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BackgroundVertebral discitis-osteomyelitis (VDO) is a devastating infection of the spine that is challenging to distinguish from noninfectious mimics using computed tomography and magnetic resonance imaging. We and others have developed novel metabolism-targeted positron emission tomography (PET) radiotracers for detecting living Staphylococcus aureus and other bacteria in vivo, but their head-to-head performance in a well-validated VDO animal model has not been reported.MethodsWe compared the performance of several PET radiotracers in a rat model of VDO. [11C]PABA and [18F]FDS were assessed for their ability to distinguish S aureus, the most common non-tuberculous pathogen VDO, from Escherichia coli.ResultsIn the rat S aureus VDO model, [11C]PABA could detect as few as 103 bacteria and exhibited the highest signal-to-background ratio, with a 20-fold increased signal in VDO compared to uninfected tissues. In a proof-of-concept experiment, detection of bacterial infection and discrimination between S aureus and E coli was possible using a combination of [11C]PABA and [18F]FDS.ConclusionsOur work reveals that several bacteria-targeted PET radiotracers had sufficient signal to background in a rat model of S aureus VDO to be potentially clinically useful. [11C]PABA was the most promising tracer investigated and warrants further investigation in human VDO.

A polymeric coordination compound [Zn2(PABA)2(H2O)2Cl2]n (1) (where PABA is para-aminobenzoic acid) has been synthesized and characterized. We examined and explicated the porosity of the compound and employed a low-temperature nitrogen adsorption technique at 77 kelvins. Throughout the experiments, the nitrogen partial pressure ranged from 0.005 to 0.995 P/P0, aligning with the nitrogen adsorption and desorption curves. The surface area (SBET) was found to be 1945.72 m2/g with a micropore area of 361.56 m2/g that ensures the material's ability to effectively adsorb small molecules. The nitrogen adsorption behavior on this compound is not only facilitates a deeper comprehension of its textural and structural attributes but also unveils potential applications, especially in pharmaceutical domains. Additionally, Hirschfeld surface analysis was performed, yielding interatomic interaction percentages on the Hirschfeld surface. [ABSTRACT FROM AUTHOR]

A CuII coordination polymer, catena-poly[[[aquacopper(II)]-bis(μ-4-aminobenzoato)-κ2N:O;κ2O:N] monohydrate], {[Cu(pABA)2(H2O)]·H2O}n (pABA = p-aminobenzoate, C7H4NO2−), was synthesized and characterized. It exhibits a one-dimensional chain structure extended into a three-dimensional supramolecular assembly through hydrogen bonds and π–π interactions. While the twinned crystal shows a metrically orthorhombic lattice and an apparent space group Pbcm, the true symmetry is monoclinic (space group P2/c), with disordered Cu atoms and mixed roles of water molecules (aqua ligand/crystallization water). The luminescence spectrum of the complex shows an emission at 345 nm, cf. 349 nm for pABAH.

A Cu11 coordination polymer, catefta-poly[[[aquacopper(II)]-bis(μ-4-amino-benzoato)-K²N:O;K²O:N] monohydrate], {[Cu(pABA)2(H2O)]⋅H2O}n (pABA = p-aminobenzoate, C7H4NO2-), was synthesized and characterized. It exhibits a one-dimensional chain structure extended into a three-dimensional supra-molecular assembly through hydrogen bonds and π-π interactions. While the twinned crystal shows a metrically orthorhombic lattice and an apparent space group Pbcm, the true symmetry is monoclinic (space group P2/c), with disordered Cu atoms and mixed roles of water molecules (aqua ligand/crystallization water). The luminescence spectrum of the complex shows an emission at 345 nm, cf. 349 nm for pABAH. [ABSTRACT FROM AUTHOR]

Biosyntheses of para-aminobenzoic acid (PABA) and its downstream folic acid metabolites are essential for one-carbon metabolism in all life forms and the targets of sulfonamide and trimethoprim antibiotics. In this study, we identified and characterized two genes (pabA and pabBC) required for PABA biosynthesis in Listeria monocytogenes. Mutants in PABA biosynthesis were able to grow normally in rich media but not in defined media lacking PABA, but growth was restored by the addition of PABA or its downstream metabolites. PABA biosynthesis mutants were attenuated for intracellular growth in bone marrow-derived macrophages, produced extremely small plaques in fibroblast monolayers, and were highly attenuated for virulence in mice. PABA biosynthesis genes were upregulated upon infection and induced during growth in broth in a strain in which the master virulence regulator, PrfA, was genetically locked in its active state (PrfA*). To gain further insight into why PABA mutants were so attenuated, we screened for transposon-induced suppressor mutations that formed larger plaques. Suppressor mutants in relA, which are predicted to have higher levels of (p)ppGpp, and mutants in codY, which is a GTP-binding repressor of many biosynthetic genes, partially rescued the plaque defect but, notably, restored the capacity of the mutants to escape from phagosomes and induce the polymerization of host cell actin. However, these suppressor mutant strains remained attenuated for virulence in mice. These data suggest that even though folic acid metabolites exist in host cells and might be available during infection, de novo synthesis of PABA is required for L. monocytogenes pathogenesis.

