Preparation of a pH-sensitive pantoprazole-imprinted polymer and evaluation of its drug-binding and -releasing properties

The aim of this work was to synthesize a pantoprazole-imprinted polymer(MIPs)and study its binding and release properties in an aqueous media.Methacrylic acid(MAA),methacrylamide(MAAM),hydroxyethyl methacrylate(HEMA),and 4-vinyl pyridine(4VP)were tested as functional monomers.Different solvents were also applied as polymerization media under heat or UV radiation.The optimized MIP was prepared in chloroform as a solvent,4-vinyl pyridine as a functional monomer,and ethylene glycole dimethacrylate(EGDMA)as a crosslinker monomer under UV irradiation.Binding and release properties of MIP were studied in comparison with a non-imprinted polymer(NIP)in aqueous media,at different pH values.The protective effect of polymer for drugs against acidic conditions was evaluated at pH 2.Results indicated that the MIP had superior binding properties compared to NIP for pantoprazole.The percentage of drug released from MIP was significantly less than from NIP at all pH values,which was attributed to the presence of imprinted cavities in the MIP matrix.MIP also had a stronger protective effect for pantoprazole in acidic media,in comparison with NIP.     

Kinetics studies of nano-structured iron catalyst in Fischer-Tropsch synthesis

Kinetic parameters of nano-structured iron catalyst in Fischer-Tropsch synthesis (FTS) were studied in a wide range of synthesis gas conversions and compared with conventional catalyst. The conventional Fe/Cu/La catalyst was prepared by co-precipitation of Fe and Cu nitrates in aqueous media and Fe/Cu/La nanostructure catalyst was prepared by co-precipitation in a water-in-oil micro-emulsion. Nano-structured iron catalyst shows higher FTS activity. Kinetic results indicated that in FTS rate expression, the rate constant (k) increased and adsorption parameter (b) decreased by decreasing the catalyst particle size from conventional to nano-structured. Since increasing in the rate constant and decreasing in the adsorption parameter affected the FTS rate in parallel direction, the particle size of catalyst showed complicated effects on kinetic parameters of FTS reaction.     

Synthesis of 1‐(Cyclohexylamino)‐2‐(aryl)pyrrolo[1,2‐a]quinoline‐3‐carbonitrile Derivatives Using a Mild,Four‐Component Reaction

1‐(Cyclohexylamino)‐2‐(aryl)pyrrolo[1,2‐a]quinoline‐3‐carbonitrile derivatives were synthesized in an efficient method from four‐component condensation reaction between cyclohexyl isocyanide, quinoline, malononitrile, and aromatic aldehydes in the presence of a catalytic amount of titanium dioxide (TiO₂) in CH₂Cl₂ at ambient temperature in good yields. Silica gel column chromatography was employed for HCN elimination and then 1, 3 hydrogen shift was led to form final products 5a , 5b , 5c , 5d , 5e .     

An efficient and simple synthesis of α-amino phosphonates as ‘drug like’ molecules catalyzed by silica-supported perchloric acid (HClO4–SiO2)

An efficient and direct protocol is described for the preparation of α-amino phosphonates derivatives by employing a multi-component, one-pot condensation reaction of aldehyde, amine and trialkyl phosphite in the presence of silica-supported perchloric acid (3 mol%) under solvent-free conditions. The thermal solvent-free green procedure offers advantages such as shorter reaction time, simple work-up, high yield, recovery and reusability of catalyst.     

X‐ray structural analysis and theoretical studies of new phosphite‐derived ylides

The reaction between dialkyl acetylenedicarboxylates and NH heterocyclic compounds in the presence of triethyl phosphite leads to stable phosphorus ylide derivatives in good yields. The X‐ray crystallographic data and theoretical study show that there is a resonance between two bonds of C₁₉P₁ and C₁₉₁O₁₉₁ in phosphorus ylide 4d . This compound crystallizes in the orthorhombic system, space group (Pca2₁), with unit cell parameters a = 17.3699(3) Å, b = 13.5500(2) Å, c = 18.4627(3) Å, α = 90°, β = 90°, γ = 90°, Z = 8, and V = 4345.4(12) ų. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:715–722, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20739     

One-pot three-component synthesis of functionalized spirolactones by means of reaction between aromatic ketones, dimethyl acetylenedicarboxylate, and N-heterocycles

A simple and convenient one-pot multi-component reaction has been described for the synthesis of functionalized spirolactones. This strategy demonstrated three-component reaction between aromatic ketones (11H-indeno[1,2-b]quinoxalin-11-one) and dimethyl acetylenedicarboxylate (DMAD) in the presence of N-heterocycles, such as pyridine, quinoline, and isoquinoline in CH₂Cl₂ at ambient temperature without use of any catalyst or activator.     

