N-bromosuccinamide Research Articles

DETERMINATION OF THE ANTIHYPERTENSIVE DRUGS CAPTOPRIL, ATENOLOL, AND METOPROLOL IN DOSAGE FORMS

Three antihypertensive drugs Captopril (CPL), Atenolol (ATL), and Metoprolol (MTL) have been estimated sensitively and selectively by a single spectrophotometric method using neutral red dye NLR. The method is based on oxidation of the drugs by known excess of N-bromosuccinamide (NBS) in the first reaction step followed by the oxidation of NLR dye with the exceed ed amount of NBS, as the concentration of the drug compounds increase, the color of the dye increase, the dye exhibits absorbance peak at 523 nm. The linearity range was from 1 to 10 µg/ml for the three drugs, the molar absorptivity values were 2.1164 × 105, 1.9202× 104, and 57.934× 104 l.mol-1.cm-1 for CPL, ATL, and MTL respectively, the sensitivity index of Sand’ll were 0.0102, 0.0138, and 0.01182 µg/cm2 for CPL, ATL, and MTL respectively. LOD values for the three drugs ranged from 0.00405 to 0.00547 and LOQ values were ranged from 0.0135 to 0.0182 respectively, the method exhibits good applicability to the dosage forms and high confidence as compared with standard method and standard addition method.

Transition Metal‐Free Sulfenylation of C−H Bonds for C−S Bond Formation in Recent Years: Mechanistic Approach and Promising Future

AbstractTransition metal‐free sulfenylation of C−H bonds for C−S bond formation has recently emerged as sustainable protocols for the functionalisation of various molecules. Researchers have extensively developed such protocols for the construction of biologically relevant sulfur scaffolds. There has been a gradual shift from metal‐catalyzed to metal‐free C−S bond formation methodologies, because the latter offer environmentally benign and inherently safe access to novel synthetic routes in organic chemistry. The present review offers a dynamic discussion on recent advances in transition metal‐free C−S bond formation via C−H bond functionalization using different surrogate sulfenylating reagents. The review has comprehensively been devoted to radical and ionic mechanistic approaches. Some simple and eco‐friendly reagents for sulfenylation viz. tertbutyl hydrogen peroxide (TBHP), hydrogen peroxide (H2O2), iodine/potassium persulphate (I2/K2S2O8), inorganic bases, strong organic acids, iodine, I2/triphenyl phosphine (PPh3), N‐chlorosuccinamide (NCS), N‐bromosuccinamide (NBS), potassium iodate (KIO3), I2/bovine serum albumin (BSA), tetrabutyl ammonium iodide (TBAI)/HBr and graphene oxide along with their mechanistic approach has been detailed in this review. Moreover, modern methods for the C−S bond formation i. e., biocatalyst, electrochemical and visible light induced sulfenylation, and traditional sulfenylation methodologies have also been incorporated.

A New Indirect Sensitive and Green CFIA Method for Assay of α-cypermethrin Insecticide in Pure Form, Biological and Industrial Samples Using N-Bromo Succinamide as Oxidizing Agent in Acidic Medium

A new simple, sensistive and green environmental method of Flow-injection/merging zones technique was developed for indirect determination of α-cypermethrin pesticide in pure form, industrial and biological samples. This method based on oxidation reaction of pesticide (α-cypermethrin) with a calculated increase of N-bromosuccinamide (NBS) in acidic medium then react with Tartrazine dye (TART) and estimation of the excess of the oxidizing agent by measuring the residual absorption of TART (yellow color) at λmax = 430nm, this method is a green chemistry, low cost and less consumption of poisonous chemical reagents. The limit of detection and limit of quantification for this method are 0.05 μg.ml-1 and 0.17 μg.ml-1 respectively, RSD% = 0.69% and the recovery is about = 102.15%. Chemical and physical parameters was optimized that effect on the pesticide reaction. The calibration curve was linear within concentration range (0.5 – 30) μg.mL-1 with sampling through put is about 65 sample.hour-1; the results of determination were compared with those given by trusted method (HPLC). No significant differences between both methods regarding in terms of accuracy and precision at 95% dependability level.

