Synthesis, spectra and biomimetic properties of copper(II)-copper(II) and copper(II)-zinc(II) binuclear complexes with CuN5 chromophores

X-band electron spin resonance (ESR) and UV-vis spectra of a homobinuclear [(Bipy)2Cu-E-Im-Cu(Bipy)2](BF4)3 and a heterobinuclear [(Bipy)2Cu-E-Im-Zn(Bipy)2](BF4)3 complexes, E-Im=2-ethylimidazolate ion have been described as possible models for superoxide dismutase (SOD). Magnetic moment and ESR spectral measurements of the homobinuclear complex have shown an antiferromagnetic exchange interaction. From pH-dependent ESR and UV-vis spectral measurements studies, these complexes have been found to be stable over 8.5-10.5 pH range. These complexes catalyze the dismutation of superoxide (O2-) at biological pH. All the observations indicate that these complexes act as good possible models for superoxide dismutase.     

Synthesis of Privileged Scaffolds by Using Diversity‐Oriented Synthesis

An elegant reagent‐controlled strategy has been developed for the generation of a diverse range of biologically active scaffolds from a chiral bicyclic lactam. Reduction of the chiral lactam with LAH or alkylation with LHMDS to trigger different cyclization reactions have been shown to generate privileged scaffolds, such as pyrrolidines, indolines, and cyclotryptamines. Their amenability to substitution allows us to create various compound libraries by using these scaffolds. In silico studies were used to estimate the drug‐like properties of these compounds. Selected compounds were subjected to anticancer screening by using three different cell lines. In addition, all these compounds were subjected to antibacterial screening to gauge the spectrum of biological activity that was conferred by our DOS methodology. Gratifyingly, with no additional iterative cycles, our method directly generated anticancer compounds with potency at low nanomolar concentrations, as represented by spiroindoline 14 .     

Favipiravir (SARS-CoV-2) degradation impurities: Identification and route of degradation mechanism in the finished solid dosage form using LC/LC–MS method

Favipiravir finished dosage was approved for emergency use in many countries to treat SARS-CoV-2 patients. A specific, accurate, linear, robust, simple, and stability-indicating HPLC method was developed and validated for the determination of degradation impurities present in favipiravir film-coated tablets. The separation of all impurities was achieved from the stationary phase (Inert sustain AQ-C18, 250 × 4.6 mm, 5-μm particle) and mobile phase. Mobile phase A contained KH₂PO₄ buffer (pH 2.5 ± 0.05) and acetonitrile in the ratio of 98:2 (v/v), and mobile phase B contained water and acetonitrile in the ratio of 50:50 (v/v). The chromatographic conditions were optimized as follows: flow rate, 0.7 mL/min; UV detection, 210 nm; injection volume, 20 μL; and column temperature, 33°C. The proposed method was validated per the current International Conference on Harmonization Q2 (R1) guidelines. The recovery study and linearity ranges were established from the limit of quantification to 150% optimal concentrations. The method validation results were found to be between 98.6 and 106.2% for recovery and r² = 0.9995–0.9999 for linearity of all identified impurities. The method precision results were achieved below 5% of relative standard deviation. Forced degradation studies were performed in chemical and physical stress conditions. The compound was sensitive to chemical stress conditions. During the study, the analyte degraded and converted to unknown degradation impurities, and its molecular mass was found using the LC–MS technique and established degradation pathways supported by reaction of mechanism. The developed method was found to be suitable for routine analysis of research and development and quality control.     

Studies on nessler's reagent and nessler's precipitate part II

The composition of the precipitate formed when the Nessler's reagent is treated with ammonia, is assumed as NH_n-1Hg₂I_n, aq. and has been studied potentiometrically from iodine-hypoiodite-system. It has been observed that the value of n depends on the concentrations of [HgI₄]^-2 and OH^- ions as well as on the amount of ammonia added and it may vary from 1 to 3. The colour of the precipitate deepens from brown to chocolate as the value of n increases.     

