Journal of the Iranian Chemical Society
Volume:8 Issue: 1, Mar 2011

Most organisms that have adapted to environmental stresses have done so by production and accumulation of certain small organic molecules, known as osmolytes that arose by natural selection and have the ability to stabilize intracellular proteins against the environmental stress. It is well known that osmolytes stabilize proteins and induce folding of aberrant proteins and therefore, it is of therapeutic use for a large number of protein misfolding diseases. Thus, it is very important that the present knowledge of the ability and mechanism of osmolyte-induced protein folding and structural stabilization should reach to researchers working in different avenues. In around 40 years of research, we have gained great advances in various aspects of protein folding and structural stabilization induced by osmolytes. To summarize and discuss the original findings, many short review articles and few long reviews have also been available but almost all have focuses on specific aspects. To get a clear picture of the effect of osmolytes on protein folding and structural stabilization, it is necessary for the benefits of the general readers, to combine and discuss all findings made during its 40 years of life. This review article is therefore, designed to give a collective knowledge on almost all facets of the progresses made on osmolyte-protein interaction to-date.

A one-pot, catalyst- and solvent-free approach has been developed for the stereoselective synthesis of fluorinated tetrahydropyrimido[1,2-b]benzothiazoles. The three-component condensation reaction of an aldehyde and a trifluoromethyl β-dicarbonyl compound in the presence of 2-aminobenzothizole occurs in high yields at 90 °C.

A simple, high performance liquid chromatographic method has been developed for the simultaneous determination of glipizide, rosiglitazone, pioglitazone, glibenclamide and glimepiride in pharmaceutical dosage forms and human plasma. The elution was performed using a mobile phase mixture of 0.05% Triethylamine (pH-3.5, adjusted with ortho phosphoric acid), acetonitrile and methanol in the ratio of 55:15:30 at a flow rate of 1 ml min-1 on a phenomenex C18 column (150 × 4.6 mm, i.d., 5 µm) at ambient temperature. The drugs were monitored at a wavelength of 248 nm and were separated within 20 min. Mixtures of formulations were prepared in suitable dilutions and plasma samples were prepared by extraction with acetonitrile. The method was successful in detecting the drugs at a concentration of less than 0.1 µg ml-1 for each drug and %RSD for intra- and inter-day studies was found to be less than 4.34 for all the selected concentrations. Moreover, the method was validated as per ICH guidelines and the results were found to be within the acceptable range. Hence, the proposed method can be used for the routine quality control of the drugs and can also be applied to pharmacokinetic studies.

A simple, green and inexpensive water-based procedure was developed to extract oleuropein from olive leaf samples. Extraction was optimized in terms of the solvent, pH of the solvent, temperature and time of extraction. The experimental results revealed that deionised water adjusted to pH 3, at 60 °C for 4 h had the highest extraction efficiency. Samples were lyophilized and stored in tight containers at -18 °C until the analysis. Oleuropein was identified by comparing the retention time of the extracts with standard compound using UV detector at 280 nm. The method of analysis was based on RP-HPLC, with a mobile phase of water (adjusted to pH 3):acetonitrile (80:20 v/v) with a flow rate of 1 ml min-1. Linear dynamic range and limit of detection were found to be 50-900 mg ml-1 and 9.5 mg ml-1, respectively. Intra- and inter-day precision of the method were calculated as RSD% of 1.2 and 5.7, respectively. Olive leaves gathered from various cultivars of Iran were analyzed by the method and results showed that olive leaves from Shiraz had the highest oleuropein content (about 13 mg g-1). The developed method can be used in industry for proper mass production of this compound that is of great significance in medicine as well as food and cosmetics industry.

