RESUMO
Naphthenic acids, NAs, are a major contaminant of concern and a focus of much research around remediation of oil sand process affected waters, OSPW. Using activated carbon adsorbents are an attractive option given their low cost of fabrication and implementation. A deeper evaluation of the effect NA structural differences have on uptake affinity is warranted. Here we provide an in-depth exploration of NA adsorption including many more model NA species than have been assessed previously with evaluation of adsorption kinetics and isotherms at the relevant alkaline pH of OSPW using several different carbon adsorbents with pH buffering to simulate the behaviour of real OSPW. Uptake for the NA varied considerably regardless of the activated carbon used, ranging from 350 mg/g to near zero highlighting recalcitrant NAs. The equilibrium data was explored to identify structural features of these species and key physiochemical properties that influence adsorption. We found that certain NA will be resistant to adsorption when hydrophobic adsorbents are used. Adsorption isotherm modelling helped explore interactions occurring at the interface between NA and adsorbent surfaces. We identified the importance of NA hydrophobicity for activated carbon uptake. Evidence is also presented that indicates favorable hydrogen bonding between certain NA and surface site hydroxyl groups, demonstrating the importance of adsorbent surface functionality for NA uptake. This research highlights the challenges associated with removing NAs from OSPW through adsorption and also identifies how adsorbent surface chemistry modification can be used to increase the removal efficiency of recalcitrant NA species.
Assuntos
Ácidos Carboxílicos , Poluentes Químicos da Água , Adsorção , Ácidos Carboxílicos/química , Poluentes Químicos da Água/química , Carvão Vegetal/química , Modelos Químicos , Cinética , Concentração de Íons de HidrogênioRESUMO
The higher prevalence of cancer and the unmet need for antioxidant/anti-inflammatory chemotherapeutic compounds with little side effect are of utmost importance. In addition, the increased likelihood of failure in clinical trials along with increasing development costs may have diminished the range of choices among newer drugs for clinical use. This has dictated the necessity to seek out novel medications by repurposing as it needs less time, effort, and resources to explore new uses of a current or unsuccessful medication. In this study, we examined the biological activity of 10 potential quinoline derivatives. Given the half-maximal inhibitory concentration (IC50 value) in lipopolysaccharide (LPS) induced inflammation of RAW264.7 mouse macrophages, all commercial FQs and selected quinolines (quinoline-4-carboxlic and quinoline-3-carboxylic acids) exerted impressively appreciable anti-inflammation affinities versus classical NSAID indomethacin without related cytotoxicities in inflamed macrophages. Conversely, all 14 tested compounds lacked antioxidative DPPH radical scavenging capacities as compared to ascorbic acid. Gemifloxacin, considerably unlike markets FQs, indomethacin and quinoline derivatives, exerted exceptional and differential antiproliferation propensities in colorectum SW480, HCT116, and CACO2, pancreatic PANC1, prostate PC3, mammary T47D, lung A375, and melanoma A549 adherent monolayers using the sulforhodamine B colorimetric method versus antineoplastic cisplatin. All quinoline derivatives and gemifloxacin alike, but not levofloxacin, ciprofloxacin, or indomethacin, displayed substantially selective viability reduction affinities in prolonged tumor incubations of cervical HELA and mammary MCF7 cells. Specifically kynurenic acid (hydrate), quinoline-2-carboxylic acid, quinoline-4-carboxylic acid, quinoline-3-carboxylic acid, and 1,2-dihydro-2-oxo-4-quinoline carboxylic acids possessed the most remarkable growth inhibition capacities against mammary MCF7 cell line, while quinoline-2-carboxylic acid was the only quinoline derivative with significant cytotoxicity on cervical HELA cancer cells. It is highly speculated that chelation with divalent metals via co-planarity with close proximity of the COOH and the N atom could have the potential molecular mechanism for optimally promising repurposed pharmacologies. Conclusively, this study revealed the considerably profound repurposed duality of cytotoxicity and anti-inflammation pharmacologies of quinoline derivatives. Activity-guided structural modifications of the present nuclear scaffolds can be inherently linked to the betterment and enhancement of their repurposed pharmacologies.
