Antimicrobial Ionic Liquids: Ante-Mortem Mechanisms of Pathogenic EPEC and MRSA Examined by FTIR Spectroscopy.

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.

Ionic Liquid Gating Induces Anomalous Permeation through Membrane Channel Proteins.

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.

Impact of an Ionic Liquid Solution on Horseradish Peroxidase Activity.

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.

Protein Interface Regulating the Inserting Process of Imidazole Ionic Liquids into the Cell Membrane.

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.

Development of ionic-liquid-impregnated activated carbon for sorptive removal of PFAS in drinking water treatment.

Adsorption of per- and poly-fluoroalkyl substances (PFAS) on activated carbon (AC) is considerably hindered by the surface water constituents, degrading the ability of the AC adsorption process to remove PFAS in drinking water treatment. Herein, we developed ionic-liquid-impregnated AC (IL/AC) as an alternative to AC for PFAS sorption and demonstrated its performance with real surface water for the first time. Ionic liquids (ILs) of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (IL(C2)) and 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (IL(C6)) were selected from among 272 different ILs using the conductor-like screening model for realistic solvents (COSMO-RS) simulation. Impregnation of the ILs in AC was verified using various analytical techniques. Although the synthesized IL/ACs were less effective than pristine AC in treating PFAS in deionized water, their performances were less impacted by the surface water constituents, resulting in comparable or sometimes better performances than pristine AC for treating PFAS in surface water. The removal efficiencies of 10 wt% IL(C6)/AC for six PFAS were 1.40-1.96 times higher than those of pristine AC in a surface water sample containing 2.6 mg/L dissolved organic carbon and millimolar-level divalent cation concentration. PFAS partitioning from the surface water to ILs was not hindered by dissolved organic matter and was enhanced by the divalent cations, indicating the advantages of IL/ACs for treating significant amounts of PFAS in water. The synthesized IL/ACs were effective at treating coexisting pharmaceutical and personal-care products in surface water, showcasing their versatility for treating a broad range of water micropollutants.

Dicationic imidazole ionic liquid stationary phase for preservative detection and its application under mixed mode of HILIC/RPLC/IEC.

BACKGROUND: Food safety has always been a great concern, and the detection of additives is vital to ensuring food safety. Therefore, there is a necessity to develop a method that can quickly and efficiently separate and detect additives in food. High performance liquid chromatography is widely used in the analysis and testing of food additives. Ionic liquids have attracted wide attention in the preparation of high performance liquid chromatography stationary phases owing to their high stability, low vapor pressure and adjustable structure. RESULTS: We developed a novel dicationic imidazole ionic liquid stationary phase for the simultaneous determination of organic preservatives (sodium benzoate, potassium sorbate) and inorganic preservatives (nitrate and nitrite) in foodstuffs under mixed-mode chromatography. The method had the advantages of easy operation, high reproducibility, good linearity and precision. In the detection of these four preservatives, the limit of detection ≤0.4740 mg⋅L-1 and the limit of quantification ≤1.5800 mg⋅L-1. The intra-day and inter-day precision were less than 4.02%, and the recovery rate was 95.90∼100.19 %. At the same time, we also characterized the stationary phase, explored the mechanism and evaluated the chromatographic performance. The stationary phase was able to operate under the mixed mode of reversed phase/hydrophilic interaction/ion exchange chromatography, and it was capable of separating hydrophilic substances, hydrophobic substances, acids, and inorganic anionic substances with good separation efficiency and had high column efficiency. SIGNIFICANCE: In summary, the stationary phase has a promising application in the routine analysis of organic and inorganic preservatives in food. In addition, the stationary phase has good separation ability for hydrophilic, hydrophobic, ionic substances and complex samples, making it a prospective material for chromatographic separation.

Ionic liquid-functionalized mesoporous multipod silica for simultaneously effective extraction of aflatoxin B1 and its two precursors from grain.