Electrochemical oxidation of catechols (1) has been studied in the presence of cathodically generated 3-amino-4-hydroxycoumarin(3a) as a nucleophile in aqueous solutions, using cyclic voltammetry and controlled-potential coulometry. The results indicate that the o-benzoquinones derived from catechols (1) participate in Michael addition reaction with 3-amino-4-hydroxycoumarin(3a) to form the corresponding new heterocyclic compounds (7) (oxidized form of coumestan derivatives). The electrochemical process consists of a multi-step including (a) cathodic reduction of 4-hydroxy-3-nitrocoumarin (3) to 3-amino-4-hydroxycoumarin (3a), (b) anodic oxidation of catechols (1) to related o-benzoquinone (2), (c) the Michael addition reaction of 3-amino-4-hydroxycoumarin (3a) to o-benzoquinone (2), and (d) anodic oxidation of formed adduct. The paired electrochemical synthesis of compounds 7a and 7b has been successfully performed in a one-pot process at carbon rods as working and counter electrodes in an undivided cell.

A biosensor was developed for the detection of lactate dehydrogenase (LDH) enzyme using a lactate modified pencil graphite electrode (PGE). The sensor relies on the immobilization of the lactate on PGE, and LDH detection is based on the decrease of lactate peak current following oxidation to pyruvate in the presence of LDH. Square wave voltammetric technique was used for the assay of signals in the range of -0.6 to 0.8 V and a frequency of 25 Hz for the determination of LDH. The dependence of the response was investigated in terms of reaction time, washing time and LDH and NAD+ amounts. Also, the electrochemical behavior of LDH treatment on the lactate modified PGE was studied. The electrode showed good selectivity, repeatability and an operational stability of about 90% of its original response for two weeks. Moreover, the sensor displayed a linear response range from 0.36- 2.13 U µl-1 for LDH with a detection limit of 0.16 U µl-1. The response time of the LDH-treated lactate modified PGE was found to be 2 s. The relative standard deviation (RSD) obtained was 3.5% (for LDH 0.71 U µl-1 and n = 3).

The synthetic, structural, spectroscopic and analytical properties of steric hindered Schiff-base ligand [N-(3,5-di-tert-butylsalicylaldimine)-1-(2-Aminoethyl) piperazine (HL)] and its mononuclear Cu(II), Co(II) and Ni(II) complexes are described. The new unsymmetric steric hindered Schiff base ligand containing a donor set of NONO was prepared by the reaction of 1-(2-Aminoethyl) piperazine with 3,5-di-tert-butylsalicylaldehyde. Certain metal complexes of this ligand were synthesized by treating an ethanolic solution of the ligand with an equimolar amount of metal salts. The ligand and its metal complexes were characterized by FT-IR, UV-Vis, 1H NMR, elemental analysis, molar conductivity and magnetic susceptibility techniques. The reaction of this ligand in a 1:2 mole ratio with metal acetate afforded mononuclear metal complexes. The molar conductivity (ΛM) values of the metal complexes of Ni(II), Co(II) and Cu(II) were in the range of 6.4 to 9.8 Ω-1 cm2 mol-1 at room temperature. Preconcentration and separation of Cu2+ from aqueous solution using N-(3,5-di-tert-butylsalicylaldimine)-1-(2-Aminoethyl) piperazine (HL) as a new extractant were studied. The extraction experiments were carried out at various pHs. While Cu2+ showed the highest extractability and selectivity at pH 7.0, extractions of Co2+ and Ni2+ were unsuccessful due to precipitate formation.

In this paper, a new simple method is presented for the estimation of the toxicity of nitroaromatic compounds including some well-known explosives. This method can predict the 50% lethal dose concentration for rats (LD50) as the estimation of toxicity in vivo. The prediction of LD50 of nitroaromatics through a new general correlation is based on the number of alkyl and nitro groups per molecular weight of the nitroaromatic compound as a core function. The existence of some specific structural parameters can decrease or increase the predicted results on the basis of the core function. The predicted results of various nitroaromatic compounds afford reliable prediction of LD50 with respect to experimental data. Prediction of toxicity for 28 nitroaromatic compounds, where the experimental data were available, and new nitroaromatic derivatives produce comparable results to those of several models of Quantitative Structure Activity Relation (QSAR).

