4-acetylbenzoic Acid Research Articles

Synthesis, Structural Characterization，DFT，Hirschfeld Surface and Catalytic Activity of a New Zn (II) Complex of 4-Acetylbenzoic Acid

A new Zn(II) complex of 4-acetylbenzoic acid, namely [ZnL2(H2O)2] (1) (HL = 4-acetylbenzoic acid) has been synthesized in water-ethanol (v:v = 1:2) solution using zinc acetate dihydrate, 4-acetylbenzoic acid, and NaOH as reactants. The structure of complex (1) has been characterized by IR and X-ray single-crystal diffraction. X-ray diffraction analysis of complex (1) reveals that the Zn(II) ion is six-coordinated in a distorted octahedral coordination geometry with four carboxylic O atoms from two different bidentate 4-acetylbenzoic acid ligands (O1, O2, O1a, O2a) and two O atoms from two coordinated water molecules (O4 and O4a). Complex (1) forms 1D chained structure by the intermolecular and intramolecular O-H···O hydrogen bonds, and further forms a three-dimensional network structure by the π-π interaction of benzene rings and intermolecular O-H···O hydrogen bonds. The singlet ground-state geometry of the complex (1) were optimized using the PBE0 functional. The intermolecular interactions of complex (1) were quantitatively analysed by 3D Hirschfeld surface analysis and associated 2D fingerprint plots. The catalytic activity of complex (1) has been tested for the oxidation of benzyl alcohol under O2 atmosphere. Copyright © 2023 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).

A toxicological study on photo-degradation products of environmental ibuprofen: Ecological and human health implications

Increasing quantities of pharmaceutical waste in the environment have disrupted the balance of ecosystems, and may have subsequent effects on human health. Although a handful of previous studies have shown the impacts of pharmaceutically active compounds on the environment, the toxicological effects of their degradation products remain largely unknown. In the current study, the photo-degradation products of environmental ibuprofen were assessed for both ecotoxicological and human health effects using a series of in vitro assays. Here, six of the major degradation products are synthesized with high purity (>98%) and characterized with 1HNMR, 13CNMR, FT-IR and HRMS. To evaluate human health effects, three gut microbiota species, Lactobacillus acidophilus, Enterococcus faecalis and Escherichia coli, and two human cell lines, HEK293T and HepG2, are exposed to various concentrations of ibuprofen and its degradation products. On L. acidophilus, the ibuprofen degradation product (±)-(2R,3R)-2-(4-isobutylphenyl)-5-methylhexan-3-ol shows a greater toxic effect while ibuprofen enhances its growth at lower concentrations. At higher concentrations, ibuprofen shows at least a 2-fold higher toxicity compared to that of its degradation products. However, E. faecalis shows little or no effect upon exposure to these compounds. An induction of the SOS response in E. coli is observed but limited to only ibuprofen and 4-acetylbenzoic acid. In human cell line studies, survival of both HEK293T and HepG2 cell lines is profoundly impaired by the photo-degradation products of (±)- (2R,3R)-2-(4-isobutylphenyl)-5-methylhexan-3-ol, (±)-(2R,3S)-2-(4-isobutylphenyl)-5-methylhexan-3-ol, and (±)-1-(4-(1-hydroxy-2methylpropyl)phenyl)ethan-1-one. In this work, the bioluminescence bacterium, Aliivibrio fischeri, is used as a model to assess environmental impact. Both ibuprofen and its degradation products inhibit the growth of this gram-negative bacteria with the primary compound showing the most significant impact. Overall, our results highlight that some of the degradation products of ibuprofen can be more toxic to human kidney cell line and liver cell line than the parent compound while ibuprofen can be more toxic to human gut microbiota and A. fischeri than ibuprofen degradation products.

