4-bromobenzoyl Chloride Research Articles

Design, synthesis, characterization, antimicrobial activity, cytotoxicity, molecular docking, and in-silico ADMET analysis of the novel cefuroxime derivatives

This research aims to design and synthesize novel derivatives of Cefuroxime to evaluate their antibacterial effectiveness in comparison to Cefuroxime and to decrease resistance.Schotten Baumann's reaction synthesizes anhydride from acyl chlorides and carboxylate anion. Cefuroxime sodium was reacted with benzoyl chloride, 4-bromobenzoyl chloride, and 4-nitrobenzoyl chloride to make benzoyl derivatives. The derivatives were characterized using spectral analysis. Antimicrobial activity, cytotoxicity, in-silico molecular docking with nine different class of (Penicillin Binding Proteins) PBPs, and ADMET analysis were assessed for the analogs.Three molecules, Cef-1, Cef-2, and Cef-3, are synthesized from benzoyl derivatives. In various organisms, the derivatives outperformed Cefuroxime in antimicrobial activity. In many organisms, Cef-1 has the highest zone of inhibition. Cef-1 and Cef-3 inhibit Klebsiella pneumoniae better than Cef-2 and Cefuroxime. The greatest Cef-2-induced inhibition zone in Salmonella Typhimurium was 29.33 ± 0.47 mm. Significant antimicrobial susceptibility test activity was observed with lower inhibitory concentration (12.5 μg/ml) of derivatives compared to Cefuroxime across many species. Compound cytotoxicity is low, according to research. The consensus docking scores show that all synthesized derivatives bind better than cefuroxime. According to the results of the study, Cef-3 has the strongest correlation with PBP1a, PBP2a, PBP3, PBP4, and PBP6, whereas Cef-2 has a stronger association with PBP1b, PBP2b, PBP2x, and PBP5. Like Cef-2, Cef-1 has a greater affinity for PBP2x. Docking research indicated that all drugs bound better than Cefuroxime, indicating superior antibacterial efficacy. The ADMET studies showed oral bioavailability increased by increasing lipophilicity score 0.17 and cefuroxime 0.11.

Efficient Antibacterial/Antifungal Activities: Synthesis, Molecular Docking, Molecular Dynamics, Pharmacokinetic, and Binding Free Energy of Galactopyranoside Derivatives.

The chemistry and biochemistry of carbohydrate esters are essential parts of biochemical and medicinal research. A group of methyl β-d-galactopyranoside (β-MGP, 1) derivatives was acylated with 3-bromobenzoyl chloride and 4-bromobenzoyl chloride in anhydrous N,N-dimethylformamide/triethylamine to obtain 6-O-substitution products, which were subsequently converted into 2,3,4-tri-O-acyl derivatives with different aliphatic and aromatic substituents. Spectroscopic and elemental data exploration of these derivatives confirmed their chemical structures. In vitro biological experiments against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) revealed ascending antifungal and antibacterial activities compared with their antiviral activities. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) experiments were performed for two derivatives, 3 and 9, based on their antibacterial activities. Most of these derivatives showed >780% inhibition of fungal mycelial growth. Density functional theory (DFT) was used to calculate the chemical descriptors and thermodynamic properties, whereas molecular docking was performed against antibacterial drug targets, including PDB: 4QDI, 5A5E, 7D27, 1ZJI, 3K8E, and 2MRW, and antifungal drug targets, such as PDB: 1EA1 and 1AI9, to identify potential drug candidates for microbial pathogens. A 100 ns molecular dynamics simulation study revealed stable conformation and binding patterns in a stimulating environment by their uniform RMSD, RMSF, SASA, H-bond, and RoG profiles. In silico pharmacokinetic and quantitative structure-activity relationship (QSAR) calculations (pIC50 values 3.67~8.15) suggested that all the designed β-MGP derivatives exhibited promising results due to their improved kinetic properties with low aquatic and non-aquatic toxicities. These biological, structure-activity relationship (SAR) [lauroyl-(CH3(CH2)10CO-) group was found to have potential], and in silico computational studies revealed that the newly synthesized MGP derivatives are potential antibacterial/antifungal candidates and can serve as therapeutic targets for human and plant pathogens.

