Direct Extraction of Sodium Hydroxide by Calix[4]pyrrole-Based Ion-Pair Receptors.

Described in this work are calix[4]pyrrole-based ion-pair receptors, cis/trans-1 and cis/trans-2, designed for the extraction of sodium hydroxide. An X-ray diffraction analysis of a single crystal of the cis-1·NaOH isomer isolated from a mixture of cis/trans-1 revealed a unique dimeric supramolecular structure. An average dimer in toluene-d8 solution was inferred on the basis of diffusion-ordered spectroscopy (DOSY). Support for the proposed stoichiometry came from density functional theory (DFT) calculations. The structural stability of the dimeric cis-1·NaOH complex in toluene solution was further confirmed by ab initio molecular dynamics (AIMD) simulation with explicit representation of solvent. Under conditions of liquid-liquid extraction (LLE), purified receptors cis- and trans-2 were both found to remove NaOH from a pH 11.01 aqueous source phase into toluene with extraction efficiencies (E%) of 50-60% when used equimolar to NaOH. However, in all cases, precipitation was observed. Complexities associated with precipitation could be avoided by immobilization of the receptors onto a chemically inert poly(styrene) resin by means of solvent impregnation. The use of solvent-impregnated resins (SIRs) eliminated precipitation in solution while retaining the extraction efficiency toward NaOH. This allowed both the pH and salinity of the alkaline source phase to be lowered.

Fluorescent copolymer aggregate sensor for lithium chloride.

We report a copolymeric fluorescent sensor that is selective for lithium chloride. The two constituent polymers comprise pendent triphenylethylene (TPE) moieties for aggregate induced emission (AIE) along with either strapped-calix[4]pyrrole or secondary ammonium groups that drive aggregation via self-assembly upon polymer mixing. Addition of LiCl in acetonitrile disrupts the strapped-calix[4]pyrrole/secondary ammonium chloride salt host-guest crosslinks leading to disaggregation of the polymer chains and a decrease in TPE emission. The lack of AIE perturbation upon addition of NaCl, KCl, MgCl2 or CaCl2 provides for high selectivity for LiCl relative to potential interferants. This supramolecular dual polymer approach could serve as a complement to more traditional sensor systems.

Selective Separation of Lithium Chloride by Organogels Containing Strapped Calix[4]pyrroles.

Reported herein are two functionalized crown ether strapped calix[4]pyrroles, H1 and H2. As inferred from competitive salt binding experiments carried out in nitrobenzene-d5 and acetonitrile-d3, these hosts capture LiCl selectively over four other test salts, viz. NaCl, KCl, MgCl2, and CaCl2. Support for the selectivity came from density functional theory (DFT) calculations carried out in a solvent continuum. These theoretical analyses revealed a higher innate affinity for LiCl in the case of H1, but a greater selectivity relative to NaCl in the case of H2, recapitulating that observed experimentally. Receptors H1 and H2 were outfitted with methacrylate handles and subject to copolymerization with acrylate monomers and cross-linkers to yield gels, G1 and G2, respectively. These two gels were found to adsorb lithium chloride preferentially from an acetonitrile solution containing a mixture of LiCl, NaCl, KCl, MgCl2, and CaCl2 and then release the lithium chloride in methanol. The gels could then be recycled for reuse in the selective adsorption of LiCl. As such, the present study highlights the use of solvent polarity switching to drive separations with potential applications in lithium purification and recycling.

Synthetic Na+/K+ exchangers promote apoptosis by disturbing cellular cation homeostasis.

A number of artificial cation ionophores (or transporters) have been developed for basic research and biomedical applications. However, their mechanisms of action and the putative correlations between changes in intracellular cation concentrations and induced cell death remain poorly understood. Here, we show that three hemispherand-strapped calix[4]pyrrole-based ion-pair receptors act as efficient Na+/K+ exchangers in the presence of Cl- in liposomal models and promote Na+ influx and K+ efflux (Na+/K+ exchange) in cancer cells to induce apoptosis. Mechanistic studies reveal that these cation exchangers induce endoplasmic reticulum (ER) stress in cancer cells by perturbing intracellular cation homeostasis, promote generation of reactive oxygen species, and eventually enhance mitochondria-mediated apoptosis. However, they neither induce osmotic stress nor affect autophagy. This study provides support for the notion that synthetic receptors, which perturb cellular cation homeostasis, may provide new small molecules with potentially useful apoptotic activity.

Strapped calix[4]pyrroles: from syntheses to applications.

Supramolecular chemistry is a central topic in modern chemistry. It touches on many traditional disciplines, such as organic chemistry, inorganic chemistry, physical chemistry, materials chemistry, environmental chemistry, and biological chemistry. Supramolecular hosts, inter alia macrocyclic hosts, play critical roles in supramolecular chemistry. Calix[4]pyrroles, non-aromatic tetrapyrrolic macrocycles defined by sp3 hybridized meso bridges, have proved to be versatile receptors for neutral species, anions, and cations, as well as ion pairs. Compared to the parent system, octamethylcalix[4]pyrrole and its derivatives bearing simple appended functionalities, strapped calix[4]pyrroles typically display enhanced binding affinities and selectivities. In this review, we summarize advances in the design and synthesis of strapped calix[4]pyrroles, as well as their broad utility in molecular recognition, supramolecular extraction, separation technology, ion transport, and as agents capable of inhibiting cancer cell proliferation. Future challenges within this sub-field are also discussed.