Abiotic degradation and environmental toxicity of ibuprofen: Roles of mineral particles and solar radiation

The growing medical and personal needs of human populations have escalated release of pharmaceuticals and personal care products into our natural environment. This work investigates abiotic degradation pathways of a particular PPCP, ibuprofen, in the presence of a major mineral component of soil (kaolinite clay), as well as the health effects of the primary compound and its degradation products. Results from these studies showed that the rate and extent of ibuprofen degradation is greatly influenced by the presence of clay particles and solar radiation. In the absence of solar radiation, the dominant reaction mechanism was observed to be the adsorption of ibuprofen onto clay surface where surface silanol groups play a key role. In contrast, under solar radiation and in the presence of clay particles, ibuprofen breaks down to several fractions. The decay rates were at least 6-fold higher for irradiated samples compared to those of dark conditions. Toxicity of primary ibuprofen and its secondary residues were tested on three microorganisms: Bacillus megaterium, Pseudoaltermonas atlantica; and algae from the Chlorella genus. The results from the biological assays show that primary PPCP is more toxic than the mixture of secondary products. Overall, however, biological assays carried out using only 4-acetylbenzoic acid, the most abundant secondary product, show a higher toxic effect on algae compared to its parent compound.

Cytotoxicity and apoptotic activity of novel organobismuth(V) and organoantimony(V) complexes in different cancer cell lines

Novel organobismuth(V) and organoantimony(V) complexes of Ph3ML2 type were synthesized, in which L = deprotonated 2-acetylbenzoic acid (2AcBH), 4-acetylbenzoic acid (4AcBH) or 5-acetylsalicylic acid (5AcSH) and M = bismuth(V) or antimony(V). Complexes [Ph3Bi(2AcB)2] (1) [Ph3Sb(4AcB)2] (2), [Ph3Bi(4AcB)2] (3) and [Ph3Sb(5AcS)2.CHCl3] (4) were characterized by elemental analysis, IR, and NMR. Crystal structures of 2 and 4 were determined by single crystal X-ray diffraction. In vitro cytotoxic activities against cancerous (human chronic myelogenous leukemia, K562 and murine metastatic melanoma, B16F10) and healthy non-cancerous (murine fibroblasts, L929 and murine melanocytes, Melan-A) cells showed that, compared to free ligands, both of the metal complexes are more active as anticancer agents at low concentration in cancerous cell lines, but also possessed toxic effect at comparatively higher concentration towards the non-cancerous cells. The organobismuth(V) complex Ph3Bi(2AcB)2 was found to be more active than the Ph3BiCl2 metal precursor against the tumor cell lines and exhibited the highest selectivity index. Moreover, evaluation of the pro-apoptotic activity of Ph3Bi(2AcB)2 in B16F10 cells, by quantifying the cellular DNA using flow cytometry, indicates that cell cycle arrest and cell apoptosis contribute to the drug cytotoxicity. This work supports the great potential of organobismuth(V) dicarboxylate complexes as anticancer agents.

Removal and transformation products of ibuprofen obtained during ozone- and ultrasound-based oxidative treatment.

The oxidation of ibuprofen (IBP) in water was evaluated using oxidative treatments: ozonation, sonication, hydrogen peroxide addition and combinations of these processes. After 20 minutes of treatment, ozone coupled with hydrogen peroxide at pH 7, 15 °C, an ozone dose of 16 mg/L and a hydrogen peroxide concentration of 7.1 mg/L was found to have the highest IBP (95%) and chemical oxygen demand (COD) (41%) removals. A synergistic effect was observed for the combined ozonation/sonication process, which might be explained by an improved mass transfer of ozone in the solution due to the presence of ultrasonic pressure waves. Transformation products were detected in the treated solutions. The nature of five of these products was confirmed by liquid chromatography-mass spectrometry (LC-MS), including 4-isobutylacetophenone (4-IBAP), oxo-IBP, 4-acetylbenzoic acid, 4-ethybenzaldehyde and oxalic acid. In addition, COD analyses for each experiment showed that the ratio of %COD removal to %IBP removal was highest with sonication; suggesting that this oxidative process offers other mechanisms of removal which may lead to further degradation of products formed. This study presents the first data on removal of IBP by sonication coupled to ozonation and provides some insight into the potential of this combined treatment approach for the removal of contaminants of emerging concern.