Assuntos
Anti-Inflamatórios , Antineoplásicos , Antioxidantes , Ácidos Carboxílicos , Proliferação de Células , Quinolinas , Quinolinas/química , Quinolinas/farmacologia , Humanos , Camundongos , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Células RAW 264.7 , Antineoplásicos/farmacologia , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Lipopolissacarídeos/farmacologia , Linhagem Celular Tumoral , Relação Estrutura-AtividadeRESUMO
Docetaxel (DTX) has become widely accepted as a first-line treatment for metastatic breast cancer; however, the frequent development of resistance provides challenges in treating the disease.C60 fullerene introduces a unique molecular form of carbon, exhibiting attractive chemical and physical properties. Our study aimed to develop dicarboxylic acid-derivatized C60 fullerenes as a novel DTX delivery carrier. This study investigated the potential of water-soluble fullerenes to deliver the anti-cancer drug DTX through a hydrophilic linker. The synthesis was carried out using the Prato reaction. The spectroscopic analysis confirmed the successful conjugation of DTX molecules over fullerenes. The particle size of nanoconjugate was reported to be 122.13 ± 1.63 nm with a conjugation efficiency of 76.7 ± 0.14%. The designed conjugate offers pH-dependent release with significantly less plasma pH, ensuring maximum release at the target site. In-vitro cell viability studies demonstrated the enhanced cytotoxic nature of the developed nanoconjugate compared to DTX. These synthesized nanoscaffolds were highly compatible with erythrocytes, indicating the safer intravenous route administration. Pharmacokinetic studies confirmed the higher bioavailability (~ 6 times) and decreased drug clearance from the system vis-à-vis plain drug. The histological studies reveal that nanoconjugate-treated tumour cells exhibit similar morphology to normal cells. Therefore, it was concluded that this developed formulation would be a valuable option for clinical use.
Assuntos
Antineoplásicos , Neoplasias da Mama , Ácidos Carboxílicos , Sobrevivência Celular , Docetaxel , Sistemas de Liberação de Medicamentos , Fulerenos , Fulerenos/química , Fulerenos/administração & dosagem , Docetaxel/administração & dosagem , Docetaxel/farmacocinética , Docetaxel/farmacologia , Docetaxel/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Humanos , Feminino , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Antineoplásicos/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Ácidos Carboxílicos/química , Tamanho da Partícula , Portadores de Fármacos/química , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Nanoconjugados/química , Ratos , Células MCF-7 , Disponibilidade BiológicaRESUMO
DNA N6-methyladenine (6mA) demethylase ALKBH1 plays an important role in various cellular processes. Dysregulation of ALKBH1 is associated with the development of some cancer types, including gastric cancer, implicating a potential therapeutic target. However, there is still a lack of potent ALKBH1 inhibitors. Herein, we report the discovery of a highly potent ALKBH1 inhibitor, 1H-pyrazole-4-carboxylic acid derivative 29. The structure-activity relationship of this series of compounds was also discussed. Because of the poor cell membrane permeability of 29, we prepared a prodrug of 29 (29E), which showed excellent cellular activities. In gastric cancer cell lines HGC27 and AGS, 29E treatment significantly increased the abundance of 6mA, inhibited cell viability, and upregulated the AMP-activated protein kinase (AMPK) signaling pathway. In addition, the hydrolysis product 29 showed high exposure in mice after administration of 29E. Collectively, this research provides a new potent ALKBH1 inhibitor, which could serve as a lead compound for subsequent drug development.
