Aromatic Acids Research Articles

Nutrient and moisture limitations reveal keystone metabolites linking rhizosphere metabolomes and microbiomes

Plants release a wealth of metabolites into the rhizosphere that can shape the composition and activity of microbial communities in response to environmental stress. The connection between rhizodeposition and rhizosphere microbiome succession has been suggested, particularly under environmental stress conditions, yet definitive evidence is scarce. In this study, we investigated the relationship between rhizosphere chemistry, microbiome dynamics, and abiotic stress in the bioenergy crop switchgrass grown in a marginal soil under nutrient-limited, moisture-limited, and nitrogen (N)-replete, phosphorus (P)-replete, and NP-replete conditions. We combined 16S rRNA amplicon sequencing and LC-MS/MS-based metabolomics to link rhizosphere microbial communities and metabolites. We identified significant changes in rhizosphere metabolite profiles in response to abiotic stress and linked them to changes in microbial communities using network analysis. N-limitation amplified the abundance of aromatic acids, pentoses, and their derivatives in the rhizosphere, and their enhanced availability was linked to the abundance of bacterial lineages from Acidobacteria, Verrucomicrobia, Planctomycetes, and Alphaproteobacteria. Conversely, N-amended conditions increased the availability of N-rich rhizosphere compounds, which coincided with proliferation of Actinobacteria. Treatments with contrasting N availability differed greatly in the abundance of potential keystone metabolites; serotonin and ectoine were particularly abundant in N-replete soils, while chlorogenic, cinnamic, and glucuronic acids were enriched in N-limited soils. Serotonin, the keystone metabolite we identified with the largest number of links to microbial taxa, significantly affected root architecture and growth of rhizosphere microorganisms, highlighting its potential to shape microbial community and mediate rhizosphere plant-microbe interactions.

Potential Therapeutic Approach using Aromatic l-amino Acid Decarboxylase and Glial-derived Neurotrophic Factor Therapy Targeting Putamen in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative illness characterized by specific loss of dopaminergic neurons, resulting in impaired motor movement. Its prevalence is twice as compared to the previous 25 years and affects more than 10 million individuals. Lack of treatment still uses levodopa and other options as disease management measures. Treatment shifts to gene therapy (GT), which utilizes direct delivery of specific genes at the targeted area. Therefore, the use of aromatic L-amino acid decarboxylase (AADC) and glial-derived neurotrophic factor (GDNF) therapy achieves an effective control to treat PD. Patients diagnosed with PD may experience improved therapeutic outcomes by reducing the frequency of drug administration while utilizing provasin and AADC as dopaminergic protective therapy. Enhancing the enzymatic activity of tyrosine hydroxylase (TH), glucocorticoid hormone (GCH), and AADC in the striatum would be useful for external L-DOPA to restore the dopamine (DA) level. Increased expression of glutamic acid decarboxylase (GAD) in the subthalamic nucleus (STN) may also be beneficial in PD. Targeting GDNF therapy specifically to the putaminal region is clinically sound and beneficial in protecting the dopaminergic neurons. Furthermore, preclinical and clinical studies supported the role of GDNF in exhibiting its neuroprotective effect in neurological disorders. Another Ret receptor, which belongs to the tyrosine kinase family, is expressed in dopaminergic neurons and sounds to play a vital role in inhibiting the advancement of PD. GDNF binding on those receptors results in the formation of a receptor-ligand complex. On the other hand, venous delivery of recombinant GDNF by liposome-based and encapsulated cellular approaches enables the secure and effective distribution of neurotrophic factors into the putamen and parenchyma. The current review emphasized the rate of GT target GDNF and AADC therapy, along with the corresponding empirical evidence.

Emerging Gene Therapies for Alzheimer's and Parkinson's Diseases: An Overview of Clinical Trials and Promising Candidates.

Gene therapy as a disease-modifying therapeutic approach for neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), is a promising avenue. Promising results in the preclinical studies involving rodents and nonhuman primates utilizing gene therapy have led to multiple clinical trials evaluating various genes of interest for AD and PD. In AD, clinical trials are assessing gene therapy involving brain-derived neurotrophic factor (BDNF) and other targets such as apolipoprotein E2 (APOE2) and human telomerase reverse transcriptase (hTERT). In PD, clinical trials are evaluating gene therapy delivering neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF). Additionally, gene therapy delivering enzymes aromatic L-amino acid decarboxylase (AADC) and glutamic acid decarboxylase (GAD) are also being evaluated for PD. All these trials primarily utilized adeno-associated virus (AAV) to deliver the above transgene of interest. This review summarizes the current clinical trials involving gene therapy for AD and PD. It also discussesthe challenges and opportunities associated with the gene therapy approach in AD and PD and ongoing developments related to increasing the safety and efficacy of the gene therapy for long-term outcomes, which include evaluation of various serotypes and administration routes. This comprehensive review emphasizes translating preclinical findings into clinical trials, further directions, and the potential for this promising therapeutic approach to alleviate neurodegenerative disease.

