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A C 2 symmetric L-phenylalanine-derived pseudopeptide has been synthesized for selective and sensitive recognition of Zn(II) ions in aqueous-organic media. The pseudopeptidic probes exhibit intracellular Zn(II) ion-sensing capabilities as demonstrated via live-cell fluorescence studies on RAW264.7 cells. Hence, we present a bioinspired pseudopeptide for potential biological applications involving intracellular Zn(II) ion detection.

The reaction mechanism for the cycloaddition of CO 2 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 CO 2 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.

A new family of C 2 -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 CO 2 -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. CO 2 desorption temperatures of ca. 70 °C were assigned to the thermodynamically favoured recovery of the supramolecular gel.

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.

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.

Prolinamides are well-known organocatalysts for the HSiCl 3 reduction of imines; however, custom design of catalysts is based on trial-and-error experiments. In this work, we have used a combination of computational calculations and experimental work, including kinetic analyses, to properly understand this process and to design optimized catalysts for the benchmark (E)- N -(1-phenylethylidene)aniline. The best results have been obtained with the amide derived from 4-methoxyaniline and the N -pivaloyl protected proline, for which the catalyzed process is almost 600 times faster than the uncatalyzed one. Mechanistic studies reveal that the formation of the component supramolecular complex catalyst-HSiCl 3 -substrate, involving hydrogen bonding breaking and costly conformational changes in the prolinamide, is an important step in the overall process.

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.

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.

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 IC 50 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.

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.

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.