Grouping of short alkyl-chain branched carboxylic acids for developmental toxicity.

Read-across (RAx) and grouping of chemicals into categories are well-known concepts in toxicology. Recently, ECHA proposed a grouping approach for branched-chain carboxylic acids (BCAs) including more than 60 branched-chain saturated carboxylic acids for hazard identification. Grouping was based only on structural considerations. Due to developmental effects of two members, ECHA postulated that "all short carbon chain acids … are likely reproductive and developmental toxicants". This work analyzes available data for BCAs. The number of compounds in the group can be significantly reduced by eliminating metal and organic salts of BCAs, compounds of unknown or variable composition, and complex reaction products or biological materials (UVCB compounds). For the resulting reduced number of compounds, grouping is supported by similar physicochemical data and expected similar biotransformation. However, analysis of adverse effects for compounds in the group and mechanistic information show that BCAs, as a class, do not cause developmental effects in rats. Rather, developmental toxicity is limited to selected BCAs with specific structures that share a common mode of action (histone deacetylase inhibition). Thus, the proposed grouping is unreasonably wide and the more detailed analyses show that structural similarity alone is not sufficient for grouping branched-chain carboxylic acids for developmental toxicity.

Divergent Functionalization of Styrenes via Radical/Polar Crossover with CO2 and Sodium Sulfinates.

Sulfones and carboxylic acids are prominent motifs widely present in the chemical structure of agrochemicals, pharmaceuticals and many other highly valuable compounds. Herein, we describe a conjunctive strategy for the precise installation of these functionalities onto styrenes using sodium sulfinates and CO2 as coupling partners. The protocol allowed the preparation of carboxy-sulfonylated compounds in good yields and broad functional group tolerance. Additionally, taking advantage of the leaving group ability of the sulfone moiety, a one-pot photocatalytic carboxy-sulfonylation-elimination strategy was developed for the synthesis of α-aryl-acrylates.

Tug-of-War Driven by the Structure of Carboxylic Acids: Tuning the Size, Morphology, and Photocatalytic Activity of α-Ag2WO4.

Size and morphology control during the synthesis of materials requires a molecular-level understanding of how the addition of surface ligands regulates nucleation and growth. In this work, this control is achieved by using three carboxylic acids (tartaric, benzoic, and citric) during sonochemical syntheses. The presence of carboxylic acids affects the kinetics of the nucleation process, alters the growth rate, and governs the size and morphology. Samples synthesized with citric acid revealed excellent photocatalytic activity for the degradation process of Rhodamine B, and recyclability experiments demonstrate that it retains 91% of its photocatalytic activity after four recycles. Scavenger experiments indicate that both the hydroxyl radical and the hole are key species for the success of the transformation. A reaction pathway is proposed that involves a series of dissolution-hydration-dehydration and precipitation processes, mediated by the complexation of Ag+. We believe these studies contribute to a fundamental understanding of the crystallization process and provide guidance as to how carboxylic acids can influence the synthesis of materials with controlled size and morphology, which is promising for multiple other scientific fields, such as sensor and catalysis fields.

S/X ratio impacts the profile and kinetics of carboxylic acids production from the acidogenic fermentation of dairy wastewater.

The acidogenic fermentation of dairy wastewater (DW) was evaluated for carboxylic acids (CA) production, investigating the influence of substrate/microorganism (S/X) ratio and applying different mathematical models to the bioproduct formation data. The experiments were performed in batch reactors for 28 days, and four S/X ratios were tested (0.8, 1.2, 1.6, and 1.9 gCOD gVSS-1). The S/X ratio increase did not influence the percentage of DW conversion into carboxylic acids (42-44%), but the productivity was positively affected (100-200% in general). Acetic acid was the CA formed in the highest concentration for all experiments, followed by propionic and butyric acids. Exponential models were better suited to describe this kinetics process. Therefore, according to the estimated kinetic parameters, the S/X ratio 1.6 was more suitable for CA production from acidogenic fermentation of dairy wastewater, in which the concentrations of longer CA, such as propionate and butyrate, were formed in higher quantities. In addition, it was determined a correlation between the S/X ratio and kinetic parameters like degradation/production rate constant (K) and maximum productivity rate (µm).

Choline chloride-based deep eutectic solvents as potential solvent for extraction of phenolic compounds from olive leaves: Extraction optimization and solvent characterization.