Enhanced Ion Cluster Size of Sulfonated Poly (Arylene Ether Sulfone) for Proton Exchange Membrane Fuel Cell Application.

A successful approach towards enhancement in ion cluster size of sulfonated poly (arylene ether sulfone) (SPAES)-based membranes has been successfully carried out by encapsulating basic pendent branches as side groups. Modified SPAES was synthesized by condensation polymerization followed by bromination with N-bromosuccinamide (NBS) and sulfonation by ring opening reaction. Various molar ratios of branched polyethyleneimine (PEI) were added to the SPAES and the developed polymer was designated as SPAES-x-PEI-y, where x denoted the number of sulfonating acid group per polymer chain and y represents the amount of PEI concentration. Polymer synthesis was characterized by 1H-NMR (Nuclear magnetic resonance) and FT-IR (Fourier-transform infrared spectroscopy) analysis. A cumulative trend involving enhanced proton conductivity of the membranes with an increase in the molar ratio of PEI has been observed, clearly demonstrating the formation of ionic clusters. SPAES-140-PEI-3 membranes show improved proton conductivity of 0.12 Scm−1 at 80 °C. Excellent chemical stability was demonstrated by the polymer with Fenton’s test at 80 °C for 24 h without significant loss in proton conductivity, owing to the suitability of the synthesized hybrid membrane for electrochemical application. Moreover, a single cell degradation test was conducted at 80 °C showing a power density at a 140 mWcm−2 value, proving the stable nature of synthesized membranes for proton exchange membrane fuel cell application.

Development and validation of spectrophotometric and spectrofluorimetric methods for determination of cilnidipine

Purpose: To develop simple and reliable quantitative methods for the determination of cilnidipine (CLD) in pharmaceutical tablets.Methods: Two simple and sensitive methods (spectrophotometric and spectrofluorimetric) were developed for the determination of cilnidipine (CLD) in pure form and in a pharmaceutical preparation. Spectrophotometric method (A) is based on oxidation of CLD with a known excess amount of Nbromosuccinamide (NBS) in acidic medium, followed by addition of methyl orange indicator and absorbance measurement at 510 nm. The spectrofluorimetric method (B) is based on oxidation of CLD to cerium (IV), followed by measurement of fluorescence emission of Ce (III) at 350 nm. Factors that affect the performance of the two methods were studied and optimized.Results: The spectrophotometric and spectrofluorimetric procedures were successfully used for measuring CLD levels in pharmaceutical dosage form, in the ranges of 2.0 - 25.0 and 0.25 - 11.2 μg/mL, at detection limits of 1.05 and 0.13 μg/mL, respectively. There were no significant differences between the proposed methods and a standard reference method (p < 0.05).Conclusion: The developed methods provide simple and reliable procedures for quantitative measurement of CLD in bulk and tablet forms.
 Keywords: Cilnidipine, Oxidation, Spectrophotometric, Spectrofluorimetric, Drug formulation

Spectrophotometric Determination of Benzocaine via Oxidation and Bleaching Colour of Rifampicin Dye

Benzocaine(BENZ) has been estimated by indirect spectrophotometric method. The suggested method based on oxidation of BENZ via N-bromosuccinamide (NBSA) in presence of hydrochloric acid, then the unreacted or the excess NBSA was immerse in bleaching the colour of rifampicin dye(REFPD),the absorbance of unreacted REFPD has been estimated at wavelength 476 nm (the highest absorption of REFPD) .The measured absorbance is directly proportional to the amount of BENZ in the solution. All parameters affected the oxidation of BENZ and bleaching the colour of REFPD and the optimum values have been fixed. Beer’s law(linearity) of the method is in the range of 2 to 15 μ.g.ml−1, the molar absorptivity value equal to 4.295 x 10 3 l.mol−1.cm−1 and the Sandall’s index for sensitivity is calculated and equal to 0.0384 μg.cm−2. The suggested method has an application part included estimation of BENZ in its pharmaceutical formulation (sterile ear drops).