Plasma metabolomic profiling reveals a novel circulating biomarker signature in chronic pruritus of unknown origin

Chronic pruritus of unknown origin (CPUO) is characterized by chronic itch for 6 weeks or greater without an identifiable primary cause. Studies are needed to investigate circulating blood biomarkers to elucidate disease pathogenesis. The objective of this study was to investigate changes in circulating blood metabolites in CPUO patients and to identify potential therapeutic targets. Our cross-sectional study collected plasma from 11 CPUO patients and 11 matched control patients for mass-spectrometry based metabolite data analysis. 15 metabolites differed significantly in the blood of CPUO patients compared to controls, including nine amino acids (isoleucine, L-tyrosine, threonine, DL-tryptophan, L-valine, methionine, glycine, lysine, and L-phenylalanine), four amino acid derivatives (creatinine, DL-carnitine, acetyl-L-carnitine, and indole-3-acrylic acid), and two aromatic and fatty acid derivatives (2-hydroxycinnamic acid and oleamide). These metabolites were also correlated with itch severity. Metabolic set enrichment analysis (MSEA) identified downregulation of several pathways in CPUO: phenylalanine, tyrosine, tryptophan biosynthesis; catecholamine biosynthesis; and glycine, serine, and threonine metabolism. Our study identified decreases in several circulating plasma metabolites in CPUO patients and downregulation of pathways related to catecholamine biosynthesis and tryptophan biosynthesis, providing insight into the pathogenesis of CPUO.

Green synthesis of iron nanoparticles (Fe(NPs)) using plant extract from Eucalyptus grandis: characterization and determination of the catalytic potential for reduction of 4-nitrophenol

This study assessed a green synthesis method for iron nanoparticles (Fe(NPs)), using Eucalyptus grandis leaf extract, to reduce waste generation and diminish the use of conventional chemical inputs, such as Sodium Borohydride (NaBH4), without significant losses in catalytic activity. Various volumetric ratios of plant extract and NaBH4 were tested to understand how this variation would affect the morphological, structural, and catalytic power of the material. In the conducted analyses, a reduction in the crystallinity of Fe(NPs) was observed for proportions above 25% of the extract. However, the particle size remained stable among different syntheses, with iron ions showing improved dispersion for proportions of 40% and 50% of the extract. Regarding stabilization, characteristic bands of aromatic compounds, alcohols, ethers and carboxylic acids were identified, indicating the extract's involvement in coating the metallic cores. To assess the catalytic performance, studies were conducted on the catalytic reduction of the contaminant 4-nitrophenol to 4-aminophenol, using Fe(NPs) as catalysts. The results revealed conversions above 80% for Fe(NPs) synthesized with volumetric proportions of up to 40% of the plant extract, suggesting that substituting the chemical agent did not significantly affect the catalytic activity of the biocatalyst. Finally, ecotoxicological tests performed with Lemna minor and artemia salina demonstrated a significant reduction in the toxicity of the contaminant 4-nitrophenol, as well as the biocompatibility of the obtained Fe(NPs). Keywords: iron oxides, stabilization, vegetable coating.

Pd-catalysed regioselective cross dehydrogenative coupling of quinazolinones with aromatic carboxylic acids

A simple protocol for a regioselective cross dehydrogenative reaction of 2-aryl-quinazolinones with different phenyl carboxylic acids was developed using a palladium catalyst facilitated by CH activation. Simple and readily accessible aromatic carboxylic acids were utilized as a source of benzoxylate. A one-pot method proceeded with great regioselectivity and offered mono benzoxylation product with moderate to excellent yield.