Diagnosis of Biotinidase deficiency (BTD) is extremely important to avoid several neurodevelopmental problems in early childhood. Colorimetric and fluorometric methods lack specificity and selectivity due to several interferences resulting in a high number of false positive results. We developed an HPLC method for BTD activity in serum with fluorescent detection. In colorimetric assays, biotinidase attacks the amide linkage of the artificial substrate biotinidyl-4-aminobenzoic acid (B-PABA) and releases p-aminobenzoic acid (PABA), which is converted to a purple dye by diazotization reaction. The newly developed method injects the reaction mixture directly into the HPLC column and quantifies using a six-point calibration curve without coupling and diazotization reaction. The method is linear over the 5–1000 μmol/L range. The detection and quantitation limits were 2.5 μmol/L and 5.0 μmol/L, respectively. When compared with colorimetric assay, the correlation coefficient (R2) was 0.9963. The within-assay and between-assay precision was

Tools for noninvasive detection of bacterial pathogens are needed but are not currently available for clinical use. We have previously shown that para-aminobenzoic acid (PABA) rapidly accumulates in a wide range of pathogenic bacteria, motivating the development of related PET radiotracers. In this study, 11C-PABA PET imaging was used to accurately detect and monitor infections due to pyogenic bacteria in multiple clinically relevant animal models. 11C-PABA PET imaging selectively detected infections in muscle, intervertebral discs, and methicillin-resistant Staphylococcus aureus-infected orthopedic implants. In what we believe to be first-in-human studies in healthy participants, 11C-PABA was safe, well-tolerated, and had a favorable biodistribution, with low background activity in the lungs, muscles, and brain. 11C-PABA has the potential for clinical translation to detect and localize a broad range of bacteria.

Abstract Background Microbial production of aromatic chemicals is an attractive method for obtaining high-performance materials from biomass resources. A non-proteinogenic amino acid, 4-amino-3-hydroxybenzoic acid (4,3-AHBA), is expected to be a precursor of highly functional polybenzoxazole polymers; however, methods for its microbial production have not been reported. In this study, we attempted to produce 4,3-AHBA from glucose by introducing 3-hydroxylation of 4-aminobenzoic acid (4-ABA) into the metabolic pathway of an industrially relevant bacterium, Corynebacterium glutamicum. Results Six different 4-hydroxybenzoate 3-hydroxylases (PHBHs) were heterologously expressed in C. glutamicum strains, which were then screened for the production of 4,3-AHBA by culturing with glucose as a carbon source. The highest concentration of 4,3-AHBA was detected in the strain expressing PHBH from Caulobacter vibrioides (CvPHBH). A combination of site-directed mutagenesis in the active site and random mutagenesis via laccase-mediated colorimetric assay allowed us to obtain CvPHBH mutants that enhanced 4,3-AHBA productivity under deep-well plate culture conditions. The recombinant C. glutamicum strain expressing CvPHBHM106A/T294S and having an enhanced 4-ABA biosynthetic pathway produced 13.5 g/L (88 mM) 4,3-AHBA and 0.059 g/L (0.43 mM) precursor 4-ABA in fed-batch culture using a nutrient-rich medium. The culture of this strain in the chemically defined CGXII medium yielded 9.8 C-mol% of 4,3-AHBA from glucose, corresponding to 12.8% of the theoretical maximum yield (76.8 C-mol%) calculated using a genome-scale metabolic model of C. glutamicum. Conclusions Identification of PHBH mutants that could efficiently catalyze the 3-hydroxylation of 4-ABA in C. glutamicum allowed us to construct an artificial biosynthetic pathway capable of producing 4,3-AHBA on a gram-scale using glucose as the carbon source. These findings will contribute to a better understanding of enzyme-catalyzed regioselective hydroxylation of aromatic chemicals and to the diversification of biomass-derived precursors for high-performance materials.

Abstract A simple, rapid, precise, accurate and sustainable spectrofluorimetric method (SFM) was developed, validated and applied for the determination of 4-aminobenzoic acid and aromatic amino acids (phenylalanine, tryptophan and tyrosine). These compounds are used in biopharmaceutical formulations and therefore must be analyzed by quality control laboratories to meet the criteria established in pharmacopoeias. In general, potentiometric titration (PT) is described in the compendia as the official analytical technique. However, this method showed low sensitivity and selectivity, and moreover was performed with a non-aqueous solvent (acetic acid), which led to higher consumption of reagents and consequently to the formation of residues. Therefore, the SFM was developed in aqueous medium at pH 7.2 using phosphate buffer. It was successfully validated according to the ICH guidelines and showed good linearity range (r>0.999), specificity, accuracy and precision (within and between days) and robustness. The test results were compared between the SFM and PT using raw material samples, while according to the F- and t-tests at 95% confidence level, no statistical difference was found between the methods.

