Cholinium-based Ionic Liquids Research Articles

Extraction of caffeine from coffee husk employing choline-based ionic liquids: Optimization of the process and theoretical study on solute-salts interactions

The effectiveness of a series of five aqueous solutions of choline (Ch)-based ionic liquids (IL), where the corresponding counterions were propanoate [Prop], hexanoate [Hex], nicotinate [Nic], citrate [Cit], and tartrate [Tar], was compared to extracting caffeine (Caf) from a sample of coffee husk (CH), an abundant agro-industrial by-product. The [Ch][Hex] was the most efficient of the series, whereas no significant differences were found among the others. A response surface methodology (RSM) using a three-factor central composite design 23 was used to optimize the process, considering temperature (T), solid/liquid ratio (R) and [Ch][Hex] concentration (C) as the more influential variables. The estimated optimal conditions for the extraction were 95 °C, 0.021 g/mL, and 2.34 M, respectively, which yield 4347.50 ± 115 mgCaf/kgCH; in addition, the [Ch][Hex] solution was reusable, at least twice, without drastically reducing its efficiency. On the other hand, the non-covalent interactions between ILs and caffeine within the complexes IL-Caf were obtained at a DFT level of calculation, including temperature and the solvation effect of water, through AIM and NCI analyses. A net of hydrogen bonds can be observed among the components of the complexes, the strongest ones taking place between hydrogen atoms and hydroxyl or carboxylic groups of the anions, mainly in the citrate and tartrate anions. In contrast, weak hydrogen bonds and van der Waals interactions are predominant between hexanoate and caffeine. Thus, a hydrotropic effect seems to be the driving force in the extraction of the alkaloid with [Ch][Hex]. Thermochemistry of the complexation process was also calculated, and findings were in good agreement with experimental results for the ILs under study.

Effect of choline amino acid ionic liquids on maize seed germination and endogenous plant hormone levels.

Prior research has established choline-based ionic liquids (ILs) as safe for various organisms. However, their impact on plants has been underexplored. To identify effective eco-friendly ILs, we synthesized seven choline amino acid ([Chl][AA]) ILs and analyzed their physiological influence on maize seed germination. In contrast to the traditionally used N-octyl pyridinium bromide IL, these seven [Chl][AA] ILs exhibited substantially lower toxicity. Moreover, within a broad treatment concentration range (10-100 mg L-1), these ILs notably enhanced maize germination indices and root and shoot growth. Specifically, treatment with 100 mg L-1 choline tryptophan resulted in a 21.2% increase in germination index compared to those of control maize. Compared to the control, the application of choline serine, choline aspartic acid, choline phenylalanine, and choline tryptophan at 100 mg L-1 led to respective increases of 23.9%, 21.5%, 22.5%, and 24.5% in maize shoot length. Analysis of endogenous hormones and free amino acid contents revealed elevated levels of growth-promoting plant hormones (gibberellic acid and zeatin) in maize shoot tips, as well as increased contents of major amino acids (glutamate, glycine, and arginine) following treatment with different [Chl][AA] ILs at 100 mg L-1. These findings indicate that [Chl][AA] holds promise for the development and application of novel low-toxicity ILs.

Crystallization of isoniazid in choline-based ionic liquids: Physicochemical properties and anti-tuberculosis activity