An approach towards the oxidation of 2-amino-4H-chromenes to 2-imino-2H-chromenes

A novel method for the synthesis of 2-imino-2H-benzo[h]chromenes via the sequential addition of N-chlorosuccinimide and triethylamine to 2-amino-4H-benzo[h]chromenes has been established. This reaction protocol represents an efficient synthetic strategy to form iminochromene derivatives under mild reaction conditions, which utilizes readily accessible aminochromenes as starting materials and tolerates a wide range of substrates.     

Development,stability-indicating assessment,and evaluation of influential method conditions using a full factorial design for the determination of Nintedanib esylate-related impurities

The design of an appropriate analytical method for assessing the quality of pharmaceuticals requires a deep understanding of science, and risk evaluation approaches are appreciated. The current study discusses how a related substance method was developed for Nintedanib esylate. The best possible separation between the critical peak pairs was achieved using an X-Select charged surface hybrid Phenyl Hexyl (150 × 4.6) mm, 3.5 μm column. A mixture of water, acetonitrile, and methanol in mobile phase-A (70:20:10) and mobile phase-B (20:70:10), with 0.1% trifluoroacetic acid and 0.05% formic acid in both eluents. The set flow rate, wavelength, and injection volumes were 1.0 ml/min, 285 nm, and 5 μl, respectively, with gradient elution. The method conditions were validated as per regulatory requirements and United States Pharmacopeia general chapter < 1225 >. The correlation coefficient for all impurities from the linearity experiment was found to be > 0.999. The % relative standard deviation from the precision experiments ranged from 0.4 to 3.6. The mean %recovery from the accuracy study ranged from 92.5 to 106.5. Demonstrated the power of the stability-indicating method through degradation studies; the active drug component is more vulnerable to oxidation than other conditions. Final method conditions were further evaluated using a full-factorial design. The robust method conditions were identified using the graphical optimization from the design space.     

Synthesis, characterization and biological activity of ternary copper(II) complexes containing polypyridyl ligands

Ternary copper(II) complexes involving polypyridyl ligands in the coordination sphere of composition [Cu(tpy)(phen)](ClO4)2 (1), [Cu(tpy)(bipy)](ClO4)2 (2), [Cu(tptz)(phen)](ClO4)2 (3) and [Cu(tptz)(bipy)](BF4)2 (4) where tpy = 2,2':6',2'-terpyridine, tptz = 2,4,6-tri(2-pyridyl)-1,3,5-triazine, phen = 1,10-phenanthroline and bipy = 2,2'-bipyridine have been synthesized and characterized by elemental analysis, magnetic susceptibility, X-band e.p.r. spectroscopy and electronic spectroscopy. Single crystal X-ray of (1) has revealed the presence of a distorted square pyramidal geometry in the complex. Magnetic susceptibility measurements at room temperature were in the range of 1.77-1.81 BM. SOD and antimicrobial activities of these complexes were also measured. Crystal data of (1): P-1, a = 9.3010(7) A, b = 9.7900(6) A, c = 16.4620(6) A, Vc = 1342.73(14) A3, Z = 4. The bond distance of CuN in square base is 2+/-0.04 A.     

Paper disk electrophoresis in the determination of isoelectric points of amino acids

Summary A method is described for studying the mobility of different amino acids in buffer solutions of different p_H using the paper disk electrophoretic apparatus. From the mobility of amino acids the isoelectric point of individual amino acids has been calculated. The results obtained are in good agreement with those obtained by others.     

Reagent‐Based DOS: Developing a Diastereoselective Methodology to Access Spirocyclic‐ and Fused Heterocyclic Ring Systems

Herein, we report a diversity‐oriented‐synthesis (DOS) approach for the synthesis of biologically relevant molecular scaffolds. Our methodology enables the facile synthesis of fused N‐heterocycles, spirooxoindolones, tetrahydroquinolines, and fused N‐heterocycles. The two‐step sequence starts with a chiral‐bicyclic‐lactam‐directed enolate‐addition/substitution step. This step is followed by a ring‐closure onto the built‐in scaffold electrophile, thereby leading to stereoselective carbocycle‐ and spirocycle‐formation. We used in silico tools to calibrate our compounds with respect to chemical diversity and selected drug‐like properties. We evaluated the biological significance of our scaffolds by screening them in two cancer cell‐lines. In summary, our DOS methodology affords new, diverse scaffolds, thereby resulting in compounds that may have significance in medicinal chemistry.