Background: Microbial production of aromatic chemicals is an attractive method for obtaining high-performance materials from biomass resources. A non-proteinogenic amino acid, 4-amino-3-hydroxybenzoic acid (4,3-AHBA), is expected to be a precursor of highly functional polybenzoxazole polymers; however, methods for its microbial production have not been reported. In this study, we attempted to produce 4,3-AHBA from glucose by introducing 3-hydroxylation of 4-aminobenzoic acid (4-ABA) into the metabolic pathway of an industrially relevant bacterium, Corynebacterium glutamicum. Results: Six different 4-hydroxybenzoate 3-hydroxylases (PHBHs) were heterologously expressed in C. glutamicum strains, which were then screened for the production of 4,3-AHBA by culturing with glucose as a carbon source. The highest concentration of 4,3-AHBA was detected in the strain expressing PHBH from Caulobacter vibrioides (CvPHBH). A combination of site-directed mutagenesis in the active site and random mutagenesis via laccase-mediated colorimetric assay allowed us to obtain CvPHBH mutants that enhanced 4,3-AHBA productivity under deep-well plate culture conditions. The recombinant C. glutamicum strain expressing CvPHBHM106A/T294S and having an enhanced 4-ABA biosynthetic pathway produced 13.5 g/L (88 mM) 4,3-AHBA and 0.059 g/L (0.43 mM) precursor 4-ABA in fed-batch culture using a nutrient-rich medium. The culture of this strain in the chemically defined CGXII medium yielded 9.8 C-mol% of 4,3-AHBA from glucose, corresponding to 12.8% of the theoretical maximum yield (76.8 C-mol%) calculated using a genome-scale metabolic model of C. glutamicum. Conclusions: Identification of PHBH mutants that could efficiently catalyze the 3-hydroxylation of 4-ABA in C. glutamicum allowed us to construct an artificial biosynthetic pathway capable of producing 4,3-AHBA on a gram-scale using glucose as the carbon source. These findings will contribute to a better understanding of enzyme-catalyzed regioselective hydroxylation of aromatic chemicals and to the diversification of biomass-derived precursors for high-performance materials. [ABSTRACT FROM AUTHOR]

The researches have been carried out to study the effect of 4-aminobenzoic acid on the growth, lipid synthesis, and fractional composition of lipids in the biomass of Streptomyces massasporeus CNMN-Ac-06 strain. Under laboratory conditions, during cultivation of S. massasporeus CNMN-Ac-06 strain, various concentrations of 4-aminobenzoic acid were added to the SP-I complex medium. The maximum amount of biomass in comparison with the control sample was obtained by cultivation of the strain on SP-I complex medium supplemented with 4-aminobenzoic acid in concentration of 1.37 g/L - 24.99±1.1 g/L, and the amount of total lipids in it was 1.96±0.08 g/L, by 32.28% more in comparison with the control sample. An increase in the phospholipid fraction was obtained on the SP-I complex medium supplemented with 4-aminobenzoic acid in a concentration of 2.74 g/L - 24.39% (when in control sample - 20.70%). Triglyceride and sterol fractions increased on the SP-I complex medium supplemented with 4-aminobenzoic acid in concentration of 1.37 g/L - 18.46% and 20.54%, respectively (when in control sample - 10.55% and 6.80%, respectively). [ABSTRACT FROM AUTHOR]

This work was done to synthesize tetrazole dye and Z-scan measurement of the synthesized tetrazole compounds has been carried out and interesting results about the origin of positive nonlinear absorption coefficients of dye molecules were obtained. Investigation of linear optical properties of synthesized dyes was done with the help of visible UV absorption, and fluorescence emission spectrum. Also, the electronic characteristics and molecular geometry of the sensitizers were optimized using density functional theory (DFT), and the influence of dye structure on their nonlinear optical performances was studied. Four new dyes with D–π–A architecture were discussed, in which diphenylamine and carbazole units act as donors, methine groups act as conjugated bridge units, and tetrazole derivatives act as acceptor units. Diphenylamine, carbazole, methine, and tetrazole derivatives are, respectively, donor, conjugate, and bridge acceptor units in the structure of these dyes. Moreover, nonlinear absorption and refractive indexes of the synthesized tetrazole components were measured using the Z-scan technique equipped with a 50 mW CW Nd-Yag laser. The nonlinear absorption coefficient of tetrazole derivations was obtained and was positive, and it was demonstrated that the origin of the so-called reverse saturation absorption of dye molecules in low intensities is the electrostriction effect which is due to polarization of the molecules which has an inverse relation with the Homo–Lumo energy gap of the components. [ABSTRACT FROM AUTHOR]

