Expeditious Discovery of Small-Molecule Thermoresponsive Ionic Liquid Materials: A Review.

Ionic liquids (ILs) are a class of low-melting molten salts (<100 °C) constituted entirely of ions, and their research has gained tremendous attention in line with their remarkably growing applications (>124,000 publications dated 30 August 2023 from the Web of ScienceTM). In this review, we first briefly discussed the recent developments and unique characteristics of ILs and zwitterionic liquids (ZILs). Compared to molecular solvents and other conventional organic compounds, (zwitter) ionic liquids carry negligible volatility and are potentially recyclable and reusable. For structures, both ILs and ZILs can be systematically tailor-designed and engineered and are synthetically fine-tunable. As such, ionic liquids, including chiral, supported, task-specific ILs, have been widely used as powerful ionic solvents as well as valuable additives and catalysts for many chemical reactions. Moreover, ILs have demonstrated their value for use as polymerase chain reaction (PCR) enhancers for DNA amplification, chemoselective artificial olfaction for targeted VOC analysis, and recognition-based affinity extraction. As the major focus of this review, we extensively discussed that small-molecule thermoresponsive ILs (TILs) and ZILs (zwitterionic TILs) are new types of smart materials and can be expeditiously discovered through the structure and phase separation (SPS) relationship study by the combinatorial approach. Using this SPS platform developed in our laboratory, we first depicted the rapid discovery of N,N-dialkylcycloammonium and 1,3,4-trialkyl-1,2,3-triazolium TILs that concomitantly exhibited LCST (lower critical solution temperature) phase transition in water and displayed biochemically attractive Tc values. Both smart IL materials were suited for applications to proteins and other biomolecules. Zwitterionic TILs are ZILs whose cations and anions are tethered together covalently and are thermoresponsive to temperature changes. These zwitterionic TIL materials can serve as excellent extraction solvents, through temperature change, for biomolecules such as proteins since they differ from the common TIL problems often associated with unwanted ion exchanges during extractions. These unique structural characteristics of zwitterionic TIL materials greatly reduce and may avoid the denaturation of proteins under physiological conditions. Lastly, we argued that both rational structural design and combinatorial library synthesis of small-molecule TIL materials should take into consideration the important issues of their cytotoxicity and biosafety to the ecosystem, potentially causing harm to the environment and directly endangering human health. Finally, we would concur that before precise prediction and quantitative simulation of TIL structures can be realized, combinatorial chemistry may be the most convenient and effective technology platform to discover TIL expeditiously. Through our rational TIL design and combinatorial library synthesis and screening, we have demonstrated its power to discover novel chemical structures of both TILs and zwitterionic TILs. Undoubtedly, we will continue developing new small-molecule TIL structures and studying their applications related to other thermoresponsive materials.

Prediction of adverse health outcomes using an electronic frailty index among nonfrail and prefrail community elders.

BACKGROUND: Early recognition of older people at risk of undesirable clinical outcomes is vital in preventing future disabling conditions. Here, we report the prognostic performance of an electronic frailty index (eFI) in comparison with traditional tools among nonfrail and prefrail community-dwelling older adults. The study is to investigate the predictive utility of a deficit-accumulation eFI in community elders without overt frailty. METHODS: Participants aged 65-80 years with a Clinical Frailty Scale of 1-3 points were recruited and followed for 2 years. The eFI score and Fried's frailty scale were determined by using a semiautomated platform of self-reported questionnaires and objective measurements which yielded cumulative deficits and physical phenotypes from 80 items of risk variables. Kaplan-Meier method and Cox proportional hazards regression were used to analyze the severity of frailty in relation to adverse outcomes of falls, emergency room (ER) visits and hospitalizations during 2 years' follow-up. RESULTS: A total of 427 older adults were evaluated and dichotomized by the median FI score. Two hundred and sixty (60.9%) and 167 (39.1%) elders were stratified into the low- (eFI ≤ 0.075) and the high-risk (eFI > 0.075) groups, respectively. During the follow-up, 77 (47.0%) individuals developed adverse events in the high-risk group, compared with 79 (30.5%) in the low-risk group (x2, p = 0.0006). In multivariable models adjusted for age and sex, the increased risk of all three events combined in the high- vs. low-risk group remained significant (adjusted hazard ratio (aHR) = 3.08, 95% confidence interval (CI): 1.87-5.07). For individual adverse event, the aHRs were 2.20 (CI: 1.44-3.36) for falls; 1.67 (CI: 1.03-2.70) for ER visits; and 2.84 (CI: 1.73-4.67) for hospitalizations. Compared with the traditional tools, the eFI stratification (high- vs. low-risk) showed better predictive performance than either CFS rating (managing well vs. fit to very fit; not discriminative in hospitalizations) or Fried's scale (prefrail to frail vs. nonfrail; not discriminative in ER visits). CONCLUSION: The eFI system is a useful frailty tool which effectively predicts the risk of adverse healthcare outcomes in nonfrail and/or prefrail older adults over a period of 2 years.