BACKGROUND: Aflatoxin B1 (AFB1) and its precursors contaminate food and agricultural products, posing a significant risk to food safety and human health, but simultaneous and effective extraction and determination of AFB1 and its precursors with varied structures is still a challenging task. RESULTS: In this study, a bisimidazolium-type ionic liquid functionalized mesoporous multipod silica (SiO2@mPMO-IL(im)2) was fabricated to extract AFB1 and its two precursors, i.e., averantin and sterigmatocystin. The SiO2@mPMO-IL(im)2 could simultaneously extract three targets with varied structures based on the multipods, mesopores, and multifunctional groups. The density functional theory calculations further verified the multiple interactions between SiO2@mPMO-IL(im)2 and targets. The fabricated SiO2@mPMO-IL(im)2 could effectively extract and determine three targets in grains by combing with dispersive solid-phase extraction and high-performance liquid chromatography. Good linearity (r2 > 0.9978), low LODs (0.9-1.5 µg kg-1) and LOQs (3.0-4.5 µg kg-1), satisfactory spiked recoveries (92.5%-106.8%) and high precisions (RSD<6.4%) were observed. SIGNIFICANCE AND NOVELTY: This work demonstrates the feasibility of SiO2@mPMO-IL(im)2 for simultaneous and effective extraction of toxins with varied structures and provides a promising sample preparation for the analysis of AFB1 and its precursors in grain samples.

Extraction of lignin-containing nanocellulose fibrils from date palm waste using a green solvent.

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.

Binary mixture of ionic liquid and span 80 for oil spill remediation: Synthesis and performance evaluation.

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.

Dissolution of cellulose in imidazolium-based double salt ionic liquids.

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.

Purification of exopolysaccharide produced from Lactobacillus spp. using ionic-liquid as adjuvant in alcohol/salt-based aqueous two-phase system for its antidiabetic properties.

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.

Solvation of Model Biomolecules in Choline-Aminoate Ionic Liquids: A Computational Simulation Using Polarizable Force Fields.

One can foresee a very near future where ionic liquids will be used in applications such as biomolecular chemistry or medicine. The molecular details of their interaction with biological matter, however, are difficult to investigate due to the vast number of combinations of both the biological systems and the variety of possible liquids. Here, we provide a computational study aimed at understanding the interaction of a special class of biocompatible ionic liquids (choline-aminoate) with two model biological systems: an oligopeptide and an oligonucleotide. We employed molecular dynamics with a polarizable force field. Our results are in line with previous experimental and computational evidence on analogous systems and show how these biocompatible ionic liquids, in their pure form, act as gentle solvents for protein structures while simultaneously destabilizing DNA structure.

Mechanisms of Biological Effects of Ionic Liquids: From Single Cells to Multicellular Organisms.

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.

Exceptional stability of ultrasmall cubic copper metal nanoclusters - a molecular dynamics study.

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.

Preparation of amino acid chiral ionic liquid and visual chiral recognition of glutamine and phenylalanine enantiomers.

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.

New Insights into the Hygroscopic Character of Ionic Liquids: Study of Fourteen Representatives of Five Cation and Four Anion Families.

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.

The Imidazolium Ionic Liquids Toxicity is Due to Their Effect on the Plasma Membrane.

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.

Curcumin-Based Ionic Liquid Hydrogel for Topical Transdermal Delivery of Curcumin To Improve Its Therapeutic Effect on the Psoriasis Mouse Model.

Psoriasis is a systemic, recurrent, chronic autoimmune skin disease. However, psoriasis drugs have poor skin permeability and high toxicity, resulting in low bioavailability and affecting their clinical application. In this study, we propose a curcumin-based ionic liquid hydrogel loaded with ilomastat (Cur-Car-IL@Ilo hydrogel), which can effectively maintain the sustained release of drugs and improve the skin permeability of drugs. We used a model of imiquimod-induced psoriasis and demonstrated that local application of Cur-Car-IL@Ilo hydrogel can improve skin lesions in mice with significantly reduced expression levels of inflammatory factors, matrix metalloproteinase 8, and collagen-I. The expressions of iron death-related proteins SLC7A11 and ASL4 were significantly decreased after treatment with Cur-Car-IL@Ilo hydrogel. Flora analysis showed that the content of anaerotruncus, proteus, and UCG-009 bacteria in the gut of psoriatic mice increased. The levels of paludicola, parabacteroides, prevotellaceae_UCG-001, escherichia-shigella, and aerococcus decreased, and the levels of some of the above bacteria tended to be normal after treatment. Therefore, the curcumin-based ionic liquid hydrogel can be used as a multifunctional, nonirritating, noninvasive, and highly effective percutaneous treatment of psoriasis.

Toward Greater DNA Stability by Leveraging the Proton-Donating Ability of Protic Ionic Liquids.

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!