Isoniazid is a drug commonly employed in the treatment of tuberculosis. One major barrier to its widespread use is that it can undergo hydrolysis when stored inadequately, resulting in the formation of hydrazine, a toxic and carcinogenic compound. Therefore, there is a clear need for further research aimed at improving the stability of isoniazid while still maintaining its therapeutic efficiency and solubility. To this end, five choline ionic liquids (ILs) were used for synthesizing improved forms of isoniazid: (2-hydroxyethyl)-trimethylammonium hydroxide [ChOH], (2-hydroxyethyl)-trimethylammonium hydrogen sulfate [ChBis], (2-hydroxyethyl)-trimethylammonium acetate [ChAc], (2-hydroxyethyl)-trimethylammonium citrate [ChCit], and (2-hydroxyethyl)-trimethylammonium benzoate [ChBenz]. The INH:[ChOH] and INH:[ChCit] forms were obtained in powder form, and presented low solubility and a minimum inhibitory concentration for Mycobacterium tuberculosis of 100 μg/mL and 12.5 μg/mL, respectively. The INH:[ChBenz], INH:[ChBis], and INH:[ChAc] forms showed a minimum inhibitory concentration value lower than 6.2 µg/mL. In the process using [ChBis], 2-(4-pyridiniumcarbonyl)-hydrazine sulfate with a water solubility of 155.9 mg/mL at 25 °C was produced, which showed to be more soluble than isoniazid (137.9 mg/mL). Therefore, the IL used had a direct influence on the solubility, conformational structure, and stability of isoniazid. This research is highly relevant and innovative for the use of new solvents in the crystallization of drugs, especially when aiming at the improvement of their properties.

Equilibrium phase behavior of ternary systems formed by polyethylene glycol + choline salts + water

The economic and environmental potentialities of the application of choline salts in aqueous two-phase systems (ATPS), as well as the incipiency of works of these ionic liquids (ILs) combined with polyethylene glycol (PEG), are the reasons for the characterization of new “green” ATPS formed by PEG (400 and 1500 g.mol−1) combined with choline-based ILs (choline chloride, choline bitartrate, and choline dihydrogen citrate). Choline chloride was preferentially concentrated in the top phase, while the lower phase was rich in PEG. The opposite behavior was observed for bitartrate and dihydrogen citrate. ATPS formed by PEG1500 exhibits a significant increase in the biphasic area as the temperature increases; while for systems formed by PEG400, this same trend is slight, demonstrating that phase segregation has an endothermic character. The salting-out effect and the hydrophobicity of the polymer explain the increase of the biphasic area with increasing the charge density of the anion and increasing polymer molar mass, respectively. The data were fitted with good correlation using the Merchuk equation for the binodal curves and Guan equation for the tie-lines.

Probing the molecular interactions between cholinium-based ionic liquids and insulin aspart: A combined computational and experimental study

Despite extensive studies revealing the potential of cholinium-based ionic liquids (ILs) in protein stabilization, the nature of interaction between ILs' constituents and protein residues is not well understood. In this work, we used a combined computational and experimental approach to investigate the structural stability of a peptide hormone, insulin aspart (IA), in ILs containing a choline cation [Ch]+ and either dihydrogen phosphate ([Dhp]−) or acetate ([Ace]−) as anions. Although IA remained stable in both 1 M [Ch][Dhp] and 1 M [Ch][Ace], [Dhp]− exhibited a much stronger stabilization effect than [Ace]−. Both the hydrophilic ILs intensely hydrated IA and increased the number of water molecules in IA's solvation shell. Undeterred by the increased number of water molecules, the native state of IA's hydrophobic core was maintained in the presence of ILs. Importantly, our results reveal the importance of IL concentration in the medium which was critical to maintain a steady population of ions in the microenvironment of IA and to counteract the denaturing effect of water molecules. Through molecular docking, we confirm that the anions exert the dominant effect on the structure of IA, while [Ch]+ have the secondary influence. The computational results were validated using spectroscopic analyses (ultra-violet, fluorescence, and circular dichroism) along with dynamic light scattering measurements. The extended stability of IA at 30 °C for 28 days in 1 M [Ch][Dhp] and [Ch][Ace] demonstrated in this study reveals the possibility of stabilizing IA using cholinium-based ILs.