Assuntos
Homólogo AlkB 1 da Histona H2a Dioxigenase , Antineoplásicos , Inibidores Enzimáticos , Pirazóis , Neoplasias Gástricas , Humanos , Relação Estrutura-Atividade , Homólogo AlkB 1 da Histona H2a Dioxigenase/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Animais , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/síntese química , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Linhagem Celular Tumoral , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Ácidos Carboxílicos/síntese química , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Simulação de Acoplamento Molecular , Camundongos Nus , Camundongos Endogâmicos BALB CRESUMO
A library of C-3 functionalized flavones was successfully provided via palladium-catalyzed amino- and aryloxycarbonylation reactions of 3-iodoflavone (1), under mild conditions. This methodology showed good functional group tolerance using a variety of amines and phenols, under an atmospheric pressure of carbon monoxide as a carbonyl source. While the flavone-3-carboxamides (2a-t) were produced in 22-79%, the flavone-3-carboxylates (4a'-l') were obtained in excellent yields (up to 88%), under identical reaction conditions, just by switching N-nucleophiles to O-nucleophiles. The convenient availability of the involved starting materials confers simplicity to this approach to design new C-3-substituted flavones of biological relevance. The solid-state structures of flavone-3-carboxamide (2r) and flavone-3-ester (4f') were further studied by single-crystal XRD analysis.
Assuntos
Flavonas , Paládio , Paládio/química , Catálise , Flavonas/química , Ácidos Carboxílicos/química , Estrutura Molecular , Amidas/química , Aminas/químicaRESUMO
Diesters of geminal diols (R-CH(O-CO-R')2, RR'C(OCORâ³)2, etc. with R = H, aryl or alkyl) are termed acylals according to IUPAC recommendations (Rule P-65.6.3.6 Acylals) if the acids involved are carboxylic acids. Similar condensation products can be obtained from various other acidic structures as well, but these related "non-classical acylals", as one might call them, differ in various aspects from classical acylals and will not be discussed in this article. Carboxylic acid diesters of geminal diols play a prominent role in organic chemistry, not only in their application as protective groups for aldehydes and ketones but also as precursors in the total synthesis of natural compounds and in a variety of organic reactions. What is more, acylals are useful as a key structural motif in clinically validated prodrug approaches. In this review, we summarise the syntheses and chemical properties of such classical acylals and show what potentially under-explored possibilities exist in the field of drug design, especially prodrugs, and classify this functional group in medicinal chemistry.
Assuntos
Química Farmacêutica , Química Farmacêutica/métodos , Ácidos Carboxílicos/química , Ácidos Carboxílicos/síntese química , Pró-Fármacos/química , Pró-Fármacos/síntese química , Estrutura Molecular , Desenho de Fármacos , Aldeídos/químicaRESUMO
Transketolase (TKL; EC 2.2.1.1) is a highly promising potential target for herbicidal applications. To identify novel TKL inhibitors, we designed and synthesized a series of 3-oxopropionamide-1-methylpyrazole carboxylate analogues and assessed their herbicidal activities. Ethyl 3-((1-((2,4-dichlorophenyl)amino)-1-oxopropan-2-yl)oxy)-1-methyl-1H-pyrazole-5-carboxylate (D15) and ethyl 1-methyl-3-((1-oxo-1-((thiophen-2-ylmethyl)amino)propan-2-yl)oxy)-1H-pyrazole-5-carboxylate (D20) exhibited superior growth inhibition activities against both the root and stem of Amaranthus retroflexus (A. retroflexus) compared to nicosulfuron and mesotrione. Additionally, D15 achieved an inhibition rate of more than 90% against the roots and stems of Digitaria sanguinalis (D. sanguinalis), outperforming the four control agents at a concentration of 200 mg/L using the small cup method. In the pre-emergence herbicidal activity test, D15 effectively inhibited D. sanguinalis by more than 90% at 150 g ai/ha, surpassing the efficacy of the control, mesotrione. Conversely, in the postemergence herbicidal activity test, D20 exhibited efficient inhibition of A. retroflexus by more than 90% at 150 g ai/ha, outperforming the control agents nicosulfuron, mesotrione, and metamifop. The results of the TKL enzyme activity test showed that the IC50 values of compounds D15 and D20 were 0.384 and 0.655 mg/L, respectively, which were close to those of the control agents. Furthermore, molecular docking and molecular dynamics simulation studies revealed that D15 and D20 interacted favorably with the TKL of Setaria viridis. Such findings highlight the promising potential of D15 and D20 as lead TKL inhibitors for the optimization of new herbicides.