Emerging impacts of ionic liquids on eco-environmental safety and human health.

Owing to their unique physicochemical properties, ionic liquids (ILs) have been rapidly applied in diverse areas, such as organic synthesis, electrochemistry, analytical chemistry, functional materials, pharmaceutics, and biomedicine. The increase in the production and application of ILs has resulted in their release into aquatic and terrestrial environments. Because of their low vapor pressure, ILs cause very little pollution in the atmosphere compared to organic solvents. However, ILs are highly persistent in aquatic and terrestrial environments due to their stability, and therefore, potentially threaten the safety of eco-environments and human health. Specifically, the environmental translocation and retention of ILs, or their accumulation in organisms, are all related to their physiochemical properties, such as hydrophobicity. Based on results of ecotoxicity, cytotoxicity, and toxicity in mammalian models, the mechanisms involved in IL-induced toxicity include damage of cell membranes and induction of oxidative stress. Recently, artificial intelligence and machine learning techniques have been used in mining and modeling toxicity data to make meaningful predictions. Major future challenges are also discussed. This review will accelerate our understanding of the safety issues of ILs and serve as a guideline for the design of the next generation of ILs.

Reaction-Based Amine and Alcohol Gases Detection with Triazine Ionic Liquid Materials.

We demonstrated in this work the use of affinity ionic liquids, AIL 1 and AIL 2, for chemoselective detection of amine and alcohol gases on a quartz crystal microbalance (QCM). These detections of gaseous amines and alcohols were achieved by nucleophilic aromatic substitution reactions with the electrophilic 1,3,5-triazine-based AIL 1 thin-coated on quartz chips. Starting with inexpensive reagents, bicyclic imidazolium ionic liquids AIL 1 and AIL 2 were readily synthesized in six and four synthetic steps with high isolated yields: 51% and 63%, respectively. The QCM platform developed in this work is readily applicable and highly sensitive to low molecular weight amine gases: for isobutylamine gas (a bacterial volatile) at 10 Hz decrease in resonance frequency (i.e., ΔF = -10 Hz), the detectability using AIL 1 was 6.3 ppb. Our preliminary investigation on detection of the much less nucleophilic alcohol gas by AIL 1 was also promising. To our knowledge, no example to date of reports based on nucleophilic aromatic substitution reactions demonstrating sensitive gas detection in these triazine ionic liquids on a QCM has been reported.

Affinity Ionic Liquids for Chemoselective Gas Sensing.

Selective gas sensing is of great importance for applications in health, safety, military, industry and environment. Many man-made and naturally occurring volatile organic compounds (VOCs) can harmfully affect human health or cause impairment to the environment. Gas analysis based on different principles has been developed to convert gaseous analytes into readable output signals. However, gas sensors such as metal-oxide semiconductors suffer from high operating temperatures that are impractical and therefore have limited its applications. The cost-effective quartz crystal microbalance (QCM) device represents an excellent platform if sensitive, selective and versatile sensing materials were available. Recent advances in affinity ionic liquids (AILs) have led them to incorporation with QCM to be highly sensitive for real-time detection of target gases at ambient temperature. The tailorable functional groups in AIL structures allow for chemoselective reaction with target analytes for single digit parts-per-billion detection on mass-sensitive QCM. This structural diversity makes AILs promising for the creation of a library of chemical sensor arrays that could be designed to efficiently detect gas mixtures simultaneously as a potential electronic in future. This review first provides brief introduction to some conventional gas sensing technologies and then delivers the latest results on our development of chemoselective AIL-on-QCM methods.