Electrochemical sensors with polymeric films as a sensitive layer are of high interest in current electroanalysis. A voltammetric sensor based on multi-walled carbon nanotubes (MWCNTs) and electropolymerized 4-aminobenzoic acid (4-ABA) has been developed for the simultaneous determination of synthetic food azo dyes (sunset yellow FCF and tartrazine). Based on the voltammetric response of the dyes' mixture, the optimal conditions of electropolymerization have been found to be 30-fold potential scanning between −0.3 and 1.5 V, at 100 mV s−1 in the 100 µmol L−1 monomer solution in phosphate buffer pH 7.0. The poly (4-ABA)-based electrode shows a 10.5-fold increase in its effective surface area and a 17.2-fold lower electron transfer resistance compared to the glassy carbon electrode (GCE). The sensor gives a sensitive and selective response to sunset yellow FCF and tartrazine, with the peak potential separation of 232 mV in phosphate buffer pH 4.8. The electrooxidation parameters of dyes have been calculated. Simultaneous quantification is possible in the dynamic ranges of 0.010–0.75 and 0.75–5.0 µmol L−1 for both dyes, with detection limits of 2.3 and 3.0 nmol L−1 for sunset yellow FCF and tartrazine, respectively. The sensor has been tested on orange-flavored drinks and validated with chromatography. [ABSTRACT FROM AUTHOR]

• ABA modification increased the optical band gap of NiO x from 3.65 eV to 3.71 eV. • The grain size of perovskite on ABA modified NiO x increased by over 28%. • The efficiency of the PSCs was enhanced to 19.1% via the modified NiO x. • After 6 days, the unpackaged PSCs decay to about 70 % of pristine efficiency. The quality of the interface between the nickel oxide (NiO x) and the perovskite contact is essential to the efficiency and stability of the device. How to effectively suppress the reaction at the interface between NiO x and perovskite is the key to improve the interface quality. Herein, a simple and scalable interface enhancement strategy for building efficient and stable perovskite solar cells (PSCs) using 4-aminobenzoic acid (ABA) molecules to modify the sputtered NiO x surface as the hole transport layers (HTLs). Meanwhile, ABA molecules not only reduce the defect density and improve the quality of perovskite films (PVK), but also improve the carrier extraction ability of NiO x and reduce interfacial non-radiative recombination. Eventually, the optimized inverted device efficiency is increased to 19.1%, and the device stability is significantly improved under unencapsulated atmospheric conditions. This provides a reference for the commercial development of PSCs. [ABSTRACT FROM AUTHOR]

Imaging studies are frequently used to support the clinical diagnosis of infection. These techniques include computed tomography (CT) and magnetic resonance imaging (MRI) for structural information and single photon emission computed tomography (SPECT) or positron emission tomography (PET) for metabolic data. However, frequently, there is significant overlap in the imaging appearance of infectious and noninfectious entities using these tools. To address this concern, recent approaches have targeted bacteria-specific metabolic pathways. For example, radiolabeled sugars derived from sorbitol and maltose have been investigated as PET radiotracers, since these are efficiently incorporated into bacteria but are poor substrates for mammalian cells. We have previously shown that para-aminobenzoic acid (PABA) is an excellent candidate for development as a bacteria-specific imaging tracer as it is rapidly accumulated by a wide range of pathogenic bacteria, including metabolically quiescent bacteria and clinical strains, but not by mammalian cells. Therefore, in this study, we developed an efficient radiosynthesis for [11C]PABA, investigated its accumulation into Escherichia coli and Staphylococcus aureus laboratory strains in vitro, and showed that it can distinguish between infection and sterile inflammation in a murine model of acute bacterial infection.

Acylthiourea (ATU) compounds 4-(3-(furan-2-carbonyl)thioureido)benzoic acid (1), 4-(3-(thiophene-2-carbonyl)thioureido)benzoic acid (2), and 4-(3-(benzoyl)thioureido)benzoic acid (3) were synthesized and characterized by NMR (1H and 13C), FT-IR, UV–Vis and mass spectrometry. The molecular structures of compounds 1 and 2 were confirmed by single crystal X-ray diffraction studies. An electrochemical method employing Nafion (Nf)–ATU (1–3)–multi-walled carbon nanotubes (MWCNTs)-modified glassy carbon (GC) electrode (Nf/ATU/MWCNTs/GC) has been developed for the determination of DHCl. Electrochemical studies were carried out in phosphate buffer by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). DHCl was detected at 1.1 V vs Ag/AgCl (3 M KCl). The proposed sensor for the determination of DHCl was investigated with three acylthiourea derivatives (1, 2, and 3) under optimized experimental conditions using blood plasma samples. The lowest detection limit toward DHCl was 0.09 mM. [ABSTRACT FROM AUTHOR]