Assuntos
Amaranthus , Herbicidas , Simulação de Acoplamento Molecular , Pirazóis , Herbicidas/farmacologia , Herbicidas/química , Herbicidas/síntese química , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Amaranthus/efeitos dos fármacos , Amaranthus/crescimento & desenvolvimento , Relação Estrutura-Atividade , Digitaria/efeitos dos fármacos , Digitaria/enzimologia , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Raízes de Plantas/química , Raízes de Plantas/crescimento & desenvolvimento , Estrutura Molecular , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/crescimento & desenvolvimentoRESUMO
The escalating levels of hazardous pharmaceutical contaminants, specifically nonsteroidal anti-inflammatory drugs (NSAIDs), in groundwater reservoir surfaces and surface waterway systems have prompted substantial scientific interest regarding their potential deleterious effects on both aquatic ecosystems and human health. Extraction of those pollutants from wastewater is quite challenging. Hence, the development of economic, sustainable, and scalable techniques for capturing and removing those pollutants is crucial to ensure water safety. Herein, we demonstrate a physicochemically stable, reusable, porous Hf(IV)-based cationic metal-organic framework (MOF), namely, 1'@MeCl for the aqueous phase adsorption-based removal of NSAIDs (diclofenac, naproxen, ibuprofen) from the wastewater environment. The highly positively charged surface of the 1'@MeCl MOF enables it to selectively extract more than 99% of diclofenac, naproxen, and ibuprofen contaminants within less than 30 s. With fast adsorption kinetics, very high adsorption capacities (Qe) were achieved at neutral pH for diclofenac (482.9 mg/g), naproxen (295.9 mg/g), and ibuprofen (219.5 mg/g). Moreover, the influence of changes in pH and coexisting anions on the adsorption property of the 1'@MeCl MOF was studied. Furthermore, the adsorption efficiency of 1'@MeCl in different real water environments was ensured by performing diclofenac, naproxen, and ibuprofen adsorption from tap, river, and lake water. Moreover, a 1'@MeCl-anchored cellulose acetate-chitosan membrane was developed successfully to demonstrate the membrane-based extraction of diclofenac, naproxen, and ibuprofen from contaminated water. Furthermore, a molecular-level mechanistic study was performed through experimental and computational study to propose the plausible adsorption mechanisms for diclofenac, naproxen, and ibuprofen over the surface of 1'@MeCl.
Assuntos
Anti-Inflamatórios não Esteroides , Estruturas Metalorgânicas , Poluentes Químicos da Água , Estruturas Metalorgânicas/química , Adsorção , Poluentes Químicos da Água/isolamento & purificação , Poluentes Químicos da Água/química , Concentração de Íons de Hidrogênio , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Diclofenaco/química , Diclofenaco/isolamento & purificação , Naproxeno/química , Naproxeno/isolamento & purificação , Ibuprofeno/química , Ibuprofeno/isolamento & purificação , Propriedades de Superfície , Ácidos Carboxílicos/química , Ácidos Carboxílicos/isolamento & purificação , Estrutura Molecular , Teoria da Densidade Funcional , Cátions/químicaRESUMO
Despite the remarkable developments of the Ugi reaction and its variants, the use of ammonia in the Ugi reaction has long been recognized as impractical and unsuccessful. Indeed, the ammonia-Ugi reaction often requires harsh reaction conditions, such as heating and microwave irradiation, and competes with the Passerini reaction, thereby resulting in low yields. This study describes a robust and practical ammonia-Ugi reaction protocol. Using originally prepared ammonium carboxylates in trifluoroethanol, the ammonia-Ugi reaction proceeded at room temperature in high yields and showed a broad substrate scope, thus synthesizing a variety of α,α-disubstituted amino acid derivatives, including unnatural dipeptides. The reaction required no condensing agents and proceeded without racemization of the chiral stereocenter of α-amino acids. Furthermore, using this protocol, we quickly synthesized a novel dipeptide, D-Leu-Aic-NH-CH2Ph(p-F), which exhibited a potent inhibitory activity against α-chymotrypsin with a Ki value of 0.091 µM.