Cellulose nanocrystal surface modification via grafting-from sonogashira coupling of poly(ethynylene-fluorene)

Cellulose nanocrystals (CNCs) were grafted with poly(2-ethynylene-9,9-dihexyl fluorene) via Sonogashira cross-coupling chemistry to yield environmentally friendly, composite nanoparticles. CNCs were first surface functionalized with 4-bromobenzoyl chloride to provide aryl halide tethering sites for Sonogashira cross-coupling. Poly(ethynylene fluorene) was then grafted-from the bromide functionalized CNC (s-Br-CNC) surface. The intermediate product, s-Br-CNC, was characterized by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy (XPS), validating the success of the esterification reaction and giving an approximate degree of substitution. The grafted product, g-PEF-CNC, was analyzed and validated using XPS, showing the expected trends in C1s deconvolutions with addition of solely carbon based polymer. Grafted chains were cleaved via acid hydrolysis and were revealed to be n = 2–4 short chain oligomers thru analysis by matrix assisted laser desorption/ionization-time of flight mass spectrometry. A number of the potential end group pairs were observed. As such, the authors have successfully demonstrated and analyzed a novel grafted composite nanomaterial based on renewable nanocellulose substrates and semiconductive conjugated polymers.

Synthesis of brominated bisamides and their application to the suzuki coupling

Two brominated bisamides were developed by this protocol. Compounds were synthesized either by 4-bromobenzoyl chloride and ethylenediamine or by ortho-phenylenediamine. The choice of the diamine led to the desired products, which were characterized by IR, 1H NMR, 13C NMR and XRD techniques.Compounds were applied to the Suzuki coupling. They were efficient for bromides with activating and deactivating substituent groups. In the reaction performed at low temperature and in short time, with yields over 95%, it was fundamental to choose the palladium source.

Synthesis, spectroscopic characterization, X-ray diffraction studies and in-vitro antibacterial activities of diorganotin(IV) derivatives with N-methyl-4-bromobenzohydroxamic acid

Three new diorganotin(IV) complexes (CH3)2Sn(mbbha)2 (2), (C4H9)2Sn(mbbha)2 (3), (C6 H5)2Sn(mbbha)2 (4), of N-methyl-4-bromobenzohydroxamic acid (Hmbbha) (1) have been synthesized by 2:1 condensation ratio of the parent hydroxamic acid with (CH3)2SnO, (C 4H9)2SnO and (C6H5)2SnO in toluene. Ligand has been synthesized by the reaction of 4-bromobenzoyl chloride and N-methylhydroxylamine hydrochloride. Elemental analysis, IR, multinuclear 1H, 13C, 119Sn NMR spectroscopic techniques have been utilized to investigate the bonding and coordination modes of the ligand and its derivatives. It is found on the basis of spectroscopic and structural investigations that hydroxamate ligand acts as a bidentate chelator and coordinated to tin via carbonyl oxygen and deprotonated hydroxy group. The structures of complexes (3) and (4) have been deduced by X-ray crystallography which reveals octahedral geometry around tin in (C4H9)2Sn(mbbha)2 (3) and (C6 H5)2Sn(mbbha)2 (4) derivatives. The in-vitro antibacterial activities of ligand and its derivatives have been evaluated against one Gram positive and three Gram negative bacterial strains. The derivative (2) has displayed remarkable potency against both Gram positive and Gram negative strains. Anti-pathogenic results have been verified statistically.