Selection of an appropriate solvent is of interest in the pharmaceutical industry. In some case, a mixture of solvents has a more solubility than the pure solvents. A predictive model such as the UNIFAC model can be employed to predict the solubility to reduce the cost of tests. However, the accuracy of the UNIFAC model should be evaluated to ensure the results of this model. In this work, the accuracy of the UNIFAC model is studied in predicting the solubility of 4-aminobenzoic acid in the binary mixtures of methanol, ethanol, acetone, and water. First, the UNIFAC model is used to predict the solubility of 4-aminobenzoic acid in the binary mixtures and then the binary mixtures whose solubility are high are selected to measure their solubility of 4-aminobenzoic acid and to compare with the results of the model. The experimental data showed that the solubility of 4-aminobenzoic acid in the binary mixtures of methanol-acetone (where the mole fraction of methanol is 0.65) and ethanol-acetone (where the mole fraction of ethanol is 0.2) is significantly higher than that of the pure solvents. However, the UNIFAC model predicted the maximum solubility of 4-aminobenzoic acid in methanol-acetone mixture where the mole fraction of methanol was 0.38 and, in the ethanol-acetone mixture where the mole fraction of ethanol was 0.3. Thus, the UNIFAC model can be used for an initial estimation of the maximum solubility in the mixtures; however, this model is not precise model for accurate prediction of the solubility of 4-aminobenzoic acid.

In the realm of electrocatalytic CO 2 reduction (ECR) reactions, the challenges of instability and self-reducibility present significant obstacles to the practical application of bismuth oxide-based catalysts. Herein, Bi 2 O 3 pre-catalyst was synthesized and surface-modified with 4-aminobenzoic acid (PABA). Theoretical studies confirmed that PABA was effectively grafted through oxygen vacancies on the Bi 2 O 3 surface, leading to electronic rearrangement. PABA efficiently prevented surface Bi3+ on Bi 2 O 3 from self-reducing to Bi0 during the ECR reaction. The Bi 2 O 3 PABA pre-catalyst transformed into the active Bi 2 O 2 CO 3 PABA ECR catalyst via electrolyte mediation. A Faraday efficiency of 98.6 % for formate was achieved at −1.1 V vs. RHE, with a wide potential window of 800 mV. The current density reached 210 mA cm–2 in a 2×2 cm2 flow cell system. Theoretical calculations illustrate that PABA facilitates stabilizing the *OCHO intermediate, diminishing the adsorption barrier. These results may provide valuable insights for designing highly selective ECR catalysts through interface engineering. [Display omitted] • Bi 2 O 2 CO 3 -PABA catalyst was successfully computationally predicted and synthesized. • Bi 2 O 2 CO 3 -PABA shows an excellent CO 2 -to-formate selectivity as the electrocatalyst. • Bi 2 O 2 CO 3 -PABA has an 800 mV active window and industry-competitive current density. • Modification with PABA can effectively prevent the self-reduction of Bi 2 O 2 CO 3. • PABA modification lowers the *OCHO adsorption energy, enhancing formate selectivity. [ABSTRACT FROM AUTHOR]

In this study, a simple stability-indicating HPLC method for determination of folic acid and its related substances in tablets was optimized and validated. Chromatographic separation was performed on Inertsil C8, 250 x 4.6 mm, 5 µm, using isocratic elution with mobile phase consisting of methanol and phosphate buffer (pH=6,4) (12:88, v/v %). The injection volume was 5 µL and the eluted compounds were monitored at 280 nm. The flow rate was 0.7 mL/min and the column temperature was maintained at 30 °C. Forced degradation studies were conducted to investigate the stability-indicating ability of the method. The method was validated according to the ICH guideline requirements with respect to selectivity/specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. The results from the forced degradation study confirmed satisfactory resolution between folic acid and obtained specified impurities (imp. A, imp. C, imp. D, imp. E and PABA) as well as satisfactory resolution between all other formed degradation products, proving that the method is stability-indicating. The optimized and validated method is selective and precise, capable of detecting and quantifying all folic acid related substances. The obtained results from validation parameters imply that the proposed method is suitable for its purpose and can be used for routine quantification of folic acid and its related substances in tablets. [ABSTRACT FROM AUTHOR]

A combined experimental and theoretical study is presented to predict and analyze the inhibition efficiency and adsorption mechanism of 4-aminobenzoic acid molecule for copper corrosion in molar nitric acid. Experimentally, the investigation has been performed through polarization curves, electrochemical impedance spectroscopy (EIS), scanning electron microscopy, energy-dispersive X-ray spectrometry, and atomic force microscopy studies. Theoretically, the inhibition effect of 4-aminobenzoic acid on copper corrosion is evaluated from the DFT/B3LYP/6-311+G(d,p) calculated frontier molecular orbital (FMO) energies, global and local reactivity descriptors defined within the conceptual density functional theory (CDFT), electrostatic potential (ESP) mapping, and conformational analysis while the mechanism of adsorption onto the copper surface is studied from DFT-based molecular dynamics simulation. We obtained a good correlation between theoretical energy gap and the experimental corrosion inhibition efficiency for copper by amino acids. The experimental and theoretical findings show good agreement in both gas phase and water, establishing 4-aminobenzoic acid as a potent inhibitor of copper corrosion under acidic conditions. [ABSTRACT FROM AUTHOR]