A new signal processing approach was developed to improve the simultaneous spectrophotometric determination of trimethoprim (TMP) and sulphamethoxazole (SMX) in their binary mixtures without using any chemical pre-treatment. This approach was essentially based on the continuous wavelet transform (CWT) of the absorption spectra of the target compounds and their samples. A set of continuous wavelet transforms was applied. Biorthogonal with 2.4 order (BIOR2.4), Coiflets with 2 order (COIF2), Daubechies with 3 order (DB3) and Haar (HAAR) were found to be suitable for the quantitative resolution of the two-component mixture containing TMP and SMX compounds. The confirmation of the determination results obtained by applying the BIOR2.4, COIF2, DB3 and HAAR wavelet families was achieved by first derivative spectrophotometry (DS1) analysis of the same mixtures. The validation of the above-mentioned signal processing methods was tested by analyzing various binary mixtures of the related compounds, and by using the standard addition technique. The simultaneous determination of TMP and SMX in commercial tablets was assessed by using the proposed signal processing tools.

A simple, rapid and low cost method for determination of phthalic acid esters (PAEs) including Dimethyl phthalate (DMP), Diethyl phthalate (DEP), Di-n-butyl phthalate (DBP) and Butylbenzyl phthalate (BBP) in water samples was investigated. The method is based on the extraction of PAEs with coacervate made up of decanoic acid reverse micelles and the subsequent determination by HPLC-UV. Effect of parameters such as concentration of tetrahydrofuran (THF) (2-40% v/v) and decanoic acid (20-400 mg in 40 ml total volume), ionic strength (0.0-0.1 M NaCl), pH (1-4) and stirring time (2-60 min) on recoveries (Rs) and enrichment factors (EFs) were investigated and optimized. The optimum condition for extraction was the stirring of 36 ml of water sample with 4 ml of THF containing 100 mg of decanoic acid for 10 min and its centrifugation (10 min, 3500 rpm). Recoveries and enrichment factors of PAEs mainly depended on the amount of decanoic acid and THF making up the coacervate and were not affected by ionic strength of the sample solution (up to 0.1 M of NaCl), pH (1-4), and stirring time (2-60 min). Recoveries, enrichment factors, LODs and relative standard deviations (RSD%) for PAEs were between 87-94%, 187-202, 0.22-0.30 µg l-1 and 2-5%, respectively. This method was applied to determine PAEs in tap water, river water, and sea water samples. No PAEs were found in tap water. The amount of DMP and DEP in the Babolrood River was 0.87 and 0.67 µg l-1, while in the Caspian Sea was 0.49 and 0.52 µg l-1, respectively.

Mathematical modeling of methylene blue (MB) signal in ssDNA and dsDNA on pencil graphite electrode is described. A DNA biosensor was developed based on MB signal. The probe and target DNAs were 20 mer oligonucleotides corresponding to consensus sequence of HPV major capsid protein L1 gene. Hybrids of various complementary and non-complementary oligonucleotides with the probe were considered as dsDNA with different hybridization degrees. Modeling was developed by incorporation of only the stable forms of dsDNA hybrids. Effect of hybridization degree on current signal in various forms was studied. A factor named AHP (Average Hybridization Percentage) for verifying the hybridization events was defined. Results showed that there is a significant mathematical relation between the calculated AHP and MB signals.

4H-Pyrans and coumarins were synthesized through one-pot reactions using ZnO/MgOsolid sample containing ZnO nanoparticles as an efficient reusable catalyst in ionic liquid, [bmim]BF4. The catalyst is inexpensive and readily available, stable and storable, easily recycled and reused for several cycles with consistent activity. The procedure offers advantages in terms of high yields, short reaction times, and mild solvent-free reaction conditions.

A series of new imidazolium-type ionic liquids based on polyethylene glycol have been prepared. The new recyclable temperature-dependant phase-separation system comprised of [C12minPEG800]Br and methylcyclohexane was also developed and successfully applied to the dichloromethylation of some aromatic hydrocarbons to prepare dichloromethyl-substituted hydrocarbons in excellent yields. The ionic liquid could be excellent recycled without any apparent loss of catalytic activity and little loss of weight even after 8 times recycling.