Thermodynamics of the solubility of 4-acetylbenzoic acid in different solvents from 303.15 to 473.15 K

Solubility data of the solid–liquid equilibrium of 4-acetylbenzoic acid in aqueous and different organic solvents is essential for industrial design and theoretical studies. The solubility of 4-acetylbenzoic acid in water, acetic acid, p-cymene, tert-butylbenzene, and water-acetic acid (1:1vol.) mixture was measured within a temperature range of 303.15 to 473.15K. Solubility was measured by the isothermal method and the resulting data were analyzed by regression analysis. The solubility of 4-acetylbenzoic acid was the highest in acetic acid, followed by the water-acetic acid (1:1vol.) mixture, p-cymene, tert-butylbenzene, then water. The results correlated well with the modified Apelblat equation and the Buchowski–Książczak λH equation. The calculated solubilities by using modified Apelblat solubility model were in good agreement with the experimental data. The percentage of average relative deviations of the correlation is 0.27 for solubility of 4-acetylbenzoic acid in acetic acid solvent.

Determination and modeling of aqueous solubility of 4-position substituted benzoic acid compounds in a high-temperature solution

Accurate experimental determination of the aqueous solubility of 4-position substituted benzoic acid compounds in a high-temperature solution and its correlation are presented. The temperature effect dependence of aqueous solubility was investigated in the range from 303.15 to 473.15K. The solubility prediction is essential for rapid design and optimization of separation, purification and formulation processes in the chemical industry. Solubility data were determined using a simple and reliable apparatus and analyzed by the classical titration method. Experimental data were regressed with the modified Apelblat equation and the λH equation. The λH equation gave good agreement with all experimental data. A solubility model modified from the λH equation was used to correlate the experimental data. The percentage of average relative deviations of these correlations was 1.40% for the solubility of 4-acetylbenzoic acid in an aqueous solution.

Chemical oxidation of ibuprofen in the presence of iron species at near neutral pH

The objective of this work was to evaluate the removal of ibuprofen (IBP) using the oxidants hydrogen peroxide (H2O2) and sodium persulfate (Na2S2O8). The ability of magnetite (Fe3O4) to activate persulfate (PS) and H2O2 for the oxidation of IBP at near neutral pH was evaluated as well. The use of soluble Fe2+ to activate H2O2 and Na2S2O8 was also investigated. H2O2 and Na2S2O8 were inactive during the sixty-minute experiments when used alone. However, activation using Fe2+ increased the removal to 95% in the presence of H2O2 (Fenton reaction) and 63% in the presence of Na2S2O8 at pH 6.6. Chemical oxygen demand (COD) removal was also greater for Fenton oxidation (65%) than for iron-activated PS oxidation (25%). Activation of H2O2 and PS by Fe3O4 was only observed at a high oxidant concentration and over 48h of reaction time. A second order rate kinetic constant was determined for H2O2 (3.0∗10−3M−1s−1) and Na2S2O8 (1.59∗10−3M−1s−1) in the presence of Fe3O4. Finally, several of the degradation products formed during oxidation of IBP in the presence of H2O2 and Na2S2O8 (activated by Fe2+) were identified. These include oxalic acid, pyruvic acid, formic acid, acetic acid, 4-acetylbenzoic acid, 4-isobutylacetophenone (4-IBAP) and oxo-ibuprofen.

PEGylation of Octreotide Using an α,β-unsaturated-β'-mono-sulfone Functionalized PEG Reagent.

PEGylation is a well-established technique utilized to overcome the problems related to the therapeutic applications of peptides and proteins. Reasons for the PEGylation of these biological macromolecules include reducing immunogenicity, proteolytic degradation and rapid clearance from blood circulation. Octreotide is an octapeptide analogue of naturally-occurred somatostatin. This peptide has elimination half-life of less than 2 h that requires frequent daily subcutaneous or intravenous administration. To address this issue, octreotide modification was investigated using bis-thiol alkylating PEG reagent. The required bis-thiol alkylating reagent (V) was prepared from commercially available 4-acetyl benzoic acid in five steps. Octreotide disulfide bond was mildly reduced to liberate the two cysteine sulfur atoms followed by bis-alkylation to form PEGylated peptide. The PEG modification process was monitored through the reverse phase HPLC and (1)H-NMR analysis. According to the HPLC chromatograms of PEGylation reaction, the peak with 30 min retention time was identified to be PEG-octreotide. In addition, (1)H-NMR analysis showed a 7.44% degree of PEG substitution.

