Bis Derivatives Research Articles

One-pot nucleophilic substitution-double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives.

The nucleophilic substitution of benzylic bromides with sodium azide was combined with a subsequent copper-catalyzed (3 + 2) cycloaddition with terminal alkynes. This one-pot process was developed with a simple model alkyne, but then applied to more complex alkynes bearing enantiopure 1,2-oxazinyl substituents. Hence, the precursor compounds 1,2-, 1,3- or 1,4-bis(bromomethyl)benzene furnished geometrically differing bis(1,2,3-triazole) derivatives. The use of tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) as ligand for the click step turned out to be very advantageous. The compounds with 1,2-oxazinyl end groups can potentially serve as precursors of divalent carbohydrate mimetics, but the reductive cleavage of the 1,2-oxazine rings to aminopyran moieties did not proceed cleanly with these compounds.

New Boron Containing Acridines: Synthesis and Preliminary Biological Study.

The synthesis of the first conjugates of acridine with cobalt bis(dicarbollide) are reported. A novel 9-azido derivative of acridine was prepared through the reaction of 9-methoxyacridine with N3CH2CH2NH2, and its solid-state molecular structure was determined via single-crystal X-ray diffraction. The azidoacridine was used in a copper (I)-catalyzed azide-alkyne cycloaddition reaction with cobalt bis(dicarbollide)-based terminal alkynes to give the target 1,2,3-triazoles. DNA interaction studies via absorbance spectroscopy showed the weak binding of the obtained conjugates with DNA. The antiproliferative activity (IC50) of the boronated conjugates against a series of human cell lines was evaluated through an MTT assay. The results suggested that acridine derivatives of cobalt bis(dicarbollide) might serve as a novel scaffold for the future development of new agents for boron neutron capture therapy (BNCT).

A convenient approach for the synthesis of 4,4'-((substituted phenyl)methylene)bis(3-methyl-1H-pyrazol-5-ol) and their antioxidant and antimicrobial activities

A facile one-pot, three component, convenient approach for the synthesis of 4,4'-((substituted phenyl)methylene)bis(3-methyl-1H-pyrazol-5-ol) derivatives (3a–l) has been accomplished from the reaction of two moles of 5-methyl-2,4-dihydro-3H-pyrazol-3-one (1), with one mole various aromatic aldehydes (2a–l) in the presence ZnO nanoparticles as an efficient heterogeneous catalyst under microwave irradiation (MWI) and solvent-free conditions in good to excellent yields. The major advantages of the present method are, short reaction times, magnetically recyclable catalyst and high yields. The newly synthesized compounds were synthesized and characterized by melting point, IR, NMR, mass spectra. Furthermore the compounds were evaluated for their antioxidant and antimicrobial activities which showed good activities when compared to standards.

Synthesis and Anti-Breast Cancer Potency of Mono- and Bis-(pyrazolyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine) Derivatives as EGFR/CDK-2 Target Inhibitors.

The target mono- and bis-(6-pyrazolyltriazolo-thiadiazine) derivatives 4a-c and 6a-d were synthesized using a straightforward protocol via reaction of 3-bromoacetylpyrazole 2 with 4-amino-s-triazole-3-thiols 3a-c and bis(4-amino-5-mercapto-s-triazol-3-yl)alkanes 5a-d, respectively. The bis(6-pyrazolyl-s-triazolo[3,4-b][1,3,4]thiadiazine) derivatives 8a,b and 10 were also constructed by reaction of the triazolo[3,4-b][1,3,4]thiadiazine-3-thiol 4c with the proper dibromo compounds 7a,b and 9, respectively. Structures of the new substances were determined by spectroscopic and analytical data. Compounds 4b, 4c, and 6a showed potent cytotoxicity against MCF-7 (IC50 = 3.16, 2.74, and 0.39 μM, respectively) and were safe against the MCF-10A cells. Compounds 4b, 4c, and 6a also showed promising dual EGFR and CDK-2 inhibition activities, particularly 6a was the most effective (IC50 = 19.6 and 87.9 nM, respectively), better than Erlotinib and Roscovitine. Compound 6a treatment induced EGFR and CDK-2 enzyme inhibition by 97.18% and 94.11%, respectively, at 10 μM (the highest concentration). Compound 6a notably induced cell apoptosis in MCF-7 cells, increasing the cell population by total apoptosis 43.3% compared to 1.29% for the untreated control group, increasing the cell population at the S-phase by 39.2% compared to 18.6% (control).

