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1.
Int J Mol Sci ; 25(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731923

RESUMO

Ionic liquids (ILs) have gained considerable attention due to their versatile and designable properties. ILs show great potential as antibacterial agents, but understanding the mechanism of attack on bacterial cells is essential to ensure the optimal design of IL-based biocides. The final aim is to achieve maximum efficacy while minimising toxicity and preventing resistance development in target organisms. In this study, we examined a dose-response analysis of ILs' antimicrobial activity against two pathogenic bacteria with different Gram types in terms of molecular responses on a cellular level using Fourier-transform infrared (FTIR) spectroscopy. In total, 18 ILs with different antimicrobial active motifs were evaluated on the Gram-negative enteropathogenic Escherichia coli (EPEC) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). The results showed that most ILs impact bacterial proteins with increasing concentration but have a minimal effect on cellular membranes. Dose-response spectral analysis revealed a distinct ante-mortem response against certain ILs for MRSA but not for EPEC. We found that at sub-lethal concentrations, MRSA actively changed their membrane composition to counteract the damaging effect induced by the ILs. This suggests a new adaptive mechanism of Gram-positive bacteria against ILs and demonstrates the need for a better understanding before using such substances as novel antimicrobials.


Assuntos
Escherichia coli Enteropatogênica , Líquidos Iônicos , Staphylococcus aureus Resistente à Meticilina , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Líquidos Iônicos/química , Líquidos Iônicos/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Escherichia coli Enteropatogênica/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana
2.
J Am Chem Soc ; 146(19): 13588-13597, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38695646

RESUMO

Membrane channel proteins (MCPs) play key roles in matter transport through cell membranes and act as major targets for vaccines and drugs. For emerging ionic liquid (IL) drugs, a rational understanding of how ILs affect the structure and transport function of MCP is crucial to their design. In this work, GPU-accelerated microsecond-long molecular dynamics simulations were employed to investigate the modulating mechanism of ILs on MCP. Interestingly, ILs prefer to insert into the lipid bilayer and channel of aquaporin-2 (AQP2) but adsorb on the entrance of voltage-gated sodium channels (Nav). Molecular trajectory and free energy analysis reflect that ILs have a minimal impact on the structure of MCPs but significantly influence MCP functions. It demonstrates that ILs can decrease the overall energy barrier for water through AQP2 by 1.88 kcal/mol, whereas that for Na+ through Nav is increased by 1.70 kcal/mol. Consequently, the permeation rates of water and Na+ can be enhanced and reduced by at least 1 order of magnitude, respectively. Furthermore, an abnormal IL gating mechanism was proposed by combining the hydrophobic nature of MCP and confined water/ion coordination effects. More importantly, we performed experiments to confirm the influence of ILs on AQP2 in human cells and found that treatment with ILs significantly accelerated the changes in cell volume in response to altered external osmotic pressure. Overall, these quantitative results will not only deepen the understanding of IL-cell interactions but may also shed light on the rational design of drugs and disease diagnosis.


Assuntos
Líquidos Iônicos , Simulação de Dinâmica Molecular , Líquidos Iônicos/química , Líquidos Iônicos/farmacologia , Humanos , Aquaporina 2/metabolismo , Aquaporina 2/química , Água/química , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Sódio/química , Sódio/metabolismo
3.
J Am Chem Soc ; 146(19): 13247-13257, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38701006

RESUMO

Horseradish peroxidase (HRP) is an enzyme that oxidizes pollutants from wastewater. A previous report indicated that peroxidases can have an enhancement in initial enzymatic activity in an aqueous solution of 0.26 M 1-ethyl-3-methylimidazolium ethyl sulfate ([EMIm][EtSO4]) at neutral pH. However, the atomistic details remain elusive. In the enzymatic landscape of HRP, compound II (Cpd II) plays a key role and involves a histidine (H42) residue. Cpd II exists as oxoferryl (2a) or hydroxoferryl (2b(FeIV)) forms, where 2a is the predominantly observed form in experimental studies. Intriguingly, the ferric 2b(FeIII) form seen in synthetic complexes has not been observed in HRP. Here, we have investigated the structure and dynamics of HRP in pure water and aqueous [EMIm][EtSO4] (0.26 M), as well as the reaction mechanism of 2a to 2b conversion using polarizable molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations. When HRP is solvated in aq [EMIm][EtSO4], the catalytic water displaces, and H42 directly orients over the ferryl moiety, allowing a direct proton transfer (PT) with a significant energy barrier reduction. Conversely, in neat water, the reaction of 2a to 2b follows the previously reported mechanism. We further investigated the deprotonated form of H42. Analysis of the electric fields at the active site indicates that the aq [EMIm][EtSO4] medium facilitates the reaction by providing a more favorable environment compared with the system solvated in neat water. Overall, the atomic level supports the previous experimental observations and underscores the importance of favorable electric fields in the active site to promote catalysis.


