyl group into position 1 of the pyrazolo[3,4-d]pyrimidine system reduces the yield of the corresponding intramolecular cyclization product at N⁷ as a result of concurrent formation of acyclic addition product. DOI     

Crystal structure of 9-(5,5-dimethyl-2,4,5,6-tetrahydro-1<Emphasis Type="Italic">H</Emphasis>-phenalen-2-yl)-5,5,9-trimethyl-5,6,8,9-tetrahydrocyclopenta[<Emphasis Type="Italic">a</Emphasis>]phenalen-10(4<Emphasis Type="Italic">H</Emphasis>)-one

The structure of 9-(5,5-dimethyl-2,4,5,6-tetrahydro-1H-phenalen-2-yl)-5,5,9-trimethyl-5,6,8,9-tetrahydrocyclopenta[а]phenalen-10(4H)-one was determined by X-ray crystallography. The intermolecular interaction energies were calculated by the atom-atomic approach for the crystal structure. The character of the crystal structure and the structural subclass were established.     

7,8,9-trimethyl-1-phenyl-3<Emphasis Type="Italic">H</Emphasis>-pyrrolo[2,1-<Emphasis Type="Italic">d</Emphasis>][1,2,5]triazepin-4(5<Emphasis Type="Italic">H</Emphasis>)-one. Synthesis and reactions

A strategy was developed for the synthesis of 7,8,9-trimethyl-1-phenyl-3H-pyrrolo[2,1-d][1,2,5]-triazepin-4(5H)-one, reactions of its functionalization at the С⁴ atom and aza rings fusion at the С⁴?N³ bond were explored. The formation mechanism of the pyrrolo-1,2,5-triazepinone scaffold was suggested.     

Synthesis and structure of (bis(3,5-dimethyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-yl)methane)diiodocobalt(II)

A cobalt(II) iodide complex with bis(3,5-dimethyl-1H-pyrazol-1-yl)methane (L) CoLI₂ has been synthesized, and its single crystals have been obtained. The complex compound was characterized by electron spectroscopy and X-ray diffraction analysis. The compound crystallizes in the monoclinic system (a = 8.4044(4) Å, b = 13.3120(5) Å, c = 14.5824(7) Å; β = 94.7290(10)°; V = 1625.92(13) ų; Z = 4; ρ^calc = 2.112 g/cm³; space group P2₁/m). The structure of the complex is molecular mononuclear. L is a cyclic bidentate ligand; the coordination polyhedron of cobalt is a CoN₂I₂ tetrahedron formed by the nitrogen atoms of the pyrazole fragments L and iodine atoms. The complex has π-π stacking interactions between the pyrazole rings of CoLI₂ molecules, binding the molecules into infinite chains along the b axis.     

Regioselectivity in the reactions of <Emphasis Type="Italic">N</Emphasis>-(polychloroethylidene)-sulfonamides with 1<Emphasis Type="Italic">H</Emphasis>-pyrrole and 1-methyl-1<Emphasis Type="Italic">H</Emphasis>-pyrrole

N-(2,2,2-Trichloroethylidene)arenesulfonamides react with 1H-pyrrole and 1-methyl-1H-pyrrole to give the corresponding N-[2,2,2-trichloro-1-(1H-pyrrol-2-yl)ethyl]arenesulfonamides. The reaction of N-(2,2,2-trichloroethylidene)trifluoromethanesulfonamide with pyrrole leads to a mixture of 2-mono-and 2,5-disubstituted pyrroles, whereas in the reaction with 1-methyl-1H-pyrrole only the 2-substituted compound is formed. N-(2,2-Dichloro-2-phenylethylidene)-4-methylbenzenesulfonamide reacts with 1H-pyrrole to form N-[2,2-dichloro-2-phenyl-1-(1H-pyrrol-2-yl)ethyl]-4-methylbenzenesulfonamide, and its reaction with 1-methyl-1H-pyrrole gives a mixture of 2-and 3-monosubstituted derivatives. The results of quantum-chemical calculations of the initial reactants and products indicate that the process is orbital-controlled. A good agreement is observed between the experimental data and theoretical conclusions concerning the dependence of the reaction regioselectivity on the nature of substituents in the electrophile molecule.     

Reactions of 2-(2-propynylsulfanyl)-5,6,7,8-tetrahydrobenzo[<Emphasis Type="Italic">b</Emphasis>]thieno[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(<Emphasis Type="Italic">3H</Emphasis>)-one with arylsulfenyl chlorides

2-(2-propynylsulfanyl)-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidin-4(3H)-one with arylsulfenyl chlorides in chloroform gave products of anti-Markownikoff Ad _E-addition. The use of nitromethane as solvent in the presence of lithium perchlorate additives favored intramolecular electrophilic cyclization into 1-arylsulfanyl-1,2,6,7,8,9-hexahydro-4H-benzo[4,5]thieno[3,2-e][1,3]thiazolo[3,2-a]-pyrimidin-5-one.     

