The Debye length and anionic transport properties of composite membranes based on supported ionic liquid-like phases (SILLPS).

An analysis of the ionic transport properties of BMIM [NTf2] in supported ionic-liquid-like phase (SILLP)-based membranes has been carried out based on experimental impedance spectroscopy measurements. The direct current (dc)-conductivity was analyzed to determine the temperature and frequency dependence. The fit of the loss tangent curve data with the Cole-Cole approximation of the electrode polarization model provides the conductivity, diffusivity, and density of charge carriers. Among these quantities, a significant increase in conductivity is observed when an ionic liquid is added to the polymeric matrix containing imidazolium fragments. The use of a recent generalization of Eyring's absolute rate theory allowed the elucidation of how the local entropy restrictions, due to the porosity of the polymeric matrix, control the conductive process. The fit of the conductivity data as a function of temperature manifests the behavior of the excess entropy with respect to the temperature. The activation entropy and enthalpy were also determined. Our results correlate the Debye length (LD) with the experimental values of conductivity, electrode polarization relaxation time, and sample relaxation time involved. Our work provides novel insights into the description of ionic transport in membranes as the diffusivity, mobility, and free charge density depend on the LD. Moreover, we discuss the behavior of the polarization relaxation time, the sample relaxation time, and the static permittivity as a function of the temperature.

Basically, nucleophilicity matters little: towards unravelling the supramolecular driving forces in enzyme-like CO2 conversion.

The reaction mechanism for the cycloaddition of CO2 to styrene oxide in the presence of macrocyclic pseudopeptides has been studied using DFT methods. Computational calculations indicate that the unprecedented catalytic behaviour previously observed experimentally, in which the most reactive species was not the most nucleophilic but the most basic one, can be associated to the tight cooperativity between several supramolecular interactions promoted by simple peptidomimetics able to display a synzymatic behaviour. This bizarre catalytic performance afforded remarkable conversions of a sluggish substrate like styrene oxide into the desired cyclic carbonate, even under relatively mild reaction conditions, opening the way for the practical use of CO2 as a raw material in the preparation of valuable chemicals. Furthermore, the remote modification of essential structural features of the macrocycle (synzyme engineering) permitted the driving forces of the synzymatic system to be analyzed, stressing the crucial synergic effect between an elegantly preorganized oxyanion hole and additional aromatic interactions.

Unravelling the Supramolecular Driving Forces in the Formation of CO2-Responsive Pseudopeptidic Low-Molecular-Weight Hydrogelators.

A new family of C2-symmetric pseudopeptides with a high functional density for supramolecular interactions has been synthetized through the attachment of four amino acid subunits to a diamino aliphatic spacer. The resulting open-chain compounds present remarkable properties as low-molecular-weight hydrogelators. The self-assembled 3D networks were characterized by SEM analyses, observing regular nanofibres with 80-100 nm diameters. Spectroscopic and molecular modelling experiments revealed the presence of strong synergic effects between the H-bonding and π-π interactions, with the best results obtained for the homoleptic tetra-pseudopeptide derived from l-Phe. In addition, these bioinspired hydrogels possessed pH- and CO2-responsive sol-gel transitions. The formation of ammonium carbamate derivatives in the presence of carbon dioxide led to a detrimental change in its adequate self-assembly. CO2 desorption temperatures of ca. 70 °C were assigned to the thermodynamically favoured recovery of the supramolecular gel.

Continuous Flow Processes as an Enabling Tool for the Synthesis of Constrained Pseudopeptidic Macrocycles.

Herein we report our efforts to develop a continuous flow methodology for the efficient preparation of pseudopeptidic macrocyclic compounds containing the hexahydropyrrolo-[3,4-f]-isoindolocyclophane scaffold and involving four coupled substitution reactions in the macrocyclization process. Appropriate design of a supported base permitted the continuous production of the macrocycles even at large scales, taking advantage of the positive template effect promoted by the bromide anions. In addition, the use of flow protocols allowed a ca. 20-fold increase in productivity as well as reducing the environmental impact almost 2 orders of magnitude, in comparison with the related batch macrocyclization process.

Structure-antitumor activity relationships of tripodal imidazolium-amino acid based salts. Effect of the nature of the amino acid, amide substitution and anion.

