Green synthesis of 1,2,3‐triazoles via Cu2O NPs on hydrogen trititanate nanotubes promoted 1,3‐dipolar cycloadditions

Cu₂O nanoparticles supported on hydrogen trititanate nanotubes (Cu₂O/HTNT) catalysts have been efficiently catalyzed the multicomponent synthesis of 1,2,3‐triazoles in water at room temperature from different azide precursors, for example organic halides, sulfonates and anilines. The catalysts were synthesized by hydrothermal & wet‐impregnation methods and was characterized by HR‐TEM, EDS, XRD, XPS, N₂‐adsorption desorption and ICP‐MS analysis. The catalyst could be recycled by centrifugation and reused up to seven cycles. The 1‐benzyl‐4‐(4‐chlorophenyl)‐1H‐1,2,3‐triazole ( 25 ) structure was proven by single crystal X‐ray diffraction studies.     

A non‐natural dinucleotide containing an isomeric l‐related deoxy­nucleoside: dinucleotide inhibitors of anti‐HIV integrase activity

The first X‐ray crystal structure of a non‐natural dinucleotide, 5′‐O‐phosphoryl‐1′‐deoxy‐2′‐isoadenylyl‐(3′ → 5′)‐cytidine 6.5‐hydrate (pIsodApC), C₁₉H₂₆N₈O₁₃P₂·6.5H₂O, belonging to a family of dinucleotides that contain an isomeric nucleoside component, is described. A complex system of hydrogen bonds between water mol­ecules and various sites on the dinucleotide was found. All H atoms were located from electron‐density difference maps, which allowed identification of protonation sites. Compounds of this family have been found to bind at the active site of HIV integrase and to be inhibitors of this key viral enzyme. These dinucleotides are completely resistant to cleavage by exonucleases; an abnormal dihedral angle twist in an inter­nucleotide phosphate bond revealed in the X‐ray crystal structure may be contributing to this unusual stability towards nucleases.     

Removal of chemical oxygen demand,nitrogen, and heavy metals using a sequenced anaerobic-aerobic treatment of landfill leachates at 10-30 degrees C

As a first step of treatment of landfill leachates (total chemical oxygen demand [COD]: 1.43–3.81 g/L; total nitrogen: 90–162 mg/L), performance of laboratory upflow anaerobic sludge bed reactors was investigated under mesophilic (30°C), submesophilic (20°C), and psychrophilic (10°C) conditions. Under hydraulic retention times (HRTs) of about 0.3 d, when the average organic loading rates (OLRs) were about 5 g of COD/(L·d), the total COD removal accounted for 81% (on average) with the effluent concentrations close to the anaerobic biodegradability limit (0.25 g of COD/L) for mesophilic and submesophilic regimes. The psychrophilic treatment conducted under an average HRT of 0.34 d and an average OLR of 4.22 g of ducted under an average HRT of 0.34 d and an average OLR of 4.22 g of COD/(L·d) showed a total COD removal of 47%, giving effluents (0.75 g of COD/L) more suitable for subsequent biologic nitrogen removal. All three anaerobic regimes used for leachate treatment were quite efficient for elimination of heavy metals (Fe, Zn, Cu, Pb, Cd) by concomitant precipitation in the form of insoluble sulfides inside the sludge bed. The application of aerobic/anoxic biofilter as a sole polishing step for psychrophilic anaerobic effluents was acceptable for elimination of biodegradable COD and nitrogen approaching the current standards for direct discharge of treated waste-water.     

Scan-rate-dependent melting transitions of interleukin-1 receptor (type II): elucidation of meaningful thermodynamic and kinetic parameters of aggregation acquired from DSC simulations

The role of thermal unfolding as it pertains to thermodynamic properties of proteins and their stability has been the subject of study for more than 50 years. Moreover, exactly how the unfolding properties of a given protein system may influence the kinetics of aggregation has not been fully characterized. In the study of recombinant human Interleukin-1 receptor type II (rhuIL-1R(II)) aggregation, data obtained from size exclusion chromatography and differential scanning calorimetry (DSC) were used to model the thermodynamic and kinetic properties of irreversible denaturation. A break from linearity in the initial aggregation rates as a function of 1/T was observed in the vicinity of the melting transition temperature (T(m) approximately 53.5 degrees C), suggesting significant involvement of protein unfolding in the reaction pathway. A scan-rate dependence in the DSC experiment testifies to the nonequilibrium influences of the aggregation process. A mechanistic model was developed to extract meaningful thermodynamic and kinetic parameters from an irreversibly denatured process. The model was used to simulate how unfolding properties could be used to predict aggregation rates at different temperatures above and below the T(m) and to account for concentration dependence of reaction rates. The model was shown to uniquely identify the thermodynamic parameters DeltaC(P) (1.3 +/- 0.7 kcal/mol-K), DeltaH(m) (74.3 +/- 6.8 kcal/mol), and T(m) with reasonable variances.     

Isonucleosides with Exocyclic Methylene Groups

Synthesis of isonucleosides 13 , 14 , 16 , and 17 , bearing an exocyclic methylidene group at the sugar moiety, starting from a 3‐keto sugar is described. The keto compound was converted to the methylene‐sugar 10b (Scheme 1), which was coupled with nucleobases by means of the Mitsunobu reaction. The coupling reaction with adenine and 8‐azaadenine produced both the N⁹‐ and N³‐nucleosides (see 13 and 14 , resp.; Scheme 2). The structures of 13a and 14a were confirmed by single‐crystal X‐ray data. Synthesis of the pyrimidine compounds was also approached from the β‐amino sugar 20 that was prepared using a Gabriel‐synthesis methodology (Scheme 3).     