Evaluation of protection performances of novel synthesized bis-oxindole-based derivatives for the corrosion of aluminum in acidic environment

Three bis(3-schiff base-indoline-2-one) derivatives, 3(a-c), and two bis-spirotriazole-indole derivatives, 5(a,b), were synthesized and were evaluated as inhibitors for the corrosion of Al in 1.0 M HCl at 303 K. Weight loss (WL) method was applied for evaluation of the inhibition efficiencies (% IEs) of all synthesized compounds while WL in addition to potentodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS) were employed in case of the compound that has the highest% IE values. The collected results illuminated that the synthesized compounds were discovered to be efficient inhibitors and their% IEs were set to vary with their concentrations, structures, and the corrosive medium concentration. WL outcomes revealed that, the order of% IEs of the synthesized compounds was: 5a ≈ 5b > 3a > 3b ≥ 3c. The acquired high% IEs of such compounds were attributed to their potent adsorption on the Al surface and production of a protective film, and this adsorption was agreed with Langmuir adsorption isotherm. The kinetics of corrosion inhibition by the synthesized compounds appeared a negative-first order process confirming the gained higher values of% IEs of such compounds. PDP results indicated that the compound 5a behaves as a mixed inhibitor with a cathodic majority. The results acquired from the three utilized tools were set to be in a good agreement with each other's confirming the validity of the obtained results.

A novel bis(intercalating) agent for DNA based on the bis(benzoquinolizinium) derivative

A novel bis(intercalating) agent for DNA based on the bis(benzoquinolizinium) derivative

Ring-Opening Polymerization of Lactones Catalyzed by Silicon-Based Lewis Acid

Many catalysts containing various elements at their active sites have been reported for the ring-opening polymerization (ROP) of cyclic esters. However, to our knowledge, silicon-based catalysts for ROP have never been reported. Here we report the ROP of cyclic esters and cyclic carbonates catalyzed by the derivatives of bis(perchlorocatecholato)silane (Si(catCl)2), which is a neutral silicon-based Lewis acid recently reported by Greb et al. The catalyst systems show high activity for the ROP of seven- and six-membered ring monomers such as ε-caprolactone, δ-valerolactone, and trimethylene carbonate to produce the polymers with molecular weights up to 32 kg/mol. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and nuclear magnetic resonance analysis of the obtained polymers indicates the predominant formation of cyclic polymers.

Synthesis and Structural Characterization of p-Carboranylamidine Derivatives.

In this contribution, the first amidinate and amidine derivatives of p-carborane are described. Double lithiation of p-carborane (1) with n-butyllithium followed by treatment with 1,3-diorganocarbodiimides, R-N=C=N-R (R = iPr, Cy (= cyclohexyl)), in DME or THF afforded the new p-carboranylamidinate salts p-C2H10B10[C(NiPr)2Li(DME)]2 (2) and p-C2H10B10[C(NCy)2Li(THF)2]2 (3). Subsequent treatment of 2 and 3 with 2 equiv. of chlorotrimethylsilane (Me3SiCl) provided the silylated neutral bis(amidine) derivatives p-C2H10B10[C{iPrN(SiMe3)}(=NiPr)]2 (4) and p-C2H10B10[C{CyN(SiMe3)}(=NCy)]2 (5). The new compounds 3 and 4 have been structurally characterized by single-crystal X-ray diffraction. The lithium carboranylamidinate 3 comprises a rare trigonal planar coordination geometry around the lithium ions.