6,7-Dimethoxy-3,4-dihydroisoquinolin-1(2<Emphasis Type="Italic">H</Emphasis>)-ylidenoacetonitrile in some fusion reactions

6,7-Dimethoxy-3,4-dihydroisoquinolin-1-ylacetonitrile in the enamine form readily reacts with acyl iso(thio)cyanates affording in high yields 1,2-fused oxo- and thioxodihydropyrimidoisoquinolines and thiouracyloisoquinolines. The reaction of the enamine with primary amines of diverse classes in the presence of 2 equiv of formaldehyde resulted in 1,2-fused N-substituted tetrahydropyrimidinoisoquinolines whose yields depended on the basicity and sterical accessibility of the reagent. Fused 5-hydroxyindolo-, dioxopyrrolo-, pyrroloisoquinolines formed in medium yields in the one-stage reactions of the enamine with p-benzoquinone, oxalyl chloride, and β-nitrostyrene respectively. The reaction of 1-cyanomethyl-6,7-dimethoxydihydroisoquinoline with acrylonitrile leads to the formation of 1,2-fused iminopyridinoisoquinoline easily hydrolysable to pyridine derivative and readily reacting by the amidine group with aroyl chlorides and arylsulfonyl chlorides.     

Three-component heterocyclization of 5-(arylmethylidene)pyrimidine-2,4,6(1<Emphasis Type="Italic">H</Emphasis>,3<Emphasis Type="Italic">H</Emphasis>,5<Emphasis Type="Italic">H</Emphasis>)-triones with aldehydes and amino acids

Previously unknown substituted 4-aryl-2,7,9-triazaspiro[4.5]decane-6,8,10-triones were synthesized in 50–70% yield by heating 5-(arylmethylidene)barbituric acids with N-methyl- or N-phenylglycine and para-formaldehyde or 4-methoxybenzaldehyde in boiling toluene for 14 h.     

Recyclization of 1,3-dialkyl-6-nitro-1<Emphasis Type="Italic">H</Emphasis>-imidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridine-2,5(3<Emphasis Type="Italic">H</Emphasis>,4<Emphasis Type="Italic">H</Emphasis>)-diones into imidazole derivatives

Treatment of 5-amino-1,3-dialkyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones with sodium nitrite in aqueous HCl gave 1,3-dialkyl-1H-imidazo[4,5-b]pyridine-2,5(3H,4H)-diones which were nitrated with potassium nitrate in sulfuric acid to 6-nitro derivatives, and the latter underwent recyclization into 4-amino-1,3-dialkyl-5-(1H-pyrazol-5-yl)-2,3-dihydro-1H-imidazol-2-ones by the action of hydrazine hydrate.     

Design,synthesis and therapeutic potential of 3-(2-(1<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">d</Emphasis>]imidazol-2-ylthio)acetamido)-<Emphasis Type="Italic">N</Emphasis>-(substituted phenyl)benzamide analogues

Background

The emergence of bacterial resistance is a major public health problem. It is essential to develop and synthesize new therapeutic agents with better activity. The mode of actions of certain newly developed antimicrobial agents, however, exhibited very limited effect in treating life threatening systemic infections. Therefore, the advancement of multi-potent and efficient antimicrobial agents is crucial to overcome the increased multi-drug resistance of bacteria and fungi. Cancer, which remains as one of the primary causes of deaths and is commonly treated by chemotherapeutic agents, is also in need of novel and efficacious agents to treat resistant cases. As such, a sequence of novel substituted benzamides was designed, synthesized and evaluated for their antimicrobial and anticancer activities.

Methodology

All synthesized compounds were characterized by IR, NMR, Mass and elemental analysis followed by in vitro antimicrobial studies against Gram-positive (Staphylococcus aureus), Gram-negative (Salmonella typhi and Klebsiella pneumoniae) bacterial and fungal (Candida albicans and Aspergillus niger) strains by the tube dilution method. The in vitro anticancer evaluation was carried out against the human colorectal carcinoma cell line (HCT116), using the Sulforhodamine B assay.

Results, discussion and conclusion

Compound W6 (MIC_{sa, st, kp}?=?5.19 µM) emerged as a significant antibacterial agent against all tested bacterial strains i.e. Gram-positive (S. aureus), Gram-negative (S. typhi, K. pneumoniae) while compound W1 (MIC_{ca, an}?=?5.08 µM) was most potent against fungal strains (A. niger and C. albicans) and comparable to fluconazole (MIC?=?8.16 µM). The anticancer screening demonstrated that compound W17 (IC₅₀?=?4.12 µM) was most potent amongst the synthesized  compounds and also more potent than the standard drug 5-FU (IC₅₀?=?7.69 µM).