Electrochemical sensors with polymeric films as a sensitive layer are of high interest in current electroanalysis. A voltammetric sensor based on multi-walled carbon nanotubes (MWCNTs) and electropolymerized 4-aminobenzoic acid (4-ABA) has been developed for the simultaneous determination of synthetic food azo dyes (sunset yellow FCF and tartrazine). Based on the voltammetric response of the dyes’ mixture, the optimal conditions of electropolymerization have been found to be 30-fold potential scanning between −0.3 and 1.5 V, at 100 mV s−1 in the 100 µmol L−1 monomer solution in phosphate buffer pH 7.0. The poly (4-ABA)-based electrode shows a 10.5-fold increase in its effective surface area and a 17.2-fold lower electron transfer resistance compared to the glassy carbon electrode (GCE). The sensor gives a sensitive and selective response to sunset yellow FCF and tartrazine, with the peak potential separation of 232 mV in phosphate buffer pH 4.8. The electrooxidation parameters of dyes have been calculated. Simultaneous quantification is possible in the dynamic ranges of 0.010–0.75 and 0.75–5.0 µmol L−1 for both dyes, with detection limits of 2.3 and 3.0 nmol L−1 for sunset yellow FCF and tartrazine, respectively. The sensor has been tested on orange-flavored drinks and validated with chromatography.

Coq9 is a polypeptide subunit in a mitochondrial multi-subunit complex, termed the CoQ-synthome, required for biosynthesis of coenzyme Q (ubiquinone or Q). Deletion of COQ9 results in dissociation of the CoQ-synthome, but over-expression of Coq8 putative kinase stabilizes the CoQ-synthome in the coq9 null mutant and leads to the accumulation of two nitrogen-containing Q intermediates, imino-demethoxy-Q6 (IDMQ6) and 3-hexaprenyl-4-aminophenol (4-AP) when para-aminobenzoic acid (pABA) is provided as a ring precursor. To investigate whether Coq9 is responsible for deamination steps in Q biosynthesis, we utilized the yeast coq5-5 point mutant. The yeast coq5-5 point mutant is defective in the C-methyltransferase step of Q biosynthesis but retains normal steady-state levels of the Coq5 polypeptide. Here, we show that when high amounts of 13C6-pABA are provided, the coq5-5 mutant accumulates both 13C6-imino-demethyl-demethoxy-Q6 (13C6-IDDMQ6) and 13C6-demethyl-demethoxy-Q6 (13C6-DDMQ6). Deletion of COQ9 in the yeast coq5-5 mutant along with Coq8 over-expression and 13C6- pABA labeling leads to the absence of 13C6-DDMQ6, and the nitrogen-containing intermediates 13C6-4-AP and 13C6-IDDMQ6 persist. We describe a coq9 temperature-sensitive mutant and show that at the non-permissive temperature, steady-state polypeptide levels of Coq9-ts19 increased, while Coq4, Coq5, Coq6, and Coq7 decreased. The coq9-ts19 mutant had decreased Q6 content and increased levels of nitrogen-containing intermediates. These findings identify Coq9 as a multi-functional protein that is required for the function of Coq6 and Coq7 hydroxylases, for removal of the nitrogen substituent from pABA-derived Q intermediates, and is an essential component of the CoQ synthome.

Intercalation of 4-amino benzoic acid (4-AB) into Zn/Al-nitrate layered double hydroxide (ZAL2) to form Zn/Al-4AB (ZALAB) compound was successfully synthesized from nitrate salt by using direct co-precipitation method. ZALAB compound was confirmed by Powder X-ray diffraction (PXRD) pattern with a basal spacing of 15.3 Å. The presence of COO- and C6H5NH2 functional groups of 4-AB at 1,517 and 1,178 cm–1 in Fourier transform infrared (FTIR) spectrum reinforced 4-AB intercalated into the resulting compound. Based on the thermal analysis, 4-AB in ZALAB compound was more stable compared to pure 4-AB. Breuneur, Emmet and Teller/Barret-Joyner-Halenda (BET/BJH) analyses demonstrated that ZALAB compound is a mesopores-type IV compound with 4.25 m² /g surface area. This material is an irregular shape with different sizes of particles. ZALAB is a potential sunscreen formulation that minimizes the harmful effect on the skin, improving pharmaceutical technology in the skincare treatment. [ABSTRACT FROM AUTHOR]

The title 1:1 salt, C7H8NO2+·C5H3N2O2− (systematic name: 4-carboxyanilinium pyrazine-2-carboxylate), was synthesized successfully by slow evaporation of a saturated solution from water–ethanol (1:1 v/v) mixture and characterized by X-ray diffraction (SCXRD, PXRD) and calorimetry (DSC). The crystal structure of the salt was solved and refined at 150 and 293 K. The salt crystallizes with one molecule of 4-aminobenzoic acid (PABA) and one molecule of pyrazinoic acid (POA) in the asymmetric unit. In the crystal, the PABA and POA molecules are associated via COOH...Narom heterosynthons, which are connected by N—H...O hydrogen bonds, creating zigzag chains. The chains are further linked by N—H...O hydrogen bonds and π–π stacking interactions along the b axis [centroid-to-centroid distances = 3.7377 (13) and 3.8034 (13) Å at 150 and 293 K, respectively] to form a layered three-dimensional structure.