Exploiting Solvate Ionic Liquids for Amine Gas Analysis on a Quartz Crystal Microbalance.

We demonstrated in this work the usefulness of solvate ionic liquids SIL 3 and SIL 4 for chemoselective detection of amine gases on a quartz crystal microbalance. This detection of gaseous amines was achieved by nucleophilic aromatic addition reactions with super electrophilic SIL 3 or SIL 4 thin-coated on quartz chips. Starting with inexpensive reagents, functional SIL 3 and SIL 4 could be readily synthesized in two short steps with high isolated yield (81 and 77%, respectively). The QCM platform developed in this work is readily applicable and highly sensitive to low molecular weight amine gases: for propylamine gas at 10 Hz decrease in resonance frequency, the sensitivity of detection using SIL 4 was 5.4 ppb. This simple and convenient assembly of neutral ligands (e.g., 1a and 1b) with Li+ ion to afford room temperature ionic liquids should be of great importance for a myriad of applications. To the best of our knowledge, no example to date of reports based on nucleophilic aromatic addition reactions demonstrating sensitive amine gas detection in solvate ionic liquids on a QCM has been reported. Furthermore, because of the high color intensity of the Meisenheimer complexes formed, our preliminary result showed that SIL 4 loaded on copier paper can be used not only as a portable amine gas sensor but also as a potential invisible ink that is only revealed by amine vapor.

Exploiting 1,2,3-Triazolium Ionic Liquids for Synthesis of Tryptanthrin and Chemoselective Extraction of Copper(II) Ions and Histidine-Containing Peptides.

Based on a common structural core of 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyridine, a number of bicyclic triazolium ionic liquids 1-3 were designed and successfully prepared. In our hands, this optimized synthesis of ionic liquids 1 and 2 requires no chromatographic separation. Also in this work, ionic liquids 1, 2 were shown to be efficient ionic solvents for fast synthesis of tryptanthrin natural product. Furthermore, a new affinity ionic liquid 3 was tailor-synthesized and displayed its effectiveness in chemoselective extraction of both Cu(II) ions and, for the first time, histidine-containing peptides.

Exploring silver ionic liquids for reaction-based gas sensing on a quartz crystal microbalance.

Reaction-based, sensitive sensing of aldehyde and ketone gases in real time was effectively achieved on QCM chips thin-coated with silver ionic liquids and , respectively. The method platform developed in this work involves straightforward synthesis of functional silver ionic liquids in water, and is label-free and highly chemoselective with superior gas reactivity for and and, most significantly, totally insensitive to moisture.

Identification of prophage gene z2389 in Escherichia coli EDL933 encoding a DNA cytosine methyltransferase for full protection of NotI sites.

Pulsed-field gel electrophoresis (PFGE) analysis revealed that the genomes of some pathogenic Escherichia coli O157:H7 strains, including EDL933, were resistant to NotI digestion. An amino acid sequence comparison suggested that the z2389 gene carried on prophage CP-933R in strain EDL933 is likely to encode a C(5)-cytosine methyltransferase. The z2389-equivalent gene was found in the NotI-resistant strains tested, but it was not detected in the NotI-susceptible strains. PFGE analysis of the wild-type EDL933 strain and of a z2389 null mutant revealed that z2389 was associated with full genome protection against NotI digestion and partial protection against EagI digestion. In vitro methylation experiments with purified recombinant protein demonstrated that Z2389 is capable of methylating NotI and EagI sites. Sequencing of bisulfite-treated DNA indicated that the methylation occurred at the first cytosine residue of the NotI recognition sequence, whereas EagI sites remained unmethylated or were methylated at the first cytosine residue. Thus, z2389 encodes a DNA cytosine methyltransferase that confers full protection to NotI sites.