Leishman’s Dye as a Novel Reagent in Spectrophotometric Determination of Chloramphenicol

By reviewing the literature, there is no indication concerning the use of Leishman’s dye in evaluating drug compounds by dye-color bleaching; hence, it is the first attempt to use Leishman’s dye as a novel reagent in the estimation of chloramphenicol (CAP) by an indirect spectrophotometric method in bulk and in its pharmaceutical preparations. The method includes the use of a great amount of N-bromosuccinamide (NBS) in the acidic medium as an oxidizing agent of the drug under investigation (CAP), and then using the residual of NBS for Leishman’s dye color bleaching. The absorbance has been measured at 622 nm (the maximum absorption of Leishman’s dye). A linear relationship was obtained for the Beer’s law with the concentration ranges from 10 to 250 μg/10 mL with acceptable values of molar absorptivity 0.58 × 104 L.mol-1.cm-1 and 0.055 μg.cm-2 of Sandell’s sensitivity index, which mean a high sensitivity. An approved estimation of CAP in its various pharmaceutical formulations was found.

One-pot synthesis of thiazolo[3,2-a]pyrimidine derivatives, their cytotoxic evaluation and molecular docking studies.

An economical, simple and efficient one-pot method has been developed for the synthesis of thiazolo[3,2-a]pyrimidine hydrobromide derivatives. 2,4-diaryl-6,7,8,9-tetrahydro-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine hydrobromides were synthesized by the α-bromination of cyclohexanone with N-Bromosuccinamide (NBS) and followed by cyclization with 3,4-dihydropyrimidine-2(1H)-thiones, respectively, in the presence of p-toluenesulfonic acid (PTSA) in acetonitrile. However when cyclohexanone was replaced by acetyl acetone and alpha-tetralone gave the corresponding 1-(3-methyl-5,7-diaryl-5H-thiazolo[3,2-a]pyrimidin-2-yl)ethan-1-one hydrobromide and 9,11-diaryl-6,11-dihydro-5H-naphtho[1',2':4,5]thiazolo[3,2-a]pyrimidine hydrobromide derivatives, respectively. The significant features of this method are novel, simple, inexpensive experimental procedure, short reaction time, and good yield. The some of the synthesized compounds were evaluated for cytotoxic activity against human lung adenocarcinoma cell line (A549), human breast carcinoma cell line (MCF-7), human cervical cancer cell line (HeLa) and human neuronal carcinoma cell lines (SKNSH). Tested compounds 5(b-e) showed the excellent anticancer activity against various cell lines. Particularly compound 5c with IC50 value of 2.2±0.6μM against A549 and compound 5e with IC50 value of 5.6±0.4μM against HeLa showed best cytotoxic effects. Furthermore, Molecular docking study was performed for some of the synthesized compounds 5(b-e) against topoisomerase-II by using Auto dock method. Docking results of the compounds 5c, 5d, and 5e exhibited higher cytotoxic activity than the standard doxorubicin.

The Organ Distribution, Characterization and Modification of Acetylcholinesterase Activity in Adult African Grasshopper: Zonocerus sp Linn.