Background: In vitro screening strategies based on the inhibition of α-glucosidase (GAA) activity have been widely used for the discovery of potential antidiabetic drugs, but they still face some challenges, such as poor enzyme stability, non-reusability and narrow range of applicability. To overcome these limitations, an in vitro screening method based on GAA@GOx@Cu-MOF reactor was developed in our previous study. However, the method was still not satisfactory enough in terms of construction cost, pH stability, organic solvent resistance and reusability. Thence, there is still a great need for the development of in vitro screening methods with lower cost and wider applicability., Results: A colorimetric sensing strategy based on GAA/(Au-Au/IrO 2 )@Cu(PABA) cascade catalytic reactor, which constructed through simultaneous encapsulating Au-Au/IrO 2 nanozyme with glucose oxidase-mimicking and peroxidase-mimicking activities and GAA in Cu(PABA) carrier with peroxidase-mimicking activity, was innovatively developed for in vitro screening of GAA inhibitors in this work. It was found that the reactor not only exhibited excellent thermal stability, pH stability, organic solvent resistance, room temperature storage stability, and reusability, but also possessed cascade catalytic performance, with approximately 12.36-fold increased catalytic activity compared to the free system (GAA + Au-Au/IrO 2 ). Moreover, the in vitro GAA inhibitors screening method based on this reactor demonstrated considerable anti-interference performance and detection sensitivity, with a detection limit of 4.79 nM for acarbose. Meanwhile, the method owned good reliability and accuracy, and has been successfully applied to the in vitro screening of oleanolic acid derivatives as potential GAA inhibitors., Significance: This method not only more effectively solved the shortcomings of poor stability, narrow scope of application, and non-reusability of natural enzymes in the classical method compared with our previous work, but also broaden the application scope of Au-Au/IrO 2 nanozyme with glucose oxidase and peroxidase mimicking activities, and Cu(PABA) carrier with peroxidase mimicking activity, which was expected to be a new generation candidate method for GAA inhibitor screening., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The crystal structure of a new Progesterone (PROG) co-crystal with para-aminobenzoic acid (PABA) showing enhanced solution properties is reported. PROG-PABA co-crystal was first identified though an in silico coformer screening process using the CSD Co-crystal deign function, then confirmed through a solution evaporation crystallisation experiment. The resulting co-crystal was characterized using single crystal X-ray diffraction, differential scanning calorimetry and Fourier-transform infrared spectroscopy. Liquid assisted grinding was selected as a suitable scale up method compared to spray drying and antisolvent methods due to minimal starting material phases in the final product. Following scale up, aqueous solubility, stability and dissolution measurements were carried out. PROG-PABA showed increased distinct aqueous solubility and dissolution compared to PROG starting material and was shown to be stable at 75 % relative humidity for 3 months. Tablets containing co-crystal were produced then compared to the Utrogestan® soft gel capsule formulation through a dissolution experiment. PROG-PABA tablets showed a substantial increase in dissolution over the course of the experiment with over 30× the amount of PROG dissolved at the 3-hour time point. This co-crystal shows positive implications for developing an improved oral PROG formulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cryopyrin-associated periodic syndrome (CAPS) is a rare hereditary inflammatory disorder encompassing a continuum of three phenotypes: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease. Distinguishing features include cutaneous, neurological, ophthalmologic, and rheumatologic manifestations. CAPS results from a gain-of-function mutation of the NLRP3 gene coding for cryopyrin, which forms intracellular protein complexes known as inflammasomes. Defects of the inflammasomes lead to overproduction of interleukin-1, resulting in inflammatory symptoms seen in CAPS. Diagnosis is often delayed and requires a thorough review of clinical symptoms. Remarkable advances in our understanding of the genetics and the molecular pathway that is responsible for the clinical phenotype of CAPS has led to the development of effective treatments. It also has become clear that the NLRP3 inflammasome plays a critical role in innate immune defense and therefore has wider implications for other inflammatory disease states.