Enzymatic acylation of cyanidin-3-O-glucoside with aromatic and aliphatic acid methyl ester: Structure–stability relationships of acylated derivatives

Anthocyanins are water-soluble pigments, but they tend to be unstable in aqueous solutions. Modification of their molecular structure offers a viable approach to alter their intrinsic properties and enhance stability. Aromatic and aliphatic acid methyl esters were used as acyl donors in the enzymatic acylation of cyanidin-3-O-glucoside (C3G), and their analysis was conducted using ultraperformance liquid chromatography–mass spectrometry (UPLC-MS). The highest conversion rate achieved was 96.41 % for cyanidin-3-O-(6″-feruloyl) glucoside. Comparative evaluations of stability revealed that aromatic acyl group–conjugated C3G exhibited superior stability enhancement compared with aliphatic acyl group derivatives. The stability of aliphatic C3G decreased with increasing carbon chain length. The molecular geometries of different anthocyanins were optimized, and energy level calculations using density functional theory (DFT) identified their sites with antioxidant activities. Computational calculations aligned with the in vitro antioxidant assay results. This study provided theoretical support for stabilizing anthocyanins and broadened the application of acylated anthocyanins as food colorants and nutrient supplements.

Fe3O4@PS-DVB microspheres modified with urea functional groups for rapid and green extraction of fluorinated aromatic carboxylic acids from tap and formation water

The present study describes the trace analysis of 23 fluorinated aromatic carboxylic acids based on the dispersive magnetic solid phase extraction (m-SPE) technique coupled with the gas chromatography coupled with mass spectrometry (GC–MS) electron ionization (EI) technique. A commercial hydrophilic-lipophilic balanced (HLB) material polystyrene divinyl benzene having urea functional groups was modified with magnetite nanoparticles and employed as a sorbent for dispersive m-SPE of fluorobenzoic acids (FBAs) from the tap and formation water samples. The extraction occurred due to π- π interaction between the aromatic ring of synthesized sorbent and the aromatic ring of FBAs, the hydrogen bond formation between the urea functional group of the sorbent and carbonyl oxygen, fluorine of the FBAs. As a result, the method was precise, rapid, reproducible, and calibrated with the coefficient of variation (R2) greater than 0.98 for all 23 compounds. The instrument detection limit (IDL) and method detection limit (MDL) were found in the range of 2.60 – 8.25 ng/mL and 0.08 – 0.28 ng/mL respectively. Extraction efficiencies were found in the range of 83.80–100 % for tap water samples and 78.41–98.92 % for formation water samples, respectively, with an enrichment factor of 33.33–66.66 and a maximum RSD of 7.07 %. The recyclability and magnetic properties of the synthesized material were also investigated, resulting in the material being reused for six cycles without impacting its performance; hence, the method offers rapid determination and high throughput analysis of FBAs. In addition, simulation studies were performed using the adsorption location tool of Material Studio, confirming the interaction sites of sorbent with FBAs. AGREE evaluated the analytical greenness of the method, and the score was found to be 0.51.

Preparation and characterization of poly (vinyl alcohol) (PVA)/basmati rice starch (BRS) blend films cross-linked with aliphatic and aromatic carboxylic acids for food preservation and packaging

Preparation and characterization of poly (vinyl alcohol) (PVA)/basmati rice starch (BRS) blend films cross-linked with aliphatic and aromatic carboxylic acids for food preservation and packaging

Gluten-free snacks based on a flour composite mixture, fortified with the Asafoetida spice (Ferula assa-foetida)

A recipe of snacks based on flour composite mixtures has been developed and scientifically substantiated with the aim of extending an assortment of flour snack products belonging to the category of specialized products. These snacks are intended for consumers adhering to the health nutrition principles and, first of all, for patients with celiac disease. Gluten-free types of flour fortified with the asafoetida spice are used in the recipe. Preliminary studies demonstrated that the formulation with a ratio of 60% rice flour, 20% pea flour and 20% chickpea flour had the highest biological value among six variants of flour mixtures. Using the mass-spectrometry method, a wide spectrum of aromatic substances belonging to different classes of organic compounds was revealed in the composition of the asafoetida spice, including aliphatic alcohols, oxo-compounds, aliphatic and aromatic carboxylic acids, esters, terpenes, phenol derivatives, heterocyclic aromatic compounds (derivatives of furan and thiophene). They have a wide spectrum of action: determine taste and aroma, show the antioxidant properties, and prevent fat rancidification. The investigations showed that addition of 0.2% of asafetida to the flour mixture not only increased the oxidative stability of snacks (induction period increased by 1.5 times), but also reduced the content of lipids. This was achieved due to a decrease in fat absorption during deep-fat frying (approximately by 1.5 times). As a result, the caloric content of the product reduced by 6.8% compared to the control, the oxidation processes were retarded and the shelf-life of snacks was extended. The results of the organoleptic assessment show that gluten-free snacks with the addition of asafetida are significantly superior to the control sample. The total score of snacks with asafetida was 24 points compared to 19 points given to the control sample. They had the most harmonious appearance, color, taste, and odor according to the profilogram of organoleptic indicators among products such as gluten-free snacks based on flour composite mixtures without additives (control), with addition of dietary fibers, with addition of the asafoetida spice and dietary fibers.