Mechanism of Pechmann condensation reaction – A quantum mechanical case study with choline-based ionic liquid

At present, many researchers are aiming to develop an efficient and re-usable green catalyst for industrially relevant chemical reactions. Particularly, Pechmann condensation reaction is an important reaction that is used to prepare Coumarin derivatives which find applications in biology and medicine. In this regard, choline based ionic liquids (CILs) are reckoned as effective eco-friendly catalysts for many organic transformations. Specifically, N,N-dimethylaminoethanol [N112OH][HSO4] (NS-CIL) was found to be the effective catalyst for promoting Pechmann condensation in an efficient manner. The present work demonstrates the detailed mechanistic investigation on the three possible pathways (A, B and C) of Pechmann condensation using NS-CIL as catalyst [RSC Adv, 2014, 4, 22946–22950]. Our computed results reveal that the pathway B which involves Electrophilic attack → Water-elimination → Trans-esterification (EWT – Route) is both thermodynamically and kinetically most favourable pathway with a relatively small activation energy of 20.23 kcal/mol at the rate-determining step. Further, NS-CIL has been identified to be a vital entity in decreasing the activation barriers by acting as proton-shuttle and in stabilizing the intermediates and transition states with weak intermolecular hydrogen bonding interactions via most-acidic N–H and O–H protons of cationic unit of NS-CIL. Thus, the mechanistic insights gained through this work will aid and impel the development of more efficient ionic liquid based green catalysts for Pechmann condensation reaction and similar other industrially important reactions.

Structural, spectral, and dynamical behaviors of biodegradable choline-based ionic liquids (CBILs) confined inside neutral and charged mxene nanopores for supercapacitor applications

This study explores the potential of using biodegradable choline-based ionic liquids (CBILs) as a more sustainable and eco-friendly alternative to classical ILs in the field of electrolyte media for energy storage devices. While previous studies have focused on electrostatic and capacitance properties, it is important to also consider dynamics and structural behavior when choosing adjustable electrolytes and electrodes. In this regard, molecular dynamics simulations were used to study the structural, spectral, and dynamical behaviors of two CBILs ([Ch][Sa] and [Ch][β-Ala]) inside MXene nanopores with varying pore size and surface charge density. As the pore size decreases, the number of hydrogen bonds in the first layer decreases from 0.447 to 0.122 and 0.154–0.063 in [Ch][Sa] and [Ch][β-Ala], respectively. Also, the presence of an aromatic ring benefits packing efficiency, causing [Sa]- to have a parallel orientation relative to MXene surface. Applying a fixed charge (1.8–7.2 μC/cm2) on MXene electrodes results in the formation of an electric double layer (EDL). At higher surface charge densities, there is slower dynamics and lower structural correlations between anions and cations. Moreover, Infrared (IR) spectra show blue and red shifts for the O-H bond in choline and carbonyl C-O stretching vibrational modes in anions, respectively, due to the interaction of anions with the MXene surface in the first layer reducing their interaction with cations. The results of our research may potentially lead to the creation of novel energy storage devices that are eco-friendly, utilizing MXene electrodes and CBILs as electrolytes.

Cholinium-Based Ionic Liquids as Promising Antimicrobial Agents in Pharmaceutical Applications: Surface Activity, Antibacterial Activity and Ecotoxicological Profile.

Cholinium-based ionic liquids are compounds increasingly studied in pharmaceutics and biomedicine to enhance bioavailability in drug delivery systems and as bioactive ingredients in pharmaceutical formulations. However, their potential as antimicrobial agents has scarcely been investigated. Herein, we explored the antimicrobial activity of a series of surface-active cholinium-based ionic liquids (Chol-ILs). For this purpose, Chol-ILs with alkyl chains of 10-16 carbon atoms were synthesized and their self-assembly in aqueous medium was investigated. Subsequently, their antimicrobial activity against a panel of clinically relevant bacteria and their ability to eradicate MRSA and P. aeruginosa PAO1 biofilms was evaluated. Finally, we analyzed the ecotoxicological profile of Chol-ILs in terms of susceptibility to aerobic biodegradation and acute aquatic toxicity against D. magna and V. fisheri. Our results reveal that cholinium-based ILs with alkyl chain lengths ≥12 C show a broad spectrum of antibacterial activity. Their antimicrobial efficacy depends on their hydrophobicity, with the C14-C16 homologs being the most effective compounds. These ILs exhibit antimicrobial activity similar to that of imidazolium ILs and quaternary ammonium antiseptics. Moreover, the longer alkyl chain Chol-ILs are able to eradicate established biofilms at concentrations as low as 16-32 µg/mL. The biodegradation rate of cholinium-based ILs decreases with alkyl chain elongation. Our results reinforce the suitability of Chol-ILs as promising multifunctional compounds for application in pharmaceutical and biomedical formulation.