Assuntos
Peroxidase do Rábano Silvestre , Líquidos Iônicos , Simulação de Dinâmica Molecular , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , Líquidos Iônicos/química , Imidazóis/química , Teoria Quântica , Soluções , Água/química
4.
J Phys Chem B ; 128(18): 4456-4463, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38691101

RESUMO

Ionic liquids (ILs) have shown promising potential in membrane protein extraction; however, the underlying mechanism remains unclear. Herein, we employed GPU-accelerated molecular dynamics (MD) simulations to investigate the dynamic insertion process of ILs into cell membranes containing membrane proteins. Our findings reveal that ILs spontaneously insert into the membrane, and the presence of membrane proteins significantly decelerates the rate of IL insertion into the membrane. Specifically, the relationship between the insertion rate and inserting free energy exhibits non-monotonic changes, which can be attributed to interfacial effects. The protein-water interface acts as trap for free ions and ionic clusters, while free ions preferentially insert into the membrane from the protein-lipid interface, which limits the insertion rate due to its narrowness. Thus, the insertion rate is governed by a combination of the free energy and interfacial effects. These findings provide valuable insights into the interfacial effects of protein-lipid bilayers and have implications for various biochemical-related applications.


Assuntos
Membrana Celular , Imidazóis , Líquidos Iônicos , Bicamadas Lipídicas , Simulação de Dinâmica Molecular , Líquidos Iônicos/química , Imidazóis/química , Membrana Celular/química , Membrana Celular/metabolismo , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Termodinâmica , Água/química
5.
Int J Biol Macromol ; 267(Pt 1): 131540, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38608992

RESUMO

Lignin-containing nanocellulose (LNC) is a compelling alternative to traditional nanocellulose (NC), it offers enhanced yields and a reduction in the demand for toxic chemicals. This research involves the isolation of LNC from date palm waste using a green hydrolysis process and its subsequent characterization. The potential of using ionic liquids (ILs) as green solvents to isolate LNC has not yet been explored. Our findings suggest that 1-ethyl-3-methylimidazolium chloride ([Emim]Cl) can hydrolyze partially delignified and unbleached lignocellulose, achieving LNC synthesis. The obtained LNC showed a higher yield than its NC counterpart and exhibited rod-shaped fibers with nanoscale diameters and micrometer lengths, indicating a high aspect ratio. Dynamic Light Scattering (DLS) results indicate average particle sizes of 143.20 nm for NC and 282.30 nm for LNC, with a narrow particle size distribution conforming their monodisperse behavior. Thermogravimetric analysis and differential scanning calorimetry revealed high thermal stability (initial degradation temperature = 222.50 °C and glass transition temperature = 84.45°C) of LNC. Moreover, the obtained LNC fibers were crystalline (crystallinity index = 52.76 %). Their activation energy (124.95 kJ/mol) was determined using the Coats-Redfern method by employing eight solid-state diffusion models. Overall, this study motivates the use of ILs as green solvents to produce lignocellulose derivatives that are suitable for various applications.


Assuntos
Celulose , Química Verde , Lignina , Phoeniceae , Solventes , Lignina/química , Solventes/química , Celulose/química , Química Verde/métodos , Phoeniceae/química , Hidrólise , Líquidos Iônicos/química , Termogravimetria , Resíduos , Temperatura , Tamanho da Partícula
6.
Mar Pollut Bull ; 202: 116311, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574502