A new catalytic method for the chemoselective oxidation of sulfides to the sulfoxides has been studied. A variety of dialkyl, alkylaryl and diaryl sulfides were subjected to the oxidation reaction by a mixture of nitro urea, derived from urea nitrate, silica sulfuric acid (SiO2-OSO3H) and catalytic amounts of ammonium bromide in CH2Cl2 at room temperature.

Several ionic liquids containing pyrrolidinium-, oxopyrrolidinium-, piperidinium-, morpholinium- and trialkylammonium-based cation are synthesized and their thermal property, refractive index, polarity, electrochemical property, and temperature dependency of dynamic viscosity, density and ionic conductivity are characterized. All tetrafluoroborate-based room temperature ionic liquids studied here have a high ionic conductivity (up to 31.4 mS cm-1). These ILs were successfully used as suitable electrolytes for the diffusion coefficient measurement of ferrocene. Absorbance solvatochromic probes Nile red is used to investigate the relative polarity of these ionic liquids and compared them with several organic solvents. The relation of fluidity to conductance is considered in terms of a Walden plot that is shown to provide a useful basis for organizing the applications of solvent media for “green” synthetic reactions.

In water, methylene blue (MB) is known to be aggregated to dimmer and trimmer at high concentration levels. We conducted a thermodynamic study on the aggregation of MB using multivariate curve resolution analysis of the visible absorbance spectra over a concentration range of 2.0 × 10-6-4.0 × 10-4 M. A hard modeling-based multivariate curve resolution method was applied to determine the dissociation constants of the MB aggregates at various temperatures ranging from 25 to 75 °C. This method was able to resolve the visible absorbance spectra as a function of MB concentration in individual temperature or simultaneously in all other temperature ranges. Utilizing the van,t Hoff relation, the enthalpy and entropy of the dissociation equilibriums were calculated. For the dissociation of both aggregates, the enthalpy and entropy changes were positive and negative, respectively.

Linear and non-linear quantitative structure property relationship (QSPR) models for predicting the gas/particle partitioning coefficients of semivolatile organic compounds were developed based on partial least squares (PLS) and artificial neural network (ANN) to identify a set of structurally based numerical descriptors. Multilinear regression (MLR) was used to build the linear QSPR models using combination of the compounds structural descriptors and topological indices related to environmental conditions such as temperature, pressure and particle size. The prediction results for PLS and ANN models give very good coefficient of determination (0.97). In consistent with experimental studies, it was shown that linear and non-linear regression analyses are useful tools to predict the relationship between the calculated descriptors and gas/particle partitioning coefficient.

A simple, clean and benign route to the synthesis of 2H-chromen-2-ones derivatives through one-pot condensation of β-ketoesters and substituted phenols in the presence of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bistetrafluoro-borateis (SelectfluorTM F-TEDA-BF4) as catalyst under solvent free reaction conditions was experimented. The application of ultrasonic irradiation improved the yields and reduced the reaction times. The use of selectfluor catalyst is feasible because of its stability, commercial value, easy handling, easy recovery and good activity. To extend our research, the ability of selectfluor for the synthesis of 2-aminochromene derivatives was also examined

Phosphomolybdic acid (H3PMo12O40) is an efficient and reusable catalyst for the synthesis of the phospha-Michael addition of phosphite esters with different types of α,Β-unsaturated malonates to produce a variety of β-phosphono malonates.

An efficient method for synthesis of nitriles has been developed using diethyl chlorophosphate in solvent and solvent-free conditions. Primary alkyl and aryl amides, efficiently are converted to the corresponding nitriles by heating in the presence of diethyl chlorophosphate in excellent yields. This method works under mild conditions with shorter reaction times.

