4-substituted Benzoic Acid Research Articles

Synthesis, characterization, in vitro antimicrobial, DNA binding activity and QSAR studies of diorganotin(IV) complexes of Schiff bases derived from 2-benzoyl-1H-indene-1,3(2H)-dione and 4-substituted benzoic acid hydrazides

A series of new diorganotin(IV) complexes of the type [R′2SnL] have been synthesized by the reaction of 2-benzoyl-1H-indene-1,3(2H)-dione Schiff bases with R′2SnCl2, (R′ = Me, Et, n-Bu, Ph) in 1:1 molar ratio. These complexes were well characterized by IR, 1H, 13C, 119Sn NMR, XRD and mass spectrometry techniques. In the search for biologically more effective antimicrobial agents, all the synthesized ligands and organotin complexes were evaluated for their in vitro antimicrobial activities against two Gram-positive and two Gram-negative bacteria, and three fungal strains by serial dilution method. The results of spectral data revealed that the complexes formed were pentacoordinated with tridentate ligands which coordinated through azomethine N and carbonyl O and carboxylate O to the central tin atom. The ligands on coordination with tin metal showed a discernible augmentation in biocidal activity, however, the Ph and Bu complexes were found to be more intoxicating. The results revealed that the synthesized complexes were more noxious toward Gram-positive strains as compared to Gram-negative strains which may be attributed to the presence of an outer lipid membrane of lipopolysaccharides. Further, QSAR studies and DNA binding studies were performed which supported that bioactivity gets enhanced on complexation.

Five Novel Non-Sialic Acid-Like Scaffolds Inhibit In Vitro H1N1 and H5N2 Neuraminidase Activity of Influenza a Virus.

Neuraminidase (NA) of influenza viruses enables the virus to access the cell membrane. It degrades the sialic acid contained in extracellular mucin. Later, it is responsible for releasing newly formed virions from the membrane of infected cells. Both processes become key functions within the viral cycle. Therefore, it is a therapeutic target for research of the new antiviral agents. Structure–activity relationships studies have revealed which are the important functional groups for the receptor–ligand interaction. Influenza virus type A NA activity was inhibited by five scaffolds without structural resemblance to sialic acid. Intending small organic compound repositioning along with drug repurposing, this study combined in silico simulations of ligand docking into the known binding site of NA, along with in vitro bioassays. The five proposed scaffolds are N-acetylphenylalanylmethionine, propanoic 3-[(2,5-dimethylphenyl) carbamoyl]-2-(piperazin-1-yl) acid, 3-(propylaminosulfonyl)-4-chlorobenzoic acid, ascorbic acid (vitamin C), and 4-(dipropylsulfamoyl) benzoic acid (probenecid). Their half maximal inhibitory concentration (IC50) was determined through fluorometry. An acidic reagent 2′-O-(4-methylumbelliferyl)-α-dN-acetylneuraminic acid (MUNANA) was used as substrate for viruses of human influenza H1N1 or avian influenza H5N2. Inhibition was observed in millimolar ranges in a concentration-dependent manner. The IC50 values of the five proposed scaffolds ranged from 6.4 to 73 mM. The values reflect a significant affinity difference with respect to the reference drug zanamivir (p < 0.001). Two compounds (N-acetyl dipeptide and 4-substituted benzoic acid) clearly showed competitive mechanisms, whereas ascorbic acid reflected non-competitive kinetics. The five small organic molecules constitute five different scaffolds with moderate NA affinities. They are proposed as lead compounds for developing new NA inhibitors which are not analogous to sialic acid.

The production of a melt-spun functionalized graphene/poly(ε-caprolactam) nanocomposite fiber

Abstract An in situ polymerization technique was used to develop localized polymers grafted onto the surface of dispersed pristine graphene sheets. A 4-substituted benzoic acid monomer was grafted to the surface of expanded graphene by ‘‘ Direct Friedel–Crafts ” acylation. The chains of poly(e-caprolactam) (PA6) that were grafted on the functionalized graphene (FG) were prepared by in situ polymerization of e-caprolactam in the presence of FG. Nanocomposite fibers with different loadings of FG were melt-spun with a piston spinning machine and a hot-roller drawing machine. FG is evenly distributed in the nanocomposite. A significant mechanical property increase of FG/PA6 nanocomposite is obtained at a low FG loading; e.g., a 65% improvement of tensile strength and a 290% improvement of Young’s modulus compared to a pure PA6 fiber is achieved at a FG loading of 0.1 wt.%. The compatibility of FG and PA6 in the nanocomposite fiber improves the thermal stability of the polymer matrix. This functionalization method paves the way for the facile fabrication of graphene-based nanocomposite fibers without disrupting the primary structures of the graphene.

Fabrication and characterization of polyamide 6-functionalized graphene nanocomposite fiber

Graphene oxide was prepared by the Hummers’ method and then functionalized with 4-substituted benzoic acid via “direct Friedel–Crafts” acylation in a mild reaction medium of polyphosphoric acid/phosphorous pentoxide (P2O5). Raman spectroscopy, differential scanning calorimetry, thermo-gravimetric analysis, and transmission electron microscopy were used to characterize the resultant structure. The results show that 4-substituted benzoic acid functionalized graphene (FG) sheets were achieved without pretreatment of oxidation. Polycaprolactam (PA6)-FG composites were prepared by in situ polymerization of e-caprolactam in the presence of FG. Nanocomposite fiber with 0.01–0.5 wt% content of FG was prepared with a piston spinning machine and hot-roller drawing machine. A significant enhancement of mechanical properties of the PA6-FG composites’ fiber is obtained at low graphene loading; that is, a 29 % improvement of tensile strength and a three times increase of Young’s modulus are achieved at a graphene loading of only 0.1 wt%. The “graft-from” methodologies pave the way to prepare graphene-based nanocomposites of condensation polymers with promising performance and functionality.