Determinants of Ion-Transporter Cancer Cell Death.

Recently, we showed that synthetic anion transporters DSC4P-1 and SA-3 had activity related to cancer cell death. They were found to increase intracellular chloride and sodium ion concentrations. They were also found to induce apoptosis (DSC4P-1) and both induce apoptosis and inhibit autophagy (SA-3). However, determinants underlying these phenomenological findings were not elucidated. The absence of mechanistic understanding has limited the development of yet-improved systems. Here, we show that three synthetic anion transporters, DSC4P-1, SA-3, and 8FC4P, induce osmotic stress in cells by increasing intracellular ion concentrations. This triggers the generation of reactive oxygen species via a sequential process and promotes caspase-dependent apoptosis. In addition, two of the transporters, SA-3 and 8FC4P, induce autophagy by increasing the cytosolic calcium ion concentration promoted by osmotic stress. However, they eventually inhibit the autophagy process as a result of their ability to disrupt lysosome function through a transporter-mediated decrease in a lysosomal chloride ion concentration and an increase in the lysosomal pH.

Uranyl dication mediated photoswitching of a calix[4]pyrrole-based metal coordination cage.

A set of self-assembled tri- and tetrapodal metal coordination cage structures (cage-1 and cage-2, respectively) constructed from the uranyl dication (UO22+) and a dibenzoic acid functionalised cis-calix[4]pyrrole (1) are described. The inherent photochemical reactivity of the uranyl dication mediates the transformation of cage-1 to cage-2via the activation of molecular oxygen.

A Comparison of the Efficacy and Safety of Non-Steroidal Anti-Inflammatory Drugs versus Acetaminophen in Symptom Relief for the Common Cold: A Meta-Analysis of Randomized Controlled Trial Studies.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are widely used for common cold symptom relief. The objective of this study was to evaluate and compare the efficacy and safety of acetaminophen and NSAIDs in common cold symptom relief using meta-analysis of randomized controlled trial. METHODS: We searched MEDLINE (PubMed), Cochrane, EMBASE, CINAHL, KMbase, KoreaMed, National Assembly Library, and Riss4u for studies released through June 2012. Two authors independently extracted the data. To assess the risk of bias, the Cochrane Collaborations risk of bias tool was used. The Review Manager ver. 5.1 (RevMan) was used for statistics. RESULTS: We identified 5 studies. The relative benefit for participants with pain relief was 1.00 (95% confidence interval [CI], 0.96 to 1.05) and I(2) = 0%. The existence of the heterogeneity between studies was not important in this study, thus subgroup analysis was not implemented. The relative benefit for participants with rhinorrhea was 1.02 (95% CI, 0.77 to 1.35) and I(2) = 0%, which also indicates the existence of heterogeneity was not important. The relative risk of adverse events was 1.14 (95% CI, 0.93 to 1.40), I(2) = 0%. There was no apparent asymmetry in the funnel plot. CONCLUSION: There was no difference between NSAIDs and acetaminophen in common cold symptom relief.

The effect of probiotics on prevention of common cold: a meta-analysis of randomized controlled trial studies.

BACKGROUND: Probiotics are currently under focus for their immune improvement function. Many studies have been performed to assess the potential efficacy of probiotics in allergic disease, viral disease, respiratory disease, as well as gastrointestinal disease. This study performed a systematic review to determine the effects of probiotics on the prevention of the common cold. METHODS: We searched MEDLINE (PubMed), EMBASE, CINAHL, and Cochrane CENTRAL for studies released through June 2011. Two authors independently extracted the data. To assess the risk of bias of included literatures, Cochrane Collaboration's risk of bias tool was used. RESULTS: We identified 10 studies in 7 articles. A total 2,894 participants, 1,588 in the probiotics group and 1,306 in the control group, were included. The effect of probiotics on the prevention of the common cold had a relative risk (RR) of 0.92 (95% CI, 0.85 to 1.00, I(2) = 26%). In the subgroup analysis, the RR of administration of probiotics for 3 months or less was 0.82 (95% CI, 0.70 to 0.97). The RR of administration of probiotics over 3 months was 1.00 (95% CI, 0.92 to 1.09). The RR of administration of probiotics without any active intervention (vitamin and mineral) was 0.87 (95% CI, 0.78 to 0.97). CONCLUSION: In this meta-analysis, there was marginal effect of probiotics on the prevention of the common cold. The results implied that probiotics had a modest effect in common cold reduction. The balance of benefit and harms needs to be considered when using probiotics for common cold prevention.