Intergenerational continuity as a key factor for efficient development of organic chemistry and metal complex catalysis in Russia

Russian Journal of Organic Chemistry -     

Isolation and structural elucidation of a key aluminoaromatic intermediate and evidence for dismutation phenomena in TMP-alumination chemistry

Lithium TMP-aluminate "(i)Bu(3)Al(TMP)Li" undergoes dismutation in THF solution to precipitate the tetraalkylaluminate [{Li.(THF)(4)}(+){Al((i)Bu)(4)}(-)], but reacts kinetically as a TMP base towards N,N-diisopropylbenzamide to afford the crystalline ortho-aluminated species [(THF)(3).Li{O([=C)N((i)Pr)(2)(C(6)H(4))}Al((i)Bu)(3)] and TMPH.     

Monoclinic zirconia nanoparticle-catalyzed regioselective synthesis of some novel substituted spirooxindoles through one-pot multicomponent reaction in a ball mill: A step toward green and sustainable chemistry

A highly efficient, green as well as atom economical protocol for the synthesis of substituted spirooxindoles from m-ZrO₂ NPs catalyzed multicomponent reaction of isatin derivatives with ethyl cyanoacetate and 1,3-dicarbonyl compounds in a ball mill has been established. Because of the simple and readily available starting materials, easy operation, and high bioactivity of substituted spirooxindoles, this strategy can be broadly applied to medicinal chemistry. The recyclability of the m-ZrO₂ Nps catalyst is another emphasis of proposed methodology.     

Applying green analytical chemistry (GAC) for development of stability indicating HPLC method for determining clonazepam and its related substances in pharmaceutical formulations and calculating uncertainty

Clonazepam contains one benzodiazepine ring in its chemical structure which makes it vulnerable to degradation. In this study, green analytical chemistry approach was applied in attempts for the development of validated stability indicating RP-HPLC method for determining clonazepam and its related substances in pharmaceutical formulation. Validation has been performed according to ICH guidelines. Assay was capable of simultaneous monitoring of the intact drug in the presence of its related substances within the same run. HPLC assay involved an ODS column and a mobile phase composed of 2% sodium dodecyl sulfate, 0.05 M sodium acetate buffer pH 3.5 and isopropanol in ratio (25:55:20) at a flow rate of 1.5 mL/min and detection was carried out at 254 nm. HPLC method allowed good resolution between the peaks that corresponded to the active pharmaceutical ingredients and its degradation products with good linearity, precision, accuracy, specificity, LOD and LOQ. The expanded uncertainty (0.33%) of the method was also estimated from method validation data. This analytical technique is not only ecofriendly but also faster than the conventional liquid chromatographic system official in the USP-36.     

Risk assessment,development and validation of a GC-ECD-based method for the quantification of cypermethrin from green pea

The present work describes the persistence, dissipation behaviour, half-life, risk assessment and novel gas chromatography method for the residue estimation of cypermethrin in green pea by spraying cypermethrin 10EC at 50 g a.i. ha⁻¹ at fruiting stage followed by another application at a 10 day interval. The sample extraction and cleanup was followed bya modified quick, easy, cheap, effective, rugged, and safe method, and the residues of cypermethrin were determined using a validated gas chromatography method. The initial deposits were found to be 1.21 mg kg⁻¹ following the application of insecticide at 50 g a.i. ha⁻¹. Cypermethrin residues declined to below the detection limit of 0.05 mg kg⁻¹ after 15 days at the recommended dosage. The half-life of cypermethrin was 2.66 days at 50 g a.i. ha⁻¹. For risk assessment studies, the waiting period of 15 days is recommended as safe for consumption for the insecticide. The GC-ECD method was validated according to the SANTE guidelines by various analytical parameters including linearity, accuracy, detection and quantification limits. The developed method is simple, selective and repeatable, and can be used for the standardization of pesticides on fruits and vegetables.     

Applying green analytical chemistry for development and validation of RP-HPLC stability indicating assay method for estimation of fenoverine in bulk and dosage form using quality by design approach

A green and robust reverse-phase liquid chromatographic method has been developed for the determination of fenoverine (FEN), by applying combined principles of green analytical chemistry and quality by design approaches on a Spherisorb C18 column (150?×?4.6?mm, 3?µm) with UV detection at 262?nm. A two level fractional factorial design (2^^7-3) Res IV was used for screening of influential chromatographic factors. The critical method parameters actively affecting critical quality attributes (CQAs) were identified and further optimized using Box–Behnken design. The predicted optimum assay conditions comprised of methanol and ammonium acetate buffer 20?mM, in an extent of 81:19% v/v individually having a flow rate of 1.0?mL/min with a column oven temperature of 33°C. The drug was stressed in hydrolytic, oxidative, reductive, thermal, and photolytic conditions. The developed method was validated successfully. The detector response was linear in the concentration of 0.5–160?µg/mL with a limit of detection (LOD) and limit of quantitation (LOQ) as 0.1 and 0.3?µg/mL, respectively. The % recovery was found to be 99.7%. The analytical method volume intensity value for developed method was 45?mL and the environment assessment tool (EAT) score was 41.07. The method is simple, environmentally benign, rapid, and robust for the determination of FEN in bulk and in its dosage form.     