Assuntos
Aminoácidos , Amônia , Dipeptídeos , Dipeptídeos/química , Dipeptídeos/síntese química , Amônia/química , Aminoácidos/química , Aminoácidos/síntese química , Ácidos Carboxílicos/química , Ácidos Carboxílicos/síntese química , Compostos de Amônio/química , Quimotripsina/antagonistas & inibidores , Quimotripsina/química , Estrutura Molecular , Técnicas de Química SintéticaRESUMO
α-Alkoxy bridgehead radicals enable intermolecular construction of sterically congested C-C bonds due to their sterically accessible nature. We implemented these radical species into total syntheses of various densely oxygenated natural products and demonstrated their exceptional versatility. Herein, we employed different precursors to generate the same α-alkoxy bridgehead radical and compared the efficacy of the precursors for coupling reactions. Specifically, the bridgehead radical of the trioxaadamantane structure was formed from α-alkoxy carboxylic acid, selenide/telluride, and acyl selenide/acyl telluride, and reacted with 4-((tert-butyldimethylsilyl)oxy)cyclopent-2-en-1-one and 5-oxo-1-cyclopentene-1-carbonitrile. The efficiency of the bridgehead radical formation and subsequent coupling reaction significantly depended on the structures of the precursors and acceptors as well as the reaction conditions. Our findings provide new insights for selecting the appropriate substrates of key coupling reactions in the total synthesis of complex natural products.
Assuntos
Ácidos Carboxílicos , Telúrio , Ácidos Carboxílicos/química , Ácidos Carboxílicos/síntese química , Telúrio/química , Estrutura Molecular , Radicais Livres/química , Compostos de Selênio/química , Compostos de Selênio/síntese química , Compostos Organosselênicos/química , Compostos Organosselênicos/síntese química , Produtos Biológicos/química , Produtos Biológicos/síntese químicaRESUMO
Inositol hexakisphosphate kinases (IP6Ks) have been studied for their role in glucose homeostasis, metabolic disease, fatty liver disease, chronic kidney disease, neurological development, and psychiatric disease. IP6Ks phosphorylate inositol hexakisphosphate (IP6) to the pyrophosphate, 5-diphosphoinositol-1,2,3,4,6-pentakisphosphate (5-IP7). Most of the currently known potent IP6K inhibitors contain a critical carboxylic acid which limits blood-brain barrier (BBB) penetration. In this work, the synthesis and testing of a variety of carboxylic acid isosteres resulted in several new compounds with improved BBB penetration. The most promising compound has an IP6K1 IC50 of 16 nM with an improved brain/plasma ratio and a favorable pharmacokinetic profile. This series of brain penetrant compounds may be used to investigate the role of IP6Ks in CNS disorders.
Assuntos
Barreira Hematoencefálica , Fosfotransferases (Aceptor do Grupo Fosfato) , Barreira Hematoencefálica/metabolismo , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Fosfotransferases (Aceptor do Grupo Fosfato)/antagonistas & inibidores , Animais , Humanos , Relação Estrutura-Atividade , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Camundongos , Masculino , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Ácidos Carboxílicos/síntese química , RatosRESUMO
Refractory naphthenic acids (NAs) are among the primary toxic compounds in oil sands process water (OSPW), a matrix with a complex chemical composition that poses challenges to its remediation. This study evaluated the effectiveness of calcium peroxide (CaO2) combined with solar radiation (solar/CaO2) as an advanced water treatment process for degrading model NAs (1,2,3,4-tetrahydronaphthalene-2-carboxylic acid, pentanoic acid, and diphenylacetic acid) in synthetic water (STW) and provide preliminary insights in treating real OSPW. Solar light and CaO2 acted synergistically to degrade target NAs in STW (>67 of synergistic factor) following a pseudo-first-order kinetic (R2 ≥ 0.95), with an optimal CaO2 dosage of 0.1 g L-1. Inorganic ions and dissolved organic matter were found to hinder the degradation of NAs by solar/CaO2 treatment; however, the complete degradation of NAs was reached in 6.7 h of treatment. The main degradation mechanism involved the generation of hydroxyl radicals (â¢OH), which contributed â¼90% to the apparent degradation rate constant (K), followed by H2O2 (4-5%) and 1O2 (0-5%). The tentative transformation pathways of three NAs were proposed, confirming an open-ring reaction and resulting in short-chain fatty acid ions as final products. Furthermore, a reduction in acute microbial toxicity and genotoxic effect was observed in the treated samples, suggesting that solar/CaO2 treatment exhibits high environmental compatibility. Furthermore, the solar/CaO2 system was successfully applied as a preliminary step for real-world applications to remove natural NAs, fluorophore organic compounds, and inorganic components from OSPW, demonstrating the potential use of this technology in the advanced treatment of oil-tailing-derived NAs.