Chemical Characterization and Biological Activities Evaluation of Myrtus communis L. Essential Oil Extraction By-Product towards Circular Economy and Sustainability.

Essential oil (EO) extraction is a widespread practice generating huge amounts of solid plant by-products a potential source of bioactive compounds, on the one hand, and a detrimental risk for the environment that needs to be carefully considered on the other hand. The present study aims to valorize Myrtus communis L. leaf by-products obtained following EO extraction using a steam distillation unit through the recovery of phenolic compounds and the evaluation of their biological activities. The total phenols, flavonoids, and proanthocyanidins contents of the ethanolic extract by-product were higher than the control (leaves without extraction of EO). Their amounts increased from 69.30 to 88.06 mg GAE/g for total phenols, from 36.31 to 70.97 mg QE for flavonoids and from 19.74 to 21.49 mg CE/g of extract for proanthocyanidins. The identification of phenolic compounds by high-performance liquid-chromatography equipped with a reversed-phase (RP-HPLC) system revealed that the by-product sample includes more gallic acid, catechin, syringic acid and luteolin 7-O-glucoside but less p-coumaric acid and kaempferol than the control. Moreover, the mid-infrared spectroscopy (MIR) showed the presence of benzene ring characteristic of phenolic compounds at 756 cm-1, esters of aromatic acids and stretching vibrations of polyphenols at 1141-1234 cm-1, C=C stretching present in phenolic acids such as coumaric acid and catechin at 1604 cm-1. The assessment of antioxidant activity revealed that the ABTS+• radical scavenging activity was significantly increased, whereas the DPPH• radical inhibition activity and the ferric reduction antioxidant power were significantly decreased. The results indicated, as well, that Myrtus communis L. leaf by-products maintained a considerable antibacterial activity depending on the tested bacterial strain. Additionally, the anti-α-amylase activity was higher for the Myrtus communis L. leaf by-product extract. Therefore, Myrtus communis L. leaf by-products of EO extraction offer phenolic compounds with significant biological activities, contributing to the sustainable development and the promotion of circular economy by the recovery of valuable inputs from plant by-products.

Synthesis of β‐Trifluoromethylated Ketones by Photocatalyzed Deoxygenative Coupling of Aromatic Acids with α‐CF3‐Substituted Styrenes

Abstractα‐Trifluoromethyl alkenes are versatile CF3‐containing feedstocks. They have been widely used to construct gem‐difluoroalkene scaffolds through β−F elimination. The application of α−CF3 alkenes as trifluoromethylating reagents has been less explored. Herein, we report an efficient route for the synthesis of β‐trifluoromethylated ketones from readily accessed α−CF3 styrenes and aromatic carboxylic acids under photoredox catalysis. The reactions proceed by phosphoranyl radical promoted deoxygenation of aromatic acids, generating acyl radicals for subsequent hydroacylation of α−CF3 styrenes. The valuable trifluoromethyl‐containing compounds could be produced in good yields under mild conditions.

Investigating the stability of aromatic carboxylic acids in hydrated magnesium sulfate under UV irradiation to assist detection of organics on Mars

The Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) instrument onboard the Mars 2020 Perseverance rover detected so far some of the most intense fluorescence signals in association with sulfates analyzing abraded patches of rocks at Jezero crater, Mars. To assess the plausibility of an organic origin of these signals, it is key to understand if organics can survive exposure to ambient Martian UV after exposure by the Perseverance abrasion tool and prior to analysis by SHERLOC. In this work, we investigated the stability of organo-sulfate assemblages under Martian-like UV irradiation and we observed that the spectroscopic features of phthalic and mellitic acid embedded into hydrated magnesium sulfate do not change for UV exposures corresponding to at least 48 Martian sols and, thus, should still be detectable in fluorescence when the SHERLOC analysis takes place, thanks to the photoprotective properties of magnesium sulfate. In addition, different photoproduct bands diagnostic of the parent carboxylic acid molecules could be observed. The photoprotective behavior of hydrated magnesium sulfate corroborates the hypothesis that sulfates might have played a key role in the preservation of organics on Mars, and that the fluorescence signals detected by SHERLOC in association with sulfates could potentially arise from organic compounds.