RESUMO

The synthesis of new surfactants helps to mitigate the environmental and financial effects of oil spills by providing efficient cleanup options. Herein, this study provides the development of a binary mixture of Span 80 and Choline myristate [Cho][Mys], a surface-active ionic liquid (SAIL) as green dispersant for oil spill remediation. The synergistic interaction at a 60:40 (w/w) ratio significantly lowered the critical micelle concentration (cmc) to 0.029 mM. Dispersion efficiency tests with Arab crude oil showed optimal performance at a 60:40 ratio of Span 80 and [Cho][Mys] (1:25 dispersant to oil ratio, v/v), achieving 81.16 % dispersion effectiveness in the baffled flask test. The binary mixture demonstrated superior emulsion stability (6 h) and the lowest interfacial tension (1.12 mN/m). Acute toxicity experiments revealed the dispersant's practical non-toxicity with an LC50 value of 600 mg/L. Overall, this environmentally benign surfactant combination shows promise as a safe and effective oil spill dispersant.


Assuntos
Recuperação e Remediação Ambiental , Líquidos Iônicos , Poluição por Petróleo , Petróleo , Tensoativos , Poluentes Químicos da Água , Líquidos Iônicos/química , Recuperação e Remediação Ambiental/métodos , Poluentes Químicos da Água/análise , Hexoses
7.
Int J Biol Macromol ; 267(Pt 1): 131331, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574918

RESUMO

The dissolution of cellulose in double salt ionic liquids (DSILs) was studied in detail and compared with the dissolution in individual constituent ionic liquids (ILs). The DSILs, [C4mim](CH3CO2)xCl1-x (x is the mole fraction of the single component ILs), were synthesized using acetate and chloride salts of 1-butyl-3-methylimidazolium. These DSILs were then used for the investigation of the solubility of cellulose in the whole mole fraction range. Commercial cellulose (CC) powder, kraft pulp (KP), and prehydrolysis kraft pulp (PHKP) of jute were chosen as cellulose sources. The solubility of cellulose increased with an increasing temperature for [C4mim](CH3CO2)0.6Cl0.4 and with increasing amount of [C4mim]Cl in DSILs. The maximum solubility of CC powder was 32.8 wt% in [C4mim](CH3CO2)0.6Cl0.4 at 100 °C, while for KP and PHKP, solubilities were 30.1 and 30.5 wt%, respectively under the identical condition. Cellulose could be regenerated from the DSILs using water as an antisolvent. Structure, morphology, and thermal stability of the regenerated cellulosic materials were analyzed. DSILs could be recycled >99 % without a discernible change in structure. This work demonstrates that DSILs display enhanced solubility over ILs system and have potential as a chemical processing methodology.


Assuntos
Celulose , Imidazóis , Líquidos Iônicos , Solubilidade , Celulose/química , Líquidos Iônicos/química , Imidazóis/química , Sais/química , Temperatura
8.
Int J Biol Macromol ; 267(Pt 2): 131376, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38608981

RESUMO

Diabetes is a chronic, metabolic disease characterized by hyperglycemia resulting from either insufficient insulin production or impaired cellular response to insulin. Exopolysaccharides (EPS) produced by Lactobacillus spp. demonstrated promising therapeutic potential in terms of their anti-diabetic properties. Extraction and purification of EPS produced by Lactobacillus acidophilus and Limosilactobacillus reuteri were performed using ethanol precipitation, followed by alcohol/salt based aqueous two-phase system (ATPS). The purification process involved ethanol precipitation followed by an alcohol/salt-based ATPS. The study systematically investigated various purification parameters in ATPS, including ethanol concentration, type and concentration of ionic liquid, type and concentration of salt and pH of salt. Purified EPS contents from L. acidophilus (63.30 µg/mL) and L. reuteri (146.48 µg/mL) were obtained under optimum conditions of ATPS which consisted of 30 % (w/w) ethanol, 25 % (w/w) dipotassium hydrogen phosphate at pH 10 and 2 % (w/w) 1-butyl-3-methylimidazolium octyl sulfate. The extracted EPS content was determined using phenol sulphuric acid method. In α-amylase inhibition tests, the inhibitory rate was found to be 92.52 % (L. reuteri) and 90.64 % (L. acidophilus), while in α-glucosidase inhibition tests, the inhibitory rate was 73.58 % (L. reuteri) and 68.77 % (L. acidophilus), based on the optimized parameters selected in ATPS. These results suggest that the purified EPS derived from the postbiotics of Lactobacillus spp. hold promise as potential antidiabetic agents.