This study evaluates the use of deep eutectic solvents (DES) prepared with choline chloride ([Ch]Cl) and carboxylic acids for phenolic compound extraction from olive leaves. These extracts were then compared to those obtained using ethanol. The effects of temperature and water addition during DES- and ethanol-based extractions were analyzed using response surface methodology. Due to the lack of solid-liquid equilibrium (SLE) data for [Ch]Cl + acetic acid, SLE, and DES density and viscosity with and without water addition were measured and analyzed. [Ch]Cl:acetic acid (54.1 °C, 50.0% water addition) extracted 15% more phenolic compounds than ethanol (54.1 °C, 0.5% water addition), according to UHPLC-MS based analyses. SLE analyses showed that [Ch]Cl + acetic acid presented a eutectic region at close to a 1:2 molar ratio. DES precursors and water addition influenced solvent physical properties and phenolic compound yield. DES was confirmed to be an innovative, strong solvent for phenolic compound extraction from olive leaves.

A kinetic study on carboxylic acids production using bovine slaughterhouse wastewater: a promising substrate for resource recovery in biotechnological processes.

Carboxylic acids (CA) are considered high added-value compounds, and their production from wastes has gained economic and environmental notoriety. However, the CA production and kinetic modeling using some agro-industrial wastewaters, such as bovine slaughterhouse wastewater (SHW), are not well reported in the literature. Therefore, the objective of this work was to evaluate the CA production potential using SHW as a substrate under acidogenic conditions and to apply mathematical models to estimate the kinetic parameters of particulate organic matter hydrolysis, soluble organic matter consumption, and CA production. Tests were carried out in quadruplicate batch reactors with a 250-mL reaction volume, with brewery sludge as inoculum and using chloroform (0.05%, v/v) for methanogenesis inhibition. The obtained yield was 0.55 g acids gCODA-1, corresponding to 0.76 gCOD gCODA-1. The production of caproic acid without the addition of electron donors was achieved. Mathematical models that describe exponential growth, such as the first-order exponential model, cone model, and Fitzhugh model, were the most suitable to describe the production kinetics of CA. Finally, SHW seems to be a promising substrate to be investigated in the carboxylic platform.

Characterization of honey of stingless bees from the Brazilian semi-arid region.

The physicochemical characteristics of honey vary according to bee species, climate, region, period of collection, processing and storage. In this context, this work aimed to perform a comparative study of the physicochemical characteristics of Melipona subnitida and M. fasciculata honey collected at different periods and regions of the State of Piauí, Brazil. Twenty-nine honey samples were collected and evaluated by principal component analysis from physicochemical analysis data. Twenty-two percent of the parameters analyzed differed between species. Evaluating the collection period, the honey of M. subnitida and M. fasciculata presented differences among themselves. The study revealed a similarity between the physicochemical parameters of the honey of the two species of bees, in addition, the time was one of the determining factors in the formation of clusters.

Drug Solubility Enhancement through the Preparation of Multicomponent Organic Materials: Eutectics of Lovastatin with Carboxylic Acids.

Lovastatin (LOV) is a drug used to treat hypercholesterolemia. Recent studies have identified its antioxidant effects and potential use in the treatment of some types of cancer. However, the low bioavailability related to its poor water solubility limits its use in solid oral dosage forms. Therefore, to improve the solubility of LOV three eutectic systems of LOV with the carboxylic acids benzoic (BEN), salicylic (SAL) and cinnamic (CIN) were obtained. Both binary phase and Tammann diagrams were constructed using differential scanning calorimetry (DSC) data of mixtures prepared from 0.1 to 1.0 molar ratios. Binary mixtures and eutectics were prepared by liquid-assisted grinding. The eutectics were further characterized by DSC and powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The LOV-BEN, LOV-SAL and LOV-CIN system formed a eutectic at an LOV mole fraction of 0.19, 0.60 and 0.14, respectively. The systems exhibited improvements in LOV solubility, becoming more soluble by five-fold in the LOV-SAL system and approximately four-fold in the other two systems. Considering that the solubility enhancements and the carboxylic acids used are generally recognized as safe by the U.S. Food and Drug Administration (FDA), the LOV eutectic systems are promising materials to be used in a solubility enhancement strategy for pharmaceutical product formulation.