2,5-Disubstituted structures of 1,3,4-oxadiazole and 1,3,4-thiodiazole for anti-inflammatory potential: DFT approach for the structural aspects

We suggest a [3 + 2] annulation method that combines aromatic acid with acyl hydrazide using p-TSA, resulting in the formation of highly substituted 1,3,4-oxadiazole derivatives. These reactions take place efficiently under specific conditions: microwave irradiation, employing a metal-free environment, utilizing the environmentally friendly solvent PEG-400, and requiring only a short reaction time. Furthermore, employing similar conditions in the presence of Lawesson's reagent yields 1,3,4-thiadiazole derivatives. This method exhibits several notable characteristics, including atom and step economy, utilization of easily accessible raw materials, and simplicity in operation. From the DFT approach, the optimized geometrical parameters are obtained using the B3LYP/6–311++G (d,p) level of theory. There is a decrease in the energy gap and NLO property increases in nature and leads to more biological activity. Notably, there was a reduction in the energy gap, accompanied by an increase in the nonlinear optical property, and suggested the synthesized compounds exhibit heightened biological activity. Furthermore, these compounds demonstrate promising anti-inflammatory and anti-diabetic activity, as evidenced by protein denaturation assay studies.

Design, Synthesis, Bioactivity, and Tentative Exploration of Action Mode for Benzyl Ester-Containing Derivatives.

The active splicing strategy has witnessed improvement in bioactivity and antifungal spectra in pesticide discovery. Herein, a series of simple-structured molecules (Y1-Y53) containing chloro-substituted benzyl esters were designed using the above strategy. The structure-activity relationship (SAR) analysis demonstrated that the fatty acid fragment-structured esters were more effective than those containing an aromatic acid moiety or naphthenic acid part. Compounds Y36 and Y41, which featured a thiazole-4-acid moiety and trifluoromethyl aliphatic acid part, respectively, exhibited excellent in vivo curative activity (89.4%, 100 mg/L Y36) and in vitro fungicidal activity (EC50 = 0.708 mg/L, Y41) against Botrytis cinerea. Determination of antifungal spectra and analysis of scanning electron microscopy (SEM), membrane permeability, cell peroxidation, ergosterol content, oxalic acid pathways, and enzymatic assays were performed separately here. Compound Y41 is cost effective due to its simple structure and shows promise as a disease control candidate. In addition, Y41 might act on a novel target through a new pathway that disrupts the cell membrane integrity by inducing cell peroxidation.

Selective Profiling of Carboxylic Acid in Crude Oil by Halogen Labeling Combined with Liquid Chromatography and High-Resolution Mass Spectrometry.

Carboxylic acids are a small but essential compound class within petroleum chemistry, influencing crude oil behaviors in production and processing and causing environmental impacts. Detailed structural information is fundamental to understanding their influence on petroleum characteristics. However, characterizing acids in crude oil remains challenging due to matrix effects, structural diversity, and low abundance. In this work, we present a new methodology for profiling carboxylic acids by liquid-liquid extraction and selective derivatization using 4-bromo-N-methylbenzylamine (4-BNMA) followed by liquid chromatography and electrospray ionization Orbitrap mass spectrometry (LC-ESI-Orbitrap MS). The fragmentation of 4-BNMA derivatives produces a unique product ion pair, m/z 169/171, enabling the identification of chromatographic fractions containing carboxylic acids. The mass spectra of the corresponding fractions are extracted, and the acids are further computationally isolated based on the isotopic pattern. The method was optimized and validated using acid standards and systematic experimental designs, assuring robustness and sensitivity for nontarget screening purposes. This method detected up to 380 carboxylic acids in six Danish North Sea crude oils, with up to two carboxyl and other heteroatom functionalities (NSO). The results indicated that the most populated species are fatty acids (double bond equivalent (DBE) = 1) and small aromatic acids (DBE = 2-6). The predominance and diversities of compound classes in different samples are consistent with their corresponding bulk properties. Polyfunctional acids (Ox, NxOx, and SxOx) were observed due to exposure to oxidation and biodegradation. Also, the approach's applicability benefits high-resolution MS analysis by simplifying data processing for crude oil and potentially other high-organic and aqueous samples.