Assuntos
Hipoglicemiantes , Líquidos Iônicos , Lactobacillus , Polissacarídeos Bacterianos , Líquidos Iônicos/química , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/farmacologia , Polissacarídeos Bacterianos/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Concentração de Íons de Hidrogênio , Etanol/química , alfa-Amilases/antagonistas & inibidores , Lactobacillus acidophilus , Sais/química
9.
Chem Rev ; 124(8): 4679-4733, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38621413

RESUMO

The review presents a detailed discussion of the evolving field studying interactions between ionic liquids (ILs) and biological systems. Originating from molten salt electrolytes to present multiapplication substances, ILs have found usage across various fields due to their exceptional physicochemical properties, including excellent tunability. However, their interactions with biological systems and potential influence on living organisms remain largely unexplored. This review examines the cytotoxic effects of ILs on cell cultures, biomolecules, and vertebrate and invertebrate organisms. Our understanding of IL toxicity, while growing in recent years, is yet nascent. The established findings include correlations between harmful effects of ILs and their ability to disturb cellular membranes, their potential to trigger oxidative stress in cells, and their ability to cause cell death via apoptosis. Future research directions proposed in the review include studying the distribution of various ILs within cellular compartments and organelles, investigating metabolic transformations of ILs in cells and organisms, detailed analysis of IL effects on proteins involved in oxidative stress and apoptosis, correlation studies between IL doses, exposure times and resulting adverse effects, and examination of effects of subtoxic concentrations of ILs on various biological objects. This review aims to serve as a critical analysis of the current body of knowledge on IL-related toxicity mechanisms. Furthermore, it can guide researchers toward the design of less toxic ILs and the informed use of ILs in drug development and medicine.


Assuntos
Líquidos Iônicos , Estresse Oxidativo , Líquidos Iônicos/química , Líquidos Iônicos/farmacologia , Animais , Humanos , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos
10.
J Mater Chem B ; 12(16): 3908-3916, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38567452

RESUMO

The fabrication of shape-selective coinage metal nanoclusters (MNCs) has promising applications due to their exceptional physical and chemical molecule-like properties. However, the stability of the specific geometry of the nanoclusters, such as their cubic shapes, is unclear and has been unraveled by assessing the nanoclusters' interactions with different environments. In this work, we investigate the morphological stability of cubic structured, coinage metal nanoclusters of varying sizes ranging from 14 to 1099 atoms. The impact of solvent environments like water and the presence of ionic liquids (IL) on the stabilization of the MNCs were assessed using molecular dynamics (MD) simulations. In general, smaller MNCs composed of less than 256 atoms encountered structural distortion easily compared to the larger ones, which preserved their cubic morphology with minimal surface aberrations in water. However, in the presence of 4M 1-butyl-1,1,1-trimethyl ammonium methane sulfonate [N1114][C1SO3] IL solution, the overall cubic shape of the MNCs was successfully preserved. Strikingly, it is observed that in contrast to the noble MNCs like Au and Ag, the cubic morphology for Cu MNCs with sizes less than 256 atoms exhibited significant stability even in the absence of IL.


Assuntos
Cobre , Nanopartículas Metálicas , Simulação de Dinâmica Molecular , Cobre/química , Nanopartículas Metálicas/química , Líquidos Iônicos/química , Tamanho da Partícula , Propriedades de Superfície , Água/química
11.
Chirality ; 36(4): e23665, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38570326

RESUMO

In this paper, the amino acid chiral ionic liquid (AACIL) was prepared with L-phenylalanine and imidazole. It was characterized by CD, FT-IR, 1H NMR, and 13C NMR spectrum. The chiral recognition sensor was constructed with AACIL and Cu(II), which exhibited different chiral visual responses (solubility or color difference) to the enantiomers of glutamine (Gln) and phenylalanine (Phe). The effects of solvent, pH, time, temperature, metal ions, and other amino acids on visual chiral recognition were optimized. The minimum concentrations of Gln and Phe for visual chiral recognition were 0.20 mg/ml and 0.28 mg/ml, respectively. The mechanism of chiral recognition was investigated by FT-IR, TEM, SEM, TG, XPS, and CD. The location of the host-guest inclusion or molecular placement has been conformationally searched based on Gaussian 09 software.