4-aminobenzoic acid (PABA), an essential nutrient for many human pathogens, but dispensable for humans, and its derivatives have exhibited various biological activities. In this study, we combined two pharmacophores using a molecular hybridization approach: this vitamin-like molecule and various aromatic aldehydes, including salicylaldehydes and 5-nitrofurfural, via imine bond in one-step reaction. Resulting Schiff bases were screened as potential antimicrobial and cytotoxic agents. The simple chemical modification of non-toxic PABA resulted in constitution of antibacterial activity including inhibition of methicillin-resistant Staphylococcus aureus (minimum inhibitory concentrations, MIC, from 15.62 µM), moderate antimycobacterial activity (MIC ≥ 62.5 µM) and potent broad-spectrum antifungal properties (MIC of ≥ 7.81 µM). Some of the Schiff bases also exhibited notable cytotoxicity for cancer HepG2 cell line (IC50 ≥ 15.0 µM). Regarding aldehyde used for the derivatization of PABA, it is possible to tune up the particular activities and obtain derivatives with promising bioactivities. [ABSTRACT FROM AUTHOR]

Abstract Background Replacement of chloride ions in cyanuric chloride give several variants of 1,3,5-triazine derivatives which were investigated as biologically active small molecules. These compounds exhibit antimalarial, antimicrobial, anti-cancer and anti-viral activities, among other beneficial properties. On the other hand, treatment of bacterial infections remains a challenging therapeutic problem because of the emerging infectious diseases and the increasing number of multidrug-resistant microbial pathogens. As multidrug-resistant bacterial strains proliferate, the necessity for effective therapy has stimulated research into the design and synthesis of novel antimicrobial molecules. Results 1,3,5-Triazine 4-aminobenzoic acid derivatives were prepared by conventional method or by using microwave irradiation. Using microwave irradiation gave the desired products in less time, good yield and higher purity. Esterification of the 4-aminobenzoic acid moiety afforded methyl ester analogues. The s-triazine derivatives and their methyl ester analogues were fully characterized by FT-IR, NMR (1H-NMR and 13C-NMR), mass spectra and elemental analysis. All the synthesized compounds were evaluated for their antimicrobial activity. Some tested compounds showed promising activity against Staphylococcus aureus and Escherichia coli. Conclusions Three series of mono-, di- and trisubstituted s-triazine derivatives and their methyl ester analogues were synthesized and fully characterized. All the synthesized compounds were evaluated for their antimicrobial activity. Compounds (10), (16), (25) and (30) have antimicrobial activity against S. aureus comparable to that of ampicillin, while the activity of compound (13) is about 50% of that of ampicillin. Compounds (13) and (14) have antimicrobial activity against E. coli comparable to that of ampicillin, while the activity of compounds (9–12) and (15) is about 50% of that of ampicillin. Furthermore, minimum inhibitory concentrations values for clinical isolates of compounds (10), (13), (14), (16), (25) and (30) were measured. Compounds (10) and (13) were more active against MRSA and E. coli than ampicillin. Invitro cytotoxicity results revealed that compounds (10) and (13) were nontoxic up to 250 µg/mL (with SI = 10) and 125 µg/mL (with SI = 5), respectively. Graphical abstract Three series of mono-, di- and trisubstituted s-triazine derivatives and their methyl ester analogues were synthesized and evaluated for their antimicrobial activity. Several compounds have antimicrobial activity against S. aureus and E. coli comparable to that of ampicillin.

Emerging evidence suggests that intestinal permeability can be potentially enhanced through cocrystallization. However, a mechanism for this effect remains to be established. In this study, we first demonstrate the enhancement in intestinal permeability, evaluated by the Caco-2 cell permeability assay, of acetazolamide (ACZ) in the presence of a conformer, p-aminobenzoic acid (PABA), delivered in the form of a 1:1 cocrystal. The binding strength of ACZ and PABA with the Pgp efflux transporter, either alone or as a mixture, was calculated using molecular dynamics simulation. Results show that PABA weakens the binding of ACZ with Pgp, which leads to a lower efflux ratio and elevated permeability of ACZ. This work provides molecular-level insights into a potentially effective strategy to improve the intestinal permeability of drugs. If the same cocrystal also exhibits higher solubility, oral bioavailability of BCS IV drugs can likely be improved by forming a cocrystal with a Pgp inhibitor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Detection of the Kirsten rat sarcoma gene ( KRAS ) mutational status is an important factor for the treatment of various malignancies. The most common KRAS -activating mutations are caused by single-nucleotide mutations, which are usually determined by using PCR, using allele-specific DNA primers. Oligonucleotide primers with uncharged or partially charged internucleotide phosphate modification have proved their ability to increase the sensitivity and specificity of various single nucleotide mutation detection. To enhance the specificity of single nucleotide mutation detection, the novel oligonucleotides with four types of uncharged and partially charged internucleotide phosphates modification, phosphoramide benzoazole (PABA) oligonucleotides (PABAO), was used to prove the concept on the KRAS mutation model. The molecular effects of different types of site-specific PABA modification in a primer or a template on a synthesis of full-length elongation product and PCR efficiency were evaluated. The allele-specific PCR (AS-PCR) on plasmid templates showed a significant increase in analysis specificity without changes in Cq values compared with unmodified primer. PABA modification is a universal mismatch-like disturbance, which can be used for single nucleotide polymorphism discrimination for various applications. The molecular insights of the PABA site-specific modification in a primer and a template affect PCR, structural features of four types of PABAO in connection with AS-PCR results, and improvements of AS-PCR specificity support the further design of novel PCR platforms for various biological targets testing.