The interaction of cholinium-based ionic liquids with different biological origin anions with albumins

The intermolecular interactions of cholinium-based ionic liquids (ILs) with biological origin anions (amino and dicarboxylic acids) with bovine serum albumin (BSA) and human serum albumin (HSA) have been studied by spectral and computational methods. The choline malonate ([Ch][Mal]), choline succinate ([Ch][Suc]) and choline valinate ([Ch][Val]) were synthesized. The changes to the state of the BSA and HSA with ILs at different concentration were observed using circular dichroism (CD) spectroscopy. At higher concentrations the ILs lead to a partial loss of ternary structure of albumins. The effect of ILs on the thermal stability of proteins was monitored by the temperature CD spectra scans. The increase of denaturation temperature of albumins with ionic liquids was observed. The interaction of ionic liquids with serum albumins was estimated by fluorescence spectroscopy technique, while the probable binding modes were identified using molecular docking. The leading cause of the increased thermal stability of albumins was found to be the formation of aggregates of proteins with ionic liquids. Cytotoxicity of ionic liquids on cancer and normal cell lines was established.

Physisorption of biodegradable choline-based ionic liquids (CBILs) and their aqueous solutions on 2D titanium carbide (MXene) nanosheets as promising media in energy storage systems

MXenes alongside ionic liquid electrolytes have been promising in energy storage systems. The nanoscopic structure of two biodegradable choline-based ionic liquids (CBILs) and their water mixtures were investigated near the MXene surface using quantum mechanics calculations and molecular dynamics simulations. Quantum mechanics calculations showed that the anion-cation interactions in the choline salicylate ([CH][SA]) are weaker than that for choline β-alaninate ([CH][β-Ala]), therefore, [SA]− tends to interact more with the MXene surface compared to [β-Ala]−. Simulation results indicated that the ionic liquids aggregate in the vicinity of the MXene surface to form a dense layer with significantly different properties compared to bulk. Applying moisture to CBIL systems reduces the ion population in the first layer and also their structural correlations. Furthermore, there is a competition between water molecules and choline cations for interaction with anions. The presence of water molecules also increases the dynamics of hydrogen bonds, ion pairs, and ion cages. Perception of the nano-scale behavior of these unique classes of ionic liquids on MXenes could be beneficial for energy storage systems like batteries and electric double-layer capacitors.

Towards the improved monitoring of bacterial infections by the isolation of DNA from human serum using ionic-liquid-based aqueous biphasic systems