Preparation and Properties of Polyamide 6-Functionalized Nanometer-Sized Graphene Composite Fiber

A novel approach to the functionalization of nanometer-sized graphene was presented in this work. Covalent bonding between the filler and matrix was formed, with minimal disruption to the sp2 hybridization of the pristine graphene sheet. Functionalization proceeded by covalently bonding a 4-substituted benzoic acid monomer to the surface of expanded graphene, via ‘‘direct Friedel-Crafts” acylation in mild reaction medium of polyphosphoric acid (PPA)/phosphorous pentoxide. Polyamide 6 (PA6)-functionalized graphene (FG) composites were prepared by in situ polymerization of ε-caprolactam in the presence of nanometer-sized FG. Nanocomposite fiber with 0.1 wt.% content of nanometer-sized FG was prepared with a piston spinning machine and hot-roller drawing machine. The nanometer-sized FG performed homogeneous dispersion in the polymer matrix. The mechanical properties of the PA6-FG composites fiber was enhanced by adding FG in the polymer matrix. The new functionalization method paves the way to prepare graphene-based nanocomposites fiber simply, without disrupting the primary structures of nanometer-sized graphene.

4-Substituted Benzoic Acids Functionalized Multi-Walled Carbon Nanotubes in Mild Polyphosphoric Acid/Phosphorous Pentoxide

Pristine multi-walled carbon nanotubes (P-MWNTs) were functionalized with 4-substituted benzoic acid via ‘‘direct’’ Friedel-Crafts acylation in mild reaction medium of polyphosphoric acid (PPA)/phosphorous pentoxide (P2O5). Raman spectroscopy, thermogravimetric analysis, transmission electron microscopy were applied in this paper to demonstrate that multi-walled carbon nanotubes inherently have functional groups on their surfaces as a result of the reaction. The overall evidence indicates that the 4-substituted benzoic acid functionalization of carbon nanotube can be achieved without oxidation as pre-treatment. Thus, aryl carbonyl moieties with different length of 4-substituted alkyl acyl amine functionalized MWNTs（F-MWNTs） can be synthesized simply, without disrupting the primary structures of the nanotubes.

Iminophosphorane-mediated one-pot synthesis of 1,3,4-oxadiazole derivatives

Reaction of 4-substituted benzoic acid derivatives with (N-isocyanimino)-triphenylphosphorane proceeds smoothly at room temperature to afford the corresponding 2-aryl-1,3,4-oxadiazoles via an intramolecular aza-Wittig reaction in excellent yields under neutral conditions. The structures of the products were deduced from their IR, 1 H NMR, and 13 C NMR spectra, and mass spectrometry.

Synthesis and characterization of novel hydrazide–hydrazones and the study of their structure–antituberculosis activity

A series of hydrazide–hydrazones, based on a series of 4-substituted benzoic acid, were synthesized, and their structures were elucidated and screened for the antituberculosis activity against Mycobacterium tuberculosis H37Rv with the help of the BACTEC 460 radiometric system. Compound 3, 4-fluorobenzoic acid [((5-nitro)thiophen-2yl) methylene]hydrazide showed the highest inhibitory activity in this series. The search of pharmacophores was done by means of the Electronic-Topological Method (ETM). The model developed in this study is supposed to be applied to the design, preparation and screening of new compounds of similar structure in order to further test and optimize the model with the eventual goal of preparing new anti-tubercular agents.

Nuclear magnetic resonance (NMR) and quantitative structure–activity relationship (QSAR) studies on the transacylation reactivity of model 1β-O-acyl glucuronides. II: QSAR modelling of the reaction using both computational and experimental NMR parameters

1. In a previously reported study, a number of 4-substituted benzoic acid acyl glucuronides were synthesized and their degradation rates determined using nuclear magnetic resonance (NMR) spectroscopy. It was shown that this reaction was strongly influenced by the nature of the substituent at the 4-position of the benzoyl moiety.2. The overall degradation reaction rates for this series of compounds have been modelled successfully using Hammett substituent constants, computational chemistry-derived partial atomic charges and the experimentally determined carbonyl carbon 13C-NMR chemical shifts of the benzoic acids and their ethyl and glucuronide esters.3. The primary contribution to reactivity is the scale of the electron-donating or -withdrawing effect of the substituent; however, additional contributions such as steric parameters must also be considered when modelling reactions outside a single chemical series.4. The derived property–reactivity relationships should find utility in medicinal chemistry efforts for optimizing chemical series in pharmaceutical discovery programmes.

The inclusion compounds of beta-cyclodextrin with 4-substituted benzoic acid and benzaldehyde drugs studied by proton nuclear magnetic resonance spectroscopy.

Inclusion compounds of some 4-substituted benzoic acid and benzaldehyde drugs with beta-cyclodextrin were prepared and characterized by IR spectroscopy, powder X-ray diffraction, thermogravimetry, and 1H-NMR spectroscopy. The thermal stability and chemical stability of these drugs were strikingly improved after inclusion. The effect of inclusion on the chemical-shifts of protons H-3 and H-5 in the NMR spectroscopy is discussed. Using the relative shift theory, the preferred inclusion mode was proposed. The center of the aromatic ring of the drug molecule was considered to be located in the cavity 1.2 A inside from the H-5 plane of beta-cyclodextrin.