Hydrogen-Bonded Self-assembly of Supramolecular Donor–Acceptor Complexes of (E)-Bis(18-crown-6)azobenzene with Bis(ammoniopropyl) Derivatives of Bipyridine and Dipyridylethylene in Acetonitrile

Hydrogen-Bonded Self-assembly of Supramolecular Donor–Acceptor Complexes of (E)-Bis(18-crown-6)azobenzene with Bis(ammoniopropyl) Derivatives of Bipyridine and Dipyridylethylene in Acetonitrile

Catalyst-Controlled Diastereoselective Synthesis of Bridged [3.3.1] Bis(Indolyl)-Oxanes and Oxepanes via Desymmetrization of Bis(Indolyl)-Cyclohexadienones.

A catalyst-controlled divergent synthesis of bridged [3.3.1] bis(indolyl)-oxanes and cis-[6.7] fused bis(indolyl) oxepanes via diastereoselective desymmetrization of bis(indolyl)-cyclohexadienones is presented for the first time. The reaction is highly atom- and step-economic, furnishing sp3-rich functionalized bis(indolyl) derivatives in good to excellent yields with wide substrate scope. The reaction proceeds through Friedel-Crafts alkylation followed by catalyst-controlled selective C-C bond formation/rearrangement. Gram scale synthesis and synthetic utility to generate bis(indolyl) alkaloid-like molecular diversity were also illustrated.

Synthesis of a new phenoxy-cyclophosphazene derivative Schiff base and its Ru(II), Co(III) complexes

In this study, a new phenoxy cyclophosphazene derivative bis(2-formyl-phenyl)4,4,6,6-bis[spiro(2’,2”-dioxy-1’,1”biphenylyl)]cyclotriphosphazene (P2) was synthesis in by the reactions between 2,2-dichloro-4,4,6,6-bis[spiro(2’,2”-dioxy-1’,1”biphenylyl)]cyclotriphosphazene (P1) with salicyl aldehyde in presence of K2CO3 at room temperature in THF under argon atmosphere, and the new phenoxy cyclophosphazene derivative Schiff bases which are containing long-chain alkyl groups and salicyl aldehyde, bis[spiro(2’,2”-dioxy-1’,1”biphenylyl)2,3-diphenoxy-2-imidododesyl]cyclotriphosphazene (P3) synthesized by condensation reactions in suitable conditions with (P2) and dodecylamine. Synthesized ligands have been investigated with the methods of FTIR, 31P NMR, Uv-vis, MS spectroscopies, elemental and thermal analysis (TGA and DSC). Co(III), Ru(II) complexes were synthesized (L/M) 1:2 ratio and characterized FTIR, UV-vis and MS spectra, together with elemental and thermal analysis.

Syntheses, characterization of three new cobalt(II) complexes with 2-phenylsuccinic acid and flexible bis(imidazole) linkers

Bis(imidazole) derivatives (obix, mbix, pbix = 1,2-/1,3-/1,4-bis((imidazol-1-yl)methyl)benzene) with Co(II) and flexible 2-phenyl succinic acid (phsucH2) afforded three coordination polymers namely, [Co(µ-phsuc)(µ-obix)]n (1), {[Co(µ-phsuc)(µ-mbix)]⋅H2O}n (2), {[Co(µ4-phsuc)(µ-pbix)0.5]⋅H2O}n (3) and they were characterized by elemental analysis, magnetic susceptibility, solid-state UV–Vis. and IR spectroscopies and single crystal X-ray diffraction techniques. The phase purities of the complexes were confirmed by powder X-ray diffraction analysis. X-ray diffraction studies have shown that compounds 1 and 2 crystallize in the monoclinic system, in the P21/c space group, while compound 3 crystallizes in the P-1 space group in the triclinic system. In all compounds, bis(imidazole) ligands act as bis(monodentate), whereas 2-phenylsuccinate ligands act as both monodentate and bidentate bridges in 1, bis(monodentate) bridges in 2, tetrakis(monodentate) bridges in 3. The complexes displayed 2D layer structures and adjacent 2D layers are joined by C–H···π interactions in 1, weak C–H···O interactions in 2, π···π stacking and weak C–H···π interactions in 3 to form a 3D supramolecular network. The contribution of the binding positions of the imidazole groups to the phenyl ring in bis(imidazole) ligands to the structure and structural diversity are also discussed. In addition, the thermal properties of the compounds were investigated in the study.