Early infection diagnosis is crucial to decrease morbidity and mortality rates. However, complex biological samples, like human blood or serum, contain high abundance proteins and metabolites that reduce the sensitivity of methods used to identify and quantify nucleic acids in bacterial infections diagnosis. To address this issue, we investigated aqueous biphasic systems (ABS) composed of polypropylene glycol 400 and cholinium-based ionic liquids (ILs) at different pH values for the pre-treatment of human serum, aiming the separation of DNA from human serum albumin (HSA) to reduce the interference on the DNA quantification by real-time PCR (qPCR). Remarkable extraction efficiencies of DNA to the IL-rich phase were obtained with all investigated systems, ranging between 90 and 100% in a single-step, with no significant losses of DNA observed (yield at the IL-rich phase > 90%). At low pH values HSA precipitates, whereas at neutral pH no HSA precipitation is observed. This trend suggests that IL-based ABS can be tuned to selectively isolate DNA from HSA by adjusting the pH. The most effective ABS identified is composed of cholinium glycolate at pH 5, allowing to completely precipitate HSA at the ABS interface and leading to an IL-rich phase enriched in DNA with high purity (>98%) that can be quantified by qPCR. Finally, it is shown that the IL-rich phase is able to maintain the DNA’s structural integrity at room temperature, for up to six months, implying that the IL-rich phase of the selected ABS could also be a suitable DNA storage medium. In summary, designed IL-based ABS can be applied as a pretreatment strategy of human serum, allowing to isolate bacterial DNA and opening new perspectives in the monitoring of bacterial infections.

A good and bad aggregation: Effect of imidazolium- and cholinium-based ionic liquids on the thermal stability of bovine serum albumin

The present work describes the effect of imidazolium- and cholinium-based ionic liquids (ILs) on the thermal stability, binding and aggregation of bovine serum albumin (BSA). The studied ILs include choline chloride [Ch][Cl], choline dihydrogenphosphate [Ch][DHP], choline acetate [Ch][OAc], 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF4], 1-octyl-3-methylimidazolium tetrafluoroborate [OMIM][BF4] 1-butyl-3-methylimidazolium trifluoromethanesulfonate [BMIM][TfO], 1-butyl-3-methylimidazolium acetate [BMIM][OAc], and 1-butyl-3-methylimidazolium methanesulfonate [BMIM][CH3SO3]. The state of BSA in presence of ILs was assessed by circular dichroism (CD), temperature dependent circular dichroism, fluorescence spectroscopy, and dynamic light scattering (DLS). The thermal stability of BSA in presence of ILs increased (above 85 °C) in all studied ILs except [OMIM][BF4]. Differences of binding ILs with BSA depending on alkyl chain length were estimated, the probable binding modes were identified using molecular docking. The influence of ILs on the aggregation of BSA at different temperatures was established. It was found that the ILs with short alkyl chain length (up to butyl) promote aggregation of the native form of BSA increasing its thermal stability.

Integrated platform resorting to ionic liquids comprising the extraction, purification and preservation of DNA

The large-scale production of therapeutically targeted-deoxyribonucleic acid (DNA) has passed through several challenges, postponing the tangible implementation of an effective, economic and sustainable manufacturing system. Such challenges comprise the need to develop an integrative downstream process able to extract, purify and long-term preserve DNA, whilst reducing the risk of degradation by endonucleases that would compromise their effectiveness as therapeutic products. In this work, three-phase partitioning (TPP) systems formed by the application of aqueous biphasic systems (ABS) composed of several biocompatible cholinium-based ionic liquids (ILs), are proposed for the separation of double stranded DNA (dsDNA) from the endonuclease deoxyribonuclease I (DNase I). By taking advantage of the tailor-made properties of ILs, dsDNA can be completely extracted to the IL-rich phase, whereas DNase I is precipitated at the ABS interphase. The ABS/TPP formed by IL cholinium glycolate ([N111(2OH)][Gly]) fulfills the aim of this work, i.e. at ensuring the technical viability of IL-based ABS/TPP for the “one-pot” extraction, purification and long-term preservation of dsDNA. The results reveal the potential of this system to be applied in the bioprocessing of DNA, particularly relevant when envisioning DNA-based therapeutic products.

Ion-Mediated Protein Stabilization on Nanoscopic Surfaces.