The antitumor activity of imidazolium salts is highly dependent upon their lipophilicity that can be tuned by the introduction of different hydrophobic substituents on the nitrogen atoms of the imidazolium ring of the molecule. Taking this into consideration, we have synthesized and characterized a series of tripodal imidazolium salts derived from L-valine and L-phenylalanine containing different hydrophobic groups and tested them against four cancer cell lines at physiological and acidic pH. At acidic pH (6.2) the anticancer activity of some of the tripodal compounds changes dramatically, and this parameter is crucial to control their cytotoxicity and selectivity. Moreover, several of these compounds displayed selectivity against the control healthy cell line higher than four. The transmembrane anion transport studies revealed moderate transport abilities suggesting that the observed biological activity is likely not the result of just their transport activity. The observed trends in biological activity at acidic pH agree well with the results for the CF leakage assay. These results strongly suggest that this class of compounds can serve as potential chemotherapeutic agents.

Preparation of Nanofibers Mats Derived from Task-Specific Polymeric Ionic Liquid for Sensing and Catalytic Applications.

Nanofibers mats derived from the task-specific functionalized polymeric ionic liquids based on homocysteine thiolactone are obtained by electrospinning them as blends with polyvinylpyrrolidone. The presence of this functional moiety allowed the post-functionalization of these mats through the aminolysis of the thiolactone ring in the presence of an amine by a thiol-alkene "click" reaction. Under controlled experimental conditions the modification can be performed introducing different functionalization and crosslinking of the electrospun fibers, while maintaining the nanostructure obtained by the electrospinning. Initial studies suggest that the nanofibers based on these functionalized polymeric ionic liquids can be used in both sensing and catalytic applications.

Unveiling anion-induced folding in tripodal imidazolium receptors by ion-mobility mass spectrometry.

The anion-induced folding of tripodal imidazolium receptors has been investigated by NMR spectroscopy, electrospray ionization ion mobility mass spectrometry and DFT calculations. Such folding can be switched by anion release upon collision induced dissociation.

Chiral Imidazolium Prolinate Salts as Efficient Synzymatic Organocatalysts for the Asymmetric Aldol Reaction.

Chiral imidazolium l-prolinate salts, providing a complex network of supramolecular interaction in a chiral environment, have been studied as synzymatic catalytic systems. They are demonstrated to be green and efficient chiral organocatalysts for direct asymmetric aldol reactions at room temperature. The corresponding aldol products were obtained with moderate to good enantioselectivities. The influence of the presence of chirality in both the imidazolium cation and the prolinate anion on the transfer of chirality from the organocatalyst to the aldol product has been studied. Moreover, interesting match/mismatch situations have been observed regarding configuration of chirality of the two components through the analysis of results for organocatalysts derived from both enantiomers of prolinate (R/S) and the trans/cis isomers for the chiral fragment of the cation. This is associated with differences in the corresponding reaction rates but also to the different tendencies for the formation of aggregates, as evidenced by nonlinear effects studies (NLE). Excellent activities, selectivities, and enantioselectivities could be achieved by an appropriate selection of the structural elements at the cation and anion.

Imidazole and Imidazolium Antibacterial Drugs Derived from Amino Acids.

The antibacterial activity of imidazole and imidazolium salts is highly dependent upon their lipophilicity, which can be tuned through the introduction of different hydrophobic substituents on the nitrogen atoms of the imidazole or imidazolium ring of the molecule. Taking this into consideration, we have synthesized and characterized a series of imidazole and imidazolium salts derived from L-valine and L-phenylalanine containing different hydrophobic groups and tested their antibacterial activity against two model bacterial strains, Gram-negative E. coli and Gram-positive B. subtilis. Importantly, the results demonstrate that the minimum bactericidal concentration (MBC) of these derivatives can be tuned to fall close to the cytotoxicity values in eukaryotic cell lines. The MBC value of one of these compounds toward B. subtilis was found to be lower than the IC50 cytotoxicity value for the control cell line, HEK-293. Furthermore, the aggregation behavior of these compounds has been studied in pure water, in cell culture media, and in mixtures thereof, in order to determine if the compounds formed self-assembled aggregates at their bioactive concentrations with the aim of determining whether the monomeric species were in fact responsible for the observed antibacterial activity. Overall, these results indicate that imidazole and imidazolium compounds derived from L-valine and L-phenylalanine-with different alkyl lengths in the amide substitution-can serve as potent antibacterial agents with low cytotoxicity to human cell lines.