Absolute Configuration of Isosilybin A by X-ray Crystallography of the Heavy Atom Analogue 7-(4-Bromobenzoyl)isosilybin A

Isosilybin A (1) is one of the major flavonolignans that constitute silymarin, an extract of the fruits (achenes) of milk thistle (Silybum marianum). The chemistry of the Silybum flavonolignans has been studied for over four decades, and the absolute configuration of 1 has been determined previously by electronic circular dichroism and X-ray crystallography via correlating the relative configuration of the phenylpropanoid moiety to the established absolute configuration of the 3-hydroxyflavanone portion of the molecule. Herein we report the X-ray crystallographic structure of the product of the reaction of 1 with 4-bromobenzoyl chloride, and, thus, the absolute configuration of 1 was established as (2R, 3R, 7″R, 8″R) directly via X-ray crystallography of an analogue that incorporated a heavy atom. The results were consistent with previously reported assignments and verified the absolute configuration of the diastereoisomer of 1, isosilybin B, and the related diastereoisomeric regioisomers, silybin A and silybin B.

Absolute configuration of neostenine

Heavy atoms bromine and iodine were incorporated into the neostenine ( 1) skeleton through reductive cleavage of the lactone ring, followed by acylation with 4-bromobenzoyl chloride, and salt formation with methyl iodide, respectively. The absolute configuration of the seven chiral centers C1, C9, C9a, C10, C11, C1 and C13 in 1 were assigned as S, S, R, R, R, R, and S, respectively, based on the Flack parameters in X-ray structure refinement, and results from the two heavy atom derivatives are consistent with each other. As many Stemona alkaloids share the same lactone and pyrrolo[1,2-α]azepine nucleus as those in 1, the facile method reported in this paper can be applied for the determination of absolute configurations of similar alkaloids.

Synthesis and Electrochemical Evaluation of Conjugates between 2′-Deoxyadenosine and Modified Anthraquinone: Probes for Hole-Transfer Studies in DNA

Photoexcitation of anthraquinones (AQ) in association with DNA results in DNA damage mainly at guanine residues, with products from thymine oxidation also observed. Studies of adenine oxidation will be aided by systems with an increased driving force for charge transfer, achieved by adding electron-withdrawing groups to the AQ ring. Attaching AQ derivatives to adenine via a bridge with two carbon atoms should enable the intended regiocontrol within the DNA duplex structure. Herein we report the synthesis of conjugates between AQ and adenine in which the AQ moieties have been modified with a formyl, a trifluoroacetyl, and two methyl ester groups. These have been synthesized by palladium coupling of tert-butyldiphenylsilyl 5'-protected 8-ethynyl-2'-deoxyadenosine with the corresponding bromoanthraquinone intermediates. Bromo intermediates bearing formyl or trifluoroacetyl were prepared by monolithiation of 2,6-dibromoanthraquinone, a step that required protection of the anthraquinone carbonyls. A bromo intermediate bearing two methyl ester groups was obtained from 1,2,4-trimethylbenzene by Friedel-Crafts acylation with 4-bromobenzoyl chloride followed by oxidation to the tricarboxylic acid, cyclization to form the anthraquinone ring, and finally esterification. Hydrogenation of the ethynyl linker gave the ethanyl linker. Cyclic voltammetry showed that the conjugate with the two ester groups and ethynyl linker was the most easily reduced of the derivatives synthesized. These derivatives, with reduction potentials favorable for electron transfer, can be used in studies of adenine oxidation in DNA.

3-(4-Bromobenzoyl)-N-phenyl-1,3-oxazolidin-2-imine

The title compound, C17H15BrN2O2, was prepared by the reaction of 2-anilino-4-methyl-2-oxazoline with 4-bromobenzoyl chloride in the presence of potassium tert-butoxide at room temperature. X-ray crystallographic analysis shows that the endo-substituted product is formed.