Synthesis of functionalized benzothiadiazine 1,1-dioxide derivatives via intramolecular CH activation reactions of trichloroacetamidine and benzenesulfonyl chloride

The synthesis of functionalized benzothiadiazine 1,1-dioxide derivatives was achieved through a novel three-component intramolecular CH activation reaction of trichloroacetonitrile, benzenesulfonyl chloride, and various primary amines. This reaction was performed in the presence of catalytic copper(I) and l-proline as the ligand in tetrahydrofuran at room temperature.     

Synthesis and structure of azole-fused indeno[2,1-c]quinolines and their anti-mycobacterial properties

Prompted by our discovery of a new class of conformationally-locked indeno[2,1-c]quinolines as anti-mycobacterials, compounds 2a and 3a (Fig. 1; MIC < 0.39 μg mL(-1) and 0.78 μg mL(-1), respectively)(14) with a freely rotating C2-imidazolo substituent, we herein describe the synthesis of pentacyclic azole-fused quinoline derivatives 4 and 5, in which we have restricted the rotation of the C2-imidazolo moiety by fusing it to the adjacent quinoline-nitrogen to give a five-membered fused azole heterocycle. The idea of locking the flexibility of the system by conformational constraint was simply to reduce its entropy, thereby reducing the overall free-energy of its binding to the target receptor. Out of 22 different azole-fused indeno[2,1-c]quinoline derivatives, seven structurally distinct compounds, 9, 15, 17, 25, 27, 28 and 29, have shown 79-99% growth inhibition of Mycobacterium tuberculosis H37Rv at a fixed dose of 6.25 μg mL(-1). The efficacies of these compounds were evaluated in vitro for 8/9 consecutive days using the BACTEC radiometric assay upon administration of single dose on day one. Of these, two compounds, 9 and 28, inhibited growth of M. tuberculosis very effectively at MIC < 0.39 μg mL(-1) (0.89 μM and 1 μM, respectively). These active compounds 9, 15, 17, 25, 27, 28 and 29 were screened for their cytotoxic effect on mammalian cells (human monocytic cell line U937), which showed that the human cell survival is almost unperturbed (100% survival), except for compound 25, hence these new compounds with new scaffolds have been identified as potent anti-mycobacterials, virtually with no toxicity. Thus these "hit" molecules constitute our important "leads" for further optimization by structure-activity relationship against TB.     

NMR study,theoretical calculations for assignment of the Z‐ and E‐isomers,and kinetics investigation of stable phosphorus ylides involving a 2‐mercapto‐4,6‐dimethyl pyrimidine

In the present work, NMR, theoretical, kinetics, and mechanism investigations were undertaken for a one‐pot condensation reaction between 2‐mercapto‐4,6‐dimethyl pyrimidine and dialkyl acetylenedicarboxylates in the presence of triphenyphosphine containing novel stable phosphorus ylides 4a–c . Herein, theoretical calculations have been employed for assignment of the most stable isomers (Z or E) of phosphorus ylides 4a,c by natural population analysis, atoms in molecules methods, and CHelpG keyword, in which E‐ 4(a, c) are more stable forms as the majors. The ¹H, ¹³C, and ³¹P NMR data of these ylides are consistent with results obtained from theoretical calculations. In addition, kinetic investigation of new ylides was undertaken by ultraviolet spectrophotometry. Useful information was obtained from studies of the effect of solvent, structure of reactants (different alkyl groups within the dialkyl acetylenedicarboxylates), and also the concentration of reactants on the rate of reactions. The proposed mechanism was confirmed according to the obtained results and a steady‐state approximation, and the first step (k₂) of the reaction was recognized as a rate‐determining step on the basis of the experimental data. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:462–474, 2010; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20632     

Synthesis of aromatic amine phosphonato ester derivatives from the stereoselective reaction between triphenyl phosphite and dimethyl acetylenedicarboxylate in the presence of derivatives of aromatic amines

Aromatic amine phosphonato esters 4a–d were obtained in excellent yields from the 1:1:1 addition reaction between triphenyl phosphite and dimethyl acetylenedicarboxylate in the presence of NH‐aromatic amines such as 2‐aminobenzophenone, 2‐aminoacetophenon, methyl‐2‐aminobenzoate, and 2‐aminobenzonitrile. In the recent works, the assignments of the configuration of 4a–d corresponding to the three‐bond carbon‐phosphorus coupling, ³Jpc, was determined on the basis of coupling constants by the Karplus equation as 2R *, 3R *or 2S *, 3S * while they were 2R *, 3S * or 2S *, 3R * in our previous works in the presence of same solvent. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:240–245, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20541