Assuntos
Aminoácidos , Líquidos Iônicos , Aminoácidos/química , Fenilalanina/química , Glutamina , Líquidos Iônicos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Estereoisomerismo
12.
Int J Mol Sci ; 25(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38673814

RESUMO

Over the past three decades, the synthesis of new ionic liquids (ILs) and the expansion of their use in newer applications have grown exponentially. From the beginning of this vertiginous period, it was known that many of them were hygroscopic, which in some cases limited their use or altered the value of their measured physical properties with all the problems that this entails. In an earlier article, we addressed the hygroscopic grade achieved by the ILs 1-ethyl-3-methylimidazolium chloride, 1-ethyl-3-methylimidazolium bromide, 1-ethyl-3-methylimidazolium methyl sulfate, 1-ethyl-3-methylimidazolium ethyl sulfate, 1-ethyl-3-methylpyridinium ethyl sulfate, 1-ethyl-3-methylimidazolium tosylate, 1-ethyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylimidazolium tetrafluoroborate, 1-dodecyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylpyridinium tetrafluoroborate, 1-butyl-1-methylpiperidinium bis(trifluoromethyl sulfonyl)imide, 1-methyl-1-propylpyrrolidinium bis(trifluoromethyl sulfonyl)imide, 1-butyl-1-methylpyrrolidinium bis(trifluoromethyl sulfonyl)imide, and methyl trioctyl ammonium bis(trifluoromethyl sulfonyl)imide. The objective was to determine the influence of the chemical nature of the compounds, exposed surface area, sample volume, agitation, and temperature. For this purpose, we exposed the samples to abrupt increases in relative humidity from 15 to 100% for days in an atmosphere chamber and then proceeded with the reverse process in a gentle manner. The results show that the sorption of water from the atmosphere depends on the nature of the IL, especially the anion, with the chloride anion being of particular importance (chloride ≫ alkyl sulfates~bromide > tosylate ≫ tetrafluoroborate). It has also been proven for the EMIM-ES and EMIM-BF4 samples that the mechanism of moisture capture is both absorption and adsorption, and that the smaller the exposed surface area, the higher the ratio of the mass of water per unit area.


Assuntos
Ânions , Cátions , Líquidos Iônicos , Líquidos Iônicos/química , Ânions/química , Cátions/química , Imidazóis/química , Molhabilidade , Água/química
13.
Biochemistry (Mosc) ; 89(3): 451-461, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38648765

RESUMO

Ionic liquids (ILs) are organic salts with a low melting point. This is due to the fact that their alkyl side chains, which are covalently connected to the ion, hinder the crystallization of ILs. The low melting point of ILs has led to their widespread use as relatively harmless solvents. However, ILs do have toxic properties, the mechanism of which is largely unknown, so identifying the cellular targets of ILs is of practical importance. In our work, we showed that imidazolium ILs are not able to penetrate model membranes without damaging them. We also found that inactivation of multidrug resistance (MDR) pumps in yeast cells does not increase their sensitivity to imidazolium ILs. The latter indicates that the target of toxicity of imidazolium ILs is not in the cytoplasm. Thus, it can be assumed that the disruption of the barrier properties of the plasma membrane is the main reason for the toxicity of low concentrations of imidazolium ILs. We also showed that supplementation with imidazolium ILs restores the growth of cells with kinetically blocked glycolysis. Apparently, a slight disruption of the plasma membrane caused by ILs can, in some cases, be beneficial for the cell.


Assuntos
Membrana Celular , Imidazóis , Líquidos Iônicos , Saccharomyces cerevisiae , Líquidos Iônicos/toxicidade , Líquidos Iônicos/química , Imidazóis/toxicidade , Imidazóis/química , Imidazóis/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo
14.
J Phys Chem B ; 128(18): 4301-4314, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38682809

RESUMO

Deoxyribonucleic acid (DNA) stability is a prerequisite in many applications, ranging from DNA-based vaccines and data storage to gene therapy. However, the strategies to enhance DNA stability are limited, and the underlying mechanisms are poorly understood. Ionic liquids (ILs), molten salts of organic cations and organic/inorganic anions, are showing tremendous prospects in myriads of applications. With a judicious choice of constituent ions, the protic nature of ILs can be tuned. In this work, we investigate the relative stability of full-length genomic DNA in aqueous IL solutions of increasing protic nature. Our experimental measurements show that the protic ionic liquids (PILs) enhance the DNA melting temperature significantly while unaltering its native B-conformation. Molecular dynamics simulations and quantum mechanical calculation results suggest that the intramolecular Watson-Crick H-bonding in DNA remains unaffected and, in addition, the PILs induce stronger H-bonding networks in solution through their ability to make multiple intermolecular H-bonds with the nucleobases and among its constituent ions, thus aiding greater DNA stability. The detailed understanding obtained from this study could bring about the much-awaited breakthrough in improved DNA stability for its sustained use in the aforesaid applications!