Selective alkylation reactions with vinamidinium salts

Vinamidinium salts react readily with enolates of ketones, esters, and lactones to produce multifunctional, synthetically-useful, dienaminones.     

Benzimidazole bearing Pd–PEPPSI complexes catalyzed direct C2-arylation/heteroarylation of N-substituted benzimidazoles

A convenient and highly efficient palladium-catalyzed direct C2-arylation/heteroarylation of N-substituted benzimidazole derivatives such as N-benzyl/3-chlorobenzyl/2,4,6-trimethylbenzyl/2,4,6-triisopropylbenzyl/aryl benzimidazoles with various aryl/heteroaryl bromides in the presence of Pd–PEPPSI (palladium-pyridine enhanced pre-catalyst preparation stabilization and initiation) complexes is reported. In order to that we have prepared a series of different symmetrical and unsymmetrical N,N′-diaralkyl benzimidazole-bearing Pd–PEPPSI complexes. Among all of the the prepared complexes, Pd–PEPPSI- 3 effectively tuned the reaction at a relatively higher rate under mild reaction conditions in an ethanol–water system. In addition, the catalytic process avoids the use of external ligand and additives. Further the reactivity was compared with commercially available copper-N-heterocyclic carbene catalyst, but the reaction was less successful. With the optimized reaction conditions, a wide range of 2-aryl/heteroaryl-N-substituted benzimidazoles were synthesized in good to excellent yields via Csp²-H/Csp²-X biaryl cross-coupling.     

Simultaneous determination of carisoprodol and aspirin in human plasma using liquid chromatography–tandem mass spectrometry in polarity switch mode: application to a human pharmacokinetic study

A simple, sensitive and rapid LC‐MS/MS‐ESI method has been developed and validated for simultaneous quantification of the carisoprodol and aspirin in human plasma. Carisoprodol was detected in positive ion mode, whereas aspirin was detected in negative ion mode. Carbamazepine and furosemide were used as internal standards (IS) for quantification of carisoprodol and aspirin, respectively. The extraction procedure involves a liquid–liquid extraction method with ter‐butyl methyl ether. Chromatographic separation was achieved on a Zorbax XDB‐Phenyl (4.6 × 75 mm, 3.5 µm) column using an isocratic mobile phase (5 mm ammonium acetate:methanol, 20:80, v/v) at a flow rate of 0.8 mL/min with a total run time of 2.2 min. A detailed method validation was performed as per the FDA guidelines. The standard curves found to be linear in the range of 25.5–4900 and 15.3–3000 ng/mL for carisoprodol and aspirin, respectively. The results met the acceptance criteria. Carisoprodol and aspirin were found to be stable in various stability studies. The validated method was successfully applied to a pharmacokinetic study following co‐administration of carisoprodol (250 mg) and aspirin (75 mg) tablets by oral route to human volunteers. Copyright © 2012 John Wiley & Sons, Ltd.     

Investigation of thermal conductivity and rheological properties of vegetable oil based hybrid nanofluids containing Cu–Zn hybrid nanoparticles

Vegetable oils (Ground nut) are being investigated to serve as a possible substitute for non-biodegradable mineral oils, which are currently being used as metal-cutting fluids in machining processes. In this study, thermophysical properties of hybrid nanofluids (vegetable oil) to be used as metalworking cutting fluids are investigated. In-situ synthesis of copper (Cu) and zinc (Zn) combined hybrid particles is performed by mechanical alloying with compositions of 50:50, 75:25, and 25:75 by weight. Characterizations of the synthesized powder were carried out using X-ray diffraction, a particle size analyzer, FE-SEM, and TEM. Hybrid nanofluids with all the three combinations of hybrid nanoparticles were prepared by dispersing them into a base fluid (vegetable oil). The thermophysical properties, such as thermal conductivity and viscosity, were studied for various volume concentrations and at a range of temperatures. Experimental results have shown enhancement in thermal conductivity in all cases and also an increase in viscosity. The enhancement in viscosity is similar in all three combinations, as the particle size and shape are almost identical. The enhancement in thermal conductivity is higher in Cu–Zn (50:50), resulting in better enhancement in thermal conductivity due to the Brownian motion of the particles and higher thermal conductivity of the nanoparticles incorporated.     

ZnII‐ and AuI‐Catalyzed Regioselective Hydrative Oxidations of 3‐En‐1‐ynes with Selectfluor: Realization of 1,4‐Dioxo and 1,4‐Oxohydroxy Functionalizations

Catalytic 1,4‐dioxo functionalizations of 3‐en‐1‐ynes to (Z)‐ and (E)‐2‐en‐1,4‐dicarbonyl compounds are described. This regioselective difunctionalization was achieved in one‐pot operation through initial alkyne hydration followed by in situ Selectfluor oxidation. The presence of pyridine alters the reaction chemoselectivity to give 4‐hydroxy‐2‐en‐1‐carbonyl products instead. A cooperative action of pyridine and Zn^II assists the hydrolysis of key oxonium intermediate.