Current Chinese Chemistry - Volume 2, Issue 1, 2022

C-Methylation of organic substrates was accomplished with a number of methylating agents other than methane, methanol, and methyl metals. They include methyl halides (MeX, X = I, Br, Cl, F), methyl-containing halogenated reagents, methyl peroxides, dimethyl carbonate (DMC), dimethylsulfoxide (DMSO), N,N-dimethyl formamide (DMF), diazomethane, formate salts, trioxane, CO/H2, CO2/H2, and dimethyl ether (DME). Under particular conditions, some methyl-containing molecules such as polymethylbenzenes, methylhydrazine, tris(diethylamino) sulfonium difluorotrimethylsilicate, methyl tosylate, long-chain alkyl alcohols, and acetic acid unexpectedly C-methylated a variety of organic substrates. A few cases of C-methylation were only reported to occur in the absence of catalysts. Otherwise, transition metal complexes as catalysts in conjunction with specific ligands and bases were ubiquitously present in most C-methylation reactions. Of the reactions, Suzuki-Miyaura-type cross-coupling remained of paramount importance in making ¹¹CH3-bearing positron emission tomography tracers (PETs), one of the best applications of such methylation. Methylation proceeded at C(aromatic)-X, C(sp³)-X C(sp²)-X, and C(sp)-X of substrates (X = H, halogen). Ortho-methylation was regioselectively observed with aromatic substrates when they bear moieties such as pyridyl, pyrimidyl, amide, and imine functionalities, which were accordingly coined ‘ortho-directing groups’.

Background: Detection of explosives (Nitroaromatic compounds) is one of the major issues faced in global security and, to date, remains a challenge even though some materials are developed for their detection. This study introduces the use of polyvinylpyrrolidone (PVP), a non-conjugated conducting polymer, as a potential fluorophore for sensing nitroaromatics. The stimuli-response of fluorescence of PVP on interaction with energetic nitroaromatics was investigated in the present study.

Methods: Fluorescence quenching studies of 5% PVP was carried out by the addition of varying concentration of quenchers (m-dinitrobenzene, trinitrobenzene and 2,4,6-trinitrophenol). To study the effect of different solvents on fluorescence quenching, two different solvents were used, i.e., water and ethanol. The quenching studies of PVP with dinitrobenzene and trinitrobenzene were carried out in ethanol and 2,4,6-trinitrophenol was carried out in the water.

Results: The maximum emission peak intensity of PVP was observed at 445 nm in ethanol and 420 nm in water, which was quenched upon the gradual addition of quenchers. This shift in maximum peak intensity of PVP was understood from the change in the solvent polarity. UV-Visible and FT-IR studies were also carried out to understand the nature of interaction taking place between the quenchers and PVP. The limit of detection (LOD) was observed as 1.8x10^-3 M, 2.5x10^-6 M, and 3.9x10^-6 M for picric acid, dinitrobenzene and trinitrobenzene, respectively.

Conclusion: The results envisage PVP as a potential candidate for sensing energetic nitroaromatics with good sensitivity.

Objective: A simple, rapid, precise and accurate RP-HPLC stability indicating method was developed and validated for the estimation of Febuxostat in bulk drug and marketed tablet formulation.

Methods: The chromatographic separation was achieved on Agilent C18 (250 x 4.6 mm, 5 µm) using solvent 15 mM ammonium acetate buffer (pH 4.8) and acetonitrile (30:70 v/v) as a mobile phase at flow rate of 1 mL/min and ambient column temperature analysis were carried out at detection wavelength of 315 nm.

Results: The method was validated for linearity, precision, accuracy, specificity, LOD and LOQ, and robustness. The linearity was studied in the concentration range of 5-25 µg/mL and correlation coefficient was found to be 0.999. The limit of detection and the limit of quantitation were found to be 0.37 µg/mL and 1.13 µg/mL. Febuxostat was subjected to stress conditions of degradation, including acidic, alkaline, oxidation, photolytic and thermal degradation. Febuxostat is more sensitive toward acidic condition than oxidation and less sensitive towards alkaline, thermal and photolytic degradation.

Conclusion: The method is simple, reliable, sensitive and precise, which could separate the drug and their degraded product formed under various stress conditions; thus it can be employed as stability-indicating method for the determination of FBX in bulk and pharmaceutical dosage form.