Novel Silver Complexes Based on Phosphanes and Ester Derivatives of Bis(pyrazol-1-yl)acetate Ligands Targeting TrxR: New Promising Chemotherapeutic Tools Relevant to SCLC Management

Bis(pyrazol-1-yl)acetic acid (HC(pz)2COOH) and bis(3,5-dimethyl-pyrazol-1-yl)acetic acid (HC(pzMe2)2COOH) were converted into the methyl ester derivatives 1 (LOMe) and 2 (L2OMe), respectively, and were used for the preparation of silver(I) complexes 3-5. The Ag(I) complexes were prepared by the reaction of AgNO3 and 1,3,5-triaza-7-phosphaadamantane (PTA) or triphenylphosphine (PPh3) with LOMe and L2OMe in methanol solution. All Ag(I) complexes showed a significant in vitro antitumor activity, proving to be more effective than the reference drug cisplatin in the in-house human cancer cell line panel containing examples of different solid tumors. Compounds were particularly effective against the highly aggressive and intrinsically resistant human small-cell lung carcinoma (SCLC) cells, either in 2D and 3D cancer cell models. Mechanistic studies revealed their ability to accumulate into cancer cells and to selectively target Thioredoxin (TrxR), thus leading to redox homeostasis unbalance and ultimately inducing cancer cell death through apoptosis.

A Simple Way to Obtain a Decachloro Derivative of Cobalt Bis(dicarbollide)

A simple synthetic way to obtain a decachloro derivative of cobalt bis(dicarbollide) has been found. The reaction of cesium salt of cobalt bis(dicarbollide) anion with aluminum chloride in chloroform under reflux conditions results in Cs[3,3′-Co(4,7,8,9,12-Cl5-1,2-C2B9H6)2] of high purity and good yield.

Novel bis-amide-based bis-thiazoles as Anti-colorectal Cancer Agents Through Bcl-2 Inhibition: Synthesis, In Vitro, and In Vivo studies.

Some heterocycles having bisamide linkage are receiving much interest due to their remarkable biological potencies and they are naturally occurring. Some bisamides and thiazole derivatives were found to inhibit the protein levels of Bcl-2 significantly. This prompted us to synthesize new bis(heterocyclic) derivatives having bisamide function to explore their anti-cancer activities. Novel bis-amide-based bis-thiazoles and thiadiazoles were synthesized by reaction of a new bisthiosemicarbazone with a variety of hydrazonoyl chlorides, a-chloroacetylacetone and haloacetic acid derivatives. Most of the synthesized derivatives were tested for colorectal (HCT-116) and breast (MCF-7) cell lines using the MTT assay, with the apoptotic investigation through flow cytometric and RT-PCR analyses. Some derivatives were found to be highly cytotoxic against HCT-116 cells with an IC50 range of (10.44-13.76 μM) compared to 5-fluorouracil (5-FU) (IC50 = 11.78 μM). One product significantly stimulated apoptotic colorectal cancer cell death by 27.24-fold (50.13% compared to control 1.84%) by arresting the cell cycle at the G2/M phase. The obtained results revealed that compound 7f was more cytotoxic against HCT-116 cells than 5-FU. Compound 7f remarkably enhanced apoptotic colorectal cancer cell death and upregulated the propapoptotic genes (P53, BAX and Capases-3,-8,-9) and downregulated the anti-apoptotic gene, B-cell lymphoma 2 (Bcl-2). In vivo study exhibited that 7f-treatment caused tumor inhibition ratio (TIR%) of 50.45% compared to 54.86% in the 5-FU treatment, with a significant reduction in tumor mass and volume. The anti-tumor activity of compound 7f was accompanied by ameliorated hematological and biochemical analyses, histopathological improvement in treated liver tissues, and the immunohistochemical staining revealed Bcl-2 inhibition in agreement with the in vitro results. Compound 7f is an interesting candidate for further development as a chemotherapeutic anti-cancer agent.