Polymeric Ionic Liquids Derived from L-Valine for the Preparation of Highly Selective Silica-Supported Stationary Phases in Gas Chromatography.

A series of silica-supported polymeric ionic liquid (PIL)-based stationary phases derived from a vinylic L-valine ionic liquid monomer and divinylbenzene (DVB) as the crosslinking agent have been prepared and studied as gas chromatographic stationary phases. These coated gas chromatographic columns exhibited good thermal stabilities (230-300 °C) and high efficiencies (1700-2700 plates/m), and were characterized using a linear solvation parameter model in order to understand the effects of the amount of DVB on the features of the resulting composite systems. Their retention behavior and separation efficiencies were demonstrated using the Grob test. By tuning the crosslinking degree for the IL-derived stationary phase, the separation selectivity and resolution of different compounds were improved. The different retention behaviors observed for many analytes indicate that these stationary phases may be applicable as new types of GC stationary phases.

Urea-Based Low-Molecular-Weight Pseudopeptidic Organogelators for the Encapsulation and Slow Release of (R)-Limonene.

Low-molecular-weight compounds containing alkylurea fragments attached to the amino end of different miminalistic pseudopeptidic structures have been shown to be excellent organogelators in a variety of organic solvents and liquid organic compounds of different nature. The formation of gels in this work is defined through rheological measurements for those cases where G' > G''. Both the topology and the symmetry of the corresponding urea compounds play a role in defining their organogelator behavior. This can also be tuned by the presence of additional supramolecular guests, as is the case for suberic acid. These compounds also achieve the gelation of relevant active substances such as terpene natural oils and complex mixtures of flavors and fragrances. This provides a simple and mass-efficient supramolecular system for the quantitative encapsulation of active substances, without the need for any additional solvent or complex processes, and their consequent controlled release.

Highly Selective Anion Template Effect in the Synthesis of Constrained Pseudopeptidic Macrocyclic Cyclophanes.

Herein, we report the synthesis of a novel family of constrained pseudopeptidic macrocyclic compounds containing the hexahydropyrrolo[3,4-f]isoindolocyclophane scaffold and involving four coupled substitution reactions in the macrocyclization process. Although the increase in the number of steps involved in the macrocyclization could lead to a larger number of possible side products, the optimization of the methodology and the study of the driving forces have made it possible to obtain the desired macrocycles in excellent yields. A thorough computational study has been carried out to understand the macrocyclization process, and the results obtained nicely agree with experimental data. Moreover, the bromide anion had a clear catalytic template effect in the macrocyclization reaction, and surprisingly, the chloride anion had a negative template effect in opposition to the results obtained for analogous macrocycles. The parameters responsible for the specific kinetic template effect observed have been studied in detail.

Chiral catalysts immobilized on achiral polymers: effect of the polymer support on the performance of the catalyst.

Positive effects of the polymeric support on the performance of supported chiral catalysts, in terms of activity, stability and selectivity-enantioselectivity, have been reported when the support is properly selected and optimized opening the way to the design of more efficient catalytic systems.

Cu2+ recognition by N,N'-benzylated bis(amino amides).

Two new C2-symmetric N,N'-benzylated bis(amino amides) have been synthesised and their interaction with different transition metals studied using a variety of techniques including UV-Vis and CD spectroscopy or ESI-MS. The determination of the corresponding stability constants with Cu2+ has been possible, in H2O/CH3CN 7/3 v/v, for one of these ligands (4) using potentiometric titrations. The results obtained reveal that N-benzylation affords significant changes to their properties and is accompanied by an appreciable decrease in the corresponding complexation stability constants. However, this, along with the low kinetics associated to Ni2+, facilitates the recognition of Cu2+ by 4 that can be followed by the naked-eye up to the submillimolar range. Very interestingly, the chiral nature of this ligand provides an intense and well defined CD curve for the corresponding Cu2+ complex, very sensitive to the coordination geometry, facilitating the analysis of this interaction even at the µM range. The formation by both ligands (3 and 4) of square planar complexes with Cu2+ and Ni2+ displaying a 1 : 1 stoichiometry was confirmed by their X-ray crystal structures.