Interfacial charge-transfer transitions enable photovoltaic conversion with CO2-fixation products.

We demonstrate that organic-inorganic interfacial charge-transfer transitions enable favourable photovoltaic conversion with CO2-fixation products such as aromatic carboxylic acids, verifying a new possibility of CO2-fixation products in the development of optoelectronic conversion materials.

PuERF008-PuFAD2 module regulates aroma formation via the fatty acid pathway in response to calcium signaling in ‘Nanguo’ pear

Calcium acts as a secondary messenger in plants and is essential for plant growth and development. However, studies on the pathway of aroma synthesis in ‘Nanguo’ pear (Pyrus ussriensis Maxim.) are scarce. In this study, a bioinformatics analysis of transcriptomic data from calcium-treated ‘Nanguo’ pear was performed, which identified two fatty acid desaturases, PuFAD2 and PuFAD3, and eight AP2/ERF transcription factors, all exhibiting the same expression patterns. Transient expression experiments showed overexpression of PuFAD2 and PuFAD3 significantly increased the levels of aromatic substrates linoleic acid, hexanal, linolenic acid, and (E)-2-hexenal, but RNAi (RNA interference) had the opposite expression. Promoter sequences analysis revealed that PuFAD2 and PuFAD3 have ERE (estrogen response element) motifs on their promoters. The strongest activation of PuFAD2 by PuERF008 was verified using a dual-luciferase reporting system. Additionally, yeast one-hybrid and electrophoretic mobility shift assays revealed PuERF008 could active PuFAD2. Transient overexpression and RNAi analyses of PuERF008 showed a strong correlation with the expression of PuFAD2. This study provides insights into the process of aroma biosynthesis in ‘Nanguo’ pear and offers a theoretical basis for elucidating the role of calcium signaling in aroma synthesis.

Crystal structure and stimulus-responsive properties of three functional compounds containing 1-carboxyethyl-4,4′-bipyridine

Herein, three compounds containing the neutral viologen derivative, 1-carboxyethyl-4,4′-bipyridine (CEbpy) have been synthesized, (CEbpy)·(H2TPDC)·2H2O (1) [Co(CEbpy)(TPDC)(H2O)4]·3H2O (2) and [Cd3(CEbpy)2(TPDC)3·7H2O]n (3) (H2TPDC = thiophene-2,5-dicarboxylic acid). Compound 1 is a supramolecular assembly, linked by non-covalent interactions to constitute the donor-acceptor (D-A) system. Compound 2 owns a zero-dimensional (0D) isolated structure in which metal ions are coordinated with CEbpy and fully deprotonated (TPDC)2- ligands. Compound 3 exhibits a three-dimensional (3D) framework of trinuclear metal clusters, where each metal atom forms its own distinct linear one-dimensional (1D) chain along a specific axis. Although the three compounds comprise the same bipyridinium moiety and aromatic acid, their chromic behaviors are different. Compounds 1 and 3 exhibit reversible photochromism, while 2 reveals hydrochromism upon heating. Additionally, photo-modulated fluorescence as well as their potential applications in inkless erasable printing have been studied.

Ligand-enabled ruthenium-catalyzed meta-C−H alkylation of (hetero)aromatic carboxylic acids

Carboxylates are ideal directing groups because they are widely available, readily cleavable and excellent linchpins for diverse follow-up reactions. However, their use in meta-selective C−H functionalizations remains a substantial unmet catalytic challenge. Herein, we report the ruthenium-catalyzed meta-C–H alkylation of aromatic carboxylic acids with various functionalized alkyl halides. A bidentate N-ligand increases the electron density at the metal center of ortho-benzoate ruthenacycles to the extent that single-electron reductions of alkyl halides can take place. The subsequent addition of alkyl radicals is exclusively directed to the position para to the CAr–Ru bond, i.e., meta to the carboxylate group. The resulting catalytic meta-C−H alkylation extends to a wide range of (hetero)aromatic carboxylic acids including benzofused five-membered ring heteroarenes but no pyridine derivatives in combination with secondary/tertiary alkyl halides, including fluorinated derivatives. It also allows site-selective C5−H alkylation of 1-naphthoic acids. The products are shown to be synthetic hubs en route to meta-alkylated aryl ketones, nitriles, amides, esters and other functionalized products.