Assuntos
DNA , Ligação de Hidrogênio , Líquidos Iônicos , Simulação de Dinâmica Molecular , Prótons , Líquidos Iônicos/química , DNA/química , Conformação de Ácido Nucleico
17.
Org Biomol Chem ; 22(17): 3477-3489, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38602033

RESUMO

Selective degradation of disease-causing proteins using proteolysis targeting chimeras (PROTACs) has gained great attention, thanks to its several advantages over traditional therapeutic modalities. Despite the advances made so far, the structural chemical complexity of PROTACs poses challenges in their synthetic approaches. PROTACs are typically prepared through a convergent approach, first synthesizing two fragments separately (target protein and E3 ligase ligands) and then coupling them to produce a fully assembled PROTAC. The amidation reaction represents the most common coupling exploited in PROTACs synthesis. Unfortunately, the overall isolated yields of such synthetic procedures are usually low due to one or more purification steps to obtain the final PROTAC with acceptable purity. In this work, we focused our attention on the optimization of the final amidation step for the synthesis of an anti-SARS-CoV-2 PROTAC by investigating different amidation coupling reagents and a range of alternative solvents, including ionic liquids (ILs). Among the ILs screened, [OMIM][ClO4] emerged as a successful replacement for the commonly used DMF within the HATU-mediated amidation reaction, thus allowing the synthesis of the target PROTAC under mild and sustainable conditions in very high isolated yields. With the optimised conditions in hand, we explored the scalability of the synthetic approach and the substrate scope of the reaction by employing different E3 ligase ligand (VHL and CRBN)-based intermediates containing linkers of different lengths and compositions or by using different target protein ligands. Interestingly, in all cases, we obtained high isolated yields and complete conversion in short reaction times.


Assuntos
Líquidos Iônicos , Proteólise , Líquidos Iônicos/química , Líquidos Iônicos/síntese química , Ubiquitina-Proteína Ligases/metabolismo , SARS-CoV-2 , Amidas/química , Amidas/síntese química , Humanos , Ligantes , Estrutura Molecular , Antivirais/química , Antivirais/síntese química , Antivirais/farmacologia , Quimera de Direcionamento de Proteólise
18.
Environ Sci Pollut Res Int ; 31(19): 28706-28718, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38558336

RESUMO

Developing adsorbent materials with high adsorptive dephosphorization (ADP) is significant for treating phosphate from aqueous solutions and eutrophic water. Herein, the MIL-101(Cr) framework was entrapped ionic liquid (IL) of 1-butyl-3-methylimidazoliumbromide ionic liquid ([C4mem]+[Br]-) using a ship-in-a-bottle approach to obtain novel adsorbents [C4mem]+[Br]-@MIL-101(Cr) contained varied IL contents, namely C4mem@MIL-101. The characterization results revealed that the formed [C4mem]+[Br]- molecules interacted with the MIL-101(Cr) frameworks, enhanced their stability, and offered additional adsorption sites. The batch adsorptions of phosphate showed that the optimized C4mem@MIL-101 adsorbent loaded with ~ 7% IL-based N content had the highest phosphate absorbing capacity of ~ 200 mg/g, outperforming the pristine MIL-101(Cr) and other adsorbents. The ADP efficiency was facilitated in the acidic media, where the phosphate ions of H2PO4- and HPO42- captured onto the C4mem@MIL-101 via several interactions, including electrostatic attraction, H-bonds, and chemical interactions. In the meantime, the coexisting anions diminished the phosphate adsorption because they competed with the pollutants at adsorption sites. Furthermore, phosphate treatment under the continuous fixed-bed conditions showed that 1 g of the polyvinyl alcohol (PVA)-mixed C4mem@MIL-101 pellets purified 25 l of water containing phosphate with a 1 mg/l concentration. The results suggest that the novel [C4mem]+[Br]-@MIL-101(Cr) structure had a high potential for treating phosphate in aqueous solutions.