Assuntos
Peróxidos , Poluentes Químicos da Água , Peróxidos/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade , Ácidos Carboxílicos/química , Campos de Petróleo e Gás , Purificação da Água/métodos , Naftalenos/química , Luz SolarRESUMO
In this investigation, we detail the synthesis of silver nanoparticles (AgNPs) via a precise chemical vacuum deposition (CVD) methodology, aimed at augmenting the analytical performance of laser desorption/ionization mass spectrometry (LDI-MS) for the detection of low-molecular-weight analytes. Employing a precursor supply rate of 0.0014 mg/s facilitated the formation of uniformly dispersed AgNPs, characterized by SEM and AFM to have an average diameter of 33.5 ± 1.5 nm and a surface roughness (Ra) of 11.8 nm, indicative of their homogeneous coverage and spherical morphology. XPS and SEM-EDX analyses confirmed the metallic silver composition of the nanoparticles with Ag peak splitting, reflecting the successful synthesis of metallic Ag. Comparative analytical evaluation with traditional MALDI matrices revealed that AgNPs significantly reduce signal suppression, thereby enhancing the sensitivity and specificity of LDI-MS for low-molecular-weight compounds such as triglycerides, saccharides, amino acids, and carboxylic acids. Notably, the application of AgNPs demonstrated a superior linear response for triglyceride signals with regression coefficients surpassing 0.99, markedly outperforming conventional matrices. The study further extends into quantitative analysis through nanoparticle-based laser desorption/ionization (NALDI), where AgNPs exhibited enhanced ionization efficiency, characterized by substantially lower limits of detection (LOD) and quantification (LOQ) for tested standards. Particular attention was paid to lipids with a detailed examination of their fragmentation pathways. These results highlight the significant potential of AgNPs synthesized via CVD to transform the analytical detection and quantification of low-molecular-weight compounds using NALDI. This approach offers a promising avenue for expanding the scope of analytical applications in mass spectrometry and introducing innovative methodologies for enhanced precision and sensitivity.
Assuntos
Nanopartículas Metálicas , Prata , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Prata/química , Nanopartículas Metálicas/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Aminoácidos/análise , Aminoácidos/química , Peso Molecular , Triglicerídeos/análise , Triglicerídeos/química , Ácidos Carboxílicos/química , Ácidos Carboxílicos/análise , Limite de DetecçãoRESUMO
Several conjugates between folic acid and a series of kinetically stable lanthanide complexes have been synthesized, using amide coupling and azide-alkyne cycloaddition methodologies to link the metal-binding domain to folate through a variety of spacer groups. While all these complexes exhibit affinity for the folate receptor, it is clear that the point of attachment to folate is essential, with linkage through the γ-carboxylic acid giving rise to significantly enhanced receptor affinity. All the conjugates studied show affinities consistent with displacing biological circulating folate derivatives, 5-methyltetrahydrofolate, from folate receptors. All the complexes exhibit luminescence with a short-lived component arising from ligand fluorescence overlaid on a much longer lived terbium-centered component. These can be separated using time-gating methods. From the results obtained, the most promising approach to achieve sensitized luminescence in these systems requires incorporating a sensitizing chromophore close to the lanthanide.