Performance of 3­[4­(bromomethyl)phenyl]­7­(diethylamino) coumarin as a derivatization reagent for the analysis of medium and long chain fatty acids using HPLC with LIF detection.

Knowledge of the profile of fatty acids, including the profile of long chain fatty acids, is an important parameter for many areas like human health, food sciences, and the study of gene expression in plant tissues, among others. Moreover, very long chain fatty acids occur at low concentrations in many biological samples. The 3­[4­(bromomethyl)phenyl]­7­(diethylamino)coumarin (MPAC­Br) reagent is an improved version of the coumarin bromomethyl-type reagents, used for the fluorescent labeling of carboxylic acids in a variety of sample types. Derivatization reactions are always a matter of concern in routine analyses, as they are seen as a time demanding step and a source of errors in analytical chemistry. MPAC­Br is studied in the present work, including the robustness of its derivatization reaction, the stability of its derivatives, the limits of its detection and the repeatability of its results. An optimized version of its protocol was applied to determine the content and profiles of both medium and long chain fatty acids in eight samples of oils and fats. It was shown that the proposed derivatization reaction is a reliable, robust, fast and convenient method for the analysis of these compounds.

Unveiling the oxidative metabolism of Achatina fulica (Mollusca: Gastropoda) experimentally infected to Angiostrongylus cantonensis (Nematoda: Metastrongylidae).

For the first time, alterations in the oxidative metabolism of Achatina fulica experimentally infected with different parasite loads of Angiostrongylus cantonensis were determined. For this, the hemolymph activities of lactate dehydrogenase (LDH) and hexokinase and the glucose concentrations in the hemolymph, as well as the polysaccharide reserves in the digestive gland and cephalopedal mass, were assessed. Additionally, the contents of some carboxylic acids in the hemolymph of infected and uninfected snails were determined by high-performance liquid chromatography (HPLC), permitting a better understanding of the alterations related to the host's oxidative metabolism. As the main results, activation of oxidative pathways, such as the glycolytic pathway, was demonstrated in response to the increase in the activity of hexokinase. This tendency was confirmed by the decrease in the contents of glucose in the hemolymph of parasitized snails, indicating that the infection by A. cantonensis alters the host's metabolism, and that these changes are strongly influenced by the parasite load. This metabolic scenario was accompanied by activation of the anaerobic fermentative metabolism, indicated not only by an increase in the activity of (LDH), but also by a reduction of the content of pyruvic acid and accumulation of lactic acid in the hemolymph of parasitized snails. In this circumstance, maintenance of the host's redox balance occurs through activation of the fermentative pathways, and LDH plays a central role in this process. Together, the results indicate that A. cantonensis infection induces activation of the anaerobic metabolism of A. fulica, characterized not only by the accumulation of lactic acid, but also by a reduction in the pyruvic acid and oxalic acid contents in the hemolymph of the infected snails.

Determination of neutral diols and carboxylic acids formed during glycerol electrooxidation by capillary electrophoresis with dual C4D.

Methods for determination of glycerol and its electrooxidation products (neutral diols and carboxylates) by capillary electrophoresis (CE) with dual capacitively coupled contactless conductivity detectors (C4D) are presented. Glycerol, dihydroxyacetone and glyceraldehyde were detected as anionic borate complexes in less than 3min under counter Electroosmotic Flow (EOF) mode (resolution of the critical pair of 1.8). Limits of detection (LODs) of 15, 15 and 10µmolL-1 were obtained for glycerol, dihydroxyacetone and glyceraldehyde, respectively. Two methods of separation were used for the separation of carboxylates. The first one used the same Back Ground Electrolyte (BGE) containing borate, and the second used a BGE (pH 6.1) composed by 2-(N-morpholino)ethanesulfonic acid (MES), L-Histidine and a flow modifier. Better separation and LODs for carboxylates were obtained using Mes/Histidine as BGE. However, along with the non-applicability of this BGE to the determination of neutral diols, observation of the C4D signals at two different points of the capillary (10 and 50cm apart from the injection tip) revealed interaction of the flow modifier with some species (mesoxalate and glyoxylate). The electrooxidation of a glycerol sample in alkaline media on an 8cm2 gold working electrode was evaluated by the developed methods. After 16h of electrolysis, 87% of the glycerol had been oxidized and formate, glycolate, hydroxypyruvate and glycerate were detected as the main products.