Polymeric micelles for the pH-dependent controlled, continuous low dose release of paclitaxel

Poly(ethylene glycol)- block-poly(aspartate-hydrazide) (PEG-p(Asp-Hyd)) was modified using either levulinic acid (LEV) or 4-acetyl benzoic acid (4AB) attached via hydrazone bonds. Paclitaxel (PTX) conjugated to the linkers formed PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX). PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX) assemble into unimodal polymeric micelles with diameters of 42 nm and 137 nm, respectively. PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX) at a 1:1 and 1:5 molar ratio assemble into unimodal mixed polymeric micelles with diameters of 85 and 113 nm, respectively. PEG-p(Asp-Hyd-LEV-PTX) micelles release LEV-PTX faster at pH 5.0 than at pH 7.4 over 24 h. At pH 7.4 mixed polymeric micelles at 1:5 ratio show no difference in LEV-PTX release from PEG-p(Asp-Hyd-LEV-PTX) micelles. Mixed polymeric micelles at 1:5 molar ratio gradually release LEV-PTX at pH 5.0, with no release of 4AB-PTX. PEG-p(Asp-Hyd-LEV-PTX) micelles and mixed polymeric micelles exert comparable cytotoxicity against SK-OV-3 and MCF-7 cancer cell lines. In summary, mixed polymeric micelles based on PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX) offer prospects for pH-dependent release of PTX, offering a novel prodrug strategy for adjusting its pharmacokinetic and pharmacodynamic properties for cancer therapy. If successful this delivery system offers an alternative new mode of delivery for paclitaxel with a new scope for its efficacy along with a minimal synthetic framework needed to accomplish this.

Application of a modified version of Habeeb's trinitrophenylation method for the characterization of hapten–protein conjugates in a reversed micellar medium

We describe here a protocol for determining the epitope density of hapten–carrier conjugates at the nanomolar level. Conjugates of bovine serum albumin (BSA) and hen egg albumin (OVA) were prepared with two model haptens: 4-acetyl benzoic acid (ABA) as a chromophoric carboxylic hapten and cholesterol hemisuccinate (Chol HS) as a carboxylic derivative of a nonchromophoric hydroxylated hapten. Small-scale but valuable haptenization of carriers was achieved (≈4.3 nmol with an input molar ratio of hapten to carrier within the range from 50:1 to 100:1) that proved yet compatible with immunogenicity and antibody detection. We used a modified version of the amide bond-generating mixed anhydride method of Erlanger performed in a reversed micellar medium. Microsample aliquots of the coupling reaction (carriers plus activated haptens) or control experiment (carriers plus nonactivated haptens) mixtures were directly subjected to trinitrophenylation in the reversed micellar medium. The results for carrier substitution were strongly correlated ( r 2=0.94; n=12) with those obtained by other methods such as UV analysis (for ABA) and chromatographic determination (for Chol HS). This method was found directly applicable to other hapten–carrier conjugates coupled by the same procedure, provided that the haptens do not absorb at about 335 and 420 nm (absorption peaks of trinitrophenyl groups). With this simple, rapid, reproducible and low-cost analysis method, the separation of uncoupled hapten and conjugate is unnecessary. This facilitates the optimization of reaction conditions. Finally, using this procedure, kinetic studies of conjugate formation can be carried out in a very simple manner.

An improved method for the production of antibodies to lipophilic carboxylic hapten using small amount of hapten-carrier conjugate

A rapid, simple and low cost procedure for preparing minute amount of hapten-protein conjugates was developed using 4-acetyl benzoic acid (ABA) and two other closely related small chromophoric haptens. The amide bond-generating mixed anhydride method of Erlanger was modified to promote conjugation to various proteins (bovine serum albumin, ovalbumin, casein and hemocyanin) or to a synthetic homopolymer (Poly- dl-lysine). The key process in this synthesis is the use of a reversed micellar medium allowing strong carrier haptenization as determined by spectrophotometric measurement at characteristic hapten absorption peaks. This coupling procedure is applicable to as little hapten material as 0.2 μmol and is disclosed to be most valuable for other rare lipid haptens which pose analytical problem in biological fluids and matrices. Specific mice polyclonal antibodies were produced following multiple intraperitoneal injections of (ABA) 23–BSA conjugate as revealed by indirect and competitive ELISA. Calculated K D for the interaction of the antibodies with free ABA was found to be 5×10 −5 M.