Cu(2+), Zn(2+), and Ni(2+) Complexes of C2-Symmetric Pseudopeptides with an Aromatic Central Spacer.

Two new tetradentate C2-symmetric pseudopeptidic ligands derived from Val and Phe containing two amino and two amido groups and a central o-substituted aromatic spacer have been prepared. Their complexes with Cu(2+), Zn(2+), and Ni(2+) have been studied by potentiometry, UV-vis spectrophotometry, FT-IR, and ESI-MS. The presence of the aromatic spacer provides Cu(2+) complexes with stability constants several orders of magnitude higher than those observed for related ligands containing aliphatic central spacers. Besides, the formation of [MH-2L] complex species is favored. Crystal structures for the corresponding Cu(2+) and Ni(2+) have been obtained, revealing the metal atom in an essentially square-planar geometry, although, in several instances, the oxygen atom of an amide carbonyl of a second complex species can act as a fifth coordination site. In the case of Zn(2+), the only crystal structure obtained displays a square-pyramidal arrangement of the metal center. Finally, preliminary experiments show the catalytic activity of some of these complexes, in particular, Zn(2+) complexes, for epoxide ring-opening with using aniline as the nucleophile in a ligand accelerated process.

Gas chromatographic analysis of fatty acid methyl esters of milk fat by an ionic liquid derived from L-phenylalanine as the stationary phase.

A Gas Chromatography (GC) method has been developed for the separation and characterization of the different fatty acids in anhydrous milk fat (AMF) by means of an ionic liquid stationary phase, characterized by a monocationic imidazolium salt derived from L-phenylalanine. The inner surface of a fused silica capillary column was modified using this ionic liquid functionality and 3-aminopropyldiethoxymethyl silane. This coated GC column, which exhibited good thermal stability (270°C) and good efficiency (2700 plates/m), has been characterized using the Abraham solvation parameter model. The intra-day and inter-day precision of the method have been evaluated, obtaining relative standard deviations (RSD) from 0.99% to 4.0% and from 2.8% to 9.2%, respectively. Furthermore, recoveries from 90% and 99% have been achieved.

Application of optically active chiral bis(imidazolium) salts as potential receptors of chiral dicarboxylate salts of biological relevance.

A family of chiral bis(imidazolium) salts derived from natural amino acids has been synthesized by a simple synthetic approach and the corresponding bis(trifluoromethylsulfonyl)imide salts have been shown to be room temperature chiral ionic liquids (RTCILs). The structures and self-assembling properties of the resulting salts have been studied by (1)HNMR, ATR-FTIR, DSC, SEM and theoretical calculations. Moreover, these receptors have been applied to the enantiomeric recognition of dicarboxylic amino acids. The supramolecular complexes formed have been studied by (1)HNMR titration experiments, ATR-FTIR and DSC.

LCST-type polymers based on chiral-polymeric ionic liquids.

The self-assembly of linear polymers containing chiral IL units generates a high-order supramacromolecular structure with a complex hierarchical architecture, which is able to exhibit thermoresponsive behavior (lower critical solution temperature: LCST) with different structural elements that can be used to fine tune this LCST.

Polymer-Grafted Ti-TADDOL Complexes. Preparation and Use as Catalysts in Diels-Alder Reactions.

Different strategies have been evaluated for the preparation of polymers functionalized with chiral fragments containing the alpha,alpha,alpha',alpha'-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL) structure. Best results are obtained when TADDOL derivatives containing OH phenolic groups (17 and 18) are prepared in solution and then selectively anchored to chloromethylated polymers by reaction in THF containing NaH and small amounts of 18C6 and NBu(4)I. Resins 19 having the desired functionality have been prepared in this way. The procedure allows the efficient introduction of this functional group in PS-DVB polymers with different loading and cross-linking degrees, as well as on SMOP resins. These functionalized resins have been used to prepare Ti-TADDOL-supported complexes which have been tested as catalysts in the reaction of cyclopentadiene with 3-crotonoyl-1,3-oxazolidin-2-one. Although all the polymers obtained efficiently catalyze the reaction, only the one prepared from alpha,alpha,alpha',alpha'-tetra-3,5-dimethylphenyl-1,3-dioxolane-4,5-dimethanol induces asymmetry.