Aim: To determine the organ distribution and characterization of acetylcholinesterase in the adult African variegated grasshoppers – Zonocerus variegatus and Zonocerus elegans. (Zonocerus Sp. Linn)
 Place and Duration of the Study: The insect model: African variegated grasshoppers are gotten from the Open green fields at the Federal University of Technology, Akure, Nigeria, and research was carried out between March and June, 2016 in the Enzymology laboratory, Biochemistry department, Federal University of Technology, Akure, Nigeria.
 Methodology: Twenty (20) adults variegated grasshoppers were taken from the Open field in the University community, and taken to the Biology department for Identification. After identification, the specimen was weighed, freeze, dissected into fractions (Head, Thorax and Abdomen) and then homogenized to get the crude protein extract. The crude enzyme extract is further purified using the Ion-exchange chromatography with column bed packed with DEAE – Sephadex A50. The protein content of the purified AChE was determined using the Lowry method while the Acetylcholinesterase activity was determined by the Ellman’s assay procedures. The characterization of AChE was tested by modifying agent such as N-Bromo Succinamide (NBS) which confirms the presence of key aromatic proteins involve in catalysis at the active site of the enzyme.
 Results: The protein concentration according to their fractions: Head (35.7%), Thorax (29.2%), and Abdomen (35.1%). The AChE activity according to their fractions: Head (38.6%), Thorax (23.7%), and Abdomen (37.7%). The specific activity which relates the AChE activity to protein content is given: Head (28.8%), Thorax (40.4%), and Abdomen (30.8%). From the Organ distribution and AChE activity, it was observed that the Head Fractions has the Highest protein content, and Enzyme activity. Comparatively, there are slight differences in the Enzyme activity of the Head and Abdominal fractions which represents the two peaks in the AChE chart. As well, the thorax has the highest specific activity. The modification by the chemical agent NBS shows a drastic decrease (about 50%) in Enzyme activity and characterize enzyme active site with aromatic proteins especially tryptophan residues.
 Conclusion: Research findings shows the dominance of AChE protein in the Head region, hence high enzyme activity (useful for nervous coordination) as well as presence of tryptophan residues at the enzyme active site. The importance of research is useful in enzymology, neuroscience and public health.

N-Bromosuccinamide (NBS) mediated construction of pharmacologically important 5-Sunstituted pyrazolo[4,3-d]pyrimidin-7(6H)-ones

N-Bromosuccinamide (NBS) mediated construction of pharmacologically important 5-Sunstituted pyrazolo[4,3-d]pyrimidin-7(6H)-ones

Synthesis of S,S,O-orthoesters and 1,1-difluoroalkyl ethers via reaction of peroxides with lithiated 1,3-dithianes.

Alkyl tetrahydropyranyl peroxides (ROOTHP) transfer alkoxide (OR) to lithiated 1,3-dithianes. The derived S,S,O-orthoesters undergo fluorodesulfurization with HF/pyridine and N-bromosuccinamide (NBS) to furnish difluoromethyl ethers. The overall protocol can be applied to synthesis of both terminal (ROCF2H) and internal (ROCF2R') ethers. Application of the same set of reactions to a lithiated tris(alkylthio)alkane is shown to generate a trifluoromethyl ether.

Pitfalls in bromination reactions of zinc porphyrins: two-sided ring opening of the porphyrin macrocycle.

Reaction of [Zn(II)(TTP)] (1) (TTP = dianion of 5,10,15,20-meso-tetrakis(p-tolyl)porphyrin) with 16 equiv of N-bromosuccinamide (NBS) in methanol at reflux led to the unexpected two-sidedd open-ring brominated product [Zn(II)(C26H20N2O2Br5)2] (2). Similar observations have been made with other meso-substituted zinc porphyrins as well [Zn(II)(por)] {por = dianion of 5,10,15,20-meso-tetrakis(aryl)porphyrin; aryl = phenyl (TPP), p-(t)Bu-phenyl (TBPP), m-Cl-phenyl (TClPP)}. The respective products [Zn(II)(C24H16N2O2Br5)2] (3), [Zn(II)(C32H32N2O2Br5)2] (4), and [Zn(II)(C24H14N2O2Cl2Br5)2] (5) have been isolated in good to moderate yields and characterized by elemental analysis and UV-vis, (1)H NMR, and mass spectrometry. Additional bromination reaction of 1 with 8 equiv of NBS in a chloroform/methanol mixture led (after the two-sided ring opening) to nonmetalated brominated bi(pyrrole) product, C36H34N2O4Br4 (6). The detailed structures of complexes 1, 2, 3, and 6, available in a single crystal form, have been confirmed by X-ray diffraction analysis.

Xanthan Sulfuric Acid: An Efficient Bio-Supported and Recyclable Solid Acid Catalyst for the Synthesis of 2-minothiazole-5-carboxylates and 2-aminoselenazole-5-carboxylates

An efficient method has been developed for the synthesis of 2-amino thiazole and selenazole-5-carboxylates from β-ketoesters, thiourea or seleno urea and N-bromo succinamide by using Xanthan sulfuric acid as a solid acid catalyst. The reaction work-up is very simple and the catalyst can be easily separated from the reaction mixture and reused several times in subsequent reactions.