Insights into the spontaneity of hydrogen bond formation between formic acid and phthalimide derivatives.

We evaluated a group of phthalimide derivatives, which comprise a convenient test set for the study of the multiple factors involved in the energetics of hydrogen bond formation. Accordingly, we carried out quantum chemical calculations on the hydrogen bonded complexes formed between a sample of phthalimide derivatives with formic acid with the intent of identifying the most important electronic and structural factors related to how their strength and spontaneity vary across the series. The geometries of all species considered were fully optimized at DFT B3LYP/6-31++G(d,p), RM1, RM1-DH2, and RM1-D3H4 level, followed by frequency calculations to determine their Gibbs free energies of hydrogen bond formation using Gaussian 2009 and MOPAC 2012. Our results indicate that the phthalimide derivatives that form hydrogen bond complexes most favorably, have in their structures only one C=O group and at least one NH group. On the other hand, the phthalimide derivatives predicted to form hydrogen bonds least favorably, possess in their structures two carbonyl groups, C=O, and no NH group. The ability to donate electrons and simultaneously receive one acidic hydrogen is the most important property related to the spontaneity of hydrogen bond formation. We further chose two cyclic compounds, phthalimide and isoindolin-1-one, in which to study the main changes in molecular, structural and spectroscopic properties as related to the formation of hydrogen bonds. Thus, the greatest ability of the isoindolin-1-one compound in forming hydrogen bonds is evidenced by the larger effect on the structural, vibrational, and chemical shifts properties associated with the O-H group. In summary, the electron-donating ability of the hydrogen bond acceptor emerged as the most important property differentiating the spontaneity of hydrogen bond formation in this group of complexes.

Metabolic Pathways for Degradation of Aromatic Hydrocarbons by Bacteria.

The aim of this review was to build an updated collection of information focused on the mechanisms and elements involved in metabolic pathways of aromatic hydrocarbons by bacteria. Enzymes as an expression of the genetic load and the type of electron acceptor available, as an environmental factor, were highlighted. In general, the review showed that both aerobic routes and anaerobic routes for the degradation of aromatic hydrocarbons are divided into two pathways. The first, named the upper pathways, entails the route from the original compound to central intermediate compounds still containing the aromatic ring but with the benzene nucleus chemically destabilized. The second, named the lower pathway, begins with ring de-aromatization and subsequent cleavage, resulting in metabolites that can be used by bacteria in the production of biomass. Under anaerobic conditions the five mechanisms of activation of the benzene ring described show the diversity of chemical reactions that can take place. Obtaining carbon and energy from an aromatic hydrocarbon molecule is a process that exhibits the high complexity level of the metabolic apparatus of anaerobic microorganisms. The ability of these bacteria to express enzymes that catalyze reactions, known only in non-biological conditions, using final electron acceptors with a low redox potential, is a most interesting topic. The discovery of phylogenetic and functional characteristics of cultivable and noncultivable hydrocarbon degrading bacteria has been made possible by improvements in molecular research techniques such as SIP (stable isotope probing) tracing the incorporation of (13)C, (15)N and (18)O into nucleic acids and proteins. Since many metabolic pathways in which enzyme and metabolite participants are still unknown, much new research is required. Therefore, it will surely allow enhancing the known and future applications in practice.

The zwitterionic structure of 2-hydroxy-4-[(2-hydroxybenzylidene)amino]benzoic acid.

The title compound, C14H11NO4, exists in the solid phase in the zwitterionic form, 2-{[(4-carboxy-3-hydroxyphenyl)iminiumyl]methyl}phenolate, with the H atom from the phenol group on the 2-hydroxybenzylidene ring transferred to the imine N atom, resulting in a strong intramolecular N-H∙∙∙O hydrogen bond between the iminium H atom and the phenolate O atom, forming a six-membered hydrogen-bonded ring. In addition, there is an intramolecular O-H∙∙∙O hydrogen bond between the carboxylic acid group and the adjacent hydroxy group of the other ring, and an intermolecular C-H∙∙∙O contact involving the phenol group and the C-H group adjacent to the imine bond, connecting the molecules into a two-dimensional network in the (103) plane. π-π stacking interactions result in a three-dimensional network. This study is important because it provides crystallographic evidence, supported by IR data, for the iminium zwitterionic form of Schiff bases.