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A DFT study of H<Subscript>2</Subscript>CO and HCN adsorptions on 3<Emphasis Type="Italic">d</Emphasis>, 4<Emphasis Type="Italic">d</Emphasis>, and 5<Emphasis Type="Italic">d</Emphasis> transition metal-doped graphene nanosheets

The binding of 3d (Sc, Ti, V), 4d (Y, Zr, Nb), and 5d (La, Hf, Ta) transition metals on graphene nanosheet (TM–GNS) with hydrogen-terminated edges and the adsorption of H₂CO and HCN molecules on the pristine and TM-doped GNSs were theoretically studied using a density functional theory method. The calculation showed that all TM atoms had strong binding with GNS, in which the Ta atom displayed the strongest interaction with GNS. The H₂CO and HCN molecules showed much stronger adsorption on the TM–GNSs than that on the pristine GNS. The H₂CO showed stronger interactions with TM–GNSs than that of HCN, in which the Ta-doping displayed the strongest interactions between the GNS and H₂CO or HCN. The adsorption interactions induced dramatic changes of TM–GNS electronic properties. The results revealed that the adsorption strength and sensor ability of GNS can be greatly improved by introducing appropriate TM dopants. Therefore, TM-doped GNSs are suitable for application in H₂CO and HCN storage and sensor.     

Crystal structure and antitumor activities of a dinuclear cobalt(II) complex based on <Emphasis Type="Italic">meso</Emphasis>-1,2,3,4-tetra(1H-benzo[<Emphasis Type="Italic">d</Emphasis>]imidazol-2-yl)butane

The [Co₂(tbb)Cl₄]?4DMF complex, where tbb is meso-1,2,3,4-tetra(1H-benzo[d]imidazol-2-yl)butane, is synthesized and characterized by single crystal X-ray diffraction. For the complex: C₄₄H₅₄Co₂C_l4N₁₂O₄, M_r = 1074.65, monoclinic crystal system, space group P21/n, a = 9.2350(13) Å, b = 11.3566(15) Å, c = 23.879(3) Å, β = 90.547(2)°, V = 2504.3(6) ų, Z = 2, D_c = 1.425 g/cm³, λ = 0.71073 Å, μ(MoK_α) = = 0.929 mm^–1, F(000) = 1112, S = 1.047, R = 0.0765, and wR = 0.2110 for 13668 observed reflections with I > 2σ(I). It is a neutral dinuclear complex. One meso-1,2,3,4-tetra(1H-benzo[d]imidazol-2-yl)butane coordinates two cobalt(II) ions. Each cobalt(II) ion is formed by two tbb nitrogen atoms and two chloride ions. The antiproliferative activities of the complex are screened by MTT assay against Eca109 cancer cells. The complex exhibits inhibition on the growth of Eca109 cancer cells with IC₅₀ of 22.1±6.7 μM after 48 h treatment. The cobalt complex has potential application in treatment of Eca109 cancer. CCDC 1015791.     

Synthesis and study of macroheterocyclic compounds derived from 1<Emphasis Type="Italic">H</Emphasis>-phenalene-1,3(2<Emphasis Type="Italic">H</Emphasis>)-diimine

Symmetrical macroheterocyclic compounds are synthesized by the reaction of 1H-phenalene-1,3(2H)-diimine with m-phenylenediamine, 2,6-diaminopyridine, and 2,5-diamino-1,3,4-thiadiazole. IR and UV spectral data are given.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 8, 2004, pp. 1355–1359.Original Russian Text Copyright © 2004 by Berezina, Vorobev, Vorobeva, Andreikina.This revised version was published online in April 2005 with a corrected cover date.     

3-aryl(alkyl)quinazoline-2,4(1<Emphasis Type="Italic">H</Emphasis>,3<Emphasis Type="Italic">H</Emphasis>)-diones and their alkyl derivatives

Two-stage reaction of methyl anthranilate with aryl(alkyl) isocyanates in keeping with the quantumchemical calculations and XRD analysis resulted in 3-aryl(alkyl)quinazoline-2,4(1H,3H)-diones that by treatment with alkyl halides, phenacyl bromides, esters and amides of chloroacetic acid were converted into the corresponding 1-alkyl derivatives.     

Synthesis of 7-(furan-2-yl)-7,8,10,10a-tetrahydro-6<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">c</Emphasis>]-chromen-6,9(6a<Emphasis Type="Italic">H</Emphasis>)-diones

Methods of synthesis were developed for 7-(furan-2-yl)-substituted 7,8,10,10a-tetrahydrobenzo[c] chromen-6,9-diones by regioselective [4+2]-cycloaddition of coumarin-3-carboxylic acids to 2-(3-trimethylsiloxybuta- 1,3-dien-1-yl)furans. The [4+2]-cycloaddition was efficiently catalyzed with L-proline.