The emergence of nanoparticles in biomedical applications has made their interactions with proteins inevitable. Nanoparticles conjugated with proteins and peptide-based constructs form an integral part of nanotherapeutics and have recently shown promise in treating a myriad of diseases. The proper functioning of proteins is critical to achieve their biological functions. However, interface issues result in the denaturation of proteins, and the loss of orientation and steric hindrance can adversely affect the function of the conjugate. Furthermore, surface-induced denaturation also triggers protein aggregation, resulting in amyloid-like species. Understanding the mechanistic underpinnings of protein-nanoparticle interactions and controlling their interfacial characteristics are critical and challenging due to the complex nature of the conjugates. In this milieu, we demonstrate that ionic liquids can be suitable candidates for stabilizing protein-nanoparticle interactions by virtue of their excellent protein-preserving properties. We also probe the previously unexplored mechanism of ion-mediated stabilization of the protein molecules on the nanoparticle surface. The protein-nanoparticle conjugates consist of lysozyme and choline-based ionic liquids characterized by optical and electron microscopy techniques combined with surface-sensitive plasmon-enhanced Raman spectroscopy. Furthermore, atomistic molecular dynamics simulations of the conjugates delineate interfacial interactions of the protein molecules and the modulation by the ions, particularly the conformational changes and the dynamic correlation when the protein and specific ionic liquid molecules are adsorbed on the nanoparticle surface. The combined experimental and computational studies showed the synergistic behavior of the ions of the ionic liquids, specifically the orientation and coverage of the anions aided by the cations to control the surface interactions and hence the overall protein stability. These studies pave the way for using ionic liquids, particularly their biocompatible counterparts in nanoparticle-based complexes, as stabilizing agents for biomedical applications.

Extraction of protein with protease inhibitor activity from Brazilwood (Caesalpinia echinata LAM.) seeds using choline-based ionic liquids

Proteolytic inhibitors are low molecular weight proteins that prevent protein hydrolysis and are used against moderate to high severity diseases. Some plants can produce these protease inhibitors, such as Brazilwood seeds (Caesalpinia echinata LAM.). This work aimed to optimise the extraction of proteins from Brazilwood seeds with proteolytic inhibitory activity, using choline-based ionic liquid. The seeds were characterised in terms of their dimensions (15 mm in length, 11 mm in width and 4.8 mm in thickness), centesimal composition (moisture - 9.21%, ash - 3.37%, lipids - 32.6%, total fibre - 0.80%, crude proteins - 17.2%, carbohydrates - 36.8%), energy (510 Kcal.100 g-1) and major fatty acid (linoleic acid - 43%). Protein extraction was performed by maceration of the Brazilwood seeds using ionic liquids (choline bitartrate, choline chloride and choline dihydrogen citrate) and optimised using a factorial design of experiments, whose variables were the temperature and solvent concentration, with the total protein content as the response variable. The best extraction conditions were 25.42 °C, 5.42% (m/v) choline bitartrate, solid-liquid ratio 1:5, 500 rpm and pH 7.0 (1.74 mg mL−1 theoretical and 1.88 mg mL−1 experimental). The kinetic model best fitted to the experimental data was Peleg's, and the best extraction time was 15 min. Under optimised conditions, the protein extract of Brazilwood seeds provided a 60.8% inhibition of trypsin. According to the molecular docking results, the inhibition of bovine trypsin is driven by Caesalpinia echinata kallikrein inhibitor (CeKI) and the selected ionic liquid (choline bitartrate), promoting a synergistic inhibition effect.

Cholinium-based ionic liquid catalysts for polyethylene terephthalate glycolysis: understanding the role of solvent and a reappraisal of the cation contribution

A combined computational and experimental study has identified a new PET degradation pathway using cholinium-based ionicliquids, leading to a re-evaluation of the cholinium unit's role in catalysis and improved catalyst design.

Influence of the molecular structure on the tribological properties of choline-based ionic liquids as water-based additives under current-carrying lubrication

In this work, four types of choline/fatty acid ionic liquids were synthesised and used as water-based lubricant additives in an ethylene glycol system, and the tribological behaviours of the mixtures were investigated under the control of an applied electric field. Under current-carrying lubrication, the friction and wear resistances of the steel friction pair lubricated with the ionic liquid-added lubricant became more pronounced. As the number of double bonds in the fatty acid structure increases, the molecular compactness decreases, and the friction-reduction performance is affected. Mechanistic analyses indicated that the [Ch][SA] ionic liquid can strongly adsorb to the metal surface and form a tribochemical reaction film during the friction process, leading to excellent tribological properties.