Chiral Heterospirocyclic 2H‐Azirin‐3‐amines as Synthons for 3‐Amino‐2,3,4,5‐tetrahydrofuran‐3‐carboxylic Acid and Their Use in Peptide Synthesis.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Aromatic Symmetric Cyclotrimers and Poly(arylenevinylene)s with Branched Aromatic Substituents in Vinylene Groups. Synthesis and Optical Properties

New poly(arylenevinylene)s were realized by Ni0-catalyzed polymerization of aromatic dibromides, containing vinylene groups substituted completely with branched oligophenylenes. The monomers were synthesized by acylation of 1,3,5-triphenylbenzene or 1,3,5-tri-(diphenylyl)benzene with 4-bromobenzoyl chloride followed by the McMurry homocondensation in the presence of TiCl4 and Zn. Model cyclotrimers with 1,3,5-trisubstituted benzene core were synthesized and characterized. Their molar extinction coefficients and luminescence quantum yields were in the ranges (0.5–1.5)·105 M–1· cm–1 and 29–72%, respectively. The highest quantum yield 92% promising for further photophysical investigation was found for the cyclotrimer with tolan as substituent. The quantum yield of the cyclotrimers depended on both the symmetry of molecules and the amount of benzene rings in the ambience. The incorporation of the substituents of three-dimensional structure instead of benzene rings led the polymers to become rather highly emissive with fluorescence quantum yields of 22–23% in comparison to the value of 1% of polymer with benzene rings.

Crystal structure of 1-[(1'S)-1'-benzyl-2'-(4-bromobenzoyloxy)ethyl]- l-azaspiro[4.5]deca-6,9-dien-2,8-dione hydrate, C25H22NO4Br · H2O

Source of material: The title сопфоипс! was fonned in 44% yield ftom (4S)-4-benzyl-2[2-(4-hydroxyphenyl)ethyl]-2-oxazoline by new methodology (see ref. 1 ) involving oxidative cyclization with (diacetoxyiodo)benzene [PhI(OAc)2] (see ref. 2), followed by esterification of the crude azaspiro alcohol with 4-bromobenzoyl chloride, pyridine, and 4-dimethylaniinopyridine (DMAP) (see ref. 3) at room temperature.

Macrocycles. 3. Telechelic Polylactones via Macrocylic Polymerization

ε-Caprolactone (ε-CL) was polymerized with 2,2-dibutyl-2-stanna-1,3-dioxepane or 2,2-dibutyl-2-stanna-1,3,6-trioxocane as initiator. All polymerizations were conducted in bulk at monomer/initiator (M/I) ratios of 10/1, 20/1, 35/1, or 50/1 and yielded macrocyclic poly(ε-CL) with quantitative conversion. These macrocycles were reacted in situ with 4-nitrobenzoyl chloride or with thiocresyl 4-nitrobenzoate yielding the 4-nitrobenzoyl-functionalized telechelics. The completion of these ring-opening reactions was checked by 119Sn NMR spectroscopy of the reaction mixture and by 1H NMR spectroscopy of the isolated oligo(ε-CL). Analogous quantitative functionalizations of the macrocyclic oligo(ε-CL) were obtained with 4-bromobenzoyl chloride, 6-propargyloxynaphthoyl chloride, 3- or 4-maleimidobenzoyl chloride, cinnamoyl chloride, undecenoyl chloride, and methacrylic anhydride. The hydrogenation of the nitro groups and the thermal cross-linking of the propargyl ether groups were conducted as examples of the great versatility of the telechelic oligo(ε-CL)s in modification and chain extension reactions.

Diethylstilbestrol Metabolites and Analogs: Stereochemical probes for the estrogen receptor binding site