Background: Cilnidipine and Metoprolol Succinate are antihypertensive agents used in the treatment of hypertension. Methods: A pharmacokinetic study of Cilnidipine and Metoprolol Succinate in rat plasma was carried out using the chromatographic method.

Methods: The chromatographic method involved a reverse phase C18 column, using acetonitrile and pH 4.0 water in the ratio of 80:20 v/v as mobile phase, a flow rate of 1.2 ml/min, and UV detection at 231 nm. In-vivo pharmacokinetic studies were performed on rats. Rats were treated with Cilnidipine (1mg/kg) and Metoprolol Succinate (1 mg/kg) orally, and blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12 and 24 h post-treatment.

Results: The retention time of Plasma, Cilnidipine and Metoprolol Succinate was found to be 2.3, 3.1 and 5.5 min, respectively. Linearity was acceptable in the concentration range of 2-10 and 10-50 for Cilnidipine and Metoprolol Succinate, respectively. The intra-day and inter-day variances were found to be less than 2. The mean recovery of Cilnidipine and Metoprolol Succinate was 100.12 and 100.15, respectively. The assay was successfully applied to a pharmacokinetic study in rat after oral administration. After oral administration, maximal concentration (Cmax) of Cilnidipine and Metoprolol Succinate was found to be 460.01 and 642.13 (μg g/mL), and the half-life was found at 2.0 and 3.904 hours, respectively.

Conclusion: The present method was successfully applied to the pharmacokinetic study of Cilnidipine and Metoprolol Succinate in rat plasma after oral administration.

Aims: To achieve catalytic performance for the oxidation of alcohols using Ruthenium(III) metal complexes as a catalyst.

Background: Chitosan is a potential candidate, which enables the synthesis of transition metal complexes from its corresponding bidentate ligands.

Objective: The chemical modification was performed on a chitosan molecule with suitable aldehydes.

Methods: The oxidation of alcohols was performed using ruthenium metal complexes as a catalyst with pyridinium chlorochromate (PCC) as an oxidant and dichloromethane as a solvent. To a solution of alcohol (2 mmol) and dichloromethane (25 mmol), pyridinium chlorochromate (3 mmol), and ruthenium(III) complexes (0.01 mmol) were added. The solution was stirred for 12 h at room temperature. At the required time, the aldehyde/ketone was extracted with n-hexane. The n-hexane was then analyzed by GC.

Results: The ruthenium(III) complexes derived from modified chitosan Schiff bidentate ligands have resulted in good catalytic performance for the oxidation of alcohols under optimized conditions.

Conclusion: The enhanced catalytic activities of ruthenium(III) complexes were due to the presence of electron-donating groups in the Schiff base ligand.

Background: COVID-19 (SARS-CoV-2 infection) has affected almost every region of the world. Presently, there is no defined line of treatment available for it. Triphala is already proven to have a safe biological window, which is well known for its antioxidant and immunomodulatory properties.

Objective: The present work has been carried out to study Triphala's effectiveness in the treatment of COVID-19.

Methods: The Receptor-binding domain (RBD) of SARS-CoV-2 Spike Glycoprotein is responsible for the invasion into the host cell, which leads to further infection. The molecular docking (MD) was performed to explore the binding affinities (kcal/mol) of Triphala's chemical constituents and compared them with the existing drugs under investigation for the treatment of COVID-19 epidemiology.

Results: Chebulinic acid binding affinity -8.5 kcal/mol with the formation of 10 hydrogen bonds. Almost all the major chemical constituents have formed two or more hydrogen bonds with RBD of SARS-CoV-2 Spike Glycoprotein.

Conclusion: The present study showed that Triphala might perform vital roles in the treatment of COVID-19 and expand its usefulness to physicians to treat this illness. There is a need to complete the in-vitro, in-vivo biological testing of Triphala on SARS-CoV-2 disease to create more quality data. The binding mode of Chebulinic acid in the allosteric cavity allows a better understanding of RBD of SARS-CoV-2 Spike Glycoprotein target and provides insight for the design of new inhibitors. Triphala is already proven to have a safe biological window, which indicates that we can skip the pre-clinical trials. Apart from this, Triphala is well known for its antioxidant properties, which ultimately improve the immunity of the COVID-19 patient.