A molecular dynamics study of graphyne-based electrode and biocompatible ionic liquid for supercapacitor applications

• Graphyne as a promising candidate for electrochemical energy storage systems. • Electrolytes based on aqueous mixtures of the biodegradable ionic liquid. • Efficiency of low toxicity cholinium-based ionic liquids electrolytes in supercapacitor. Atomistic molecular dynamics simulations were used to investigate the properties of electrolytes based on aqueous mixtures of the biodegradable ionic liquid [Ch][Gly] with the ionic liquid [Bmim][PF 6 ] as electrolytes in graphyne supercapacitors. Energetic, structural, and electrostatic analyses were performed to describe de Electrical Double Layer (EDL) formed near de graphyne electrodes revealing preferential adsorption of [Bmim][PF 6 ] additive in both, positive and negative electrodes. From the energetic analysis, we found that although the structure and formation of the EDL are governed by the complex interaction network of both van der Waals and electrostatics, its interaction with the electrode is drastically dominated by van der Waals interactions. From electrostatic results, we found a reduction in total capacitance as the concentration of [Bmim][PF 6 ] increases but overall, we observed that cholinium-based electrolytes can perform as well as most conventional ionic liquids, but with the advantage of having a low toxicity. The comparison between graphene and graphyne supercapacitors revealed a higher capacitance for graphyne, with 2.4 μF cm −2 at 2 V, even when we compare similar values for the drop potential (which occur for different values of charge density) the higher performance of the graphyne electrode is maintained; a result that corroborates the previous findings and that indicates graphyne as a promising candidate for electrochemical energy storage systems.

Untargeted Metabolomics Sheds Light on the Secondary Metabolism of Fungi Triggered by Choline-Based Ionic Liquids.

Fungal secondary metabolites constitute a rich source of yet undiscovered bioactive compounds. Their production is often silent under standard laboratory conditions, but the production of some compounds can be triggered simply by altering the cultivation conditions. The usage of an organic salt – ionic liquid – as growth medium supplement can greatly impact the biosynthesis of secondary metabolites, leading to higher diversity of compounds accumulating extracellularly. This study examines if such supplements, specifically cholinium-based ionic liquids, can support the discovery of bioactive secondary metabolites across three model species: Neurospora crassa, Aspergillus nidulans, and Aspergillus fumigatus. Enriched organic extracts obtained from medium supernatant revealed high diversity in metabolites. The supplementation led apparently to increased levels of either 1-aminocyclopropane-1-carboxylate or α-aminoisobutyric acid. The extracts where bioactive against two major foodborne bacterial strains: Staphylococcus aureus and Escherichia coli. In particular, those retrieved from N. crassa cultures showed greater bactericidal potential compared to control extracts derived from non-supplemented cultures. An untargeted mass spectrometry analysis using the Global Natural Product Social Molecular Networking tool enabled to capture the chemical diversity driven by the ionic liquid stimuli. Diverse macrolides, among other compounds, were putatively associated with A. fumigatus; whereas an unexpected richness of cyclic (depsi)peptides with N. crassa. Further studies are required to understand if the identified peptides are the major players of the bioactivity of N. crassa extracts, and to decode their biosynthesis pathways as well.

Cholinium-Based Ionic Liquids Attenuate the Amyloid Fibril Formation of Lysozyme: A Greener Concept of Antiamyloidogenic Ionic Liquids

Cholinium-Based Ionic Liquids Attenuate the Amyloid Fibril Formation of Lysozyme: A Greener Concept of Antiamyloidogenic Ionic Liquids