Assuntos
Líquidos Iônicos , Estruturas Metalorgânicas , Fosfatos , Poluentes Químicos da Água , Purificação da Água , Líquidos Iônicos/química , Fosfatos/química , Adsorção , Estruturas Metalorgânicas/química , Purificação da Água/métodos , Poluentes Químicos da Água/química
19.
Int J Biol Macromol ; 266(Pt 2): 131230, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574909

RESUMO

Due to the biodegradable and biocompatible nature of chitin and chitosan, they are extensively used in the synthesis of hydrogels for various applications. In this work, deacetylation of chitin is carried out with alkaline poly(dimethyldiallylammonium-hydroxide) that gave a higher amount of water-soluble chitin (with 84 % of the degree of deacetylation = chitosan0.84) compared to deacetylation using NaOH. The water-soluble chitosan0.84 is used as intercalating chains for the preparation of acrylic acid and vinylimidazole-based hydrogels. The quaternization of imidazole groups is done with 1,ω-dibromoalkanes, which sets off the crosslinking in the above polymer network. A set of three chitosan0.84 intercalated hydrogels, namely Cs-C4-hydrogel, Cs-C5-hydrogel, and Cs-C10-hydrogel are prepared bearing butyl, pentyl, and decyl chains as respective crosslinkers. The swell ratios of these intercalated hydrogels are compared with those of non-intercalated hydrogels (C4-hydrogel, C5-hydrogel, and C10-hydrogel). Chitosan0.84 intercalated Cs-C10-hydrogel has excellent swelling properties (2330 % swelling ratio) among six synthesized hydrogels. SEM analysis reveals that decyl crosslinker-bearing hydrogels are highly porous. The multi-functionality of Cs-C10-hydrogel and C10-hydrogel is explored towards -the controlled release of paracetamol/urea, and methyleneblue dye absorption. These studies disclose that chitosan0.84 intercalated hydrogels are showing superior-swelling behavior, high paracetamol/urea loading capacities and better dye entrapment than their non-intercalated counterparts.


Assuntos
Acetaminofen , Quitina , Preparações de Ação Retardada , Hidrogéis , Líquidos Iônicos , Ureia , Hidrogéis/química , Hidrogéis/síntese química , Líquidos Iônicos/química , Quitina/química , Acetaminofen/química , Ureia/química , Liberação Controlada de Fármacos , Acetilação , Quitosana/química , Portadores de Fármacos/química , Portadores de Fármacos/síntese química , Polímeros/química , Polímeros/síntese química
20.
Environ Sci Pollut Res Int ; 31(20): 29513-29524, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38578595

RESUMO

Municipal sludge generated from wastewater treatment plants can cause a serious environmental and economic burden. A novel hybrid conditioning strategy was developed to enhance the dewatering performance of sludge, employing 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([C4mim][CF3SO3]) treatment combined with H2SO4 acidification. Following conditioning, the capillary suction time ( CST normalized ), the specific resistance of filtration (SRF), and moisture content of the treated sludge were decreased to 1.99 ± 0.24 (s·L/g TSS), 1.33 ± 0.05 (1012 m/kg), and 72.01 ± 0.94%, respectively. The results were superior to those achieved with sludge treated solely by H2SO4 acidification or [C4mim][CF3SO3] alone. The biomacromolecules within the sludge flocs were dissolved by [C4mim][CF3SO3], while simultaneously, the microorganisms were inactivated. Consequently, the colloidal-like structures of the sludge flocs were destroyed. Additionally, the ionizable functional groups of the biomacromolecules were instantly protonated by the introduced H+ ions, and their negative charges were neutralized during the H2SO4 acidification process. The presence of H+ ions promoted the weakening of electrostatic repulsion between the sludge flocs. As a result, an enhancement of sludge dewaterability was obtained after treatment with [C4mim][CF3SO3] and H2SO4 acidification. The finding of the intensification mechanism of sludge dewaterability brought by hybrid treatment of acidification and [C4mim][CF3SO3] provides novel insights into the field of sludge disposal.


Assuntos
Líquidos Iônicos , Esgotos , Eliminação de Resíduos Líquidos , Esgotos/química , Líquidos Iônicos/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Ácidos Sulfúricos/química , Filtração
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