On-line high performance liquid chromatography (HPLC) was used to monitor steady state reactions in three reactors (K = 3) over 48.0 h. Different numbers of chromatograms, with J = 1981 retention time points, were recorded for each of the three reactors. Peaks for each chromatogram were baseline corrected and aligned using correlation optimized warping (COW). To make a complete three-way data set of I = 266 chromatograms a cubic Hermite interpolation was performed. The applied bilinear multivariate statistical process control (MSPC) method included the unfolding PCA and the trilinear technique was PARAFAC. Unfolding in reactor (K) mode was the most informative. D-charts and Q-charts were applied to the data to determine samples which were out of control. Confidence limits were then applied to the D and Q-charts and variables with different behaviours from that encapsulated within the reference data set were located. Both bilinear and trilinear methods were found to be useful for process analysis.

A series of new azines were prepared by reaction of 2-ketoalkyl quinoline derivatives with some hydrazone in solvent free reaction conditions using ultrasonic irradiation. The application of ultrasonic irradiation improved the yields and reduced the reaction times. These azines, due to having α-acidic hydrogen next to azine group and heterocycle ring, have tautomeric forms the degree of each of which was determined on the basis of 13C NMR, 1H NMR, UV and IR spectrum. The results revealed that all compounds exist mostly in the enaminone form. We attempted to obtain criss-cross or probably Diels-Alder cycloaddition products through the reaction of some of these new azines with 2-chloroacrylonitrile as a dienophile. Some new diene systems developed from the said reactions.

A cloud point extraction-flow injection procedure is proposed for on-line determination of trace amounts of copper(II) by flame atomic absorption spectrometry. Copper(II) was extracted using the non-ionic surfactant, Triton X-114 after complex formation with N-phenyl benzohydroxamic acid at pH 5 in the presence of sodium sulfate as a salting-out agent at 25 °C. After the cloud point having been obtained in the reaction coil at room temperature, the surfactant-rich phase containing the complex was collected in a mini-column packed with cotton. Then, the complex was eluted into the nebulizer of flame atomic absorption spectrometer by passing ethanol containing 1% (v/v) nitric acid. The chemical and flow variables including pH, reagent and surfactant concentrations, sample and eluent flow rates affecting the extraction and determination were optimized and the enhancement factor was estimated to be 45. The sample throughput (15 h-1) was greater than batch technique. The calibration graph was linear in the range of 5-220 μg l-1. A good precision for 50 μg l-1 copper(II) (1.9% RSD, n = 8) and detection limit (3Sb m-1) 1.00 μg l-1 were obtained. The accuracy was assessed by the analysis of a standard reference material (NBS-364) and the obtained results were in good agreement with certified amounts of copper. The proposed method was applied to the determination of copper(II) in water and hair samples.

Triarylphosphine-borane complexes are directly useful in the Rh-catalysed hydroformylation reaction of 1-octene (or Pd-catalysed hydroformylation of 1-pentene). Mild reaction conditions provide similar yields and selectivities of the anticipated aldehyde products to reactions making use of the corresponding free phosphines as ligands. The mono- or bidentate P-B adducts undergo in situ CO-mediated deprotection the produce the free phosphine ligands. The results demonstrate that phosphine-borane complexes may be directly applied to carbonylation reactions without a prior deprotection step, with little to no change in the reaction outcome.