Synthesis of substituted N-phenylmaleimides and use in a Diels–Alder reaction: a green multi-step synthesis for an undergraduate organic chemistry laboratory

ABSTRACT

This paper describes the design and implementation of a minimally hazardous, environmentally friendly, and energy efficient sequential reaction sequence within a sophomore level Organic Chemistry lab course to efficiently synthesize N-phenylmaleimide precursors for a Diels–Alder reaction. Substituted N-phenylmaleimides are a class of very expensive precursors of considerable interest due to their biological properties and use as intermediates in synthesis. The synthesis described herein produces a substituted N-phenylmaleimide in two steps from maleic anhydride and a substituted aniline followed by its Diels–Alder reaction with 2,5-dimethylfuran. The experiment exposes students to the green chemistry principles of atom economy, use of safer chemicals, design for energy efficiency, waste reduction, and inherently safer chemistry for accident prevention and enables students to use ¹H NMR spectroscopy to characterize the products.     

Optical waveguide sensors in analytical chemistry: today’s instrumentation, applications and trends for future development

Current concepts for chemical and biochemical sensing based on detection with optical waveguides are reviewed. The goals are to provide a framework for classifying such sensors and to assist a designer in selecting the most suitable detection techniques and waveguide arrangements. Sensor designs are categorized on the basis of the five parameters that completely describe a light wave: its amplitude, wavelength, phase, polarization state and time-dependent waveform. In the fabrication of a successful sensor, the physical or chemical property of the determined species and the particular light wave parameter to detect it should be selected with care since they jointly dictate the sensitivity, stability, selectivity and accuracy of the eventual measurement. The principle of operation, the nature or the detected optical signal, instrumental requirements for practical applications, and associated problems are analyzed for each category of sensors. Two sorts of sensors are considered: those based on direct spectroscopic detection of the analyte, and those in which the analyte is determined indirectly through use of an analyte-sensitive reagent. Key areas of recent study, useful practical applications, and trends in future development of optical waveguide chemical and biochemical sensors are considered. Received: 19 January 1998 / Revised: 15 May 1998 / Accepted: 21 May 1998     

Optical waveguide sensors in analytical chemistry: today’s instrumentation, applications and trends for future development

Current concepts for chemical and biochemical sensing based on detection with optical waveguides are reviewed. The goals are to provide a framework for classifying such sensors and to assist a designer in selecting the most suitable detection techniques and waveguide arrangements. Sensor designs are categorized on the basis of the five parameters that completely describe a light wave: its amplitude, wavelength, phase, polarization state and time-dependent waveform. In the fabrication of a successful sensor, the physical or chemical property of the determined species and the particular light wave parameter to detect it should be selected with care since they jointly dictate the sensitivity, stability, selectivity and accuracy of the eventual measurement. The principle of operation, the nature or the detected optical signal, instrumental requirements for practical applications, and associated problems are analyzed for each category of sensors. Two sorts of sensors are considered: those based on direct spectroscopic detection of the analyte, and those in which the analyte is determined indirectly through use of an analyte-sensitive reagent. Key areas of recent study, useful practical applications, and trends in future development of optical waveguide chemical and biochemical sensors are considered.     

Digital microfluidics: a versatile tool for applications in chemistry, biology and medicine

Digital microfluidics (DMF) has recently emerged as a popular technology for a wide range of applications. In DMF, nanoliter to microliter droplets containing samples and reagents can be manipulated to carry out a range of discrete fluidic operations simply by applying a series of electrical potentials to an array of patterned electrodes coated with a hydrophobic insulator. DMF is distinct from microchannel-based fluidics as it allows for precise control over multiple reagent phases (liquids and solids) in heterogeneous systems with no need for complex networks of connections, microvalves, or pumps. In this review, we discuss the most recent developments in this technology with particular attention to the potential benefits and outstanding challenges for applications in chemistry, biology, and medicine.     

Theoretical designs for planar tetracoordinated carbon in Cu, Ag, and Au organometallic chemistry: a new target for synthesis

In the past 30 years, substantial efforts and progress have been made in the design and synthesis of molecules containing tetracoordinated planar carbon, by overcoming the inherent preference for tetrahedral bonding. As a result, we have studied 12 organometallic molecules containing group 11 elements (i.e., M-X; M = Cu, Ag, and Au and X = I, II, III, and IV) using density functional theory to determine whether the central carbon atom exists in a planar geometry. Our theoretical findings suggest that in such M-X species, bonding interactions between the central carbon and the coinage metal ligands and between the metal ligands (i.e., metallophilic attractions) are both important in favoring planar-tetracoordinated carbon compounds over the corresponding tetrahedral structures. The compounds studied in this work are seen as excellent targets for chemical synthesis.     