Azobenzene derivatives of 3,3’-bis(indolyl)methanes: Novel electroactive materials with antioxidant activities

A practical and efficient synthesis of new electroactive azobenzene derivatives of bis(indolyl)methanes has been achieved via the Friedel-Crafts reaction of indole with 5-arylazosalicylaldehydes using propylphosphonic anhydride (T3P®) as an activating agent. This protocol is distinguished by its operational simplicity, high product yields, short reaction time, good functional group tolerance, and environmental friendliness. The antioxidant properties of the synthesized compounds were explored by examining their radical scavenging effect on DPPH radicals and their electrochemical redox behavior was assessed using cyclic voltammetry studies.

I2‐Catalyzed Cycloisomerization of Ynamides: Chemoselective and Divergent Access to Indole Derivatives

AbstractHerein, an I2‐catalyzed unprecedented cycloisomerization of ynamides is developed, furnishing various functionalized bis(indole) derivatives in generally good to excellent yields with wide substrate scope and excellent atom‐economy. This protocol not only represents the first molecular‐iodine‐catalyzed tandem complex alkyne cycloisomerizations, but also constitutes the first chemoselective cycloisomerization of tryptamine‐ynamides involving distinctively different C(sp3)−C(sp3) bond cleavage and rearrangement. Moreover, chiral tetrahydropyridine frameworks containing two stereocenters are obtained with moderate to excellent diastereoselectivities and excellent enantioselectivities. Meanwhile, cycloisomerization and aromatization of ynamides produce pyrrolyl indoles with high efficiency enabled by I2. Additionally, control experiments and theoretical calculations reveal that this reaction probably undergoes a tandem 5‐exo‐dig cyclization/rearrangement process.

I2-CatalyzedCycloisomerization of Ynamides: Chemoselective and Divergent Access to Indole Derivatives.

Herein, an I2-catalyzed unprecedented cycloisomerization of ynamides is developed, furnishing various functionalized bis(indole) derivatives in generally good to excellent yields with wide substrate scope and excellent atom-economy. This protocol not only represents the first molecular-iodine-catalyzed tandem complex alkyne cycloisomerizations, but also constitutes the first chemoselective cycloisomerization of tryptamine-ynamides involving distinctively different C(sp3)-C(sp3) bond cleavage and rearrangement. Moreover, chiral tetrahydropyridine frameworks containing two stereocenters are obtained with moderate to excellent diastereoselectivities and excellent enantioselectivities. Meanwhile, cycloisomerization and aromatization of ynamides produce pyrrolyl indoles with high efficiency enabled by I2. Additionally, control experiments and theoretical calculations reveal that this reaction probably undergoes a tandem 5-exo-dig cyclization/rearrangement process.

Preparation and Characterization of some Bivalent Metal Complexes with bis[2-(2ethyledenebenzimidazolyl)thiocarbohydrazide] and Studies of their Antiamoebic and Antihelminthic Activities

Manifestation of various medicinal potentiality and pharmacological activities associated in a pretty large number of Benzemidazole derivatives is due to presence of imidazole nuclei present in benzimidazole nuclei, which is essential constituent of Haemoglobin, Vitamin B-12, Adenine, Guanine (present in DNA). In present investigation we had prepared and characterized the complexes of some bivalent nontransition metal like Zn(II), Cd(II), Pb(II), Hg(II) and Sn(II) complexes with quadridentate ligand of benzimidazole derivative bis[2-(2ethyledenebenzimidazole) thiocarbohydrazide] (H2bisbtch) from studies of Elemental analysis, Electrical conductance data, Infrared and H-NMR spectral data. The complexes have general composition [M(bisbtch)] and almost insoluble in aqueous medium and fairly soluble in dimethyl formamide and polar organic solvent. The antiamoebic properties of ligand and its Zn(II) complexes were investigated in detail both ligand and Zn(II) complexs showed appreciable antiamoebic and antihelminthic activities similar to albendazole and Thiobendazole

Linking polynitro hexaazaisowurtzitane cagesviaanN,N'-methylene bridge: a promising strategy for designing energetic ensembles of CL-20 derivatives and adjusting their properties

New energetic materials based onN,N′-methylene bridged polyfunctionalized cage compounds are reported in which derivatives of bis(polynitrohexaazaisowurtzitanyl)methane have both a higher enthalpy of formation and a lower friction sensitivity than CL-20.