Three complexes (bpyH)[Fe(pydc)2].4H2O (1), [Co2(pydc)2(µ-bpy)(H2O)4].4H2O (2) and [Ni(pydc)(bpy)(µ-bpy)]4.8H2O (3) were prepared from the reaction between pyridine-2,6-dicarboxylic acid, pydcH2, and 4,4`-bipyridine, bpy, with FeCl2.4H2O, CoCl2.6H2O and NiSO4.6H2O, respectively. The complex (1) crystallizes in the space group P1 of the triclinic system and contains two molecules per unit cell. The structure has been refined to a final value for R factor of 0.0355 based on 4922 reflections. The crystal structure shows that Fe(III) is coordinated to two pyridine-2,6-dicarboxylate ligands. The complexes (2) and (3) crystallize in the space group P21/c of the monoclinic system and contain two molecules per unit cell. The structure (2) has been refined to a final value for R factor of 0.0295 based on 2249 reflections. The molecular structure (2), which is a binuclear complex, contains two pyridine-2,6-dicarboxylate ligands, and a 4,4`-bipyridine bridge ligand. The structure (3) has been refined to a final value for R factor of 0.0579 based on 7721 reflections. In this structure, which is a tetramer complex, pyridine-2,6-dicarboxylate and 4,4`-bipyridine fragments act as a tri- and bidentate ligands, respectively. The protonation constants of 4,4`-bipyridine and pyridine-2,6-dicarboxylate, the equilibrium constants for the pydc-bpy system and the stoichiometry, and stability of complexation of this system with Fe3+, Co2+ and Ni2+ ions in a aqueous solution were investigated by potentiometric pH titration method. The stoichiometry of the most complexes species in solution was found to be very similar to the crystalline cited metal ion complexes.

An efficient and one-pot synthesis of thiopyrano[2,3-b]indole derivatives via Hetero Diels-Alder reaction of α,β-Unsaturated thio-oxindoles with electron poor acetylenes and Cyclic Dienophiles is described. In the proposed method the reaction is performed under neutral and one-pot reaction conditions, and also the substances can be mixed without any activation or modification and without using any catalysts.

The present study deals with the application of p-tert-butylcalix[4]arene based silica resin (4) for the removal of Congo Red (CR) from aqueous solution through batch-wise sorption. Different parameters such as pH, temperature, sorbent dosage and contact time were optimized to achieve better sorption results. It has been found that the sorption of CR dye on resin 4 was highly pH dependent and significant percent sorption (80%) was achieved at its original pH (i.e. 5.8 pH). The equation isotherms and the thermodynamic parameters such as Gibbs free energy ΔG, enthalpy ΔH and entropy ΔS were also applied to evaluate experimental data. The positive and negative value of ΔH and ΔG demonstrates that sorption process is endothermic and spontaneous in nature. It has also been noticed that the Freundlich isotherm model could provide the best fit to describe the sorption equilibrium.

A simple and efficient one-pot method for the preparation of 2-amino-5,6-dihydropyrimidin-4(3H)-one from the cyclocondensation of Meldrum's acid, aldehydes and guanidinium carbonate using a catalytic amount of amino-functionalized MCM-41 is described. This efficient technique has the advantage of giving 2-NH2-DHPM building blocks using a base catalyst in good to high yields, being completed in short reaction times and offering a simple product isolation procedure.

In continuation of our current studies on the reaction between isocyanides and electron-defficient alkenes, we would like to report our recent reseaarch on synthesizing novel derivatives of barbituric acid. The reaction of alkylidene-substituted Meldrum's acid with alkyl isocyanides in the presence of urea led to the production of the corresponding 2-(hexahydro-2,4,6-trioxopyrimidin-5-yl)-N,2-dimethylpropanamide in good to high yields. The structure of the products was in agreement with their spectroscopic data.

An efficient and solvent -free approach for regioselective thiocyanation of various substituted anilines and indoles is described. The reaction performed both on and off the alumina surface under microwave conditions. Microwave irradiation reactions under solvent-free conditions resulted in a “green-chemistry” procedure, by which thiocyanation was achieved. In comparison to other reported methods for regioselective thiocyanation of anilines and indoles on the focus of reaction times, yields and usage of oxidizing agents, the present method shows considerable advantages.

Symmetrical N,N’-alkylidene bisamides were synthesized in excellent yield by condensation of aromatic aldehydes and amides in the presence of boric acid as a catalyst under thermal and neat microwave irradiation conditions. It is the first successful report of boric acid has been used as Lewis acid catalyst for the preparation of symmetrical N,N’-alkylidene bisamides. The remarkable advantages offered by this method are green catalyst, mild reaction condition, simple procedure, fast reaction and moderate to good yield of products.