Remarkable regioselective position-10 bromination of bacteriopyropheophorbide-a and ring-B reduced pyropheophorbide-a.

Both bacteriopyropheophorbide-a and ring-B reduced pyropheophorbide-a on reacting with NBS (N-bromosuccinamide) undergo electrophilic bromination to provide 10-bromo analogs. The electronic nature of the substituents present at position-3 did not make any difference in the regioselective outcome of the brominated products. These relatively stable brominated chlorins and bacteriochlorins provide an easy way of introducing a wide variety of functionalities, which could be extremely useful in developing improved agents for biomedical applications and supramolecular chemistry.

INN-toxin, a highly lethal peptide from the venom of Indian cobra ( Naja naja) venom—Isolation, characterization and pharmacological actions

A novel toxic polypeptide, INN-toxin, is purified from the venom of Naja naja using combination of gel-permeation and ion-exchange chromatography. It has a molecular mass of 6951.6 Da as determined by MALDI-TOF/MS and the N-terminal sequence of LKXNKLVPLF. It showed both neurotoxic as well as cytotoxic activities. INN-toxin is lethal to mice with a LD 50 of 1.2 mg/kg body weight. IgY raised in chicks against basic peptide pool neutralized the toxicity of INN-toxin. INN-toxin did not inhibit cholinesterase activity. It is toxic to Ehrlich ascites tumor (EAT) cells, but it is not toxic to leukocyte culture. The toxin appears to be specific in its mode of action. Interaction of N-bromosuccinamide (NBS) with the peptide resulted in the modification of tryptophan residues and loss of lethal toxicity of INN-toxin.

A tryptophan residue is identified in the substrate binding of penicillin G acylase from Kluyvera citrophila

Penicillin acylases are important enzymes in pharmaceutical industry for the production of semi-synthetic β-lactam antibiotics via the key intermediate 6-aminopenicillanic acid. The penicillin G acylase purified from Kluyvera citrophila ( KcPGA) on modification with tryptophan-specific reagents such as N-bromo succinamide (NBS) and 2-hydroxy 5-nitrobenzylbromide (HNBB) showed partial loss of activity and substrate protection. Various solute quenchers and substrate were used to probe the microenvironment of the putative reactive tryptophan through fluorescence quenching. Homology modeling of KcPGA structure has been carried out. Docking substrate on this modeled KcPGA structure identifies the tryptophan residue that is directly influenced by substrate binding. To confirm the biological significance of this particular tryptophan, we did a sequence comparison of PGAs from various organisms. The sequence alignment clustered the matches into two sets, those closer to (>40% identical) KcPGA and had the tryptophan of interest present in them formed the first set, while those less identical (<30%) to KcPGA and the particular tryptophan absent in them formed the second set. It is clear from the reported kinetic parameters of representative members of these two sets that the affinity for penicillin G (penG) of the former class is several times better. Thus, based on our studies we suggest that the tryptophan residue in the identified position is important for binding substrate penG by the acylases.

Spectrophotometric methods for the determination of nifurtimox in bulk form and pharmaceutical formulations

Three simple and sensitive methods for the assay of Nifurtimox (NIF) which is an active antitrypanocide were developed. These methods are based on the formation of coloured species by treating either its reduction product with 3-methyl-2-benzothiazolinone hydrazone (MBTH) in the presence of ferric chloride (method A) or its hydrolysis product with 2-thiobarbituric acid (TBA) (method B) or by oxidizing it with excess N-bromosuccinamide (NBS) and determining the consumed NBS using p- N-methylaminophenol sulphate (metol)—isonicotinic acid hydrazide (INH) (method C). All variables have been optimized and the reaction mechanisms presented. Regression analysis of Beer's plot showed good correlation in the concentration range of 2.5–10, 2.5–30 and 1.25–7.5 μg/ml for methods A, B and C, respectively. No interference was observed from the additives and the validity of the methods was tested by analysing the tablets. Recoveries were 99.2–100.9%.