Indenestrol A (IA) and indenestrol B (IB) are analogs and metabolites of diethylstilbestrol (DES). These compounds have high binding affinity with the estrogen receptor (ER) but possess weak uterotropic activity. Due to their chemical structures, IA and IB exist as mixtures of enantiomers. We investigated whether the poor biological activity of these compounds was due to differential activity of the enantiomers. We also utilized these compounds as probes to determine the extent of stereochemical sensitivity in the ER ligand binding site. The IA and IB enantiomers were separated to greater than 98% purity using a chiral high pressure liquid chromatography column. Their enantiomeric nature was confirmed by mass spectrometry and NMR. The purified IA enantiomer peak 1 was derivatized with 4-bromobenzoyl chloride. The resulting di(4-bronobenzoate) IA was analyzed by x-ray crystallography and the absolute enantiomeric conformation assigned is C(3)-R. The IA enantiomers designated IA-R and A-S were assayed by competitive binding to cytosolic ER. The competitive binding index was estradiol, 100; DES, 286; IA-Rac (racemic mixture of IA), 143; IA-R, 3; and IA-S, 285; the index showed that ER demonstrates a stereochemical chiral preference. The IB enantiomers did not show a binding preference: IB, 145; IB-1, 100; and IB-2, 143. The differences in the IA enantiomer binding were shown to be due to competitive interactions by Lineweaver-Burk analysis of saturation binding of estradiol to ER in the presence of 1-, 5-, and 10-fold molar excess of competitor. Differences in binding affinity of the enantiomers could be partially explained by differences in the association rate constant (k+1) determined by association rate inhibition studies in which IA-S was 15 times more active than IA-R. Nuclear estrogen receptor levels were measured 1 h after in vivo treatment with doses of 5-20 micrograms/kg. The IA-Rac produced only 60% of the levels is compared with DES. Nuclear ER levels were checked every 30 min up to 2 h with no apparent difference, indicating that the low early levels were not due to a delayed estrogen receptor retention. When the enantiomers were tested individually only a dose of 10 micrograms/kg IA-S translocated ER to a level comparable to DES, while IA-R showed low levels at several doses. These results suggest that the poor biological activity of IA may be related to the differential ER interaction of its enantiomers.(ABSTRACT TRUNCATED AT 400 WORDS)

Studies on the Anthraquinone-azole Vat Dyes. I

1-Anilinoanthraquinones (2a-2c) having anthraquinone-oxazole ring in paraposition were synthesized, visible absorption spectra of these were compared with 1-anilino- and 1-(4-R-substituted-anilino)anthraquinones (R=NH2 or NO2), and clarified that anthraquinone-oxazole ring had electron-attractive property and its intesity was in order of nitro ≥ anthraquinone (2 : 1) oxazole > anthraquinone (1 : 2) oxazole a> anthraquinone (2 : 3) oxazole. These three kinds of dye (2a-2c) were synthesized by Ullmann condensation of 1-aminoanthraquinone and corresponding 2-(4-bromophenyl) anthraquinoneoxazole (3a-3c), respectively. 2-(4-Bromophenyl) anthraquinone-oxazoles (3a-3c) were synthesized as follows: (1). 2-Amino-3-hydroxyanthraquinone or2-amino-3-bromoanthraquinone was benzoylated with 4-bromobenzoyl chloride and each was treated for oxazole ring formation to obtain the same 2-(4-br.omophenyl) anthraquinone (2 : 3) oxazole (3a). (2). Similarly, the reaction of 1-amino-2-hydroxyanthraquinone and 4-bromobenzoyl chloride caused benzoylation and oxazole ring formation at the same time and gave 2-(4-bromophenyl) anthraquinone (1 : 2) oxazole (3b). This extraordinary reactive property was explained by intramolecular hydrogen bonding. Also, (3b) was obtainable by benzoylation of 1-amino-2-bromoanthraquinone with 4-bromobenzoyl chloride and its oxazole ring formation but the yield was low. (3). Benzoylation of 1-hydroxy-2-aminoanthraquinone with 4-bromobenzoyl chloride and its oxazole ring formation gave 2-(4-bromophenyl) anthraquinone (2 : 1)-oxazole (3c). The dyes (2a-2c), synthesized by condensation of 2-(4-bromophenyl) anthraquinone-oxazoles and 1-aminoanthraquinone, were used for dyeing of cotton by 2% IW method and following results were obtained on vat dyeing, color, and light fastness: (2a): red brown, greenish red brown, 4-5 th grade. (2b) red, red brown, 5 th grade. (2c): orange red, brownish red, 45th grade.