Assuntos
Ácido Fólico , Térbio , Humanos , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Receptores de Folato com Âncoras de GPI/metabolismo , Ácido Fólico/química , Ácido Fólico/metabolismo , Substâncias Luminescentes/química , Substâncias Luminescentes/síntese química , Térbio/química , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/químicaRESUMO
The COVID-19 pandemic highlighted the need to create and study new substances with improved lipophilicity and antimicrobial properties, such as ionic liquids (ILs), with easily tunable physicochemical properties. Most ILs possess strong antibacterial effects, but ILs containing the imidazolium cation are even more effective than the positive control. Thus, in this study, three ionic liquids with 1-butyl-3-methylimidazolium cation and various carboxylate anions (phenylacetate, benzoate, and 4-methoxyphenylacetate) were synthesized and fully characterized. The interactions between the cations and anions were discussed based on the experimental density, viscosity, and electrical conductivity. From the measured electrical conductivity and viscosity, the Walden plot is constructed and ionicity of the studied ILs is discussed. The similarities and dissimilarities among the studied ILs and their physicochemical properties are analyzed by applying the hierarchical cluster analysis and in silico calculated properties. The antimicrobial activity of the studied ionic liquids is tested on two bacterial (E. coli and P. aeruginosa) and three fungi (P. verrucosum, A. flavus, and A. parasiticus) strains, finding that they showed improved antimicrobial activity compared to the individual components.
Assuntos
Anti-Infecciosos , Ácidos Carboxílicos , Líquidos Iônicos , Líquidos Iônicos/química , Líquidos Iônicos/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Viscosidade , Imidazóis/química , Imidazóis/farmacologia , Imidazóis/síntese química , Condutividade Elétrica , Testes de Sensibilidade Microbiana , Simulação por Computador , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , COVID-19/virologiaRESUMO
Hollongdione is the first recorded example of the occurrence of a dammarane hexanor-triterpene in nature possessing antiviral and cytotoxic activity. Its simple one-stage transformation into compounds with terminal alkyne and vinyl chloride fragments via the interaction with phosphorus halides is reported. The copper(I)-catalyzed Mannich reaction of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20(21)-in 3 led to a series of aminomethylated products, while 17-carboxylic acid was obtained by ozone oxidation of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20-chloro-20(21)-en 4; the following direct amidation of the latter has been developed. The structures of all new molecules were established by spectroscopic studies that included 2D NMR correlation methods; the molecular structures of compounds 2-5 were determined by X-ray analysis.
Assuntos
Alcinos , Ácidos Carboxílicos , Bases de Mannich , Cloreto de Vinil , Alcinos/química , Ácidos Carboxílicos/química , Bases de Mannich/química , Cloreto de Vinil/química , Triterpenos/química , Estrutura Molecular , Catálise , Espectroscopia de Ressonância MagnéticaRESUMO
The success of a classic inorganic coordination compound, Cisplatin, cis-[Pt(NH3)2Cl2], as the first anticancer metallodrug started a field of research dedicated to discovering coordination compounds with antitumor activity, encompassing various metals. Among these, copper complexes have emerged as interesting candidates to develop drugs to treat cancer. In this work, mixed ligand complexes of Cu(II) with diimines (phenanthroline or 4-methylphenanthroline) and 3-(4-hydroxyphenyl)propanoate, phenylcarboxylate or phenylacetate were synthesized. They were characterized in the solid state, including a new crystal structure of [Cu2(3-(4-hydroxyphenyl)propanoate)3(phenanthroline)2]Cl·H2O. The obtained complexes presented a variety of stoichiometries. In solution, complexes were partially dissociated in the corresponding Cu-diimine complex. The complexes bound to the DNA by partial intercalation and groove binding, as assessed by Circular Dichroism, relative viscosity change and UV-Vis titration. The cytotoxicity of the complexes was determined in vitro on MDA-MB-231, MCF-7 (human metastatic breast adenocarcinomas, the first triple negative), MCF-10A (breast nontumoral), A549 (human lung epithelial carcinoma), and MRC-5 (human nontumoral lung epithelial cells), finding an activity higher than that of Cisplatin, although with less selectivity.