Quantum chemistry study of H+(H2O)8: a global search for its isomers by the scaled hypersphere search method, and its thermal behavior

The structures of the protonated water cluster H+(H2O)8 have been globally explored by the scaled hypersphere search method. On the Hartree-Fock potential energy surface 174 isomers were found, among which 168 were computed to be minima at the B3LYP/6-31+G** level, and their energies were further refined at the level of MP2/6-311++G(3df,2p). The global minimum on the potential energy surface computed at the B3LYP/6-31+G** level shows a cagelike structure with the "Eigen" motif, while the lowest-free-energy isomer has a five-membered-ring structure at 170 K and a chain form at 273 K. The present results are well in line with previous experimental findings. In addition, the ADMP (atom-centered density matrix propagation) simulation indicates that the extra proton in the lowest-free-energy isomer (170 K), which has a five-membered ring and the "Zundel" feature, is often in an asymmetrical hydrogen bond.     

In vitro and in vivo evaluation of cytotoxicity,antioxidant, antibacterial,antifungal, and cutaneous wound healing properties of gold nanoparticles produced via a green chemistry synthesis using Gundelia tournefortii L. as a capping and reducing agent

The exploitation of various plant materials for the biosynthesis of nanoparticles is considered a green technology because it does not involve any harmful chemicals. The aim of the experiment was chemical characterization and evaluation of cytotoxicity, antioxidant, antibacterial, antifungal, and cutaneous wound healing activities of gold nanoparticles using aqueous extract of Gundelia tournefortii L. leaves (AuNPs@GT). These nanoparticles were characterized by fourier transformed infrared spectroscopy (FT‐IR), field emission scanning electron microscopy (FE‐SEM), energy dispersive X‐ray spectroscopy (EDS), and UV–visible spectroscopy. DPPH free radical scavenging test was done to assess the antioxidant properties, which indicated similar antioxidant potentials for AuNPs@GT and butylated hydroxytoluene. Agar diffusion tests were applied to determine the antibacterial and antifungal characteristics. Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), and Minimum Fungicidal Concentration (MFC) were specified by macro‐broth dilution assay. AuNPs@GT indicated higher antibacterial and antifungal effects than all standard antibiotics (p ≤ 0.01). Also, AuNPs@GT inhibited the growth of all bacteria and fungi and removed them at 2‐4 mg/mL concentrations (p ≤ 0.01). In vivo experiment, after creating the cutaneous wound, the rats were randomly divided into six groups: untreated control, treatment with Eucerin basal ointment, treatment with 3% tetracycline ointment, treatment with 0.2% HAuCl₄ ointment, treatment with 0.2% G. tournefortii ointment, and treatment with 0.2% AuNPs@GT ointment. These groups were treated for 10 days. For histopathological and biochemical analysis of the healing trend, a 3 × 3 cm section was prepared from all dermal thicknesses at day 10. Use of AuNPs@GT ointment in the treatment groups substantially reduced (p ≤ 0.01) the wound area, total cells, neutrophil, and lymphocyte and remarkably raised (p ≤ 0.01) the wound contracture, hydroxyl proline, hexosamine, hexuronic acid, fibrocyte, fibroblast, and fibrocytes/fibroblast rate compared to other groups. The synthesized AuNPs@GT had great cell viability dose‐dependently (Investigating the effect of the plant on HUVEC cell line) and revealed this method was nontoxic. The results showed that the leave aqueous extract of G. tournefortii is very good bioreductant in the synthesis of gold nanoparticles for treatment of bacterial, fungal, and skin diseases.     

Stereoselective synthesis of chiral β-amino trifluoromethyl alcohol: development of a manufacturing process for a key intermediate in the production of a novel elastase inhibitor,AE-3763

We have successfully synthesized chiral β-amino trifluoromethyl alcohol (2S,3S)-7a, which is a key intermediate in the production of AE-3763, by stereoselective reduction of N-Cbz-protected 5-hydroxy-5-(trifluoromethyl)-1,3-oxazolidine 4 prepared from L-valine in 3 steps followed by alkaline hydrolysis. This new method can be applied to the industrial-scale synthesis of AE-3763.     

A simple, efficient, and green protocol for Knoevenagel condensation in a cost-effective ionic liquid 2-hydroxyethlammonium formate without a catalyst

Knoevenagel condensation of aromatic aldehydes with active methylene compounds such as malononitrile, ethylcyanoacetate, and cyanoacetamide proceeded very smoothly in reusable and cheap ionic liquid 2-hydroxyethylammonium formate at room temperature in the absence of a catalyst. Compared to other reported ionic liquids, the ionic liquid 2-hydroxyethylammonium formate shows better potential in the applications on the industrial scale with its low cost and viscosity.