Assuntos
Antineoplásicos , Complexos de Coordenação , Cobre , Fenantrolinas , Humanos , Cobre/química , Fenantrolinas/química , Fenantrolinas/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Linhagem Celular Tumoral , Ligantes , DNA/química , DNA/metabolismo , Células A549 , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Células MCF-7RESUMO
Within the new circular economy paradigm, this work evaluates the performance of tailored mixed metal oxides (MMO) anodes, based on ruthenium and antimony, for their application into an electrochemically-assisted organic refinery process. This process is designed to transform pollutants into value-added products with minimal mineralization. Oxidation of synthetic wastes consisting of phenol solutions was used to validate the electrochemical conversion of phenolic wastes into carboxylates, which are then considered as bricks to be used for electrosynthesis or to produce fuels. The MMO anodes were manufactured using two synthesis routes (Pechini method and ionic liquid method), each followed by one of three different heating treatments: furnace, microwave, and CO2 laser. The selection of the optimal electrode for the organic electrorefinery was based on a combination of physical and electrochemical properties, degradation performance of phenol to carboxylates, and long-term stability, looking for a truly sustainable solution. Results indicate that anodes synthesized by the ionic liquid (IL) method, regardless of the heating treatment, demonstrated superior performance, with larger active areas (with furnace 82 mC cm-2, microwave 97 mC cm-2, and laser 127 mC cm-2) and higher phenol degradation rates, resulting in a greater generation of carboxylates during electrolysis, yielding primarily oxalate and achieving up to 40% conversion with furnace heating. However, laser-treated anodes exhibited greater stability than furnace-made ones, attributed to the formation of an insulating TiO2 layer. Although the electrode with the longest service life did not show the best catalytic properties for minimizing mineralization, the observed variations in coatings with identical chemical compositions highlight the importance of this research. This study positions itself at the forefront of developing more efficient and sustainable electrochemical technologies for organic waste treatment.
Assuntos
Ácidos Carboxílicos , Eletrodos , Óxidos , Óxidos/química , Ácidos Carboxílicos/química , Oxirredução , Rutênio/química , Eletrólise , Antimônio/química , Técnicas Eletroquímicas/métodos , Líquidos Iônicos/química , CatáliseRESUMO
Nano zero-valent iron (NZVI) has been shown to effectively enhance the chain elongation (CE) process, addressing the issue of limited yield of medium-chain carboxylic acids (MCCA) from organic wastewater. However, the specific impact of NZVI on the metabolism of CE bacteria (CEB) is not well understood. In this study, it was aimed to investigate the mechanism by which an optimal concentration of NZVI influences CE metabolism, particularly in relation to ethanol oxidation, electron transfer, and MCCA synthesis. This was achieved through single-factor influence experiments and metagenomic analysis. The results showed that the addition of 1 g/gVSS NZVI achieved the highest MCCA yield (n-caproic acid + n-octanoic acid) at 2.02 g COD/L, which was 4.9 times higher than the control. This improvement in MCCA production induced by NZVI was attributed to several factors. Firstly, NZVI facilitated the oxidation of acetaldehyde, leading to its reduced accumulation in the system (from 18.4 % to 5.8 %), due to the optimized chemical environment created by NZVI corrosion, including near-neutral pH and a more reductive oxidation-reduction potential (ORP). Additionally, the inherent conductivity property of NZVI and the additional Fe ions released during corrosion improved the electron transfer efficiency between CEB. Lastly, both the composition of microbial communities and the abundance of unique enzyme genes confirmed the selective stimulation of NZVI on the reverse ß-oxidation (RBO) pathway. These findings provide valuable insights into the role of NZVI in CEB metabolism and its potential application for enhancing MCCA production in CE bioreactors.
Assuntos
Acetaldeído , Ácidos Carboxílicos , Ferro , Oxirredução , Ferro/química , Ferro/metabolismo , Ácidos Carboxílicos/química , Ácidos Carboxílicos/metabolismo , Acetaldeído/química , Transporte de ElétronsRESUMO
On-DNA carboxylic acids are important synthetic intermediates in the synthesis of DNA-encoded library (DEL) structures. Herein, we report an oxoammonium salt-mediated, room temperature, solution-phase oxidation of DNA-linked primary alcohols into carboxylic acids. This method exhibits a wide substrate scope, encompassing aliphatic, benzylic, and heterobenzylic alcohols, and is compatible with DEL encoding strategies. This advancement facilitates a DEL strategy to utilize unprotected alcohols as inert, masked carboxylic acids and enables access to noncommercial bifunctional carboxyl intermediates to enhance the accessible chemical diversity within DELs.